SK1512002A3 - 2-pyrazolin-5-ones - Google Patents

Abstract

Chemical compounds having structural formula (I) and physiologically acceptable salts thereof, are inhibitors of serine/threonine and tyrosine kinase activity. Several of the tyrosine kinases, whose activity is inhibited by these chemical compounds, are involved in angiogenic processes. Thus, these chemical compounds can ameliorate disease states where angiogenesis or endothelial cell hyperproliferation is a factor. These compounds can be used to treat cancer and hyperproliferative disorders.

Description

Technical field

The present invention relates to certain 2-pyrazolin-5-ones which are inhibitors of protein kinases, in particular tyrosine kinases and serine / threonine kinases, some of which are novel compounds, the present invention further relates to pharmaceutical compositions containing these pyrazolinones and methods for preparing these pyrazolinones.

BACKGROUND OF THE INVENTION

At least 400 enzymes have been identified as protein kinases. These enzymes catalyze the phosphorylation of target protein substrates. Phosphorylation typically involves a reaction involving transfer of a phosphate group from ATP to a protein substrate. The specific structure in the target substrate to which the phosphate group is transferred is a tyrosine, serine or threonine residue. Since these amino acid residues are the target structures for phosphoryl transfer, these protein kinase enzymes are commonly referred to as tyrosine kinases or serine / threonine kinases.

Phosphorylation reactions and counteracting phosphatase reactions at tyrosine, serine, and threonine residues are involved in innumerable cellular processes that underlie responses to various intracellular signals (typically mediated by cellular receptors), regulate cellular functions, and activate or deactivate cellular processes. The protein kinase cascade often participates in intracellular signal transduction, and these enzymes are important for the realization of these cellular processes. Due to their ubiquity, protein kinases may be an integral part of the plasma membrane or cytoplasmic enzymes or may be localized in the nucleus, very often as components of enzyme complexes. In many cases, these protein kinases are essential elements of the enzyme and structural protein complexes that determine when and where cellular processes will take place in the cell.

Protein tyrosine kinases

Protein tyrosine kinases (PTKs) are enzymes that catalyze the phosphorylation of specific tyrosine residues in cellular proteins. Post-translational modifications of these substrate proteins, often the enzymes themselves, act as a molecular switch regulating cell proliferation, activation, or differentiation (reviewed in Schlessinger and Ulrich, 1992, Neuron 9: 383-391). Aberrant or excess PTK activity has been observed in many diseases including benign and malignant proliferative disorders, as well as diseases resulting from inappropriate immune system activation (e.g., autoimmune disorders), allograft rejection, and graft-versus-host disease. In addition, endothelial cell-specific PTK receptors, e.g. DRC and Tie-2 mediate angiogenic processes and thereby contribute to the progression of cancer and other diseases related to inadequate vascularization (eg diabetic retinopathy, choroidal neovascularization due to age-related macular degeneration, psoriasis, arthritis, retinopathy, retinopathy) ).

Tyrosine kinases may be of the receptor type (having extracellular, transmembrane and intracellular domains) or of the non-receptor type (being completely intracellular).

Receptor tyrosine kinases (RTKs)

RTKs include a large family of transmembrane receptors with different biological activities. To date, at least nineteen (19) distinct RTK subgroups have been identified. The receptor tyrosine kinase (RTK) family includes receptors that are critical for the growth and differentiation of various cell types (Yarden and Ullrich, Ann. Rev. Biochem. 57: 433-478, 1988; Ullrich and Schlessinger, Cell 61: 243-254, 1990) ). The intrinsic function of RTKs is activated after ligand binding, resulting in phosphorylation of the receptor and multiple cellular substrates and consequently different cellular responses (Ullrich & Schlessinger, 1990, Cell 61: 203-212). Thus, receptor tyrosine kinase-mediated signal transduction is initiated by extracellular interaction with a specific growth factor (ligand), typically followed by receptor dimerization, stimulation of intrinsic protein tyrosine kinase activity, and receptor transphosphorylation. This creates the binding sites for intracellular signal transduction molecules and leads to complexes with a spectrum of cytoplasmic signaling molecules that support the respective cellular response (e.g. cell division, differentiation, metabolic effects, changes in the extracellular microenvironment) see Schlessinger and Ullrich, 1992, Neuron 9: 1-20.

Proteins with SH2 (src homology-2) or phosphotyrosine binding (PTB) domains bind activated receptor tyrosine kinases and their substrates with high affinity, thereby spreading signals to cells. Both domains recognize phosphotyrosine. (Fantl et al., 1992, Cell 69: 413423; Songyang et al., 1994, Mol. Cell. Biol. 14: 2777-2785; Songyang et al., 1993, Cell 72: 767-778; and Koch et al. , 1991, Science 252: 668-678, Shoelson, Curr Opin, Chem Biol (1997), 1 (2), 227-234; Cowburn, Curr Opin, Struct Biol (1997), 7 ( 6), 835-838). Several intracellular substrate proteins have been identified that are associated with receptor tyrosine kinases (RTKs). They can be divided into two main groups: (1) substrates having a catalytic domain; and (2) substrates which do not have this domain but serve as adapters and associate with catalytically active molecules (Syngyang et al., 1993, Cell 72: 767-778). The specificity of interactions between receptors or proteins and the SH2 or PTB domains of their substrates is determined by the amino acid residues immediately surrounding the phosphorylated tyrosine residue. For example, differences in binding affinities between SH2 domains and amino acid sequences flanking phosphotyrosine residues at self receptors correlate with observed differences in their substrate phosphorylation profiles (Songyang et al., 1993, Cell 72: 767-778). Observations suggest that the function of each receptor tyrosine kinase is determined not only by its expression model and ligand availability, but also by the system of downstream signal transduction pathways that are activated by its own receptor, as well as the timing and timing of this stimulation. Thus, phosphorylation provides an important regulatory step that determines the selectivity of signaling pathways complemented by specific growth factor receptors as well as differentiation factor receptors.

Several tyrosine kinase receptors, e.g. FGFR-1, PDGFR and c-Met, and the growth factors that bind to them, play a role in angiogenesis, although some may induce angiogenesis indirectly (Mustonen and Alitalo, J. Cell. Biol. 129: 895-898, 1995). One such receptor tyrosine kinase, known as "fetal liver kinase 1" (FLK-1), is a member of the type III RTK subclass. Another term for human FLK-1 is "the inserted domain kinase receptor" (KDR) (Terman et al., Oncogene 6: 1677-83, 1991). Another designation for FLK-1 / KDR is "vascular endothelial cell growth factor receptor 2" (VEGFR-2) because it binds VEGF with high affinity. The murine version of FLK-1 / VEGFR-2 was also called NYK (Oelrichs et al., Oncogene 8 (1): 11-15, 1993). DNA encoding murine, rat and human FLK-1 has been isolated and nucleotide and coding amino acid sequences have been published (Matthews et al., Proc. Natl. Acad. Sci. USA, 88: 9026-30, 1991; Terman et al., 1991 Terman et al., Biochem. Biophys. Res Comm. 187: 1579-86, 1992; Sarzani et al., supra, and Millauer et al., Cell 72:

835-846, 1993). Many studies, e.g. published by Millauer et al., supra, suggest that VEGF and FLK-1 / KDR / VEGFR-2 are ligand-receptor pairs that play an important role in vascular endothelial cell proliferation and blood vessel formation and growth, referred to as vasculogenesis and angiogenesis, respectively. .

I

Another type III RTK subgroup designated "fms-like tyrosine kinase-1" (Flt-1) is related to FLK-1 / KDR (DeVries et al. Science 255; 989-991, 1992; Shibuya et al. al., Oncogene 5: 519-524 (1990). Another designation for Flt-1 is "vascular endothelial cell growth factor receptor 1" (VEGFR-1). So far, members of the FLK-1 / KDR / VEGFR-2 and Flt-1 / VEGFR-2 subfamilies have been found to be primarily expressed on endothelial cells. Members of these subgroups are specifically stimulated by members of the vascular endothelial cell growth factor (VEGF) ligand family (Klagsburn and D'Amore, Cytokine & Growth Factor Reviews 7: 259-270, 1996). Vascular endothelial cell growth factor (VEGF) binds to Flt-1 with higher affinity than FLK1 / KDR and is mitogenic to quascular endothelial cells (Terman et al., 1992, supra, Mustonen et al. Supra, DeVries et al. supra). Flt-1 is believed to be an essential factor in endothelial organization during vascular development. Flt-1 expression is associated with early vascular development in mouse embryos and with neovascularization during wound healing (Mustonen and Alitalo, supra). Expression of Flt-1 in adult organs, e.g. glomeruli of the kidneys predicts an additional function of this receptor that is not related to cell growth (Mustonen and Alitalo, supra).

As mentioned above, recent evidence suggests that VEGF plays a role in stimulating both normal and pathological angiogenesis (Jakeman et al., Endocrinology 133: 848859, 1993; Kolch et al., Breast Cancer Research and Treatment 36: 139-155, 1995; Ferrara et al., Endocrine Reviews 18 (1); 4-25, 1997; Ferrara et al., Regulation of Angiogenesis (ed. LD Goldberg and EM Rosen), 209-232, 1997). In addition, VEGF has been involved in the control and enhancement of vascular permeability (Connolly, et al., J. Biol. Chem. 264: 20017-20024, 1989; Brown et al., Regulation of Angiogenesis (ed. LD Goldberg and EM Rosen), 233 -269, 997).

Various forms of VEGF resulting from alternative splicing of mRNA have been reported, including the four species described by Ferraro et al. (J. Cell. Biochem. 47: 211-218, 1991). Ferrar et al., Supra, have been identified as secreted and predominantly cell-associated VEGF species, and the protein has been found to exist in the form of disulfide-linked dimers.

Several related VEGF homologues have been identified. However, their role in normal physiological processes and diseases has not yet been explained. In addition, members of the VEGF family are often coexpressed with VEGF in many tissues and are generally capable of forming heterodimers with VEGF. This property is likely to alter receptor specificity and biological effects of heterodimers and further complicate the elucidation of their specific functions as described below (Korpelainen and Alitalo, Curr. Opin. Cell Biol., 159-164, 1998 and references cited in the present invention).

Placental growth factor (P1GF) has an amino acid sequence that shows significant identity to the VEGF sequence (Park et al., J. Biol. Chem. 269: 25646-54, 1994; Magione et al. Oncogene 8: 925-31, 1993) . As with VEGF, different P1GF species result from alternative mRNA splicing and the protein exists in dimeric form (Park et al., Supra). P1GF-1 and P1GF-2 bind to Fit-1 with high affinity and P1GF-2 also strongly binds to neuropilin-1 (Migdal et al., J. Biol. Chem. 273 (35): 2227222278), but none does not bind FLK-1 / KDR (Park et al., supra). P1GF has been reported to potentiate both the vascular permeability and the mitogenic effect of VEGF on endothelial cells, provided that VEGF is present at low concentrations (allegedly due to heterodimer formation) (Park et al., Supra).

VEGF-B is produced in the form of two isoforms (with 167 and 185 residues), which are also believed to bind to Flt-1 / VEGFR-1. VEGF-B may also play a role in regulating extracellular matrix degradation, cell adhesion and migration through modulation of urokinase-type plasminogen activator expression and activity and plasminogen activator inhibitor 1 (Pepper et al., Proc. Natl. Acad. Sci. USA (1998)). 95 (20): 11709-11714.

VEGF-C was originally cloned as a ligand for VEGFR-3 / Flt-4, which is primarily expressed by lymphatic endothelial cells. In its fully engineered form, VEGF-C can also bind KDR / VEGFR-2 and stimulate endothelial cell proliferation and migration in vitro and angiogenesis in in vivo models (Lymboussaki et al., Am. Pathol. (1998), 153 (2)). Witzenbichler et al., Am J Pathol (1998), 153 (2), 381-394). Transgenic overexpression of VEGF-C causes the proliferation and widening of only lymphatic vessels, while blood vessels remain intact. Unlike VEGF, there is no expression

Hypoxia-induced VEGF-C (Ristimaki et al., J. Biol. Chem. (1998), 273 (14), 84138418).

The last of the disclosed is VEGF-D, which is structurally very similar to VEGF-C. VEGF-D has been reported to bind and activate at least two VEGFRs, VEGFR-3 / Flt-4 and KDR / VEGFR-2. It was originally cloned as a c-fos inducible mitogen for fibroblasts and is prominently expressed in mesenchymal lung and skin cells (Achen et al., Proc. Natl. Acad. Sci. USA (1998), 95 (2), 548-553 and references in the present invention.

With respect to VEGF, VEGF-C and VEGF-D have been claimed to induce in vivo vascular permeability increases in Miles tests, provided they are injected into cutaneous tissue (PCT / US97 / 14696; WO98 / 07832 , Witzenbichler et al., Supr). The physiological role and importance of these ligands in modulating vascular hyperpermeability and endothelial responses in tissues where they are expressed remains unclear.

Recently, a virally encoded, new type of vascular endothelial growth factor, VEGF-E (NZ-7 VEGF), has been published that preferentially utilizes the KDF / Flk-1 receptor and has potent heparin-free mitotic activity (Meyer et al., EMBO J. (1999), 18 (2), 363-374, Ogawa et al., J. Biol Chem (1998), 273 (47), 31273-31282). The VEGF-E sequences have about 25% identity to mammalian VEGF and are encoded by the parapoxvirus Orf virus (OV). This parapoxvirus, which acts in sheep and goats and occasionally in humans, causes lesions with angiogenesis. VEGF-E is a dimer of wt. about 20 kDa with a non-basic domain and also has no affinity for heparin, but has a characteristic cysteine loop motif found in all mammalian VEGFs. It has also surprisingly been found to be potent and bioactive as the isoform VEGF-A, VEGF 165, capable of binding heparin. That is, both factors stimulate tissue factor (TF) release, proliferation, chemotaxis and growth of cultured vascular endothelial cells in vitro and angiogenesis in vivo. Similar to VEGF165, VEGF-E binds with high affinity to the receptor-2 VEGF (KDR), resulting in receptor autophosphorylation and a biphasic increase in free intracellular Ca ²⁺ concentration, unlike VEGF165, VEGF-E did not bind to the receptor -1 VEGF (Flt-1).

Based on established facts about other VEGF and VEGFR homologues and prior cases for ligands and receptor heterodimerization, the action of such VEGF homologues may include the formation of VEGF ligand heterodimers and / or receptor heterodimerization or binding to as yet unidentified VEGFR (Witzenbichler et al., Supra). Recent publications also suggest that neuropilin-1 (Migdal et al., Supra) or VEGFR-3 / Flt-4 (Witzenbichler et al., Supia) or receptors other than KDR / VEGFR-2 may be involved in vascular induction. permeability (Stacker SA, Vitali A., Domagala T., Nice E. and Wilks AF, Angiogenesis and Cancer Conference, Amer. Assoc. Cancer Res., Jan. 1998, Orlando, FL; Williams, Diabetelogia 40: S118- 120 (1997)) To date, no direct evidence has been provided of the essential role of DRC in VEGF-mediated vascular hyperpermeability.

Non-receptor tyrosine kinases

Non-receptor tyrosine kinases are a collection of cellular enzymes that lack extracellular and transmembrane sequences. To date, more than twenty-four individual non-receptor tyrosine kinases containing eleven (11) subfamilies (Src, Frk, Btk, Csk, Abl, Zap70, Fes / Fps, Fak, As, Ack, and LIMK) have been identified. The Src subfamily of non-receptor tyrosine kinases is composed of the largest number of PTKs and includes Src, Yes, Fyn, Lyn, Lck, Blk, Hck, Fgr, and Yrk. The Src subfamily of enzymes is associated with oncogenesis and immune responses. A more detailed discussion of the non-receptor tyrosine kinase issue is given in Bolen, 1993, Oncogene 8: 2025-2031, incorporated herein by reference.

Many tyrosine kinases, either RTKs or non-receptor tyrosine kinases, have been found to be involved in cellular signaling pathways in many pathogenic conditions, including cancer, psoriasis and other hyperproliferative disorders or hyperimmune responses.

Development of compounds to modulate PTK

Given the supposed important role that PTKs play in the control, regulation and modulation of cell proliferation, diseases and disorders associated with abnormal cell proliferation, many attempts have been made to identify "inhibitors" of receptor and non-receptor tyrosine kinases in a variety of ways, including the use of mutant ligands. Application No. 4,966,849), soluble receptors and antibodies (Application No. WO 94/10202; Kendall & Thomas, 1994, Proc. Natl. Acad. Sci 90: 10705-09; Kim et al., 1993, Nature 362: 841-). 844), RNA ligands (Jellinek, et al., Biochemistry 33: 10450-56; Takano, et al., 1993, Mol. Bio. Cell 4: 358A; Kinsella, et al. 1992, Exp. Cell Res. 199: 56-62; Wright, et al., 1992, J. Cellular Phys. 152: 448-57) and tyrosine kinase inhibitors (WO 94/03427; WO 92/21660; WO 91/15495; WO 94/14808; US Patent No. No. 5,330,992, Mariani, et al., 1994, Proc. Am. Assoc. Cancer Res. 35: 2268).

Recently, attempts have been made to identify small molecules that act as tyrosine kinase inhibitors. For example, bismonocyclic, bicyclic or heterocyclic aryl compounds (PCT WO 92/20642) and vinylene-azaindole derivatives (PCT WO 94/14808) have generally been described as tyrosine kinase inhibitors. Styryl compounds (US Patent No. 5,217,999), styryl-substituted pyridyl compounds (US Patent No. 5,302,606), certain quinazoline derivatives (EP Application No. 0 566 266 A1; Expert Opin. Ther. Pat. (1998), 8 (4) : 475-478), selenoindoles and selenides (PCT WO 94/03427), tricyclic polyhydroxyl compounds (PCT WO 92/21660) and benzylphosphonic acid compounds (PCT WO 91/15495) have been described as tyrosine kinase inhibitors in the treatment of cancer. Anilinoquinolines (PCT WO97 / 34876) and quinazoline derivatives (PCT WO97 / 22596; PCT WO97 / 42187) have been described as inhibitors of angiogenesis and vascular permeability.

In addition, attempts have been made to identify small molecules that act as serine / threonine kinase inhibitors. For example, bis (indolylmaleimide) compounds have been described as inhibitors of, in particular, the PKC serine / threonine kinase isoform whose signal transduction function is associated with a change in vascular permeability in VEGF-associated diseases (PCT WO97 / 40830; PCT WO97 / 40831).

P1-kinase inhibitors

Plk-1 is a serine / threonine kinase that is an important regulator of cell cycle progression. It plays a decisive role in the assembly and dynamic function of the mitotic spindle. It has also been shown that Plk-1 and related kinases are closely associated with the inactivation and inactivation of other cell cycle regulators, e.g., cyclin-dependent kinases. High levels of Plk-1 expression are associated with cell proliferation activities. They have also been found in malignant tumors of various origins. Plk-1 inhibitors are believed to block cancer cell proliferation by disrupting processes involving mitotic spindles and unduly activated cyclin-dependent kinases.

Cdc2 / cyclin B kinase inhibitors (Cdc2 is sometimes referred to as cdkl)

Cdc2 / cyclin B is another enzyme, serine / threonine kinase, which belongs to the family of cyclin dependent kinases (cdks). These enzymes are involved in the critical transfer between the different phases of cell cycle progression. Uncontrolled cell proliferation, which is a hallmark of cancer, is believed to be dependent upon increased cdk activities in these cells. Inhibition of increased cdk activities in cancer cells by cdc2 / cyclin B kinase inhibitors could suppress proliferation and restore normal control of cell cycle progression.

Therefore, it is important to identify active small compounds that specifically inhibit signal transduction and cell proliferation by modulating the activity of receptor and non-receptor tyrosine kinases and serine / threonine kinases, thereby regulating and modulating abnormal or inappropriate cell proliferation, differentiation or metabolism. In particular, the identification of methods and compounds that specifically inhibit the tyrosine kinase function that is essential for angiogenic processes or the formation of vascular hyperpermeability leading to edema, ascites, effusion, exudates and macromolecular extravasate and matrix deposition, as well as related disorders, could be of great benefit.

SUMMARY OF THE INVENTION

The present invention is directed to compounds of the general formula

and physiologically acceptable salts thereof, wherein R is a substituted or unsubstituted aliphatic, aromatic, heterocyclic or aralkyl group and R ² is a hydrogen atom, a lower alkyl group or an aryl group. R ¹ is a hydrogen atom or -AZ, wherein A is (CH 2) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _{n O} -, - (CH ₂ ) _n S-, - (CH 2) _n S (O) - or - (CH ₂ ) n S (O) 2 -; and Z is hydrogen, lower alkyl, aralkyl, trihalomethyl, R ³ CO-, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ ,

-C (O) NR ⁴ R ⁵ , R ³ O- or a ring system selected from the group consisting of C ₃ Cocycloalkane, benzene, pyrrole, isoxazole, isothiazole, indole, pyridine, pyrazine, pyrimidine, thiophene, imidazole, furan, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole, thiazole, benzothiazole, tetrahydrofuran, triazine and their usable A-oxides, which may optionally be substituted by one or more halogens, lower alkyl, R ³ O-, HO-, HOC (O) -, R ³ OC (O) -, trihalomethyl, nitro, aryl, -CN, -C (O) NR ⁴ R ⁵ or -NR ⁴ R ⁵ . R ³ in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 -C 6) cycloalkylalkyl and heterocyclyl-alkyl. The substituents R ⁴ and R ⁵ in each case are each independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C ₃ -C 6) cycloalkyl, heterocyclic, aralkyl, (C _{3 -} ) C 6) cycloalkyl-alkyl and heterocyclyl-alkyl; optionally the substituents R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl, optionally each is substituted with one or more moieties selected from the group consisting of lower alkyl, hydroxy, lower alkoxy-lower alkyl, aromatic, (C 1 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 -C 6) cycloalkyl-alkyl and heterocyclyl- the number index n is an integer ranging from 0 to 3.

Suitable substituents for the R group include halogens, lower alkyl groups, R ³ O-, hydroxy, HOC (O) -, R ³ OC (O) -, R ³ OC (O) R ⁶ -, R ³ OR ⁶ -, trihalomethyl , trihalomethylcarbonyl, nitro, -C (O) NR ⁴ R ⁵ , -NR ⁴ R ⁵ , R ³ CO-, - (CH 2) n R ⁷ , -C (O) (CH 2) _n R ⁷ , -C (O ) NR ⁴ (CH 2) n R ⁷ , -C (O) (CH 2) _n -R ⁷ , -C (O) - (CH ₂ ) n -C (O) -R ⁷ ,

-C (O) O (CH _{2) n} R ^7, -OC (O) (CH 2) "R ^7, -NR ⁴ C (O) (CH 2) _n R ^7, -R ⁶ NR ⁴ R ^5, R ⁶ N (R ⁴ ) -R ⁶ -R ⁷ , -R ⁶ C (O) O (CH 2) n R ⁷ , -R ⁶ OC (O) (CH 2) _n R ⁷ , -R ⁶ N [R ⁶ -R ⁷ ] 2, -R ⁶ C (O) NR ⁴ (CH 2) _n R ⁷ ,

R ⁶ NR ⁴ C (O) (CH ₂ ) n R ⁷ , -R ⁶ CH [C (O) OR ⁴ ] [NR ⁵ C (O) R ⁴ ] or a substituted aryl or aralkyl group, wherein the substituent is selected from a group consisting of halogen, trihalomethyl, hydroxy, -NR ⁴ R ⁵ , nitro, -CONR ⁴ R ⁵ , lower alkyl, R ³ O-, -C (O) OR ⁴ or -OC (O) R ³ . R ⁶ is lower alkyl or aryl. R ⁷ is alkoxy, haloalkyl, lower alkyl piperazine, hydroxy, R ³ O-, R ³ C (O) - or -NR ⁴ R ⁵ .

Suitable substituents of R ³ , R ⁴ and R ⁵ include one or more moieties selected from the group consisting of halogens, lower alkyl, hydroxy, lower alkoxy, carboxy, lower alkyl ester, trihalomethyl, preferably trifluoromethyl, nitro, phenyl, phenyl-lower alkyl (C 3 -C 6) cycloalkyl, (C 1 -C 6) cycloalkyl-alkyl, CN, amino, alkylamino, dialkylamino, -C (O) NH ₂ , -C (O) NH (alkyl) and -C (O) N (alkyl) ₂ .

Aliphatic groups include linear or branched C 1 -C 18 hydrocarbons or cyclic C 3 -C 18 hydrocarbons that are fully saturated or contain one or more unsaturated units. Lower alkyl groups are linear or branched C 1 -C 6 hydrocarbons or C 3 -C 6 cyclic hydrocarbons which are fully saturated.

Aromatic groups as used in the present invention include carbocyclic ring systems (e.g. benzyl or cinnamylidene) and condensed in

polycyclic aromatic ring systems (e.g., naphthyl). Other aromatic groups include heteroaryl ring systems (e.g., pyridine, thiophene, furan, pyrrole, imidazole, oxazole, thiazole, pyrazole, triazole, pyrimidine and pyrazine) and heteroaryl ring systems wherein the carbocyclic aromatic ring, carbocyclic non-aromatic ring or heteroaryl ring is fused to one or more additional heteroaryl rings (e.g., benzimidazole, benzothiazole, indole, tetrahydroindole, azaindole, indazole, isoxazole, isothiazole, imidazole and quinoline). An aryl group, as used herein, means an aromatic group having five or six atoms. An aralkyl group is an aromatic substituent that is attached to a compound by an aliphatic group having one to six carbon atoms. Heterocyclic group, as used herein, means a mono-, bi-, or tri-cyclic heterocyclic group that is not aromatic or has a degree of unsaturation, and unsaturation does not form an aromatic group.

Tautomers, stereoisomers, enantiomers, and mixtures of these compounds are included in the present invention. Pharmaceutically acceptable addition salts of these compounds are also included in the invention.

In one embodiment, R ² is hydrogen and R is preferably substituted indole or substituted or unsubstituted imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, pyrrole, pyrazole, 4,5,6,7 -tetrahydroindole, benzoindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene or pyrazine.

In a preferred embodiment, R ² is a hydrogen atom, the index n is zero and Z is cyclopropyl, 3-pyridyl or pyrazinyl. In another preferred embodiment, R ² is hydrogen, A is -O-, the n-index is 0 and Z is ethyl, propyl or isopropyl. In another preferred embodiment, R ² is hydrogen, A is CH 2, the index n is 2 and Z is benzene optionally substituted with halogen, trihalomethyl, hydroxy, -NR ⁴ R ⁵ , nitro, -C (O) NR ⁴ R ⁵ , lower alkyl, R ³ O-, -C (O) OR ^4, or -OC (O) R ³ .

In a preferred embodiment, the present invention is directed to a compound represented by the following general formula:

and physiologically acceptable salts thereof, wherein R is selected from the group consisting of substituted or unsubstituted:

indole, imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, 4,5,6,7-tetrahydroindole, benzoindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrrole, pyrazole, oxazole and thiazole;

R < ¹ & gt ^; is hydrogen or -AZ;

A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) n S -, - (CH ₂ ) _n S (O) - or - (CH ₂ ) _n S (O) ₂ -;

Z is hydrogen, lower alkyl, aralkyl, trihalomethyl, trihalogénmetylkarbonyl, R ³ 0C (0) -, -NR ⁴ R ^5, -C (O) NR ⁴ R ^5, R ³ CO-, R ³ 0- ring or a system selected from the group consisting of C 3 -C 6 cycloalkane, isoxazole, isothiazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole 77-oxide thereof, wherein said ring system is optionally substituted with one or more moieties selected from the group consisting of halogen, lower alkyl group, R ³ 0-, H0-, HOC (O) -, R ³ 0C (0) -, trihalomethyl, nitro, an aromatic group, (C 3 -C) cycloalkyl, heterocyclic, aralkyl, (C3-C6) cycloalkyl-alkyl, heterocyclyl-alkyl, -CN, -C (O) NR ⁴ R ⁵ or - NR ⁴ R ⁵ ;

The substituent R in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl, lower alkoxy lower

An alkyl group, an aromatic group, a (C3-C6) cycloalkyl group, a heterocyclic group, an aralkyl group, a (C3-C6) cycloalkyl-alkyl group and a heterocyclylalkyl group;

The substituents R ⁴ and R ⁵ in each case are independently hydrogen or are selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C3-C6) cycloalkyl, heterocyclic, aralkyl, (C3-C6) cycloalkyl-alkyl and heterocyclyl-alkyl;

optionally, R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl, wherein each optionally substituted with one or more moieties selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl group, an aromatic group, (C 3 -C ₆₎ cycloalkyl group, a heterocyclic group, an aralkyl group, (C 3 -C 6) cycloalkyl- alkyl and heterocyclyl-alkyl; and n is an integer of 0 to 3; provided that when R is unsubstituted indol-3-yl, then R ¹ is not -NH 2.

In another preferred embodiment, the present invention is directed to a compound represented by the following general structural formula;

and physiologically acceptable salts thereof, wherein R is selected from the group consisting of substituted or unsubstituted:

indole, imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, 4,5,6,7-tetrahydroindole, benzoindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrrole, pyrazole, oxazole and thiazole;

R < ¹ & gt ^; is hydrogen or -AZ;

A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) n O-, - (CH ₂ ) _n S-, - (CH ₂ ) _n S (O) - or - (CH ₂ ) _n S (O) ₂ -;

Z is hydrogen, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring a system selected from the group consisting of C 3 -C 6 cycloalkane, isoxazole, isothiazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole their 77-oxides, wherein said ring system may be optionally substituted with one or more moieties selected from the group consisting of halogens, lower alkyl, R ³ O-, HO-, HOC (O) -, R ³ OC (O) -, trihalomethyl, nitro, an aromatic group, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C3-C6) cycloalkyl-alkyl, heterocyclyl-alkyl, -CN, -C (O) NR ⁴ R ⁵ or - NR ⁴ R ⁵ ;

R ³ in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 6 -C 6 cycloalkyl-alkyl) and heterocyclylalkyl;

The substituents R ⁴ and R ⁵ in each case are independently hydrogen or are selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C 3 -C 8) cycloalkyl, heterocyclic, aralkyl, (C 3 -C 6) cycloalkyl-alkyl and heterocyclyl-alkyl;

optionally, R ⁴ and R ⁵ together with the nitrogen to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl groups, each is optionally substituted with one or more moieties selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C ₃ -C 6) cycloalkyl-alkyl a heterocyclyl-alkyl group; and n is an integer of 0 to 3; provided that when R is unsubstituted indol-3-yl, then R ¹ is not -NH ₂ ; and R is substituted or unsubstituted benzene or unsubstituted imidazole, 1,2,3-triazole, 1,2,4-triazole, pyridine, pyrimidine, pyrazine, pyrrole, pyrazole, oxazole or thiazole; then R ¹ is lower alkyl, (C ₃ -C 6) cycloalkyl, benzene, or -C (O) NR ⁴ R ^5, the substituents R ⁴ and R ⁵ are each independently hydrogen, lower alkyl or carbocyclic aryl .

In another preferred embodiment, the present invention is directed to a compound represented by the following general structural formula:

and physiologically acceptable salts thereof, wherein R is selected from the group consisting of substituted or unsubstituted:

indole, imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, 4,5,6,7-tetrahydroindole, benzoindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrrole, pyrazole, oxazole and thiazole;

R < ¹ & gt ^; is hydrogen or -A ^: Z;

A is - (CH _{2) n} -, - (CH _{2) n} -NH-, - _(CH2) "O-, - _(CH2)" S, - (CH _{2) n} S (O) - or - (CH ₂ ) _n S (O) ₂ -;

Z is hydrogen, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring a system selected from the group consisting of C 3 -C 8 cycloalkane, isoxazole, isothiazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran.

thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole, thiazole and N-oxides thereof, wherein said ring system may be optionally substituted with one or more moieties selected from the group consisting of halogens, lower alkyl, R ³ O-, HO-, HOC (O) -, R ³ OC (O) -, trihalomethyl, nitro, aromatic, (C3-C6) cycloalkyl, heterocyclic, aralkyl, (C3-C6) cycloalkyl-alkyl , heterocyclyl-alkyl, -CN, -C (O) NR ⁴ R ⁵ or -NR ⁴ R ⁵ ;

R ³ in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 1-6 cycloalkyl) and heterocyclylalkyl;

The substituents R ⁴ and R ⁵ in each case are independently hydrogen or are selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C3-C6) cycloalkyl, heterocyclic, aralkyl, (C3-C6) cycloalkyl-alkyl and heterocyclyl-alkyl;

optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl, wherein each is optionally substituted with one or more moieties selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 1 -C 6 cycloalkyl-alkyl) and the index n is an integer ranging from 0 to 3, provided that:

a) R is not pyrrol-3-yl or pyrrol-3-yl substituted with an alkyl or carbocyclic aryl group; and

b) R is not indol-3-yl or indol-3-yl substituted with an alkyl or carbocyclic aryl group; and

c) R is not azaindole or azaindole substituted in the 2-position by an alkyl or carbocyclic aryl group.

In another preferred embodiment, the present invention is directed to a compound represented by the following general structural formula:

and physiologically acceptable salts thereof, wherein R is a substituted pyrrole or is selected from the group consisting of substituted or unsubstituted:

indole, imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, 4,5,6,7-tetrahydroindole, benzoindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrazole, oxazole and thiazole;

R < ¹ & gt ^; is hydrogen or -AZ;

A is - (CH ₂ ) _n -, - (CH ₂ ) n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) n S (O) - or - (CH ₂ ) n S (O) ₂ -;

Z is hydrogen, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring a system selected from the group consisting of C 6 -C 6 cycloalkane, isoxazole, isothiazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, thrazole, oxrazole, oxrazole, oxrazole their T-oxides, wherein said ring system may be optionally substituted with one or more moieties selected from the group consisting of halogens, lower alkyl, R ³ O-, HO-, HOC (O) -, R ³ OC (O) -, trihalomethyl, nitro, an aromatic group, (C 3 -C) cycloalkyl, heterocyclic, aralkyl, (C ₃ -C 6) -cycloalkyl-alkyl, heterocyclyl-alkyl, -CN, -C (O) NR ⁴ R ^5, or -NR ⁴ R ⁵ ;

The substituent R ³ in each case is independently selected from the group consisting of: a lower alkyl group, a lower alkoxy lower alkyl group, an aromatic group, (C ₃ 18

C ₆ ) cycloalkyl, heterocyclic, aralkyl, (C ₃ -C ₆ -cycloalkyl-alkyl and heterocyclyl-alkyl;

The substituents R ⁴ and R ⁵ in each case are independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C ₅ -C 6) cycloalkyl, heterocyclic, aralkyl, (C ₃ -C 6) cycloalkyl -alkyl and heterocyclyl-alkyl;

optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl, wherein each optionally substituted with one or more moieties selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 -C 6) cycloalkyl-alkyl and heterocyclyl-alkyl; and n is an integer of 0 to 3; provided that:

a) when R is a substituted pyrrole, then the pyrrole is substituted with a group selected from R ³ OC (O) R ⁶ , R ³ OR ⁶ -, trihalomethyl, trihalomethylcarbonyl, - (CH 2) PR ⁷ , -O (CH 2) p R ⁷ , -C (O) N (R ⁴ ) (CH 2) p R ⁷ , -C (O) O (CH 2) _p R ⁷ ,

-OC (O) (CH ₂ ) _p R ⁷ , -R ^c N (R ⁴ ) -R ⁶ -R ⁷ , -R'XRS-R'k, -N (R ⁴ ) C (O) (CH 2) pR ⁷ , -R ⁶ NR ⁴ R ⁵ , -R ⁶ OC (O) (CH 2) pR ⁷ , -R ⁶ C (O) N (R ⁴ ) (CH 2) PR ⁷ , -R ⁶ C (O) O (CH 2) p R ⁷ ,

R ⁶ N (R ⁴ ) C (O) (CH ₂ ) _p R ⁷ , -R ⁶ CH (C (O) OR ⁴ ) (N (R ⁴ ) C (O) R ⁴ ), substituted aryl or aralkyl groups, where:

R ⁶ in each case is independently lower alkyl or aryl;

R ⁷ in each case is independently alkoxy, haloalkyl, lower alkylpiperazine, hydroxy, R ³ O-, R ³ C (O) -, or NR ⁴ R ⁵ ; and index p is an integer of 1-3;

b) when R is indol-3-yl, then indol-3-yl is substituted with a group selected from R ³ OC (O) R ⁶ , R ³ OR ⁶ -, trihalomethyl, trihalomethylcarbonyl.

-O (CH ₂₎ p R ^7, - (CH 2) p R ^7, -OC (O) (CH 2) _p R ^7, -C (O) N (R ⁴⁾ (CH 2) p R ^7, -C (O) O (CH 2) _p R ⁷ , -R ⁶ N (R ⁴ ) -R ⁶ -R ⁷ , -R ⁶ N (R ⁶ -R ⁷ ) 2, -N (R ⁴ ) C (O) (CH 2) _p R ⁷ , -R Wr ⁵ , -R ⁶ OC (O) (CH 2) p R ⁷ , -R ⁶ C (O) N (R ⁴ ) (CH 2) _p R ⁷ , -R ⁶ C (O) O (CH 2) p R ^7. R ⁶ N (R ⁴ ) C (O) (CH 2) _p R ',

-R ⁶ CH (C (O) OR ⁴ ) (N (R ⁴ ) C (O) R ⁴ ) or substituted aryl or aralkyl; and

c) when R is pyrazol-3-yl, then the pyrazol-3-yl is substituted with a group selected from R ³ OC (O) R ⁶ , R ³ OR ⁶ -, trihalomethyl, trihalomethylcarbonyl, - (CH 2) PR ⁷ , - O (CH 2) _p R ⁷ , -OC (O) (CH 2) p R ⁷ , -C (O) N (R ⁴ ) (CH 2) _p R ⁷ , -C (O) O (CH ₂ ) p R ⁷ , - R ⁶ N (R ⁴ ) -R ⁶ -R ⁷ , -R ⁶ N (R ⁶ -R ⁷ ) 2, -N (R ⁴ ) C (O) (CH 2) p R ⁷ , -R W R ⁵ , -R ⁶ OC (O) (CH ₂ ) p R ⁷ , -R ⁶ C (O) N (R ⁴ ) (CH 2) p R ⁷ , -R ⁶ C (O) O (CH 2) p R ⁷ , R ⁶ N (R ⁴ ) C (O) (CH ₂ ) _P R ⁷ ,

-R ⁶ CH (C (O) OR ⁴ ) (N (R ⁴ ) C (O) R ⁴ ) or a substituted aryl or aralkyl group.

In another preferred embodiment, the present invention is directed to a compound represented by the following general structural formula:

and physiologically acceptable salts thereof, wherein R is selected from the group consisting of substituted or unsubstituted:

indole, imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, 4,5,6,7-tetrahydroindole, benzoindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrazole, oxazole and thiazole;

R < ¹ & gt ^; is hydrogen or -AZ;

A is - (CH ₂ ) n -, - (CH ₂ ) n NH-, - (CH ₂ ) n O-, - (CH ₂ ) _n S-, - (CH ₂ ) n S (O) - or

- (CH ₂ ) n S (O) ₂ -;

Z is hydrogen, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring a system selected from the group consisting of C 3 -C 6 cycloalkane, isoxazole, isothiazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole their N-oxides, wherein said ring system may be optionally substituted with one or more moieties selected from the group consisting of halogens, lower alkyl, R ³ O-, HO-, HOC (O) -, R ³ OC (O) - , trihalomethyl, nitro, aromatic, (C ₃ -C ₆ ) cycloalkyl, heterocyclic, aralkyl, (C ₃ -C ₆ ) cycloalkyl-alkyl, heterocyclyl-alkyl, -CN, -C (O) NR ⁴ R ⁵ or -NR ⁴ R ⁵ ;

R ³ in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic, (C ₃ -C 6) cycloalkyl, heterocyclic, aralkyl, (C ₃ -C 6) a cycloalkyl-alkyl group and a heterocyclylalkyl group;

R ⁴ and R ⁵ in each case are independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C ₃ -C 6) cycloalkyl, heterocyclic, aralkyl, (C ₃ -C 6) a cycloalkyl-alkyl group and a heterocyclyl-alkyl group;

optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl, wherein each optionally substituted with one or more moieties selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C ₃ -C 6) cycloalkyl- alkyl and heterocyclyl-alkyl; and n is an integer of 0 to 3; provided that:

a) when R is unsubstituted indol-3-yl, then R ¹ is not -NH 2;

b) when R is unsubstituted or substituted benzene or unsubstituted imidazole, 1,2,3-triazole, 1,2,4-triazole, pyridine, pyrimidine, pyrazine, pyrrole, pyrazole, oxazole or thiazole; then R ¹ is lower alkyl, (C3-Cio) cycloalkyl, benzene, or -C (O) NR ⁴ R ^5, the substituents R ⁴ and R ⁵ are each independently hydrogen, lower alkyl or carbocyclic aryl ;

c) R is not pyrrol-3-yl or pyrrol-3-yl substituted with an alkyl or carbocyclic aryl group;

d) R is not indol-3-yl or indol-3-yl substituted with an alkyl or carbocyclic aryl group;

e) R is not azaindole or azaindole substituted in the 2-position by an alkyl or carbocyclic aryl group

f) when R is a substituted pyrrole, then the pyrrole is substituted with a group selected from R ³ OC (O) R ⁶ , R ³ OR ⁶ -, trihalomethyl, trihalomethylcarbonyl, -O (CH 2) PR ⁷ , - (CH 2) PR ⁷ , -OC (O) (CH 2) _p R ⁷ ,

-C (O) N (R ⁴ ) (CH 2) p R ⁷ , -C (O) O (CH 2) p R ⁷ , -R 6 R 6 -R 6 R ⁷ , -R ⁶ N (R ⁶ -R ⁷ ) ₂ ,

-N (R ⁴ ) C (O) (CH 2) p R ⁷ , -R ⁶ NR ⁴ R ⁵ , -R ⁶ OC (O) (CH 2) _p R ⁷ , -R ⁶ C (O) N (R ⁴ ) (CH ₂ ) _p R ⁷ ,

R ⁶ C (O) O (CH ₂₎ p R ^7, RW ^ CfOXCľUjpR ^7, R ⁶ CH (C (O) OR ⁴⁾ (N ^(R4) C (O) R ^4), substituted aryl or aralkyl groups, where:

R ⁶ in each case is independently lower alkyl or aryl;

R ⁷ in each case is independently alkoxy, haloalkyl, lower alkylpiperazine, hydroxy, R ³ O-, R ³ C (O) -, or NR ⁴ R ⁵ ; and index p is an integer of 1-3;

g) when R is indol-3-yl, then indol-3-yl is substituted with a group selected from R ³ OC (O) R ⁶ , R ³ OR ⁶ -, trihalomethyl, trihalomethylcarbonyl, -O (CH 2) p R ⁷ , - (CH 2) p R ⁷ , -OC (O) (CH 2) p R ⁷ , -ε (0) Ν ⁴ ) (ΟΗ 2) Λ ⁷ , -C (O) O (CH ₂ ) _p R ⁷ , -R ⁶ N (R ⁴ ) -R ⁶ -R ⁷ , -R ⁶ N (R ⁶ -R ⁷ ) 2, -N (R ⁴ ) C (O) (CH 2) p R ⁷ , -R ⁶ NR ⁴ R ³ ,

R ⁶ C (O) N (R ⁴ ) (CH 2) p R ⁷ , -R ⁶ C (O) O (CH 2) p R ⁷ , -R ⁶ OC (O) (CH 2) _p R ⁷ ,

-R ⁶ N (R ⁴ ) C (O) (CH ₂ ) p R ⁷ , -R ⁶ CH (C (O) OR ⁴ ) (N (R ⁴ ) C (O) R ⁴ ) or a substituted aryl or aralkyl group ; and

h) when R is pyrazol-3-yl, then the pyrazol-3-yl is substituted with a group selected from R ³ OC (O) R ⁶ , R ³ OR ⁶ -, trihalomethyl, trihalomethylcarbonyl, - (CH 2) p R ⁷ , -O (CH 2) p R ⁷ , -C (O) N (R ⁴ ) (CH 2) p R ⁷ , -C (O) O (CH 2) _p R ⁷ ,

-OC (O) (CH ₂ ) p R ⁷ , -R ⁶ N (R ⁴ ) -R ⁶ -R ⁷ , -R ⁶ N (R ⁶ -R ⁷ ) 2, -N (R ⁴ ) C (O) (CH ₂ ) _p R ⁷ , -r ^{6 and 4} r ⁵ .

-R ⁶ OC (O) (CH ₂ ) _p R ⁷ , -R ⁶ C (O) N (R ⁴ ) (CH 2) p R ⁷ , -R ⁶ C (O) O (CH 2) _p R ⁷ ,

R ⁶ N (R ⁴ ) C (O) (CH ₂ ) _p R ⁷ , -R ⁶ CH (C (O) OR ⁴ ) (N (R ⁴ ) C (O) R ⁴ ) or a substituted aryl or aralkyl group .

In a more preferred embodiment, the present invention provides any of the above compounds wherein A is -NH, -O-, -S-, -S (O) - or -S (O) ₂ and Z is cyclopropyl, 3-pyridyl or pyrazinyl.

In an even more preferred embodiment, the present invention provides any of the above compounds wherein A is -O-; and Z is ethyl, n-propyl or isopropyl.

In an even more preferred embodiment, the present invention provides any of the above compounds wherein A is -CH ₂ -; and Z is phenyl, wherein said phenyl is optionally substituted with one or more moieties selected from the group consisting of halogen, trihalomethyl, hydroxy, -NR ⁴ R ^5, nitro, CONR ⁴ R ^5, lower alkyl group, R ³ 0-, -C (0) 0R ^4, and -0C (0) R ^4th

In another preferred embodiment, the present invention provides any of the above compounds wherein R is substituted with one or more substituents each independently selected from the group consisting of halogen, lower alkyl group, R ³ 0-, hydroxy, H0C (0) -, R ³ OC (O) -, R ³ OC (O) R ⁶ -, R ³ OR ⁶ -, trihalomethyl, trihalomethylcarbonyl, nitro, -C (O) NR ⁴ R ⁵ , -NR ⁴ R ⁵ , R ³ CO-, - (CH 2) n R ⁷ , -O (CH 2) _n R ⁷ , -C (O) NR ⁴ (CH 2) n R ⁷ , -C (O) (CH 2) _n -R ⁷ , -C (O) - (CH 2) n C (O) -R ⁷ , -C (O) O (CH 2) _n R ⁷ , -OC (O) (CH 2) n R ⁷ , -NR ⁴ C (O) (CH 2) _n R ⁷ , -R ⁶ NR ⁴ R ⁵ , -R ⁶ N (R ⁴ ) R ⁶ -R ⁷ , -R ⁶ C (O) O (CH 2) n R ⁷ , -R ⁶ OC (O) (CH 2) n R ⁷ , R ⁶ N (R ⁶ R ⁷⁾ 2, -R ⁶ C (O) NR ⁴ (CH 2) "R ^7, R ⁶ NR ⁴ C (O) (CH _{2) n} R ^7, R ⁶ CH ( C (O) OR ⁴ ) (NR ⁵ C (O) R ⁴ ), an optionally substituted aryl group and an optionally substituted aralkyl group. Optionally substituted aryl and optionally substituted aralkyl are optionally substituted with one or more substituents selected from the group consisting of halogen, trihalomethyl, hydroxy, -NR ⁴ R ⁵ , nitro, -CONR ⁴ R ⁵ , lower alkyl, R ³ O-, -C (O) OR ⁴ and -OC (O) R ³ . R ⁶ is lower alkyl or aryl. R ⁷ is alkoxy, haloalkyl, lower alkyl piperazine, hydroxy, R ³ O-, R ³ C (O) - or -NR ⁴ R ⁵ . In one aspect of this embodiment, R is pyrrolyl, indolyl, azaindolyl, phenyl, pyrazolyl, imidazolyl, thienyl, 4,5,6,7-tetrahydroindolyl or quinolinyl. In another aspect of this embodiment, R is pyrrol-2-yl, pyrrol-3-yl, indol-2-yl, indol-3-yl, azaindol-3-yl, pyrazol-4-yl, imidazol-2-yl, imidazol-4-yl, thien-2-yl or quinolin-5-yl.

In another preferred embodiment, the present invention provides any of the above compounds wherein R ¹ is trifluoromethyl, amino, cyclopropylamino, methyl, ethyl, propyl, isopropyl, cyclopropyl,

2-methylcyclopropyl, 2,2,3,3-tetramethylcyclopropyl, 2-phenylcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, - (CH ₂ ) _p -O-phenyl, - (CH 2) _p -O- (4-methylphenyl), - (CH _{2) p} methoxyphenyl), - _{(CH2) p-O-} (4-chloro-phenyl), - _{(CH2) p-O-} (3-methyl phenyl), - _{(CH2) p-O-} (4-phenyl phenyl), - (CH2) _p-O- (4-hydroxy phenyl), - (CH2) _p-O- (4-nitrophenyl), - _{(CH2) p-O-} (4-aminophenyl), - (CH ₂ ) _p-O- (4-carbamoyl-phenyl), - _{(CH2) p-O-} (4-methoxycarbonylphenyl) -ΝΉfenyl, -NH- (4-methoxy-phenyl), -NH- (4-chlorophenyl), -NH (4-fluorophenyl), -NH- (4isopropylphenyl), isopropoxy, ethoxy, cyclopentyloxy, - (CH ₂ ) _p indolyl, - (CH ₂ ) _p -pyridyl, - (CH ₂ ) _p -benzothiazolyl, - (CH ₂ ) _p- pyrrolyl, - (CH 2) _p -tetrahydrofuryl, - (CH ₂ ) _p pyrazinyl, - (CH ₂ ) _p -furyl, - (CH ₂ ) _p -thienyl, - (CH ₂ ) _p -phenyl, - (CH ₂ ) _p - (5-methylisoxazolyl), - (CH ₂ ) _p -isoxazolyl, - (CH ₂ ) _p -pyridazinyl, - (CH ₂ ) _p -pyrimidinyl, - (CH ₂ ) _n C (O) -OMe, - ( CH ₂ ) _n -C (O) -OEt or benzyl optionally substituted with one or more atoms chlorine, fluorine, OMe, methyl or amino. Index p is an integer ranging from 1 to 3. In an aspect of this embodiment, R is optionally substituted with one or more moieties selected from the group consisting of Br, Cl, F, aminomethyl, AC / N-dimethylaminomethyl, carboxy, carboxymethyl, carboxyethyl, carbonylmethyl, carbonylethyl, methoxycarbonyl, ethoxycarbonyl, phenyl, 4-morpholinomethyl, -C (O) -O- _(CH2) 2-N (Me) _2, -C (O) -O- _{(CH2) 2-N} ( Et) ₂ , -C (O) -O-CH ₂ N (Me) ₂ , -C (O) -O- (CH ₂ ) ₂ -N (Me) ₂ , -C (O) -NH- (CH) ₂ ) ₂ -N (Me) ₂ , -CH ₂ -NH-C (O) -CF ₃ and an optionally substituted moiety selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, and phenyl, wherein the optionally substituted moiety is optionally substituted with one or more groups selected from Br, Cl, F, hydroxy, nitro, amino or lower alkyl.

In another aspect, the present invention provides a pharmaceutical composition comprising any one or more compounds of the present invention, which is also defined in the present invention, and a pharmaceutically acceptable carrier or diluent.

In another aspect, the present invention provides a method of inhibiting the activity of one or more protein kinases, comprising administering a compound of the formula:

and physiologically acceptable salts and biologically active metabolites thereof, wherein R is selected from the group consisting of substituted or unsubstituted:

aliphatic, aromatic, (C 1 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 -C 6) cycloalkyl-alkyl, and heterocyclylalkyl;

R < ¹ & gt ^; is hydrogen or -AZ;

R ² is hydrogen or is selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C 3 -C 8) cycloalkyl, heterocyclic, aralkyl, (C 3 -C 6) cycloalkyl-alkyl and heterocyclyl-alkyl;

A is - (CH ₂ ) n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) _n S (O) -, or

- (CH ₂ ) n S (O) ₂ -;

Z is hydrogen, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring a system selected from the group consisting of C 3 -C 6 cycloalkyl, isoxazole, isothiazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole their A-oxides, wherein said ring system may be optionally substituted with one or more moieties selected from the group consisting of halogens, lower alkyl, R ³ O-, HO-, HOC (O) -, R ³ OC (O) -, trihalomethyl, nitro, aryl, -CN, -C (O) NR ⁴ R ⁵ or -NR ⁴ R ⁵ ;

R ³ in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 -C 6) cycloalkyl -alkyl and heterocyclylalkyl;

R ⁴ and R ⁵ in each case are independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 5 -C 6 -cycloalkyl-) alkyl and heterocyclyl-alkyl;

optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl, wherein each is optionally substituted with one or more moieties selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic, (C3-C6) cycloalkyl, heterocyclic, aralkyl, (C3-C6) cycloalkyl-alkyl and heterocyclyl-alkyl; and n is an integer ranging from 0 to 3.

A preferred method of the above method is one wherein the inhibition of protein kinase is in a recipient in such a need.

A preferred method of any of the above methods is one wherein the compound is a mixture of stereoisomers.

A preferred method of any of the above methods is that wherein the stereoisomers are enantiomers.

A preferred method of any of the above methods is that wherein the stereoisomers are the E and Z isomers.

A preferred method of any of the above methods is one wherein the compound is a mixture of structural isomers.

A preferred method of any of the above methods is one wherein the structural isomers are tautomers.

A preferred method of any of the above methods is one wherein said protein kinase is either a receptor tyrosine kinase or a non-receptor tyrosine kinase.

A preferred method of any of the above methods is one wherein said tyrosine kinase is selected from the group consisting of DRC, Flt-1, TIE-2, FGFR, PDGFR, IGF-1R, c-Met, Lck, Src, fyn, Lyn, Blk and yes.

In another aspect, the present invention provides a method of treating or significantly inhibiting hyperproliferative disorders or inflammatory diseases in a recipient in need thereof, comprising administering to said recipient any compound of the present invention as defined herein.

In another aspect, the present invention provides a method of treating or significantly inhibiting angiogenesis in a recipient in need thereof, comprising administering to said recipient any compound of the invention as defined herein.

In another aspect, the present invention provides a method of inducing an anti-angiogenic effect in a recipient in such need, comprising administering to said recipient any compound of the present invention as defined herein.

In another aspect, the present invention provides a method of treating or inhibiting the progression of a disease or condition in a recipient in need thereof, comprising administering to said recipient any compound of the invention as defined herein, wherein said disease or condition is selected from the group consisting of cancer, arthritis, atherosclerosis, restenosis. , psoriasis, hemangioma, myocardial angiogenesis, coronary and cerebral collaterals, ischemic limb angiogenesis, corneal disease, rubeosis, neovascular glaucoma, macular degeneration, wound healing, peptic ulcer, Helenobacteria-related diseases, retinal angiogenesis, diseases, inflammatory bowel disorders, cat scratch fever, premature retinopathy, ulcers, thyroid hyperplasia, burns, trauma, acute lung injury, chronic lung disease, stroke, half hypertension, cysts, synovitis, chronic and allergic inflammation, ovarian hyperstimulation syndrome, pulmonary and cerebral edema, keloid, fibrosis, cirrhosis, adult respiratory distress syndrome, sepsis, adult respiratory distress syndrome, multiple organ syndrome, and susceptibility syndrome and susceptible edema ascites.

In another aspect, the present invention provides a method of affecting vascular hyperpermeability or edema formation in a recipient in need thereof, comprising administering to said recipient any of the compounds of the present invention as defined herein. A preferred method of the above method is employed where the effect on edema formation is anti-oedematous.

A preferred method according to any of the above methods is one wherein the protein kinase is a serine kinase.

A preferred method according to any of the above methods is one in which the protein kinase is a threonine kinase.

Particularly preferred compounds of the present invention are:

-Cyclopropyl-4 - {[(3,5-dimethyl-4- (4-methyl-1-piperazinylmethyl) pyrrol-2-ylmethyl] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3,5-dimethyl-4- (l-pyrolidinylmetylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3,5-dimethyl-4-piperidinometyIpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-dietanolaminometyl-3,5-dimethyl-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3-dimethylaminomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3-morpholinomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3-diethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[3- (4-methyl-1-piperazinylmethyl) -4,5-tetramethylene-pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [{3- (1-pyrrolidinyl) methyl-4,5-tetramethylenopyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3-piperidinomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-diethylamino-3,5-dimethyl-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4- (3,5-dibromo-4-hydroxy-benzylidene) -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-oxo-l, 5,6,7-tetrahydro-indole-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(5-Chloro-pyrrol-2-yl) -methylene] -3-cyclopropyl-2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(5-trifluoromethylpyrrole-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4- [4- (2-dimetylaminoetoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4- [4- (2-dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3-ethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4- [3- (2-dimetylaminoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4- [3- (2-dimetylamÍnoetylaminokarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4- [4- (4-morfoIinoetoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4- [4- (4-morfolinoetylaminokarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4- [3- (4-morfolinoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4- [3- (4-morfolinoetylaminokarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3,4-diethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3-cyclopropyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(5-ethoxy-4- methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(5-chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene]

2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-morpholinomethyl-pyrrol-2-yl) -methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - {[(3,5-Dimethyl-4 - [(4-methyl-l-piperazinylmethyl) pyrrol-2-yl] methylene-} -3- (3-pyridyl) 2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - [(l-pyrolidinylmetylpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(4-DietyIaminometyl-3,5-dimethyl-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-piperidinometylpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(4-Dietanolaminometyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one.

4 - [(3-Dimethylaminomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(3-morpholinomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(3-Djetylaminometyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - {[3- (4-Methyl-1-piperazinylmethyl) -4,5-tetramethylenepyrrol-2-yl] methylene} -3- (3-pyridyl) -2-pyrazolin-5-one,

3- (3-Pyridyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenopyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4 - [(3-Piperidinomethyl-4,5-tetramethylene-pyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(4-diethylamino-ethyl-3,5-dimethyl-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(4-oxo-l, 5,6,7-tetrahydro-indole-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(4-dimethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(4-bromopyridin-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(4-chloropyridin-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(5'Chlórpyrol-2-yl) methylene] -3- (3-pyridyl-2-pyrazolin-5-one,

3- (3-Pyridyl) -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [4- (2-Dimetylaminoetoxykarbonylpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [4- (2-Dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 '[(3-ethoxycarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [3- (2-Dimetylaminoetylaminokarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [4- (4-Morfolinoetoxykarbonylpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [4- (4-Morfolinoetylaminokarbonylpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [3- (4-Morfblinoetoxykarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [3- (4-Morfolinoetylaminokarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazoIin-5-one,

4 - [(3,4-Dietoxykarbonylpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - {[3- (2-amino-2-carboxyethyl) indol-2-yl] methylene} -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3- (3-pyridyl) 2-pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - {[(4-methyl-l-piperazinylmethyl) pyrrol-2-yl] methylene) -3-isopropoxy-2pyrazolin-5-one,

4 - [(3,5-dimethyl-4 - [(l-pyrolidinylmetylpyrol-2-yl) methylene] -3-izopiOpoxy-2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (piperidinometylpyrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(4-Dietanolaminometyl-3,5-dimethyl-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(3-Dimethylaminomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3-Isopropoxy-4 - [(3-morpholinomethyl-4,5-tetramethylene-pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4 - {[3- (4-methyl-l-piperazinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} 2-pyrazolin-5-one,

3-isopropoxy-4 - {[3- (l-pyrrolidinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} 2-pyrazolin-5-one,

3-Isopropoxy-4 - [(3-piperidinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrole) -2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3-isopropoxy-2-pyrazolin-5-one,

3-Isopropoxy-4 - [(4-oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(4-Bróľnpyrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(4-chloropyridin-2-yl) methylene-] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(5-chloropyridin-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3-Isopropoxy-4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4- [4- (2-Dimetylaminoetoxykarbonylpyrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4- [3- (2-Dimetylaminoetylaminokarbonylindol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4- [4- (4-morfolinoetoxykarbohylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-isopropoxy-4- [4- (4-morfolinoetylaminokarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-isopropoxy-4- [3- (4-morfolinoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3-Isopropoxy-4- [3- (4-morpholinoethylaminocarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3,4-Diethoxycarbonylpyrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - {[3- (2-amino-2-carboxyethyl) indol-2-yl] methylene) -3-isopropoxy-2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3-isopropoxy

2-pyrazolin-5-one,

4 - [(5-chloro-4-metoxykarbonylmetyI-3-methoxycarbonylpyridin-2-yl) metyléri] -3-isopropoxy

2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-morfoIinometylpyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - {[(4-methyl-l-piperazinylmethyl) pyrrol-2-yl] methylene} -3-ethoxy-2pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - [(l-pyrolidinylmetylpyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3-ethoxy-2-pyrazoiin-5-one,

4 - [(3,5-Dimethyl-4- (piperidinometylpyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4 - [(4-Dietanolaminometyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4 - [(3-dimethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

3-Ethoxy-4 - [(3-morpholinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3-Diethylaminomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

3-Ethoxy-4 - {[3- (4-methyl-l-piperazinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} 2-pyrazolin-5-one,

3-Ethoxy-4 - {[3- (l-pyrrolidinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} -2-pyrazolin-5-one,

3-Ethoxy-4 - [(3-piperidinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3-ethoxy 2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dimetylaminometylpyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

3-Ethoxy-4 - [(4-oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

3-Ethoxy-4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [4- (2-Dimethylaminoethoxycarbonylpyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethylaminocarbonylpyrol-2-yl) methylene] -3-ethoxy- 2-pyrazolin-5-one, 4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4- [3- (2-Dirnetylaminoetylaminokarbonylindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

3-Ethoxy-4- [4- (4-morfolinoetoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Ethoxy-4- [4- (4-morfolinoetylaminokarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Ethoxy-4- [3- (4-morfolinoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin-5'ón,

3-Ethoxy-4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one;

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3-ethoxy-2-pyrazolin-5-one;

3-Ethoxy-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one;

4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3-ethoxy-2-pyrazolin-5-one, 4 - {[3- (2-Amino-2-carboxyethyl) Indol-2-yl] methylene} -3-ethoxy-2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3-ethoxy-2-pyrazoline 5-one,

4 - [(3-dimethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3-morpholinomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazoIin-5-one,

4 - [(3-diethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3- (4-methyl-l-piperazinylmethyl) -4,5-tetrametylénpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

3-Pyrazinyl-4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylene-pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4 - [(3-Piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindole) -2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5 -one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(4-bromopyridin-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(4-chloropyridin-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(5-chloropyridin-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

3-Pyrazinyl-4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one; 4- [4- (2-Dimethylaminoethylaminocarbonylpyrol-2-yl) methylene] -3-pyrazinyl- 2-pyrazolin-5-one,

4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4- [3- (2-DimetylaminoetoxykarbonyÍindol-2-yl) methylene] -3-pyrazinyl-2-pyra2olin-5-one,

4- [3- (2-Dimetylaminoetylaminokarbonylindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4- [4- (4-Morfolinoetoxykarbonylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4- [4- (4-Morfolinoetylaminokarbonylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4- [3- (4-Morpholinoethoxycarbonylindol-2-yl) methylene] -3-pyrazininyl-2-pyrazolin-5-one;

4- [3- (4-Morfolinoetylaminokarbonylindol-2-yl) methylene] -3-pyrazinyl-2-pyrazoIin-5-one,

4 - [(3,5-Dimethyl-4-etoxykarbonylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimetylaminoetylamÍnokarbony]) pyrrol-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(1-Methylindol-3-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

3-Pyrazinyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one;

4 - [(Indol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3,4-Dietoxykarbonylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3- (2-amino-2-carboxyethyl) indol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2 pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2 pyrazolin-5-one,

4 - [(4-bromopyridin-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

4 - [(4-chloropyridin-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

4 - [(5-chloropyridin-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

3- (imidazol-2-yl) -4 - [(5-trifluórmetyIpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (Imidazol-2-yl) -4 - [(4-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

4- [4- (2-Dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] -3- (imidazol-2-yl) 2-pyrazolin-5-one,

4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

4- [3- (2-Dimetylaminoetylaminokarbonylindol-2-yl) methylene] -3- (imidazol-2-yl) 2-pyrazolin-5-one,

3- (imidazol-2-yl) -4- [4- (4-morfolinoetoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (imidazol-2-yl) -4- [4- (4-morfolinoetyla.minokarbonylpyrol-2-yl) -methylene-2-pyrazolin-5-one,

3- (imidazol-2-yl) -4- [3- (4-morfblinoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3- (Imidazol-2-yl) -4- [3- (4-morpholinoethylaminocarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

3- (Imidazol-2-yl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one;

4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4- [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2- pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3 (imidazol-2-yl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

3- (imidazol-2-yl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3- (imidazol-2-yl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (Imidazol-2-yl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [[3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) ) indol-2-yl] methylene} -3- (imidazol-2-yl) 2-pyrazolin-5-one,

4 - {[3- (2-amino-2-carboxyethyl) indol-2-yl] methylene} -3- (imidazol-2-yl) -2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one,

4 - [(4-bromopyridin-2-yl) methylene] -3- (l-methylcyclopropyl) -2-pyrazolin-5-one,

4 - [(4-chloropyridin-2-yl) methylene] -3- (l-methylcyclopropyl) -2-pyrazolin-5-one,

4 - [(5-chloropyridin-2-yl) methylene] -3- (l-methylcyclopropyl) -2-pyrazolin-5-one,

3- (1-Methylcyclopropyl) -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one; 4- [4- (2-Dimethylaminoethoxycarbonylpyrol-2-yl) methylene] -3- (l-methylcyclopropyl) 2-pyrazolin-5-one,

4- [4- (2-Dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] -3- (l-methylcyclopropyl) 2-pyrazolin-5-one,

4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3- (l-methylcyclopropyl) -2-pyrazolin-5-one,

4- [3- (2-DimetylaminoetoxykarbonyIindol-2-yl) methylene] -3- (l-methylcyclopropyl) 2-pyrazolin-5-one,

4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

3- (1-Methylcyclopropyl) -4- [4- (4-morpholinoethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (l-methylcyclopropyl) -4- [4- (4-morfolinoetylaminokarbonylpyrol-2-yl) methylene] 2-pyrazolin-5-one,

3- (l-methylcyclopropyl) -4- [3- (4-morfolinoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin5-one,

3- (1-Methylcyclopropyl) -4- [3- (4-morpholinoethylaminocarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

3- (1-Methylcyclopropyl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

4 - [(5-methoxy-indol-2-yl) methylene] -3- (l-methylcyclopropyl) -2-pyrazolin-5-one,

3- (1-Methylcyclopropyl) -4 - [(4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrol-2-yl) methylene] -3- (lmetylcyklopropyl) -2-pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3- (l-methylcyclopropyl) -2-pyrazolin-5-one,

4 - [(pyrrol-2-yl) methylene] -3- (l-methylcyclopropyl) -2-pyrazolin-5-one,

4 - [(Indol-2-yl) methylene] -3- (l-methylcyclopropyl) -2-pyrazolin-5-one,

4 - [(3,4-DietoxykarbonylpyroI-2-yl) methylene] -3- (l-methylcyclopropyl)) - 2-pyrazoIin-5-one,

4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- (1-methylcyclopropyl) -2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3- (lmetylcyklopropyl) -2-pyrazoIin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3- (lmetyIcyklopropyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-morfolinometylpyroI-2-yl) methylene] -3- (2-fijryl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (4-methyl-l-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (2-furyl) 2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (l-pyrolidinylmetylpyrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(3,5-dimethyl-4-piperidinometylpyrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(4-DÍetanolaminometyl-3,5-dimethyl-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(3-dimethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

3- (2-Furyl) -4 - [(3-morpholinomethyl-4,5-tetramethylene-pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3-Diethylaminoethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 3- (2-Furyl) -4 - {[3 - (4-methyl-l-piperazinylmethyl) -4,5-tetrametylénpyrol-2-yl] methylene} 2-pyrazolin-5-one,

3- (2-Furyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenopyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3- (2-Furyl) -4 - [(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one; 3,5-dimethylpyrrol-2-yl) methylene] -3- (2-phthyl) -2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (2-furyl) 2-pyrazolin-5-one,

3- (2-furyl) -4 - [(4-oxo-l, 5,6,7-tetrahydro-indole-2-yl) methylene] -2-pyrazolin-5-one,

3- (2-Furyl) -4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Bromopyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(4-chloropyridin-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(5-chloropyridin-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

3- (2-Furyl) -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4- [4- (2-Dimetylaminoetoxykarbonylpyrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4- [4- (2-Dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4- [3- (2-Dimetylaminoetylaminokarbonylindol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

3- (2-furyl) -4- [4- (4-morfolinoetoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2-furyl) -4- [4- (4-morfolinoetylaminokarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2-furyl) -4- [3- (4-morfolinoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2-Furyl) -4- [3- (4-morpholinoethylaminocarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

3- (2-Furyl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 3- (2-Furyl) -4 - [(5- methoxyindole-2-yl) methylene] -2-pyrazolin-5-one,

3- (2-Furyl) -4 - [(4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrole-2-yl) methylene] -3- (2-furyl) 2-pyrazolin-5-one,

3- (2-furyl) -4 - [(indol-3-yl) methylene] -2-pyrazoIin-5-one,

3- (2-furyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2-Furyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [[3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3- (3- (2-furyl)) - 2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2- methoxycarbonylethyl) indol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4 - {[3- (2-amino-2-carboxyethyl) indol-2-yl] methylene} -3- (2'furyl) -2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene-] -3- (2-furyl) 2-pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3- (2-furyl) 2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - [(morfolinometylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (4-methyl-l-piperazinyl) methyl-pyrrole-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (l-pyroIidinylmetylpyrol-2-yl) methylene-] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3,5-dimetylpyroI-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-piperidinometylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-Dietanolaminometyl-3,5-dimethyl-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(3-dimethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(3-morpholinomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(3-diethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[3- (4-methyl-l-piperazinylmethyl) -4,5-tetrametylénpyrot-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one,

4 - {[3- (1-Pyrrolidinylmethyl) -4,5-tetramethylenopyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(3-piperidinomethyl-4,5-tetrametylénpyroI-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4 _1, 5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-diethylamino-ethyl-3,5-dimethyl-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-Oxo-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-dimethylaminomethyl-5-methylpyrrole-2-yl) metyléri] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-bromopyridin-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-chloropyridin-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(5-chloropyridin-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

3- (2-Thienyl) -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- [4- (2-Dimetylaminoetoxykarbonylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- [4- (2-Dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- [3- (2-Dimetylaminoetylaminokarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- [4- (4-Morfolinoetoxykarbonylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- [4- (4-Morfolinoetylaminokarbonylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- [3- (4-Morfolinoetoxykarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- [3- (4-Morfolinoetylaminókarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethyl pyrrole-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(l-methyl-indol-3-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4- [3,5-dimethyl-4-etoxykarbonylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(5-methoxy-indol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one _{I '.}

4 - [(4,5-Tetrametylénpyrol-2-yl) methylene-] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimetylaminoetoxykarbonyl) pyrrol-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one,

4 - ([3,5-Dimethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrol-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(pyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(Indol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(3,4-Dietoxykarbonylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[3- (2-amino-2-carboxyethyl) indol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-bromopyridin-2-yl) methylene] -3-cyclopropoxy-2-pyrazolin-5-one,

4 - [(4-chloropyridin-2-yl) methylene] -3-cyklopiOpoxy-2-pyrazolin-5-one,

4 - [(5-Chloro-pyrrol-2-yl) -methylene] -3-cyclopropoxy-2-pyrazolin-5-one,

-Cyclopropoxy-4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-cyclopropyloxy-4 - [(4-etoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-cyclopropoxy-4- [4- (2-dimetylaminoetoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-cyclopropoxy-4- [4- (2-dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] -2-pyrazolin

5-ón,

3-cyclopropyloxy-4 - [(3-ethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3-cyclopropoxy-4- [3- (2-dimetylaminoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3-cyclopropoxy-4- [3- (2-dimetyIaminoetylaminokarbonylindol-2-yl) methylene] -2-pyrazoIin

5-one,

3-cyclopropoxy-4- [4- (4-morfolinoetoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropoxy-4- [4- (4-morpholinoethylaminocarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-cyclopropoxy-4- [3- (4-morfolinoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3-cyclopropoxy-4- [3- (4-morfolinoetylaminokarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3-cyclopropyloxy-4 - [(3,5-dimethyl-4-ethyl pyrrole-2-yl) methylene] -2-pyrazolin-5-one,

3-CykIopropoxy-4 - [(l-methyl-indol-3-yl) methylene] -2-pyrazolin-5-one,

3-cyclopropoxy-4- [3,5-dimethyl-4-etoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-cyclopropyloxy-4 - [(5-methoxy-indol-2-yl) methylene] -2-pyrazolin-5-one,

3-cyclopropyloxy-4 - [(4,5-tetrametylénpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropoxy-4 - {[3,5-dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3-cyclopropyloxy-4 - {[3,5-Dimethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-cyclopropyloxy-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3-cyclopropyloxy-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-cyclopropyloxy-4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropoxy-4 - [(3,4-diethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3-cyclopropoxy-2-pyrazolin-5-one,

4 - {[3- (2-amino-2-carboxyethyl) indol-2-yl] methylene} '3-cyclopropoxy-2-pyrazolin-5-one,

3-Cyclopropoxy-4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3-cyclopropoxy-2-pyrazolin-5-one,

4 - [(4-bromopyridin-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one,

4 - [(4-chloropyridin-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one,

4 - [(5-chloropyridin-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one,

3- [2- (5-pyrimidinylethyl)] - 4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethoxycarbonylpyrol-2-yl) methylene ] -3- [2- (5-pyrimidinylethyl)] - 2pyrazolin-5-one,

4- [4- (2-Dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2pyrazolin-5-one,

4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2rpyrazolÍn-5-one, "

4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinyIetyI)] - 2pyrazolin-5-one,

4- [3- (2-DimetylaminoetylamÍnokarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2pyrazolin-5-one,

4- [4- (4-Morfolinoetoxykarbonylpyrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2pyrazolin-5-one,

4- [4- (4-Morfolinoetylaminokarbonylpyrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2pyrazolin-5-one,

4- [3- (4-Morpholinoethoxycarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one,

4- [3- (4-Morfolinoetylaminokarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2pyrazoIin-5-one,

4 - [(3,5-Dimethyl-4-ethyl pyrrole-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one,

4 - [(l-methyl-indol-3-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one,

4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazoline

5-ón,

4 - [(5-methoxy-indol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one,

3- [2- (5-pyrimidinylethyl)] - 4 - [(4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrol-2-yl) methylene] -3- [2- (5pyrimidinyletyl)] - 2-pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one,

3- [2- (5-Pyrimidinylethyl)] - 4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(Indol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one,

4 - [(3,4-Dietoxykarbonylpyrol-2-yl) methylene-] -3- [2- (5-pyriniidinyletyl)] - 2-pyrazolin-5-one,

4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one,

4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3- [2- (5pyrimidinyletyl)] - 2-pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3- [2- (5pyrimidinyletyl)] - 2-pyrazolin-5-one,

4 - [(4-bromopyridin-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - [(4-chloropyridin-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - [(5-chloropyridin-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

3- (2-Phenylethyl) -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4- [4- (2-Dimetylaminoetoxykarbonylpyrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4- [4- (4-Morfolinoetoxykarbonylpyrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4- [4- (4-MorfolinoetylaminokarbonyIpyrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4- [3- (4-Morfolinoetoxykarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4- [3- (4-Morfolinoetylaminokarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - [(l-methyl-indol-3-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4- [3,5-dimethyl-4-etoxykarbonylpyrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - [(5-methoxy-indol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

3- (2-Phenylethyl) -4 - [(4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - [(Indol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - [(3,4-Dietoxykarbonylpyrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (2-phenylethyl) 2-pyrazolin-5-one,

4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - [(5-Ethoxy-4- methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3- (2-phenyl-ethyl) -2-pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,

4 - [(4-bromopyridin-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4 - [(4-chloropyridin-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4 - [(5-chloropyridin-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

3- [2- (4-hydroxyphenyl) ethyl] -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4- [4- (2-Dimetylaminoetoxykarbonylpyrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] 2-pyrazolin-5-one,

4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] 2-pyrazolin-5-one,

4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

3- [2- (4-hydroxyphenyl) ethyl] -4- [4- (4-morpholinoethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-hydroxyphenyl) ethyl] -4- [4- (4-rnorfolinoetylaminokarbonylpyrol-2-yl) methylene] 2-pyrazolin-5-one,

3- [2- (4-hydroxyphenyl) ethyl] -4- [3- (4-morfolinoetoxykarbonylindol-2-yl) methylene] 2-pyrazolin-5-one,

3- [2- (4-hydroxyphenyl) ethyl] -4- [3- (4-morpholinoethylaminocarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

3- [2- (4-hydroxyphenyl) ethyl] -4 - [(5-methoxy-indol-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-hydroxyphenyl) ethyl] -4 - [(4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4 - {[3,5-dirnethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one ,.

4 - [(3,4-Dietoxykarbonylpyrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4 - [(4-Bromo-pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4 - [(4-chloropyrrole-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4 - [(5-chloropyrrole-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4 - [(5-trifluoromethylpyrrole-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4 - [(4-etoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4- [4- (2-dimetylaminoetoxykarbonylpyrol-2-yl) methylene] 2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4- [4- (2-dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] 2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4 - [(3-ethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4- [3- (2-dimetylaminoetoxykarbonylindol-2-yl) methylene] -2pyrazoIin-5-one,

3- [2- (4-aminophenyl) ethyl] -4- [3- (2-dimetylaminoetylaminokarbonylindol-2-yl) methylene] 2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4- [4- (4-morfolinoetoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin

5-ón,

3- [2- (4-aminophenyl) ethyl] -4- [4- (4-morfolinoetylaminokarbonylpyrol-2-yl) methylene] 2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4- [3- (4-morfolinoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin

5-one,

3- [2- (4-aminophenyl) ethyl] -4- [3- (4-morfolinoetylaminokarbonylindol-2-yl) methylene] 2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one; 3- [2- (4-aminophenyl) ethyl] -4 - [(4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] 4 - {[3,5-dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4 - {[3,5-dimethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4 - [(3,4-dietoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- [2- (4-aminophenyl) ethyl] -2-pyrazolin-5-one,

4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- [2- (4-aminophenyl) ethyl] -2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4 - [(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- [2- (4-aminophenyl) ethyl] -4 - [(5-chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-morpholinomethyl-pyrrol-2-yl) -methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - {[(4-methyl-l-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (4-pyrimidinyl) 2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (pÍperidinometylpyrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Dietanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-dimethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (4-pyrimidinyl) 2-pyrazolin-5-one,

4 - [(3-Morpholinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-DietylamÍnometyI-4,5-tetrametylénpyrol-2-yl) methylene] -3- (4-pyrimidinyl)

2-pyrazolin-5-one,

4 - {[3- (4-Methyl-1-piperazinyl) methyl-4,5-tetramethylenepyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

3- (4-Pyrimidinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenopyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4 - [(3-Piperidinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (4-pyrimidyl) pyrazolin-5-one,

4 - [(4-Dietylarninoetyl-3,5-dimethylpyrrolidin-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-oxo-l, 5,6,7-tetrahydroindoI-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-dimethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - {[(4-methyl-l-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (5-pyrimidinyl) 2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dietylaminometylpyrol-2-yl) methylene] -3- (5-pyrimidiny.l) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (piperidinometylpyrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Dietanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-dimethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (5-pyrimidinyl) 2-pyrazolin-5-one,

4 - [(3-Morpholinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-diethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (5-pyrimidinyl) 2-pyrazolin-5-one,

4 - {[3- (4-methyl-l-piperazinyl) methyl-4,5-tetrámetylénpyrol-2-yl] methylene} -3- (5pyrimidinyl) -2-pyrazolin-5-one,

3- (5-Pyrimidinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenopyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4 - [(3-Piperidinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-diethylamino-ethyl-3,5-dimethyl-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dimethylaminomethyl-pyrrol-2-yl) -methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-oxo-l, 5,6,7-tetrahydro-indole-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-dimethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (piperidinometylpyrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Dietanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-Dimethylaminomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-Morpholinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-diethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (2-pyrimidinyl) 2-pyrazolin-5-one,

4 - {[3- (4-methyl-l-piperazinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazoIin-5-one,

3- (2-Pyrimidinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenopyrrol-2-yl] methylene} -2-pyrazolin-5-one, '´

4 - [(3-Piperidinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-diethylamino-ethyl-3,5-dimethyl-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dimethylatinomethyl-pyrrol-2-yl) -methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one.

4 - [(4-oxo-l, 5,6,7-tetrahydro-indole-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-dimethylaminomethyl-5-methylpyrrolidin-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one .

4 - [(3,5-Dimethyl-4- (l-pyrolidinylmetylpyrol-2-yl) methylene] -3- (3-pyridazinyl)

2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-piperidinometylpyrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-Dietanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3-dimethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (3-pyridazinyl) 2-pyrazolin-5-one,

4 - [(3-Morpholinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3-diethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (3-pyridazinyl) 2-pyrazolin-5-one,

4 - {[3- (4-Methyl-1-piperazinyl) methyl-4,5-tetramethylene-pyrrol-2-yl] -ethylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

- (3-Pyridazinyl) -4 - ([3- (1-pyrrolidinyl) methyl-4,5-tetramethylenopyrrol-2-yl] methylene) -2-pyrazolin-5-one,

4 - [(3-Piperidinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-diethylamino-ethyl-3,5-dimethyl-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-oxo-l, 5,6,7-tetrahydro-indole-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-dimethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - {[(4-methyl-l-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (4-pyridazinyl) 2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (l-pyrolidinylmetylpyrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (piperidinometylpyroI-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-Dietanolaminomethyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3-dimethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (4-pyridazinyl) 2-pyrazolin-5-one,

4 - [(3-Morpholinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3-diethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (4-pyridazinyl) -2pyrazoIin-5-one,

4 - {[3- (4-methyl-l-piperazinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} -3- (4pyridazinyl) -2-pyrazolin-5-one,

3- (4-Pyridazinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenopyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4 - [(3-Piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-diethylamino-3,5-dimethyl-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-oxo-l, 5,6,7-tetrahydro-indole-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-dimethylaminomethyl-5-methylpyrone-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - {[(4-methyl-l-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (5-isoxazolyl) 2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - [(1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one,

4 - [(4-Dietanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one,

4 - [(3-dimethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (5-isoxazolyl) 2-pyrazolin-5-one,

3- (5-Isoxazolyl) -4 - [(3-morpholinomethyl-4,5-tetramethylene-pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3-Diethylaminomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazoline

5-ón,

3- (5-isoxazolyl) -4 - {[3- (4-methyl-l-piperazinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} ·

2-pyrazolin-5-one,

3- (5-isoxazolyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenopyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3- (5-Isoxazolyl) -4 - [(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one,

4 - [(4-diethylamino-ethyl-3,5-dimethyl-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (5-isoxazolyl) -2-pyrazolin-5-one,

4 - [(4-oxo-l, 5,6,7-tetrahydro-indole-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one,

4 - [(4-dimethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) 2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - {[(4-methyl-l-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (5-methyl-3izoxazolyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4 - [(l-pyrolidinylmetylpyrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) 2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) 2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-piperidinometylpyrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) 2-pyrazolin-5-one,

4 - [(4-Dietanolaminometyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) 2-pyrazolin-5-one,

4 - [(3-Dimethylaminomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one,

3- (5-Methyl-3-isoxazolyl) -4 - [(3-morpholinomethyl-4,5-tetrarnethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3-Diethylaminomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one,

3- (5-methyl-3-isoxazolyl) -4 - {[3- (4-methyl-l-piperazinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} -2-pyrazolin-5-one,

3- (5-methyl-3-isoxazolyl) -4 - {[3- (l-pyrrolidinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene}

2-pyrazolin-5-one,

3- (5-Methyl-3-isoxazolyl) 4 - [(3-piperidinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one,

4 - [(4-diethylamino-ethyl-3,5-dimethyl-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) 2-pyrazolin-5-one,

4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dimetylaminometylpyrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) 2-pyrazolin-5-one,

3- (5-Methyl-3-isoxazolyl) -4 - [(4-oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5-one; >

4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one,

3-cyclopropyl-4- (1-3-[(dimethylamino) methyl] -4,5,6,7-tetrahydro-1H-2-indolylmethylidene) 4,5-dihydro-1H-5-pyrazolone, 3-Cyclopropyl-4- (1-4 - [(1,1-dimethylammonio) methyl] -3,5-dimethyl-1H-2-pyrrolylmethylidene) -4,5-dihydro-1H-5-pyrazolone maleate salt .

4- [1- (4 - [[2- (dimethylamino) ethyl] (methyl) amino] methyl-3,5-dimethyl-1 H -2-pyrrolyl) methylidene] 3- (2-pyrazinyl) -4,5 dihydro-l // - 5-pyrazolone,

4- (1-4- [2- (diethylamino) ethyl] -3,5-dimethyl-1H-2-pyrrolylmethylidene) -3- (2-pyrazinyl) -4,5-dihydro-1H-5-pyrazolone .

4-l- [4- (3-chloropropanoyl) -3,5-dimethyl-l // - 2-pyrrolyl] methylidene-3- (2-pyrazinyl) -4,5-dihydro-IZ / 5-pyrazolone,

4- (l-3 - [(dimethylamino) methyl] -4,5,6,7-tetrahydro-l // - 2-indolylmetylidén) -3- (2-pyrazinyl) -4,5-dihydro-l // - 5-pyrazolone,

4- (l-4 - [(dimethylamino) methyl] -3,5-dimethyl-IZ / 2-pyrolylmetylidén) -3- (5-methyl-3izoxazolyl) -4,5-dihydro-l // - 5 pyrazolone,

3-Cyclopropyl-4 - [(4,5-dimethyl-2-yl) methylene] -2-pyrazolin-5-one,

3-benzyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Metoxyfenyloxymetyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Phenyloxymethyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Chlórfenyloxymetyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-methoxybenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

-Benzyl-4 - {[4- (2-carboxyethyl) -3-methylpyrrol-2-yl] methylene} -2-pyrazol-5-one, 3-Benzyl-4 - {[3- (2-carboxyethyl) (4-methylpyrrol-2-yl) methylene) -2-pyrazolin-5-one; 3- (4-Methylphenyloxymethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one;

2-Amino-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Isopropoxy-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-phenyl-ethyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-phenylamino-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-methylbenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-methyl-phenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-methoxy-phenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-chlorobenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Chloro-phenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (3-Chlórfenyloxymetyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (indol-3-yl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (3-Methoxybenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (3,4-dimethoxybenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-methoxyphenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Fenylfenyloxymetyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2-phenyl-propyl) -4 - [(p'yrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (3-phenyl-propyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Hydroxyphenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3,5-Dimethylpyrrol-2-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one,

3- (4-Methylphenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

I

4 - [(3,5-Dimethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3-Ethoxy-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-nitrophenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-fluoro-phenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Chloro-phenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4,5-Dimethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethyl pyrrole-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethyl pyrrole-2-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one,

4 - {[l- (4-hydroxybutyl) pyrrol-2-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one,

3-Cyclopentyloxy-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-7 t? N-butylureido-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-isopropoxy-4 - [(4-methylpyrrole-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-aminophenylethyl) -4 - [(4-methylpyrrole-2-yl) methylene] -2-pyrazolin-5-one,

3-isopropoxy-4 - [(l-methylpyrrole-2-yl) methylene] -2-pyrazolin-5-one,

3-isopropoxy-4 - [(5-methylpyrrole-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-aminophenylethyl) -4 - [(3,5-dimethyl-4-ethyl pyrrole-2-yl) methylene] -2-pyrazolin-5-one,

3-Ethoxy-4 - [(5-methylpyrrole-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Carbamoyl-phenylethyl) -4 - [(3,5-dimethyl-4-ethylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (4-methoxycarbonylphenylethyl-2-pyrazolin-5-one),

4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3- (4-Aminophenylethyl) -4 - [(3,5-dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(5-Ethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethyl pyrrole-2-yl) methylene] -3- (4-hydroxyphenylethyl) -2-pyrazolin-5-one,

3- (ethoxycarbonylmethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Methoxyphenylaminocarbonylmethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - {(3- (2-Carboxyethyl) -4-methylpyrrol-2-yl] methylene} -3-isopropyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(pyrrol-2-yl) methylene ] -2-pyrazolin-5-one,

3-cyclobutyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (3-pyridyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [[1- (3,5-dichlorophenyl) pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(Pyrol-2-yl) methylene] -3- (2,2,3,3-tetramethylcyclopropyl) -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3,5-dimethyl-2 'yl) methylene] -2-pyrazolin-5-one,

3-Cyclopentyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2-Methylcyclopropyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4- (Benzothiazol-2-yl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4,5-Dimethyl-2-yl) methylene] -4- (3-pyridyl)] - 2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3,5-dimethyl-4-etylpyroI-2-yl) methylene] -2-pyrazolin-5-one,

3- (pyrrol-2-yl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-methylpyrrole-2-yl) methylene] -2-pyrazolin-5-one,

3- (Benzothiazol-2-yl) -4 - [(4-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3,5-Dimethylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4- [3,5-dimethyl-4-ethyl pyrrole-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(5-Methylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(5-ethyl pyrrole-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3,5-dimethyl-4-etoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-isopropoxy-4 - [(5-phenyl-pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Propyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-methyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-isopropyl-phenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (3-phenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[1- (4-hydroxybutyl) pyrrol-2-yl] methylene] -2-pyrazolin-5-one,

4 - [[4- (2-Carboxyethyl) -3-methylpyrrol-2-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one, 4 - [(4-Carboxy-3,5-dimethylpyrol-2-yl) ) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3-Isopropoxy-4 - [(4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) Methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(4-Acetyl-3,5-dimethylpyrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimetylaminoetyloxykarbonyl) pyrrol-2-yl] methylene} -3-isopropoxy-2pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2-yl] methylene} -3 isopropoxy

2-pyrazolin-5-one,

4 - [(5-Etoxykarbonylpyrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(5-carboxypyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3- (4-Chloro-phenylaminocarbonylmethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(5-phenylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (tetrahydrofuran-3-yl) -2-pyrazolin-5-one, 4 - [(4-Carboxy-3,5) -dimethylpyrol-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one, 4 - [(3,5-dimethyl-4-ethoxycarbonylpyrol-2-yl) methylene] -3- (3-pyridyl) 2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3,5-dimethyl-4-morpholinomethyl-pyrrol-2-yl) -methylene] -2-pyrazolin-5-one,

4 - [(3,4-dimethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-carboxyethyl) -3-methylpyrrole-2-yl] methylene} -3-cyclopropyl-2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3,5-dimethyl-4-dimetylaminometylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(5-etoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4,5-tetrametylénpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (2-methoxycarbonyl-ethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-ethoxycarbonyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Isopropyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (trans-2-phenylcyclopropyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclohexyl-4 - [(pyrrol-2-yl) methylene-] -2-pyrazolin-5-one,

3-cyclopropylamino-4 - [(4,5-tetrametylénpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(5-morpholinomethyl-pyrrol-2-yl) -methylene] -2-pyrazolin-5-one,

4 - [(5-Carboxypyrol-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one,

4 - [(4-chloropyridin-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4 - [(4-bromopyridin-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4 - [(5-chloropyridin-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4 [(4-chloropyridin-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one,

4 - [(4-bromopyridin-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one,

3-Pyrazinyl-4 - [(4,5-tetrametylénpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3- (3-Pyridyl) -4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Carboxy-3,5-dimethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[3,5-dimethyl-4- (2-dimethylaminoethyloxycarbonyl) pyrrol-2-yl] methylene} -2-pyrazolyn-5-one,

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethyloxycarbonyl) pyrrol-2-y]] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one maleate salt 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrole-2) yl) methylene] -3-pyrazinyl-2pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-morfolinoetylaminokarbonyl) pyrrol-2-yl] methylene-3-pyrazinyl-2pyrazolin-5-one,

4 - [(3,5-Dimethyl-2-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethyl pyrrole-2-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5-one,

4 - [(4,5-tetrametylénpyrol-2-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5-one,

4 - [(3,5-dimethyl-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(3,5-dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3,5-dimethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-etoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3,5-dimethyl-4-trifluoroacetamidomethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-aminomethyl-3,5-dimethyl-2-yl) methylene] -2-pyrazolin-5-one,

3- (benzothiazol-2-yl) -4 - [(3,5-dimethyl-2-yl) methylene] -2-pyrazoIin-5-one,

3- (Benzothiazol-2-yl) -4 - [(3,5-dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(4-Etoxykarbonylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(4-Carboxypyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one;

4 - [(3,5-Dimethyl-4-dietanoIaminometylpyrol-2-yl) methylene-] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-trifluóracetamidometylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-ethoxycarbonyl-3-phenylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (1-pyrrolidinylmethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- dimethylaminomethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (2 -thienyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-etoxykarbonylpyrol-2-yl) methylene] -3-phenyl-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethyl pyrrole-2-yl) methylene] -3-phenyl-2-pyrazolin-5-one,

4 - [(3,4-di (ethoxycarbonyl) pyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

3-Ethoxy-4 - [(4-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-pyridylethyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (1-methyl-2-phenylethyl) -2-pyrazolin-5-one,

4 - [(4-Carboxy-3,5-dimethyl-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

3-Ethoxy-4 - [(5-nitro-pyrrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Ethoxy-4 - [(4-nitropyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(4-Carboxypyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrole-2-yl) methylene-} -3-ethoxy-2pyrazolin-5-one,

4 - [(5-chloro-3-methoxycarbonyl-4-metoxykarbonylmetylpyrol-2-yl) methylene] -3-ethoxy-2pyrazolin-5-one,

4 - {[3- (2-carboxyethyl) -4-methylpyrrole-2-yl] methylene} -3-ethoxy-2-pyrazolin-5-one,

4 - {[(3,5-Dimethyl-4-etoxykarbonylpyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

3-Ethoxy-4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3-trifluoromethyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) Methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one, 3- (3-Aminophenyl) -4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -2 pyrazoline-5-one,

3-Ethoxy-4 - {[2- (4-morpholinoethyl) aminocarbonylpyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4 - [(4-Ethoxycarbonyl-3-phenylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (4-Methyl-1-piperazinylmethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one;

4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene-] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-piperidinometylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-pipendinometylpyrol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one,

4 - [(3,5-dirnethyl-4-dimetylaminometylpyrol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one,

4 - [(5-methyl-4-dimetylaminometylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3,5-Dimethyl-4- [N- (2-dimethylaminoethyl) -jY-metylaminometylpyrol-2-yl} methylene} -3pyrazinyl-2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3-dimethylaminomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazoline

5-one,

4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3,5-dimethyl-4-dimethylaminomethylpyrrole) maleate salt -2-yl) methylene] -2-pyrazolin-5-one;

4 - {[4- (3-chloropropionyl) -3,5-dimethyl-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-diethylamino-ethyl) -3,5-dimethyl-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dimetylaminometylpyrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) 2-pyrazolin-5-one,

4 - [(4-Aminomethyl-3,5-dimethyl-4- (4-hydroxy-piperidinomethyl) -pyrrol-2-yl] -methylene} -3-pyrazinyl-2-pyrazolin-5-one, maleate salt dimethyl-2-yl) methylene] -3-pyrazinyl-2-pyrazolin

5th zone,

4 - {[4- (4-Benzyl) methylpyrrole-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-hydroxyethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3,5-Dimethyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

3-Cyclopropyl-4 - {{3,5-Dimethyl-4- [2- (l-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -2-pyrazolin

5-ón,

3-Cyclopropyl-4 - {[3,5-dimethyl-4- (2-hydroxyethyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-ethylaminoethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (3-Diethylaminopropyl) - 3,5-dimethyl-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (3-hydroxypropyl) pyrrol-2-yl] methyl, ene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-dimethyl) hydrochloride 4-dimetylaminoacetylpyrol-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one,

4 - [(3,5-Dimethyl-4-dimetylaminoacetylpyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

3-Cyclopropyl-4 - ([(2-diethylaminoethyl) -3,5-dimethyl-4-pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-dimethylaminoethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (4-hydroxybutyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (4-diethylamino-butyl) -3,5-dimethyl-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-DietyIaminoetyl- / V-oxide) -3,5-dimethyl-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (l-pyrolidinylacetyl) pyrrol-2-yl] methylene-} -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(4-Dietylaminoacetyl-3,5-dimethyl-2-yl) methylene] -3-pyrazinyl-2-pyrazoIin-5-one,

4 - [(3-Isopropyl-5-methylpyrrole-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- [3- (1-pyrrolidinylpropyl)] pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(Dimethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(dimethylaminomethyl-3-isopropyl-5-methylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-ethoxyoxalyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 3-Benzyl-4 - [(indol-3- yl) methylene] -2-pyrazolin-5-one,

3-Benzyl-4 - {[1- (4-hydroxybutyl) indol-3-yl] methylene} -2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3- (4-methoxyphenyloxymethyl) -2-pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3-phenoxymethyl-2-pyrazolin-5-one,

3- (4-Chloro-phenyloxymethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3- (4-methoxybenzyl) -2-pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3- (4-metylfenyloxymetyI) -2-pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3- (4-methylbenzyl) -2-pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3-phenylamino-2-pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3- (4-methylphenylamino) -2-pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3- (4-methoxy-phenylamino) -2-pyrazolin-5-one,

3- (4-Chlorobenzyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4 - {[1- (4-hydroxybutyl) indol-3-yl] methylene) -3- (4-methoxybenzyl) -2-pyrazolin-5-one,

3- (4-Chloro-phenylamino) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3- (3-methoxybenzyl) -2-pyrazolin-5-one,

3- (3,4-dimethoxybenzyl) -4 - [(indol-3-yl) methylene-] -2-pyrazolin-5-one,

3- (4-hydroxybenzyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3- (3-Chlórfenyloxymetyl) -4 - [(indol-3-yl) methylene-] -2-pyrazolin-5-one,

3- (Indol-3-yl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3- (4-methoxyphenylethyl) -2-pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3- (4-fenylfenyloxymetyl) -2-pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3- (2-phenylpropyl) -2-pyrazoIin-5-one,

4 '[(indol-3-yl) methylene] -3- (3-phenylpropyl) -2-pyrazolin-5-one,

3- (4-Hydroxyphenylethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3- (4-methylphenylethyl) -2-pyrazolin-5-one,

3-Ethoxy-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one;

4 - {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one, 4 - {[1- (4-Hydroxybiityl) indol-3-yl] methylene 3-Phenylethyl-2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (4-nitrophenylethyl) -2-pyrazolin-5-one, 4 - [(Indol-3) yl) methylene] -3-propoxy-2-pyrazolin-5-one,

3- (4-fluoro-phenylamino) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3- (4-aminophenylethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3-isopropoxy-4 - [(2-methyl-indol-3-yl) methylene] -2-pyrazolin-5-one,

3-Isopropoxy-4 - [(7-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

4 - [(7-Methylindol-3-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one,

3-Cyclopentyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3-Isopropoxy-4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3- (4-methoxycarbonylphenylethyl) -2-pyrazolin-5-one, 3-isopropoxy-4 - [(1-isopropylindol-3-yl) methylene] -2- pyrazolin-5-one, 3- (4-Hydroxyphenylethyl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 3-Isopropyl-4 - [(indol-3-yl) ) methylene] -2-pyrazolin-5-one

3- (4-ChlórfenylaminokarbonyIrnetyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3-Ethoxycarbonylmethyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one;

4 - [(Indol-3-yl) methylene] -3- (4-methoxyphenylaminocarbonylmethyl) -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one;

4 - [(Indol-3-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

3- (2-aminocarbonylethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3-cyclobutyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3- (2-dimethylaminocarbonyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[1- (4-hydroxybutyl) indol-3-yl] methylene} -2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3- (4-pyridyl) -2-pyrazolin-5-one,

3-Cyclopentyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3- (2,2,3,3-tetramethylcyclopropyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (2-methylcyclopropyl) -2-pyrazolin-5-one,

3-Cyclohexyl-4 - {[1- (4-hydroxybutyl) indol-3-yl] methylene} -2-pyrazolin-5-one,

4 - {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -3- (4-pyridyl) -2-pyrazolin-5-one,

3- (Benzothiazol-2-yl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5-one,

3-Dimethylamino-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one;

4 - [(^ι ^ ο1-3 ^ 1) πιεΙγ1έη] -3- (ΐΌΐ-2-7ΐ) -2-γ-αΓ1ΐη-5-όη,

4 - [(indol-3-yl) methylene] -3- (6-methoxy-benzothiazol-2-yl) -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(l-methyl-indol-3-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(7-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

4 - [(1-Methylindol-3-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3-propyl-2-pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3-methyl-2-pyrazolin-5-one,

4 - [(indol-3-yl) methylene] -3-trifluoromethyl-2-pyrazolin-5-one,

4 - {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -2-pyrazol-5-one,

4 - {[l- (4-hydroxybutyl) indol-3-yl] methylene} -3-methyl-2-pyrazolin-5-one,

4 - {[l- (4-hydroxybutyl) indol-3-yl] rnetylén} -3-trifluoromethyl-2-pyrazolin-5-one,

4 - {[l- (4-hydroxybutyl) indol-3-yl] methylene} -3 - (/ tert-butyl) -2-pyrazolin-5-one,

3-Ethoxycarbonyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

4 - [(Indol-3-yl) methylene] -3- (2-methoxycarbonylethyl) -2'-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (trans-2-phenyl) -l-cyclopropyl) -2-pyrazolin-5-one,

3-Cyclobutyl-4 - {[1- (4-hydroxybutyl) indol-3-yl] methylene} -2-pyrazolin-5-one,

4 - [(6-Carboxy-1-methylindol-3-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(5-methoxy-1-methylindol-3-yl) methylene] -2-pyrazolin-5-one;

4 - [(1-Methylindol-3-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(1,7-dimethylindol-3-yl) methylene] -2-pyrazolin-5-one,

4 - [(1-Methylindol-3-yl) methylene] -3- (tetrahydrofuran-3-yl) -2-pyrazolin-5-one,

3-Cyclopropylamino-4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

4 - [(6-Carboxy-1-methylindol-3-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(1,7-Dimethylindol-3-yl) methylene] -3- isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4 - [(5-methoxy-l-methyl-indol-3-yl) methylene] -2-pyrazolin-5-one,

3- (4-Fluorophenylamino) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

4 - [(1-Methylindol-3-yl) methylene] -3-trifluoroacetamido-2-pyrazolin-5-one,

3- (4-aminophenylethyl) -4 - [(l-methyl-indol-3-yl) methylene] -2-pyrazolin-5-one,

3-Amino-4 - [(l-methyl-indol-3-yl) methylene] -2-pyrazolin-5-one,

3- (4-chlorophenylethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one,

3-Ethoxy-4 - [(l-methyl-indol-3-yl) methylene] -2-pyrazolin-5-one,

3- (5-Isoxazolyl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one,

4 - [(1-Methylindol-3-yl) methylene] -3- tert -butyl-2-pyrazolin-5-one,

4 - [(6-Carboxy-1-methylindol-3-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one;

4 - {{1-Methyl-6- [2- (4-morpholino) ethyl] aminocarbonylindol-3-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(indol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3- (4-hydroxyphenylethyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-aminophenylethyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Metoxykarbonylfenyletyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

3- (4-Karbamoylfenyletyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3-dimethylaminomethylindol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(Indol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

3-isopropoxy-4 - [(5-methoxy-indol-2-yl) methylene] -2-pyrazolin-5-one,

3-Isopropoxy-4 - [(1-methylindol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(Indo-2-yl) methylene] -3- (tetrahydrofuran-3-yl) -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(5-methoxy-indol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(5-nitroindol-2-yl) methylene] -2-pyrazolin-5-one;

4 - [(Indol-2-yl) methylene] -3-isopropylamino-2-pyrazolin-5-one,

3- (4-Carboxyphenylethyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(Indol-2-yl) methylene] -3-phenyl-2-pyrazolin-5-one,

3-isopropoxy-4 - [(3-methyl-indol-2-yl) methylene] -2-pyrazolin-5-one,

3-Isopropoxy-4 - {[3- (2-methoxycarbonyl-2-acetamidoethyl) indol-2-yl] methylene} -2-pyrazolin-5-one,

3-Ethoxy-4 - [(indol-2-yl) methylene] -2-pyrazoIin-5-one,

3-Ethoxy-4 - {[3- (4-morpholinomethyl) indol-2-yl] methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[3- (4-morpholinomethyl) indol-2-yl] methylene} -2-pyrazolin-5-one,

4 - [(5-methoxy-indol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(5-methoxy-indol-2-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5-one,

4 - [(4-chloro-6,7-dihydro-indol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4 - [(4-chloro-6,7-dihydro-indol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(4-oxo-l, 5,6,7-dihydro-indol-2-yl) methylene-] -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3-Dimetylaminometylindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one,

4 - [(7-azaindole-3-yl) methylene] -3-benzyl-2-pyrazolin-5-one,

3-Benzyl-4 - {[1- (4-hydroxybutyl) -7-azaindol-3-yl] methylene} -2-pyrazolin-5-one,

4 - [(7-Azaindol-3-yl) methylene] -3- (4-methoxyphenyloxymethyl) -2-pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) methylene] -3-isopropoxy- 2-pyrazolin-5-one,

3-Amino-4 - [(7-azaindol-3-yl) methylene] -2-pyrazolin-5-one;

4 - [(7-Azaindol-3-yl) methylene] -3- (4-methoxybenzyl) -2-pyrazolin-5-one,

4 - [(7-azaindole-3-yl) methylene] -3-phenylamino-2-pyrazolin-5-one,

4 - [(7-azaindole-3-yl) methylene] -3- (4-methylbenzyl) -2-pyrazolin-5-one,

4 - [(7-azaindole-3-yl) methylene] -3- (4-hydroxyphenylethyl) -2-pyrazolin-5-one,

4 - {[l- (4-hydroxybutyl) -7-azaindole-3-yl] methylene} -3- (4-hydroxyphenylethyl) -2-pyrazolin-5-one,

4 - [(7-azaindole-3-yl) methylene] -3-isopropyl-2-pyrazolin-5-one,

4 - [(7-azaindole-3-yl) methylene-] -3-cyclopropyl-2-pyrazolin-5-one,

4 - [(7-azaindole-3-yl) methylene] -3-cyclobutyl-2-pyrazolin-5-one,

4 - [(7-aza-indol-3-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one,

4 - [(7-azaindole-3-yl) methylene] -3-phenyl-2-pyrazolin-5-one,

4 - [(7-azaindole-3-yl) methylene] -3- (4-fluoro-phenylamino) -2-pyrazolin-5-one,

4 - [(7-azaindole-3-yl) methylene] -3-propyl-2-pyrazolin-5-one,

4 - [(7-Azaindol-3-yl) methylene] -3-methyl-2-pyrazolin-5-one;

4 - [(7-azaindol-3-yl) methylene] -3-trifliiórmetyl-2-pyrazolin-5-one,

4 - [(7-azaindole-3-yl) methylene] -3- (tert-butyl) -2-pyrazoIin-5-one,

4 - {[1- (4-Hydroxybutyl) -7-azaindol-3-yl} methylene} -3-trifluoromethyl-2-pyrazolin-5-one,

4 - [(7-aza-indol-3-yl) methylene] -3- (4-isopropyl-phenylamino) -2-pyrazoIin-5-one,

4 - [(7-azaindole-3-yl) methylene] -3- (3-methylphenylamino) -2-pyrazolin-5-one,

4 - {[l- (4-hydroxybutyl) -7-azaindole-3-yl] methylene} -3- (3-methylphenylamino) -2-pyrazolin-5-one,

4 - [(7-azaindole-3-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one,

3-Benzyl-4 - [(4-dimethylaminophenyl) methylene] -2-pyrazolin-5-one,

4 - [(4-Dimethylaminophenyl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - [(4-dimethylaminophenyl) methylene] -3-phenylethyl-2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-dimethylaminophenyl) methylene] -2-pyrazolin-5-one,

3-isopropoxy-4 - [(3-methyl-pyrazol-4-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3-methylpyrazol-4-yl) methylene] -2-pyrazolin-5-one;

4 - [(Imidazol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(imidazol-2-yl) methylene] -2-pyrazolin-5-one,

4 - [(Imidazol-4-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(thien-2-yl) methylene] -2-pyrazolin-5-one;

4 - [(Indol-3-yl) methylene] -3-isopropyl-1-methyl-2-pyrazolin-5-one,

3-Isopropoxy-4 - [(pyrrol-3-yl) methylene] -2-pyrazolin-5-one,

4 - [(8-Hydroxyquinolin-5-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {[4- (2-diethylamino-ethyl) -3,5-dimethyl-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4 - {[4- (2-diethylamino-ethyl) -3,5-dimethyl-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one;

3-Cyclopropyl-4 - [(3,5-dimethyl-4- (l-pyrolidinylmetylpyrol-2-yl) methylene] -2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[4- (2-cyclopropylaminoethyl) -3] , 5-dimethyl-2-yl] methylene} 2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[3,5-dimethyl-4- (2-Phenylaminoethyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {{3,5-dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} 2-pyrazolin-5-one,

4 - {[4- (2-carboxyethyl) -3,5-dimethyl-2-yl] methylene} -3-cyclopropyl-2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(4-diethylaminomethyl-3-isopropyl-5-methylpyrrole-2-yl) methylene] 2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[4- (1-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2-yl] ethylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {{3-isopropyl-5-methyl-4- [2- (l-pyrrolidinylethyl)] pyrrol-2-yl.} Methylene} 2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[4- (2-cyclopropylaminoethyl) -3-isopropyl-5-methylpyrol-2-yl] methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrol-2-yl} methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[3-isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {{4- [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[4- (4-dimethylamino-butyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} 2-pyrazolin-5-one,

3-Cyclopropyl-4 - [(3-cyclopropyl-4-diethylaminomethyl-5-methylpyrrole-2-yl) methylene] 2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[3-cyclopropyl-4- (l-pyrrolidinylmethyl) -5-methylpyrrole-2-yl] methylene} 2-pyrazolin-5-one,

3-Cyclopropyl-4 - {{3-cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {{3-cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2-yl} -methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[3-cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrol-2-yl] methylene} -2-pyrazole-5-one,

3-Cyclopropyl-4 - {{3-cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-1} methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[3-cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl} methylene} -2-pyrazolin-5-one,

3-Cyclopropyl-4 - {{3-cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2-yl} methylene}

2-pyrazolin-5-one,

3-Cyclopropyl-4 - {[3-cyclopropyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazoline

5-ón,

4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4- [4- (2-carboxyethyl) -3,5-dimethyl-2-yl] methylene) -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazoline

5-ón,

4 - {[4- (l-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3 pyrazinyl-2-pyrazolin-5-one;

4 - {[4- (2-Cyklopropylaminoetyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

3-Pyrazinyl-4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrol-2-yl} methylene} -2-pyrazolin-5-one,

4 - {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

3-Pyrazinyl-4 - {{4- [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [2- (l-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrole-2-yl} methylene} -2pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [4- (l-pyrrolidinyl) butyl] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[3-Cyclopropyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (l-pyrolidinylmetylpyrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylamino-ethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-ethylaminoethyl) -pyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[3,5 -Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4- {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one,

4 - {[4- (l-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (2-furyl) -2pyrazoIin-5-one,

4 - {[4- (2-carboxyethyl) -3,5-dimethyl-2-yl] methylene} -3- (2-fňryl) -2-pyrazolin-5-one,

4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

3- (2H-Furyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

3- (2-furyl) -4 - {[3-isopropyl-5-methyl-4- (4-piperidino-butyl) pyrrol-2-yl] methylene} 2-pyrazolin

5-ón,

3- (2-Furyl) -4 - {{4- [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one,

4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (2-furyl) 2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [2- (l-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene} -3- (2-furyl) 2-pyrazolin-5-one,

4- {3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2-yl} methylene} - C - (2-furyl) 2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrole-2-yl] methylene} -3- (2-furyl) 2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene} 3- (2-furyl) -2-pyrazole n-5-one,

4 - ([3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene} -3- (2-furyl) 2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [4- (l-pyrrolidinyl) butyl] pyrrol-2-yl} methylene} -3- (2-furyl) 2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one;

4 - [(3,5-Dimethyl-4- (l-pyrolidinylmetylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - ([3,5-Dimethyl-4- (2-ethylamino-ethyl) pyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-Phenylaminoethyl) pyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3- (2-thienyl) 2-pyrazolin-5-one,

4 - {[4- (2-carboxyethyl) -3,5-dimethyl-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[4- (l-PyrolidinylmetyI) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one,

4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyklopropylaminoetyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one,

ΊΟ

4 - {{4- [3- (1-Pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[3-Isopropyl-5-methyl-4- (4-piperidino-butyl) pyrrol-2-yl] methylene) -3- (2-thienyl) 2-pyrazolin-5-one,

4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrol-2-yl} methylene) -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[4- (4-dimethylamino-butyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one,

4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (2-thienyl) 2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl) methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrole-2-yl) methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrole-2-yl] methylene) -3- (2-thienyl) 2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl) methylene} -3 (2-thienyl) -2-pyrazoline-5 -one

4 - {[3-Cyclopropyl-5-methyl-4- (3-fenyImetylaminopropyl) pyrrol-2-yl] methylene) -3- (2-thienyl)

2-pyrazolin-5-one;

4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2-yl) methylene} -3- (2-thienyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-5-methyl-4- (4-cyklobutylaminobutyl) pyrrol-2-yl] methylene) -3- (2-thienyl) 2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyklopropylaminoetyl) -3,5-dimetylpyroI-2-yl] methylene-} -3- (4-pyrimidinyl) 2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-ethylaminoethyl) -pyrrol-2-yl] methylene) -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-carboxyethyl) -3,5-dimethyl-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3-isopropyl-5-methylpyrrole-2-yl) methylene] -3- (4-pyrimidinyl) 2-pyrazolin-5-one,

4 - {[4- (l-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (4-pyrimidinyl) 2-pyrazolin-5-one,

4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-cyklopropyľaminoetyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5rón,

3- (4-Pyrimidinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

4 - {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (4-dimethylamino-butyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (4-pyrimidinyl) 2-pyrazolin-5-one,

4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (4-pyrimidinyl) 2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrole-2-yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrole-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene J-3 (4-pyrimidinyl) -2-pyrazoline-5 -one

4 - {[3-Cyclopropyl-5-methyl-4- (3-fenylmetylaminopropyl) pyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2-yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4- [3-Cyclopropyl-5-methyl-4- (4-cyklobutylaminobutyl) pyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3,5-dimethyl] pyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyklopropylaminoetyl) -3,5-dimethyl-2-yl] methylene} -3- (5-pyrimidinyl) 2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-ethylaminoethyl) -pyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-carboxyethyl) -3,5-dimetylpyroI-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3-isopropyl-5-methylpyrrole-2-yl) methylene] -3- (5-pyrimidinyl) 2-pyrazolin-5-one,

4 - {[4- (l-PyrolidinyImetyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (5-pyrimidinyl) 2-pyrazolin-5-one,

4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-cyklopropylaminoetyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (5pyrimidinyl) -2-pyrazolin-5-one,

3- (5-Pyrimidinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

4 - {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene) -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene) -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (5-pyrimidinyl) 2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl) methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2-yl) methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3-cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl) methylene} 3- (5-pyrimidinyl) -2-pyrazoline-5 -one

4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene) -3- (5-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [4- (l-pyrrolidinyl) butyl] pyrrol-2-yl) methylene) -3- (5pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-5-methyl-4- (4-cyklobutylaminobutyl) pyrrol-2-yl] methylene} -3- (5pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyklopropylaminoetyl) -3,5-dimethyl-2-yl] methylene} -3- (2-pyrimidinyl) 2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-ethylamino-ethyl) pyrrol-2-yl] methylene) -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl) methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-carboxyethyl) -3,5-dirnetylpyrol-2-yl] rnetylén} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3-isopropyl-5-methylpyrrole-2-yl) methylene] -3- (2-pyrimidinyl) 2-pyrazolin-5-one,

4 - {[4- (l-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (2-pyrimidinyl) 2-pyrazolin-5-one,

4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (2-cyklopropylaminoetyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

3- (2-Pyrimidinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

4 - {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,.

4 - {{4- [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrole-2-yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (2-pyrimidinyl) 2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrole-2-yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5, methylpyrrole-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene} 3- (2-pyrimidinyl) -2-pyrazoline-5 -one

4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2-yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4- [3-Cyclopropyl-5-methyl-4- (4-cyklobutylaminobutyl) pyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyklopropylaminoetyl) -3,5-dimethyl-2-yl] methylene} -3- (3-pyridazinyl) 2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-ethylamino-ethyl) pyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {[4- (2-carboxyethyl) -3,5-dimethyl-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3-isopropyl-5-methylpyrrole-2-yl) methylene] -3- (3-pyridazinyl) 2-pyrazolin-5-one,

4 - {[4- (l-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (3-pyridazinyl) 2-pyrazolin-5-one,

4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {[4- (2-cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3- (3 pyridazinyl) -2-pyrazolin-5-one,

3- (3-Pyridazinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

4 - {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {{4- [3- (4-PyridyImetylamino) propyl] -3-isopropyl-5-methylpyrrole-2-yl} methylene} -3- (3pyridazinyl) -2-pyrazolin-5-one,

4 - {[4- (4-dimethylamino-butyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (3-pyridazinyl) 2-pyrazolin-5-one,

4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrolidin-2-yl) methylene] -3- (3-pyridazinyl) 2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [2- (l-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene} -3- (3pyridazinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2-yl} methyl en} -3- (3 pyridazinyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrole-2-yl] methylene} -3- (3pyridazinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene} 3- (3-pyridazinyl) -2-pyrazoline-5 -one

4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2-yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-5-methyl-4- (4-cyklobutyIaminobutyl) pyrrol-2-yl] methylene} -3- (3pyridazinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-DietylaminometyI-3,5-dimethyl-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyklopropylaminoetyl) -3,5-dimethyl-2-yl] methylene} -3- (4-pyridazinyl) 2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-ethylamino-ethyl) pyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {(3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3-isopropyl-5-methylpyrrole-2-yl) methylene] -3- (4-pyridazinyl) 2-pyrazolin-5-one,

4 - {[4- (l-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (4-pyridazinyl) 2-pyrazolin-5-one.

4 - {[4- (2-carboxyethyl) -3,5-dimethyl-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {[4- (2-cyklopropylaminoetyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (4pyridazinyl) -2-pyrazolin-5-one,

3- (4-Pyridazinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one,

4 - ([3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one;

4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - [(3-Cyclopropyl-4-dietyIaminometyl-5-methylpyrrole-2-yl) methylene] -3- (4-pyridazinyl) 2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2-yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrole-2-yl] methylene} -3- (4pyridazinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene} 3- (4-pyridazinyl) -2-pyrazoline-5 -one

4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [4- (l-pyrrolidinyl) butyl] pyrrol-2-yl} methylene} -3- (4pyridazinyl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-5-methyl-4- (4-cyklobutylaminobutyl) pyrrol-2-yl] methylene} -3- (4pyridazinyl) -2-pyrazolin-5-one,

4 - [(3,5-Dimethyl-4- (l-pyrolidinylmetylpyrol-2-yl) methylene] -3- (l, 2,4-triazin-3-yl) 2-pyrazolin-5-one.

4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

4 - {[4- (2-Cyklopropylanainoetyl) -3,5-dimethyl-2-yl] methylene) -3- (l, 2,4-triazin-3-yl) 2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-ethylamino-ethyl) pyrrol-2-yl] methylene} -3- (l, 2,4-triazin-3-yl) 2-pyrazolin-5-one,

4 - {[3,5-Dimethyl-4- (2-Phenylaminoethyl) pyrrol-2-yl] methylene) -3- (l, 2,4-triazin-3-yl) 2-pyrazolin-5-one,

4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl) methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazoline-5 -one

4 - {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

4 - [(4-diethylaminomethyl-3-isopropyl-5-methylpyrrole-2-yl) methylene] -3- (l, 2,4-triazin-3-yl) 2-pyrazolin-5-one,

4 - {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl) methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazoline- 5-one,

4 - {[4- (2-cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

4 - {{4- [3- (1-Pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl) methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazoline- 5-one,

4 - {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2-yl) methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazoline- 5-one,

4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl) methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazoline 5-one,

4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2-yl} methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazoline-5 -one

4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrol-2-yl] methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene} 3- (1,2,4-triazine-3- yl) -2-pyrazolin-5-one,

4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

4 - {{3-Cyclopropyl-5-methyl-4- [4- (l-pyrrolidinyl) butyl] pyrrol-2-yl) methylene) -3- (l, 2,4triazín-3-yl) -2-pyrazoline 5-one,

4 - {[3-Cyclopropyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2-yl] methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

4 - {[4- (2-diethylamino-ethyl) -5-methyl-3-trifluoromethylpyrrole-2-yl] methylene) -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-4- [2- (1-pyrrolidinylethyl)] - 3-trifluoromethylpyrrol-2-yl} methylene) -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-ethylamino-ethyl) -5-methyl-3-trifluoromethylpyrrole-2-yl] methylene) -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-4- [2- (4-pyridylmethylaminomethyl)] - 3-trifluoromethylpyrrole-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (l-imidazolyl) ethyl] -5-methyl-3-trifluoromethylpyrrole-2-yl) methylene) -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-Aminoethyl) -5-methyl-3-trifluoromethylpyrrol-2-yl] methylene) -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminoethyl) -5-methyl-3- tert -butylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-4- [2- (l-pyrrolidinylethyl)] - 3 / tert butylpyrol-2-yl) methylene) -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-Ethylaminoethyl) -5-methyl-3- tert -butylpyrrol-2-yl] methylene) -3-pyrazinyl-2-pyrazoline

5-ón,

4- {5-Methyl-4- [2- (4-pyridylmethylaminomethyl)] - 3 / tert butylpyrol-2-yl] methylene) -3-pyrazinyl ·

2-pyrazolin-5-one,

4- {{4- [2- (l-imidazolyl) ethyl] -5-methyl-3-fc / ^- cis-butylpyrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-Aminoethyl) -5-methyl-3- / e / obutylpyrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-diethylamino-ethyl) -3-ethyl-5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3-Ethyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Ethyl-4- (2-ethylaminoethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Ethyl-5-methyl 4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-ethylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminoethyl) -5-methyl-3-ethyl pyrrole-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-cyclobutyl-4- (2-diethylamino-ethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{3-cyclobutyl-5-methyl-4- [2- (l-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[3-cyclobutyl-4- (2-ethylamino-ethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{3-Cyclobutyl-5-methyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-cyclobutylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminoethyl) -5-methyl-3-cyklobutylpyrol 2Tyl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclopentyl-4- (2-diethylamino-ethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{3-Cyclopentyl-5-methyl-4- [2- (l-pyrrolidinylethyl) pyrrol-2-yl) methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[3-Cyclopentyl-4- (2-ethylamino-ethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{3-Cyclopentyl-5-methyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (l-imidazolyl) ethyl] -5-methyl-3-cyklopentylpyrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-Aminoethyl) -5-methyl-3-cyclopentylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclohexyl-4- (2-diethylamino-ethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{3-Cyclohexyl-5-methyl-4- [2- (l-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[3-Cyclohexyl-4- (2-ethylamino-ethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{3-Cyclohexyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3pyrazinyI-2-pyrazolin-5-one,

4 - {{4- [2- (l-imidazolyl) ethyl] -5-methyl-3-cyklohexylpyrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-Aminoethyl) -5-methyl-3-cyclohexylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-diethylamino-ethyl) -5-methyl-3-phenyl-pyrrol-2-yl] methylene-} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3-phenyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-ethylamino-ethyl) -5-methyl-3-phenyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3-phenyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-phenylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazoline ·

5-ón,

4 - {[4- (2-Aminoethyl) -5-methyl-3-phenylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-diethylamino-ethyl) -5-methyl-3- (4-methoxyphenyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (4-methoxyphenyl) -4- [2- (l-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl

2-pyrazolin-5-one,

4 - {[4- (2-ethylamino-ethyl) -5-methyl-3- (4-methoxyphenyl) pyrrole-2-yl] methylene) -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (4-methoxyphenyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (l-imidazolyl) ethyl] -5-methyl-3- (4-methoxyphenyl) pyrrolidin-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminoethyl) -5-methyl-3- (4-methoxyphenyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-diethylamino-ethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (2-pyridyl) -4- [2- (l-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-ethylamino-ethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (2-pyridyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (l-imidazolyl) ethyl] -5-methyl-3- (2-pyridyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-Aminoethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-diethylamino-ethyl) -5-methyl-3-pyrazinylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3-pyrazinyl-4- [2- (l-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-Ethylaminoethyl) -5-methyl-3-pyrazinylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazoline

5-ón,

4 - {{5-Methyl-3-pyrazinyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-pyrazinylpyrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Cyklopropylaminoetyl) -5-methyl-3-pyrazinylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one.

4 - {[4- (2-Diethylaminoethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (2-imidazoyl) -4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-ethylamino-ethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (2-imidazoyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- (2- (1-Imidazoyl) ethyl] -5-methyl-3- (2-imidazoyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Cyklopropylaminoetyl) -5-methyl-3- (2-imidazoyl) pyrrol-2-yl] methylene} -3-pyrazinyl

2-pyrazolin-5-one,

4 - ([4- (2-diethylamino-ethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (2-pyrimidinyl) -4- [2- (l-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - ([4- (2-ethylamino-ethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (2-pyrimidinyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (l-imidazolyl) ethyl] -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl} -methylene-3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-Cyklopropylaminoetyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazoIin-5-one,

4- [4- (2-Dietylarninoetyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl] methylene} -3-.pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (3-isoxazolyl) -4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2 pyrazolin-5-one,

4 - {[4- (2-ethylamino-ethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (3-isoxazolyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one.

4 - {{4- [2- (l-imidazolyl) ethyl] -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-Cyklopropylaminoetyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl] methylene}

3-pyrazinyl-2-pyrazolin-5-one

4 - {[4- (2-Diethylaminoethyl) -5-methyl-3- (2-furyl) pyrrol-2-yl] methylene) -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (2-furyl) -4- [2- (l-pyrrolidinylethyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-Ethylaminoethyl) -5-methyl-3- (2-furyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (2-furyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl

2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3- (2-furyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Cyklopropylaminoetyl) -5-methyl-3- (2-furyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-Diethylaminoethyl) -5-hydroxymethyl-3-isopropylpyrrol-2-yl] methylene} -3-pyrazinyl-2 pyrazolin-5-one,

4 - {{5-Hydroxymethyl-3-isopropyl-4- [2- (l-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-ethylamino-ethyl) -5-hydroxymethyl-3-isopropyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Hydroxymethyl-3-isopropyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl [methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) ethyl] -5-hydroxymethyl-3-isopropylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Cyklopropylaminoetyl) -5-hydroxymethyl-3-isopropyl-pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one,

4- [4- (2-Diethylaminoethyl) -3,5-dicyclopropylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3,5-Dicyclopropyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-EtyIaminoetyl) -3,5-dicyklopropylpyrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3,5-Dicyclopropyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2 pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) ethyl] -3,5-dicyclopropylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Cyklopropylaminoetyl) -3,5-dicyklopropylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-diethylaminomethyl) -5-methyl-3-trifluoromethylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-dimethylaminomethyl) -5-methyl-3-trifluoromethylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-4- [2- (1-pyrrolidinylmethyl)] - 3-trifluoromethylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one;

4 - {[4- (2-Ethylaminomethyl) -5-methyl-3-trifluoromethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-4- [2- (4-pyridylmethylaminomethyl)] - 3-trifluoromethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3-trifluoromethylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminomethyl) -5-methyl-3-trifluoromethylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-diethylaminomethyl) -5-methyl-3- / ERI .'- butylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-dimethylaminomethyl) -5-methyl-3-tert-butylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-4- [2- (1-pyrrolidinylmethyl)] - 3- tert -butylpyrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminomethyl) -5-methyl-3-tert-butylpyrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4- {5-Methyl-4- [2- (4-pyridylmethylaminomethyl)] - 3-tert-butylpyrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {{4- (2- (1-Imidazoyl) methyl] -5-methyl-3-tert-butylpyro 1-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminomethyl) -5-methyl-3- tert -butylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminomethyl) -3-ethyl-5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Dimethylaminomethyl) -3-ethyl-5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3-Ethyl-5-methyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Ethyl-4- (2-ethylaminomethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3-Ethyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl] methylene} 3-pyrazinyl-2pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3-ethylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminomethyl) -5-methyl-3-ethyl pyrrole-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-cyclobutyl-4- (2-diethylaminomethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[3-Cyclobutyl-4- (2-dimethylaminomethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{3-cyclobutyl-5-methyl-4- [2- (l-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[3-Cyclobutyl-4- (2-ethylaminomethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one; '

4 - {{3-cyclobutyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3-cyclobutylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminomethyl) -5-methyl-3-cyclobutylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclopentyl-4- (2-diethylaminomethyl) -5-methylpyrrole-2-yl] ľnetylén} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[3-Cyclopentyl-4- (2-dimethylaminomethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{3-Cyclopentyl-5-methyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclopentyl-4- (2-ethylaminomethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{3-Cyclopentyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one,

4- {4- [2- (l-imidazolyl) methyl] -5-methyl-3-cyklopentylpyrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-Aminomethyl) -5-methyl-3-cyklopentylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[3-Cyclohexyl-4- (2-diethylaminomethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - ([3-Cyclohexyl-4- (2-dimethylaminomethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{3-Cyclohexyl-5-methyl-4- [2- (l-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[3-Cyclohexyl-4- (2-ethylaminomethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{3-Cyclohexyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3-cyclohexyl-pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Aminomethyl) -5-methyl-3-cyclohexylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminomethyl) -5-methyl-3-phenylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-dimethylaminomethyl) -5-methyl-3-phenyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3-phenyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminomethyl) -5-methyl-3-phenyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3-phenyl-4- [2- (4-pyridylmetylaminornetyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (l-imidazolyl) methyl] -5-methyl-3-phenyl-pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-Aminomethyl) -5-methyl-3-phenyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-diethylaminomethyl) -5-methyl-3- (4-methoxyphenyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-dimethylaminomethyl) -5-methyl-3- (4-methoxyphenyl) pyrrole-2-yl] methylene} -3-pyrazinyl

2-pyrazolin-5-one,

4 - {{5-Methyl-3- (4-methoxyphenyl) -4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (4-methoxyphenyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (4-methoxyphenyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (4-methoxyphenyl) pyrrol-2-yl} methylene) -3-pyrazinyl 2-pyrazolin-5-one,

4 - {[4- (2-Aminomethyl) -5-methyl-3- (4-methoxyphenyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-diethylaminomethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-dimethylaminomethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (2-pyridyl 4- [2- (l-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (2-pyridyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (2-pyridyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (2-pyridyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one.

4 - {[4- (2-Aminomethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazoline

5-ón,

4 - {[4- (2-diethylaminomethyl) -5-methyl-3-pyrazinylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-dimethylaminomethyl) -5-methyl-3-pyrazinylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3-pyrazinyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminomethyl) -5-methyl-3-pyrazinylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3-pyrazinyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3-pyrazinylpyrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylarninomethyl) -5-methyl-3-pyrazinylpyrrol-2-yl] methylene} -3-pyrazinyl-2 pyrazolin-5-one,

4 - {[4- (2-diethylaminomethyl) -5-methyl-3- (2-iniidazoyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-Dimethylaminomethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2 pyrazolin-5-one,

4 - '{{5-Methyl-3- (2-imidazolyl) -4- [2- (l-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2-yl] methylene) -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (2-imidazolyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (2-imidazoyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2 pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminomethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Diethylaminomethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2 pyrazolin-5-one,

4 - {[4- (2-dimethylaminomethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (2-pyrimidinyl) -4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (2-pyrimidinyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminomethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-diethylamino-ethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-dimethylaminoethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (3-isoxazolyl) -4- [2- (l-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-EtyIaminometyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (3-isoxazolyl) -4- [2- (4-pyridylmetylaminornetyl)] pyrrol-2-yl) methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2 pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminomethyl) -5-methyl-3- (3-isoxazolyl) p'yrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-diethylaminomethyl) -5-methyl-3- (2-furyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-dimethylaminomethyl) -5-methyl-3- (2-furyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{5-Methyl-3- (2-furyl) -4- [2- (l-pyrolidinyImetyI)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (2-furyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Methyl-3- (2-furyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (2-furyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Cyclopropylaminomethyl) -5-methyl-3- (2-furyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-diethylaminomethyl) -5-hydroxymethyl-3-isopropyl-pyrrol-2-yl] methylene} -3-pyrazinyl

2-pyrazolin-5-one,

4 - {[4- (2-dimethylaminomethyl) -5-hydroxymethyl-3-isopropyl-pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {{5-Hydroxymethyl-3-isopropyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3 pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminomethyl) -5-hydroxymethyl-3-isopropylpyrrol-2-yl] methylene} -3-pyrazinyl-2 pyrazolin-5-one,

4 - {{5-Hydroxymethyl-3-isopropyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) methyl] -5-hydroxymethyl-3-isopropylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

5 - {[4- (2-Cyclopropylaminomethyl) -5-hydroxymethyl-3-isopropylpyrrol-2-yl] -methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-diethylaminomethyl) -3,5-dicyklopropylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {[4- (2-dimethylaminomethyl) -3,5-dicyklopropylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one,

4 - {{3,5-Dicyclopropyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {[4- (2-Ethylaminomethyl) -3,5-dicyclopropylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazoline

5-ón,

4 - {{3,5-Dicyclopropyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - {{4- [2- (1-Imidazoyl) methyl] -3,5-dicyclopropylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one,

4 - [(4-Cyclopropylaminomethyl-3,5-dicyklopropylpyrol-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one,

4 - {[3-Cyclopropylaminomethyl-5-methyl-4- (2-diethylamino-ethyl) pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {[3-Cyclopropylaminomethyl-5-methyl-4- (2-hydroxyethyl) pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one,

4 - {[3-dimethylaminomethyl-5-methyl-4- (2-diethylaminoethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, and 4 - {[3-hydroxymethyl-5-methyl 4- (2-diethylamino-ethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one.

The compounds of formula (I) may exist as salts with pharmaceutically acceptable acids. The present invention includes these salts. Examples of such salts include hydrochlorides, hydrobromides, sulfates, methanesulfonates, nitrates, maleates, acetates, citrates, fumarates, tartrates [e.g. (+) - tartrates, (-) - tartrates or mixtures thereof, including racemic mixtures], succinates, benzoates and salts with amino acids such as e.g. glutamic acid. These salts can be prepared by standard methods.

Certain compounds of formula (I) having acidic substituents may exist as salts with pharmaceutically acceptable bases. The present invention includes these salts. Examples of such salts include sodium, potassium, lysine and arginine salts. These salts can be prepared by standard methods.

Certain compounds of formula (I) and salts thereof may exist in more than one crystalline form, and the present invention includes each such crystalline form and mixtures thereof.

T

Certain compounds of formula (I) and salts thereof may also exist in the form of solvates, e.g. hydrates, and the present invention includes each of these solvates and mixtures thereof.

Certain compounds of formula (I) may contain one or more chiral centers and thus exist in different optically active forms. When the compounds of formula (I) contain a single chiral center, the compounds exist in two enantiomeric forms and the present invention includes both enantiomers and mixtures of enantiomers. Enantiomers may be resolved by standard methods, e.g. formation of diastereomeric salts which may be separated, e.g. crystallization; by formation of diastereoisomeric derivatives or complexes which may be separated, e.g. crystallization, GLC or LC; by selective reaction of one enantiomer with an enantiomerically selective agent, e.g. enzymatic esterification; or GLC or LC in a chiral environment, e.g. on a chiral auxiliary medium, e.g. silica gel with a bound chiral ligand or in the presence of a chiral solvent. Where the desired enantiomer is converted to another chemical entity by one of the above methods, an additional step is required to release the desired enantiomeric form.

Alternatively, specific enantiomers may be synthesized by asymmetric synthesis using optically active agents, substrates, catalysts or solvents, or by converting one enantiomer to the other by asymmetric transformation.

When a compound of formula (I) contains more than one chiral center, it may exist in diastereoisomeric forms. The diastereomeric pairs may be separated by standard methods, e.g. chromatography or crystallization and the individual enantiomers in each pair can be separated by the above methods. The present invention includes each diastereomer of the compounds of formula (I) and mixtures thereof.

Certain compounds of formula (I) may exist in different tautomeric forms or as different geometric isomers, and the present invention includes each tautomer and / or geometric isomer of the compounds of formula (I) and mixtures thereof.

Certain compounds of formula (I) may exist in various stable conformational forms which may be separable. Torsional asymmetry due to its limited rotation around an asymmetric single bond, e.g. due to steric hindrance or circular tension, they can enable separation of different conformers. The present invention includes each such conformational isomer of the compounds of formula (I) and mixtures thereof.

Certain compounds of formula (I) may exist in the form of a zwitterion of compounds of formula (I) and mixtures thereof.

The compounds of the present invention are effective as serine / threonine kinase and tyrosine kinase inhibitors. In particular, the compounds of the present invention are effective as inhibitors of tyrosine kinases that are important in hyperproliferative diseases, particularly angiogenesis processes. For example, certain of these compounds are inhibitors of receptor kinases, e.g. KDR, Flt-1, FGFR, PDGFR, c-Met, or IGF-1-R. Since these compounds are anti-angiogenic, they are important agents for inhibiting the progression of disease states in which angiogenesis plays an important role. Certain compounds of the present invention are effective as serine / threonine kinase inhibitors, e.g. erk, MAP kinases, cdks, Plk-1 or Raf-1. These compounds are effective in the treatment of cancer and hyperproliferative disorders. Furthermore, certain compounds are potent inhibitors of non-receptor kinases, e.g. src, lyn, lck, fck, blk, hck. These compounds are effective in the treatment of cancer, hyperproliferative disorders and immunological diseases.

The present invention provides a method of inhibiting the kinase activity of tyrosine kinases and serine / threonine kinases comprising administering a compound represented by the general formula (I) against said kinase at a concentration sufficient to inhibit the enzymatic activity of said kinase.

The present invention further encompasses the use of these compounds in pharmaceutical compositions with a pharmaceutically acetically effective amount of the above compounds and a pharmaceutically acceptable carrier or excipient. These pharmaceutical compositions can be administered to recipients to slow or stop the angiogenesis process in angiogenesis-promoting diseases or to treat edema, effusions, exudates or ascites and other conditions associated with vascular hyperpermeability. Certain pharmaceutical compositions may be administered to recipients for the treatment of cancer and hyperproliferative disorders by inhibiting serine / threonine kinases, e.g. cdk, Plk-1, erk, etc.

DETAILED DESCRIPTION OF THE INVENTION

The compounds of the present invention have anti-angiogenic properties. These anti-angiogenic properties are due, at least in part, to the inhibition of protein tyrosine kinases necessary for the angiogenic process. Therefore, these compounds can be used as active agents against disease states, e.g. arthritis, atherosclerosis, psoriasis, hemangioma, myocardial angiogenesis, coronary and cerebral collateral, ischemic limb angiogenesis, wound healing, Helicobacter-related peptic ulcer, viral-induced angiogenic syndrome, pro-menopause, fracture scratches, rubeosis, neovascular glaucoma, and retinopathy, e.g. those associated with diabetic retinopathy, premature retinopathy or age-related macular degeneration. Furthermore, some of these compounds may be used as active agents against solid tumors, malignant ascites, hematopoietic cancers and hypeproliferative disorders, e.g. thyrotropic hyperplasia (especially Graves' disease), and cysts (e.g., ovarian tree hypervascularity indicative of polycystic ovarian syndrome (Stein-Leventhala syndrome), since such diseases require blood vessel cell proliferation for growth and / or metastasis.

Furthermore, some of these compounds may be used as an active agent against burns, chronic lung disease, stroke, polyps, anaphylaxis, chronic and allergic inflammation, delayed type of hypersensitivity, ovarian hyperstimulation syndrome, cerebral edema associated with brain cancer, trauma, altitude cerebral or pulmonary edema induced by hypoxia, ocular or macular edema, ascites and other diseases in which vascular hyperpermeability, effusions, exudates, protein extravasate or edema are manifestations of the disease. The compounds will also be effective in treating disorders in which protein extravasation will result in the deposition of fibrin and extracellular matrix, promoting stromal proliferation (e.g., keloid, fibrosis, cirrhosis, and carpal tunnel syndrome)). Increased VEGF formation potentiates inflammatory processes, e.g. strengthening and activation of the monocyte. The compounds of the invention will also be effective in treating inflammatory disorders, e.g. inflammatory bowel disease (IBD) and Crohn's disease.

VEGFs are unique in that they are the only angiogenic growth factors known to contribute to vascular hyperpermeability and edema formation. It appears that vascular hyperpermeability and edema associated with the expression or application of many other growth factors can be mediated through VEGF production. Inflammatory cytokines stimulate VEGF production. Hypoxia leads to considerable regulation of VEGF in many tissues, and thus situations involving heart attack, glaucoma, ischemia, anemia, or circulatory disturbance typically use VEGF / VPF-mediated responses. Vascular hyperpermeability, associated edema, altered transendothelial exchange, and macromolecular extravasation, often accompanied by diapedesis, may result in excess matrix deposition, aberrant stromal proliferation, fibrosis, etc. Thus, VEGF-mediated hyperpermeability can contribute significantly to disorders with the aforementioned etiological features.

It is believed that the above disorders are mediated to a large extent by the activity of a protein tyrosine kinase including KDR / VEGFR-2 and / or Flt-1 / VEGFR-1 tyrosine kinase. By inhibiting the activity of these tyrosine kinases, the progression of said disorders is inhibited because the angiogenic or vascular components of the hyperpermeability of the disease states are critically reduced. The effect of certain compounds of the invention given by their selectivity for specific tyrosine kinases results in minimization of side effects that might occur if tyrosine kinase inhibitors with less selectivity were used. Certain compounds of the present invention are also potent inhibitors of FGFR, PDGFR, c-Met and IGF-1-R. These receptor kinases can potentiate, directly or indirectly, angiogenic and hyperproliferative responses in various disorders, and thus their inhibition may prevent disease progression.

The compounds of the present invention have inhibitory activity against protein kinases, which means that these compounds modulate signal transduction of protein kinases. The compounds of the present invention inhibit protein kinases from the serine / threonine kinase and tyrosine kinase family. In particular, these compounds selectively inhibit the activity of KDR / FLK-1 / VEGFR-2 tyrosine kinases. Certain compounds of the present invention also inhibit the activity of other tyrosine kinases, e.g. Flt-1 / VEGFR-1, FGFR, PDGFR, IGF-1R, c-Met, Src-subfamily kinases, e.g. Lck, Src, Fyn, yes, etc. Furthermore, some of the compounds of the present invention significantly inhibit serine / threonine kinases, e.g. PKC, MAP kinases, erk, CDKs, Plk-1 or Raf-1, which play a significant role in cell proliferation and cell cycle progression. The efficacy and specificity of the generic compounds of the invention against individual protein kinase can often be altered and optimized by variations in the nature, number and arrangement of substituents (i.e., R 1, R ₂ , R 3, R 4, R 5, R 6 and R ₇ ) and conformational constraints. Furthermore, metabolites of certain compounds may also have significant inhibitory activity against protein kinases.

The compounds of the present invention, when administered to recipients in need of such a compound, inhibit vascular hyperpermeability and edema formation in these recipients. These compounds are believed to act by inhibiting the activity of KDR tyrosine kinase, which is involved in the process of vascular hyperpermeability and edema formation.

KDR tyrosine kinase can also be referred to as FLK-1 tyrosine kinase, NYK tyrosine kinase or VEGFR-2 tyrosine kinase. KDR tyrosine kinase is activated when the vascular endothelial cell growth factor (VEGFR) or another activating ligand (e.g., VEGF-C, VEGF-D, VEGF-E, or HIV Tat protein) binds to the KDR receptor tyrosine kinase found on the surface of vascular endothelial cells. Upon activation of KDR tyrosine kinase, blood vessel hyperpermeability occurs and fluid flows from the bloodstream through the walls of the blood vessels to the interstitial spaces, thereby creating an edema area. This form of response is also often accompanied by diapedesis. Similarly, excess vascular hyperpermeability can disrupt normal molecular exchange through the endothelium in critical tissues and organs (e.g., lungs and kidneys), causing macromolecular extravasation and deposition. Following this acute response to KDR stimulation, which is believed to support the following angiogenic process, prolonged stimulation of KDR tyrosine kinase leads to proliferation and chemotaxis of vascular endothelial cells and formation of new vessels. By inhibiting KDR tyrosine kinase activity by either blocking the production of activated ligand, blocking the binding of activated ligand to the KDR receptor tyrosine kinase, preventing dimerization and transphosphorylation of the receptor, inhibiting the enzyme activity of KDR tyrosine kinase (by inhibiting the phosphorylation function of the enzyme) Mukhopedhyay et al., Cancer Res. 5: 1278-1284 (1998) and related references), hyperpermeability, as well as associated extravasation, subsequent edema formation and matrix deposition, and angiogenic responses can be inhibited and minimized.

One group of preferred compounds of the present invention has the ability to inhibit KDR tyrosine kinase activity without significantly inhibiting Flt-1 tyrosine kinase activity (Flt-1 tyrosine kinase is also referred to as VEGFR-1 tyrosine kinase). Both KDR tyrosine kinase and Flt-1 tyrosine kinase are activated by VEGF binding to KDR tyrosine kinase receptors and Flt-1 tyrosine kinase receptors, respectively. Since Flt-1 tyrosine kinase activity may mediate important events in endothelial supply and vascular functions, inhibition of this enzyme activity may have toxic or adverse effects. At least, this inhibition is unnecessary due to blocking of angiogenic responses, induction of vascular hyperpermeability and edema formation, so this is not necessarily necessary and does not result in any benefit to the recipient. Certain preferred compounds of the present invention are unique in that they inhibit the activity of one VEGF receptor tyrosine kinase (KDR), which is activated by an activated ligand, but do not inhibit other receptor tyrosine kinases, e.g. Flt-1, which are also activated by certain activated ligands. Therefore, preferred compounds of the present invention are selective inhibitors of tyrosine kinase activity.

The compounds of the present invention are also effective in treating ulcers (ulcers) - bacterial, fungal, Mooren ulcers and ulcerative colitis.

The compounds of the present invention are also effective in the treatment of conditions in which undesired angiogenesis, edema or stromal deposition occurs in viral infections, e.g. Herpes simplex, Herpes Zoster, AIDS, parapoxvirus, psoriasis, Kaposi's sarcoma, protozoal infections and toxoplasmosis, endometriosis, ovarian hyperstimulation syndrome, preeclampsia, menometrorrhagia, systemic lupus, sarcoidosis, synovitis, inflammatory bowel disease, anemia of the intestine, anemia, anemia, anemia pemftgoid, Paget's disease, hyperviscosity syndrome, Osler-Weber-Rendu's disease, chronic inflammation, chronic lung disease, asthma, rheumatoid arthritis and osteoarthritis, and edema following trauma, burns, radiation or stroke.

The compounds of the present invention are also effective in the treatment of ocular events such as e.g. ocular and macular edema, ocular neovascular disease, scleritis, radial keratotomy, uveitis, vitritis, myopia, papilla physiological excision, chronic retinal detachment, laser treatment complications, conjunctivitis, stargardt's disease and retinal degeneration and Eales.

The compounds of the present invention are also effective in the treatment of cardiovascular conditions, e.g. atherosclerosis, restenosis, vascular occlusion of obstructive carotid disease.

The compounds of the present invention are also effective in the treatment of cancer-related indications such as solid tumors, sarcomas (in particular Ewing's sarcoma and osteosarcoma), retinoblastoma, rhabdomyosarcomas, neuroblastoma, hematopoietic malignancies including leukemia and lymphoma, pleural or pericardial effusion ascites.

The compounds of the present invention are also effective in the treatment of Crow-Fukase Syndrome (POEMS) and diabetic conditions, e.g. glaucoma, diabetic retinopathy and microangiopathy.

It is believed that the above disorders are significantly mediated by the activity of protein tyrosine kinases including VEGF receptors (e.g., KDR and Flt-1). By inhibiting the activity of these receptor tyrosine kinases, the progression of these disorders is inhibited since the angiogenic component of the disease state is greatly reduced. The effect of the compounds of the present invention due to selectivity for specific tyrosine kinases leads to minimization of side effects that could occur if less selective tyrosine kinase inhibitors were used.

In another aspect, the present invention provides compounds of formula I as defined above (including exceptions) for use as medicaments, particularly as inhibitors of protein kinase activity, e.g. tyrosine kinase, serine kinase and threonine kinase activities. In yet another aspect, the present invention provides the use of the compounds of formula (I) as defined above (including exceptions) in the manufacture of a medicament for inhibiting protein kinase activity.

The following terms are used in the present invention:

The term "physiologically acceptable salts" refers to those salts which retain the biological activity and properties of the free bases and which are prepared by reaction of inorganic acids, e.g. hydrochloric, hydrobromic, sulfuric, nitric, phosphoric or organic acids, e.g. sulfuric, carboxylic, organic phosphoric, riethanesulfonic, ethanesulfonic, p-toluenesulfonic, salicylic, lactic, tartaric, etc.

The term "alkyl" refers to an aliphatic hydrocarbon comprising straight and branched chain groups having 1 to 6 carbon atoms or cyclic hydrocarbons having 3 to 6 carbon atoms.

The term "alkoxy" refers to an "O-alkyl group" in which the "alkyl group" is as defined above

Pharmaceutical formulations

The compounds of the present invention may be administered to human or animal subjects as such or in pharmaceutical compositions in which they are admixed with suitable carriers or excipients (tom) at dosages sufficient to treat or ameliorate vascular hyperpermeability, edema and related disorders.

100

Mixtures of these compounds can also be administered to patients as a simple mixture or in suitable prepared pharmaceutical preparations. A therapeutically effective dose further refers to an amount of the compound or compounds that is sufficient to prevent or attenuate inappropriate neovascularization, progression of hyperproliferative disorders, edema, VEGF-related hyperpermeability and / or VEGF-associated hypotension. Techniques for preparing and administering compounds can be found in "Remington's Pharmaceutical Sciences", Mack Publishing Co., Easton, PA, last edition.

Routes of administration

Suitable routes of administration may be e.g. oral, in the form of eye drops, rectal, transmucosal, topical or intestinal administration, parenteral delivery including intramuscular, subcutaneous and intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal or intraocular injections.

Alternatively, the compound may be administered by a local rather than a systemic route, e.g. injecting the compound directly into the edema site, often in a depot or sustained release formulation.

in

Further, the drug may be administered as a target-specific administration, e.g. a liposome coated with an endothelial, cell-specific antibody.

Composition / Formulation

The pharmaceutical compositions of the present invention may be manufactured in a standard manner, e.g. by standard mixing, dissolving, granulating, dragee-making, milling, emulsifying, encapsulating, sealing or lyophilizing.

Thus, pharmaceutical compositions for use according to the present invention may be prepared in a standard manner using one or more physiologically acceptable carriers containing excipients and excipients which facilitate processing of the active compounds into preparations used in a pharmaceutical process. The preparation itself depends on the route of administration chosen.

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For injection, the agents of the present invention may be prepared in aqueous solutions, preferably in physiologically compatible buffers such as Hanks' solution, Ringer's solution or saline-based buffer. For transmucosal administration, penetrants that are suitable for overcoming a given barrier are used in the formulation. These penetrators are generally known. and

For oral administration, the compounds can be readily prepared by combining the active compounds with standard pharmaceutically acceptable carriers. These carriers make it possible to prepare the compounds of the present invention in the form of tablets, pills, dragees, capsules, solutions, gels, syrups, injectables, suspensions, etc., for oral ingestion of the medicament by the patient to be treated. Pharmaceutical preparations for oral use can be prepared by combining the active compound with a solid excipient, optionally grinding the resulting mixture, and after adding suitable excipients, if necessary, by processing the mixture of granules to obtain tablets or dragees. Suitable excipients are especially fillers, e.g. sugars including lactose, sucrose, mannitol or sorbitol; cellulosic preparations, e.g. corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth, methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidone (PVP). If desired, disintegrating agents such as cross-linked polyvinylpyrrolidone, agar or alginic acid or salts thereof, e.g. sodium alginate.

Dragees are provided with suitable coatings. Concentrated sugar solutions may be used for this purpose, which may optionally contain gum arabic, talc, polyvinylpyrrolidone, carbopol gel, polyethylene glycol and / or titanium dioxide, shellac solutions and suitable organic solvents or solvent mixtures. Organic dyes or pigments may be added to tablets or dragee coatings to identify or characterize different combinations of active compound doses.

Pharmaceutical preparations that can be used orally include capsules made of gelatin as well as soft, sealed capsules made of gelatin and a plasticizer, such as e.g. glycerol or sorbitol. The capsules may contain the active ingredients in admixture with fillers, e.g. lactose, binders, e.g. starches, and / or lubricants, such as e.g. talc or magnesium stearate, and optionally stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, e.g. fatty oils, mineral oils or liquid polyethylene glycols. In addition, they can

102 stabilizers should be added. All formulations for oral administration should be in dosages suitable for such administration.

For buccal administration, the formulations may be in the form of tablets or lozenges formulated in conventional manner.

For administration by inhalation, the compounds of the present invention are normally delivered in the form of an aerosol spray in a nebulizer or in a compressed pack with a suitable propellant, e.g. dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gases. In the case of a pressurized aerosol, a "valve" can be used to deliver the exact amount of substance. Capsules and cartridges, e.g. from gelatin, for use in an inhaler or insufflator, may be prepared by a process in which a powder mixture of the compound and a suitable powder base, e.g. lactose or starch.

The compounds may be prepared for parenteral administration by injection, e.g. bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g. in ampoules or in multi-dose containers, with added preservative. The formulations may be e.g. in the form of suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain auxiliary agents, e.g. suspending, stabilizing and / or dispersing agents.

Pharmaceutical formulations for parenteral administration include aqueous solutions of the active compounds in a water-soluble form. In addition, suspensions of the active compounds may be prepared as appropriate oily injection suspensions. Suitable lipophilic solvents or carriers include fatty oils, e.g. sesame oil, or esters of synthetic fatty acids, e.g. ethyl oleate or triglycerides, or liposomes.

Water injection. suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethylcellulose, sorbitol or dextran. Optionally, the suspensions may also contain suitable stabilizers or agents which increase the solubility of the compounds, thereby making it possible to prepare highly concentrated solutions.

Alternatively, the active ingredient may be in powder form for constitution with a suitable carrier, e.g. sterile pyrogen-free water.

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The compounds may also be prepared as rectal preparations, e.g. suppositories or retention enemas containing standard suppository bases, e.g. cocoa butter or other glycerides.

In addition to the above formulations, compounds may also be prepared as a depot preparation. These long duration formulations may be administered by implantation (e.g., subcutaneously or intramuscularly or by intramuscular injection). In this way, compounds can be prepared with suitable polymeric or hydrophobic materials (e.g. as an emulsion in an acceptable oil) or ion exchangers or as sparingly soluble derivatives, e.g. sparingly soluble salts.

An example of a pharmaceutical carrier for the hydrophobic compounds of the present invention is a cosolvent system comprising benzyl alcohol, a non-polar surfactant, an organic polymer, water-miscible and an aqueous phase. The cosolvent system may be a VPD cosolvent system. VPD is a solution of 3 vol% benzyl alcohol, 8 vol% non-polar polysorbate 80 surfactant and 65 vol% polyethylene glycol 300 and made up to a final volume with absolute ethanol. The VPD cosolvent system (VPD: 5W) consists of VPD diluted 1: 1 with 5% dextrose in aqueous solution. This cosolvent system dissolves hydrophobic compounds well and has low toxicity by systemic administration. Naturally, the proportions of the cosolvent system can be varied considerably, but so as to maintain the characteristics of its solubility and toxicity. In addition, the individual components of the cosolvent system may be varied: e.g. other non-polar, low-toxicity surfactants may be used in place of polysorbate 80; the particle size of the polyethylene glycol may vary; other biocompatible polymers can replace polyethylene glycol, e.g. polyvinylpyrrolidone; and other sugars or polysaccharides may replace dextrose.

Alternatively, another delivery system for hydrophobic pharmaceutical compounds may be used. For hydrophobic drugs, standard examples of carriers and carriers utilized in this method are liposomes and emulsions. Certain organic solvents, e.g. dimethylsulfoxide, but usually at the expense of greater toxicity. In addition, the compounds may be delivered by a sustained release system, e.g. semipermeable matrices of solid hydrophobic polymers containing the therapeutic agent. Various sustained-release substances are employed in this technique. Sustained-release capsules may, depending on their own

The chemical character of the compound releases the compounds over a period of several weeks to 100 days. Depending on the chemical nature and biological stability of the therapeutic reagent, additional protein stabilization strategies may be used.

The pharmaceutical preparations may also contain a suitable solid or carriers or excipients of the goal phase. Examples of such carriers or excipients include, but are not limited to, calcium carbonate, calcium phosphate, various sugars, starches, cellulose derivatives, gelatin, and polymers, e.g. polyethylene glycols.

A large number of compounds of the present invention may be in the form of a salt with pharmaceutically compatible counterions. Pharmaceutically compatible salts may be prepared with many acids including, but not limited to, hydrochloric, sulfuric, acetic, lactic, tartaric, malic, succinic, etc. Salts tend to be much more soluble in aqueous or other protonated solvents than their corresponding free bases.

Effective dose

Pharmaceutical compositions suitable for use in the present invention include those in which the active ingredients are present in an effective amount to achieve the desired effect. More specifically, a therapeutically effective amount is an amount sufficient to prevent or ameliorate existing symptoms in the subject being treated. Determination of effective amounts is a standard routine.

For any compound used in the method of the present invention, the therapeutically effective dose can first be determined by cell culture assays. For example, the dose can be assayed in cell and animal models to achieve circulating concentration that includes an IC 50 determined from cell culture assays (i.e., the concentration of test compound that is required to achieve 50% possible inhibition of the protein kinase activity). In some cases, it is appropriate to determine the IC 50 value in the presence of 3-5% serum albumin as this assay approximates the binding effects of plasma proteins on the compound. This information can be used in human subjects to more accurately determine effective doses. Most preferred compounds for systemic administration effectively inhibit protein kinase signaling in intact cells at levels that are safely achievable in plasma.

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A therapeutically effective dose means that amount of the compound that results in amelioration of the patient's symptoms. The toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical methods on cell cultures or experimental animals, e.g. to determine the maximum tolerated dose (MTD) and ED50 (the concentration of the substance that produces 50% of the maximum dose effect). The dose ratio between toxic and therapeutic effects is determined by the therapeutic index and can be expressed as the ratio between MTD and ED50. Compounds having high therapeutic indices are preferred. Data obtained from cell culture assays and animal studies can be used to determine the dose range intended for human subjects. The dose of such a compound lies preferably within a range of concentrations in the systemic circulation that include the ED 50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. The exact formulation, route of administration, and dose may be selected by the physician in accordance with the patient's condition (see Fingl et al., 1975, in "Pharmacological Basis of Therapeutics", Chapter 1, p. 1). In crisis management, an acute bolus or infusion may be used to achieve a rapid response to achieve MTD.

Dosage amount and interval can be individually adjusted to achieve a plasma level of the active moiety that is sufficient to maintain kinase modulating effects or minimum effective concentration (MEC). The MEC value will be different for each compound, but can be determined from in vitro data; e.g. the concentration required to achieve 50-90% inhibition of protein kinase by the assays described in the present invention. The dosages required to achieve the MEC will depend on the individual characteristics and route of administration. However, HPLC or bioassays may be used to determine plasma concentrations.

Intervals between doses can also be determined using the MEC value. Compounds should be administered according to a regimen that maintains plasma levels above the MEC for 10-90% of the time, preferably between 30-90% and most preferably 5090%, until the desired improvement in the symptoms is achieved. In cases of topical administration or selective uptake, the effective local drug concentration may not correspond to the plasma concentration.

The amount of preparation administered will depend upon the subject being treated, its weight, the severity of the affliction, the route of administration, and the judgment of the physician concerned.

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Packaging technique

The formulations, if desired, may be in the form of a package or container of medicament, which may contain one or more unit dosage forms containing the active ingredient. The package may e.g. contain a metal or plastic foil, e.g. soft transparent packaging. The pack or container of the medicament may be distributed along with the instructions for administration. Compositions comprising a compound of the present invention may also be prepared in a compatible pharmaceutical carrier that are placed in an appropriate container and labeled to treat the indicated condition.

In some formulations, it may be beneficial to use the compounds of the present invention in very small particle size, e.g. those obtained by fluid energy milling.

The use of the compounds of the present invention in the manufacture of pharmaceutical compositions is set forth in the following description. In this specification, the term "active compound" means any compound of the present invention, but in particular any compound that is the end product of one of the above examples.

(a) Capsules

When preparing capsules, 10 parts by weight of the active compound and 240 parts by weight of lactose can be deagregated and mixed. The composition may be filled into solid gelatin capsules, each capsule containing a unit dose or unit dose fraction of the active compound.

(b) Tablets

Tablets may be prepared from the following ingredients. Mass fractions Active compound 10 lactose 190 Maize starch 22 polyvinylpyrrolidone 10 Magnesium stearate 3

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The active compound, lactose and part of the starch may be deagregated, mixed and the resulting mixture may be granulated with a solution of polyvinylpyrrolidone in ethanol. The dry granulate may be admixed with magnesium stearate and starch residue. The mixture may then be compressed in a tabletting machine, each tablet containing a unit dose or part of a unit dose of the active compound.

c) Tablets with enteric coating

Tablets may be prepared as described in (b) above. The tablets may then be enteric coated in a standard manner with a solution of 20% cellulose acetate phthalate and 3% diethyl phthalate in a 1: 1 mixture of ethanol and water.

d) Suppositories

In the preparation of suppositories, 100 parts by weight of the active compound may be admixed with 1300 parts by weight of a triglyceride-based suppository matrix, and the resulting mixture may be dosed into the suppositories, each containing a therapeutically effective amount of the active ingredient.

In the compositions of the present invention, the active compound may, if desired, be associated with other compatible pharmacologically active ingredients. For example, the compounds of the present invention may be administered in combination with one or more other pharmaceutical agents that inhibit or prevent VEGF production, attenuate intracellular responses to VEGF, block intracellular signal transduction, inhibit vascular hyperpermeability, reduce inflammation, or inhibit or prevent edema formation, or not . The compounds of the present invention may be administered before, after, or concurrently with another pharmaceutical agent by any suitable route of administration. Other pharmaceutical agents include, but are not limited to, antiedemic steroids, NSAIDS, ras inhibitors, anti-TNF agents, anti-IL-1 agents, antihistamines, PAF-antagonists, COX-1 inhibitors, COX-2 inhibitors, NO inhibitors synthases, PKC inhibitors and PI3 kinase inhibitors. The compounds of the present invention and other pharmaceutical agents act either additively or synergistically. Thus, administration of another such combination of agents that inhibits angiogenesis, vascular hyperpermeability, and / or inhibits edema formation may

108 to provide greater mitigation of the harmful effects of hyperproliferative diseases, angiogenesis, vascular hyperpermeability or edema than administration of either substance alone. Combinations with antiproliferative or cytotoxic chemotherapy or radiation are contemplated in the treatment of malignant disorders.

The present invention also encompasses the use of a compound of Formula I as a medicament.

Both Src and Syk kinases play key roles in regulating immune functions. The Src family currently includes Fyn, Lck, Fgr, Fes, Lyn, Src, Yes, Hck, and Blk. The Syk family currently includes only Zap and Syk. The Janus kinase family is involved in the growth factor transduction and pro-inflammatory cytokine signals involving many receptors. Although BTK and ITK, members of the Tec family of kinases, play a less well-known role in immunobiology, their modulation by inhibitors may have a therapeutic benefit. RIP, IRAK-1, IRAK-2, NIK, TPL-2 / COT, IKK-1 and 1KK-2 kinases are involved in signal transduction pathways of key pro-inflammatory cytokines TNF and IL-1. The compounds of formula (I), by virtue of their ability to effectively inhibit one or more of these kinases, can act as immunomodulatory agents that are effective for allograft stabilization and treatment of autoimmune diseases. Because of their ability to regulate T cell activation or potentiation of inflammatory processes, these compounds could be used to treat these autoimmune diseases. The transplants, due to the rejection phenomenon, whether the host-graft-response in solid organs or the graft-versus-host reaction in bone marrow, are limited by the toxicity of commonly available immunosuppressants and thus an effective drug with improved therapeutic index would be very beneficial. Gene-based experiments have shown a significant role for Src in osteoclast biology, the cells responsible for bone resorption. The compounds of formula (I) may also be effective in the treatment of osteoporosis, osteopetrosis, Paget's disease, tumor-induced hypercalcemia and bone metastasis due to the ability of Src to be regulated.

A large number of protein kinases have been shown to be proto-oncogenic. Chromosome disruption (at the Itk kinase disruption point on chromosome 5), translocation as in the case of the Abl gene with BCR (Philadelphia Chromosome), shortening in cases such as c-Kit or EGFR, or mutation (e.g. Met) results in the formation of dysregulatory proteins that cause the conversion of proto-oncogenic products to oncogenic products. In other tumors, oncogenesis is controlled by autocrine or

109 paracrine interactions between the ligand and the growth factor receptor. Members of the src kinase family typically participate in downstream signal transduction, thereby potentiating oncogenesis and may themselves become oncogenic due to overexpression or mutation. By inhibiting the protein kinase activity of these proteins, these diseases can be cured. Vascular restenosis may involve a process of FGF and / or PDGF-propagated proliferation of smooth muscle and endothelial cells. In vivo ligand stimulation of FGFR, PDGFR, IGF1-R and c-Met is proangiogenic and potentiates angiogenesis-dependent disorders. Inhibition of FGFr, PDGFr, c-Met or IGF1-R kinase activity may be an effective strategy for inhibiting this phenomenon. Thus, compounds of formula (I) that inhibit the kinase activity of normal or aberrant c-kit, c-met, c-fms, src family members, EGFr, erbB2, erbB4, BCR-Abl, PDGFr, FGFr, IGF1-R and others receptor or cytosolic tyrosine kinases may play an important role in the treatment of benign and neoplastic proliferative diseases.

In many pathological conditions (e.g., solid primary tumors and metastases, Kaposi's sarcoma, rheumatoid arthritis, blindness due to inappropriate eye neovascularization, psoriasis, and atherosclerosis), disease progression after persistent angiogenesis is contingent. Polypeptide growth factors often produced by diseased tissue or accompanying inflammatory cells and their corresponding specific endothelial cell receptor tyrosine kinases (e.g., KDR / VEGFR-2, Flt-1 / VEGFR-1, Tie-2 / Tek and Tie) are essential for stimulating endothelial cell growth, migration, alignment, differentiation and assembly of new functional vasculators. VEGF-mediated VEGF-stimulation of VEGFR kinase is believed to play an important role in the development of tumor ascites, cerebral and pulmonary edema, pleural and pericardial effusions, hypersensitivity-type dysfunction and delayed-dementia-type reactions after trauma, burns, ischemia, diabetic complications, endometriosis, adult respiratory distress syndrome (ARDS), hypotension and hyperpermeability associated with post cardiopulmonary bypass and ocular edema resulting in glaucoma or blindness due to inappropriate neovascularization. In addition to VEGF, the recently identified VEGF-C and VEGFD and virally encoded VEGF-E or HIV-Tat protein may also cause a vascular hyperpermeability response mediated by VEGFR kinase stimulation. Tie-2 is also expressed in a selective population of hematopoietic stem cells, v

110, which may cause recruitment, adhesion, regulation and differentiation (Blood, 4317-4326 (1997)), this Tie-2-expressing population may serve as circulating angiogenic endothelial progenitors. Certain agents represented by the general formula (I) capable of blocking the kinase activity of specific endothelial cell kinases could therefore inhibit the progression of diseases involving these conditions.

Therefore, the compounds of formula (I) or salts thereof or pharmaceutical compositions containing a therapeutically effective amount thereof may be used in the treatment of benign and neoplastic proliferative diseases and immune system disorders. These diseases include autoimmune diseases, e.g. rheumatoid arthritis, thyroiditis, type 1 diabetes, multiple sclerosis, sarcoidosis, inflammatory bowel disease, Crohn's disease, myasthenia gravis and systemic lupus erythematosus; psoriasis, organ transplant rejection (e.g., kidney rejection, graft versus host), benign and neoplastic proliferative diseases, human cancers, e.g. cancers of the lung, breast, stomach, bladder, colon, pancreas, ovaries, prostate and rectum, and hematopoietic malignancies (leukemia and lymphoma) and diseases involving inappropriate vascularization, e.g. diabetic retinopathy, retinopathy of prematurity, choroidal neovascularization due to age-related macular degeneration and infantile hemangiomas in human subjects. In addition, these inhibitors may be effective in the treatment of disorders including edema mediated by VEGF, ascites, eusions and exudates, including e.g. macular edema, cerebral edema, acute pulmonary injury and adult respiratory distress syndrome (ARDS).

The compounds of the present invention may also be effective in the prophylaxis of the above diseases.

In a further aspect of the present invention there is provided the use of a compound of formula (I) or a salt thereof in the manufacture of a medicament for the treatment of vascular hyperpermeability, angiogenesis-dependent disorders, proliferative diseases and / or immune system disorders in mammals, especially humans.

The present invention also provides a method of treating vascular hyperpermeability, inadequate neovascularization, proliferative diseases and / or immune system disorders, which comprises administering to a mammal, particularly a human, in need of such treatment, a therapeutically effective amount of a compound of formula (I).

111

The in vitro potency of the compounds in inhibiting these protein kinases can be determined by the methods described below.

The potency of the compounds can be determined by the amount of inhibition of phosphorylation of an exogenous substrate (e.g., a synthetic peptide (Z. Songyang et al., Nature. 373: 536-539) by comparing the test compound to a control.

Production of KDR Tyrosine Kinase Using Baculovirus System:

The coding sequence for the human KDR intracellular domain (aa789-1354) was generated by PCR using cDNA isolated from HUVEC cells. The poly-His6 sequence was introduced at the N-terminus of this protein. This fragment was cloned into the pVL1393 transfection vector at the XbaI and Not I site. Recombinant baculovirus (BV) was generated by cotransfection with BaculoGold Transfection reagent (PharMingen). Recombinant BV was plaque purified and verified by Western analysis. For protein production, SF-9 cells were grown in SF-900-II medium at 2 x 10 6 / ml and infected at a number of units forming 0.5 plaque per cell (MOI). Cells were harvested 48 hours after infection.

Purification of the DRC

SF-9 cells expressing (His) eKDR (aa789-1354) were lysed by adding 50 ml of Triton X-100 lysis buffer (20 mM Tris, pH 8.0, 137 mM NaCl, 10% glycerol, 1% Triton X-100, 1 mM PMSF) , 10 µg / ml aprotinin, 1 µg / ml leupeptin) into cell pellets from 1 L cell culture. The lysate was centriRigated 19,000 rpm. per min. on a Sorval SS34 rotor for 30 minutes at 4 ° C. The cell lysate was applied to a 5 ml NiCl ₂ chelating sepharose column equilibrated with 50 mM HEPES, pH 7.5, 0.3 M NaCl. KDR was eluted with the same buffer containing 0.25 M imidazole. Individual fractions were analyzed by SDS-PAGE and ELISA (see below) to measure kinase activity. The purified KDR was poured into 25 mM HEPES, pH 7.5, 25 mM NaCl, 5 mM DTT buffer and stored at -80 ° C.

112

Generation and purification of human Tie-2 kinase

The coding sequence for the human intracellular domain of Tie-2 (aa775-1124) was generated by PCR using cDNA pieces isolated from human placenta as templates. The poly-His6 sequence was introduced at the N-terminus and this construct was cloned into the pVL 1939 transfection vector at the Xba 1 and Not 1 sites. Recombinant BV was generated by cotransfection with BaculoGold Transfection reagent (PharMingen). Recombinant BV was plaque purified and verified by Western analysis. For protein production, insect SF-9 cells were grown in SF-900-II medium at 2 x 10 6 / ml and infected at a number of units forming 0.5 plaque per cell (MOI). The purification of the His-tagged kinase used in screening was similar to that of KDR.

Formation and purification of human Flt-1 tyrosine kinase

The baculovirus expression vector pVL1393 (Phar Mingen, Los Angeles, CA) was used. The nucleotide sequence encoding poly-His6 was located in the nucleotide region 5 'of the entire intracellular domain of human Flt-1 kinase (amino acids 786-1338). The nucleotide sequence encoding the kinase domain was generated by PCR and cDNA libraries isolated from HUVEC cells. The histidine residues allowed affinity purification of the protein in a similar manner to KDR and ZAP70. SF-9 insect cells were infected at 0.5 multiplicity and harvested 48 hours after infection.

Source of EGFR Tyrosine Kinase

EGFR was purchased from Sigma (Cat # E-3641; 500 units / 50 μΐ) and the EGF ligand was purchased from Oncogen Research Products / Calbiochem (Cat # PF011-100).

ZAP70 Expression

The baculovirus expression vector pVL1393 (Phar Mingen, Los Angeles, CA) was used. The nucleotide sequence encoding amino acids M (H) 6 of LVPRgS was located in the nucleotide region 5 'of the entire ZAP70 (amino acids 1-619).

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The nucleotide sequence coding for the ZAP70 region was generated by PCR and cDNA libraries isolated from T cells immortalized by Jurkat. Histidine residues allowed affinity purification of the protein (see infra). The LVPR9S bridge creates a recognition sequence for proteolytic cleavage by thrombin allowing removal of the affinity tag from the enzyme. SF-9 insect cells were infected with 0.5 multiplicity of infection and harvested 48 hours after infection.

Extraction and purification of ZAP70

SF-9 cells were lysed in a buffer consisting of 20 mM Tris, pH 8.0, 137 mM NaCl, 10% glycerol, 1% Triton X-100, 1 mM PMSF, 10 µg / ml aprotinin, 1 µg / ml leupeptin and 1 mM ortovanadate solution). The soluble lysate was applied to a chelating column of Sepharose HiTrap (Pharmacia) equilibrated in 50 mM HEPES, pH 7.5, 0.3 M NaCl. The fusion protein was eluted with 250 mM imidazole. The enzyme was stored in a buffer containing 25 mM HEPES, pH 7.5, 25 mM NaCl, 5 mM DTT buffer.

Source Lck

Lck or truncated forms of Lck can be obtained from commercial sources (e.g., from Upstate Biotechnology Inc. (Saranac Lake, N.Y.) and Santa Cruz Biotechnology Inc. (Santa Cruz, Ca.)) or purified by standard methods from known natural or recombinant sources.

Solid state enzyme-linked immunoassay (ELISA) performed with PTK.

Solid phase enzyme immunoassay (ELISA) was used to detect and measure the presence of tyrosine kinase activity. The ELISA was performed in a standard manner as described e.g. Volier, et al., 1980, "Enzyme-linked Immunosorbent Assay," In: Manual of Clinical Immunology, 2d ed., Edited by Rose and Friedman, 359-371 Am.Soc. of Microbiology, Washington, D.C.

Said method was adapted to determine activity with respect to a specific PTK. For example, preferred methods of performing ELISA experiments are given below. Modification of these protocols to determine the activity of compounds in other receptor family members

114

PTK as well as non-receptor tyrosine kinases are standard routines. To determine the selectivity of the inhibitor, a universal PTK substrate (e.g., a poly (Glu ₄ Tyr) irregular copolymer with a molecular weight of 20000-50000) was used together with ATP (typically 5 μΜ) at approximately twice the concentration from the Km of the tests.

The following procedure was used to determine the inhibitory effect of the compounds of the present invention on the activity of KDR, Flt-1, FU-4 / VEGFR-3, Tie-2, EGFR, FGFR, PDGFR, IGF-1-R, c-Met, and ZAP70:

Buffers and solutions:

PGTPoly (Glu, Tyr) 4: 1

Storage of powder at -20 ° C. Dissolve the powder in phosphate buffered saline (PBS) to a volume of 50 mg / ml. Store 1 ml aliquots at -20 ° C. If plates are prepared, dilute to 250 µg / ml in Gibco PBS.

Reaction Buffer: 100 mM Hepes, 20 mM MgCl 4, 4 mM MnCl 2, 5 mM DTT, 0.02% BSA, 200 μΜ NaVO ₄ , pH 7.10.

ATP: Store aliquots of 100 mM at -20 ° C. Dilution to 20 μΜ in water.

Wash Buffer: PBS with 0.1% Tween 20

Antibody Dilution Buffer: 0.1% bovine serum albumin (BSA) in PBS

TMB Substrate: Mixing TMB Substrate and 9: 1 Peroxide Solution immediately prior to use or using Neogen K-Blue Substrate Blocking Solution: IM Phosphoric Acid Procedure

1. Plate preparation

Dilute a stock solution of PGT (50 mg / ml, frozen) in PBS to 250 μg / ml. Add (125 μΙ / well) to high affinity ELISA plates having modified grain (Corning # 25805-96). Add 125 μΐ PBS to blank wells. Coat with sealing tape and incubate overnight at 37 ° C. 1x wash with 250 μΐ wash buffer a

115 for 2 hours at 37 ° C in a dry incubator. Store coated plates in a sealed container at 4 ° C until use.

2. Reaction with tyrosine kinase:

preparation of inhibitor solutions at four times the concentration in 20% DMSO in water.

- preparation of reaction buffer

- preparation of the enzyme solution so that the required units are at 50 μΐ, eg. for KDR lng / μΐ of a total of 50 ng / well in the reactions. Keeping on ice.

- preparation of a 4xATP solution at a concentration of 20 μΜ from a 100 mM stock solution in water. Keeping on ice.

- addition of 50 μΐ enzyme solution per well (typically 5-50 ng enzyme per well depending on specific kinase activity)

- addition of 25 μΐ 4x inhibitor

- addition of 25 μΐ 4x ATP to determine inhibition

- incubation at room temperature for 10 minutes

- stop the reaction by adding 50 μΐ 0.05N HCl per well

- plate washing ** Final concentrations for reaction: 5 μΜ ATP, 5% DMSO

3. Binding of antibodies

- dilution of 1 mg / ml aliquot of PY20-HRP (Pierce) antibody (phosphotyrosine antibody) to 50 ng / ml in 0.1% BSA in PBS by 2-step dilution (100x, then 2x0x).

- Add 100 μΐ Ab per well. Incubate at room temperature for 1 hour. Incubate at 4 ° C for 1 hour.

- 4x plate washing

4. Color reactions

- preparation of TMB substrate and addition of 100 μΐ per well

- OD monitoring at 650 nm until 0.6 is reached

116

- stopping the reaction by IM phosphoric acid. Shake on a plate detector, instantaneous reading of OD at 450 nm.

Optimal incubation times and enzyme reaction conditions may vary slightly and are empirically determined for each batch.

For Lck, a reaction buffer of 100 mM MOPSO, pH 6.5, 4 mM MnCl ₂ , 20 mM MgCl _2, 5 mM DTT, 0.2% BSA, 200 mM NaVO ₄ was used under similar conditions.

Compounds of formula (I) may be therapeutically effective in treating diseases including both identified, including those not listed herein, as well as unidentified protein tyrosine kinases that are inhibited by the compounds of formula (I). All of the compounds of the present invention significantly inhibit KDR kinase at concentrations of 50 micromoles or less. Some compounds of the present invention also significantly inhibit other PTKs, e.g. lck at concentrations of 50 micromoles or less.

Source Cdc2

Human recombinant enzyme and assay buffer can be obtained from commercial sources (New England Biolabs, Beverly, MA. USA) or purified from known natural or recombinant sources by standard methods.

Test with Cdc2

Slightly modified reagents obtained from commercial sources were used in the process. The reaction was carried out in a buffer of 50 mM Tris pH 7.5, 100 mM NaCl, 1 mM EGTA, 2 mM DTT, 0.01% Brij, 5% DMSO and 10 mM MgCl ₂ (commercial buffer) supplemented with fresh 300 μΜ ATP (31 pCi / ml). ) and 30 µg / ml of IIIss type histone as final concentrations. The reaction volume was 80 μΐ with the enzyme units contained. The reaction was allowed to proceed for 20 minutes at 25 ° C in the presence or absence of inhibitor and was terminated by the addition of 120 μΐ 10% acetic acid. The substrate was separated from the unincorporated label by applying the mixture to phosphocellulose paper, washing for 5 minutes (3 x 75 mM phosphoric acid). Impulses were measured in the presence of a liquid scintillator on a beta-meter.

117

Certain compounds of the present invention significantly inhibited cdc2 at concentrations of 50μΜ or less.

Source of PKC kinase

The catalytic PKC subunit can be obtained from commercial sources (Calbiochem).

PKC kinase assay

The radiochemical kinase assay used was based on the published method, see Yasuda, I., Kirshimoto, A., Tanaka, S., Tominaga, M., Sakurai, A., Nishizuka, Y. Bichemical and Biophysical Research Communication 3: 166, 1220. 1227 (1990). All reactions were performed in a kinase buffer consisting of 50 mM Tris-HCl pH 7.5, 10 mM MgCl ₂ , 2 mM DTT, 1 mM EGTA, 100 μΜ ATP, 8 μΜ peptide, 5% DMSO and ³³ P ATP (8 Ci / mM). Compound and enzyme were mixed in the reaction flask and the reaction was initiated by the addition of ATP and substrate mixture. After termination of the reaction by adding 10 μΙ of stop buffer (5 mM ATP in 75 mM phosphoric acid), a portion of the mixture was applied to a phosphocellulose filter. The loaded samples were washed (3x) in 75 mM phosphoric acid at room temperature for 5 to 15 minutes. Incorporation of the radiolabel was quantified by measuring liquid scintillation.

Source of the enzyme Erk2

Recombinant mouse enzyme and assay buffer can be purchased from commercial sources (New England Biolabs, Beverly MA, USA) or purified from natural or recombinant sources by standard methods. .

Erk2 enzyme assay

The reaction was carried out in a buffer consisting of 50 mM Tris pH 7.5, 1 mM EGTA, 2 mM DTT, 0.01% Brij, 5% DMSO, and 10 mM MgCl ₂ (commercial buffer) supplemented with fresh 100 μΜ ATP (31 μΟί / 30ηΙ) and 30 μΜ of myelin basal protein under conditions recommended by the supplier. Reaction volumes and methods for testing incorporated radiolabel are described in PKC assays (see supra).

118

In vitro models of T-cell activation

Upon activation of mitogen or antigen, T cells are induced to secrete IL-2, a growth factor that supports their subsequent proliferation phase. Therefore, either IL-2 production or cell proliferation of primary T-cells or respective T-cell lines can be measured to replace T-cell activation. Both these assays and individual parameters are well described in the literature (in Current Protocols in Immunology, Vol 2, 7.10.1-7,11,2).

T cells can be activated by co-culture with an allogeneic cell stimulator, a process referred to as an irreversible mixed lymphocyte reaction. The peripheral blood monocyte responder and stimulator is purified by Ficoll-Hypaque gradient (Pharmacia) according to the supplier's instructions. Stimulator cells are mitotically inactivated by reaction with mitomycin C (Sigma) or gamma radiation. Responder and stimulator cells are co-cultured at a 2: 1 ratio in the presence or absence of the test compound. Typically, 10 ⁵ responders are mixed with 5 x 10 ⁴ stimulators and plated (in a volume of 200 μΐ) in a U-bottom microtiter plate (Costar Scientific). Cells are cultured in RPMI 1640 supplemented with either fetal bovine serum (Hyclone Laboratories) inactivated by heating or pooled human AB serum from male donors, 5 x 10 ^-5 M 2-mercaptoethanol and 0.5% DMSO. One day before collection (typically on the third day) at

0.5 µCi of H thymidine (Amersham) was incorporated into the cultures. Cultures were harvested (Betaplate harvester, Wallac) and isotope uptake was evaluated by liquid scintillation (Betaplate, Wallac).

The same culture system can be used to determine T-cell activation by measuring IL-2 production. Eighteen to twenty-four hours after initiation of the culture, the supernatant was removed and the IL-2 concentration was measured by ELISA (R and D systems) according to the supplier's instructions. .

In vivo models of T-cell activation

The in vivo efficacy of the compounds can be tested in known animal models by directly measuring T-cell activation or T-cell activation in which effectors have been demonstrated.

T cells can be activated in vivo by ligation of the constant portion of the T cell receptor with the anti-CD3 monoclonal antibody (Ab). In this model, 10 µg anti-CD3 Ab was intraperitoneally administered intraperitoneally to BALB / c mice hours before bleeding. Animals that

119 to receive the test drug, was pre-treated with a single dose of the compound one hour prior to anti-CD3 Ab administration. Serum levels of anti-inflammatory cytokines interferonγ (IFN-γ) and tumor necrosis factor-α (TNF-α), indicators of T-cell activation, were measured by ELISA. A similar model utilizes the in vivo activation of T cells with a specific antigen, e.g. hemocyanin of cone (KLH), and subsequent secondary in vitro exposure of drained lymph node cells to the same antigen. As mentioned above, cytokine production measurement was used to determine the activation state of cultured cells. On day 0, C57BL / 6 mice were immunized subcutaneously with 100 gg of KLH emulsified in complete Freund's adjuvant (CFA). Animals were pretreated with the compound one day prior to immunization and then on the first, second and third days after immunization. The drained lymph nodes were harvested on day 4 and their cells were cultured at 6 x 10 ⁶ per ml in tissue culture medium (RPMI 1640 supplemented with inactivated fetal bovine serum (Hyclone Laboratories 5 x 10 ^-5 M 2-mercaptoethanol and 0, Interleukin-2 (IL-2) autocrine T-cell growth factor and / or IFN-γ levels were then determined by ELISA in culture supernatants.

Compounds can also be tested in animal models simulating human disease. These are represented e.g. experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis (CIA). EAE models that mimic aspects of human multiple sclerosis have been described in both mice and rats (reviewed by FASEB J. 5: 2560-2566, 1991 mouse model: Lab. Invest. 4 (3): 278, 1981; rodent model: J. Immunol., 146 (4): 1163-8, 1991). Mice and rats were immunized with an emulsion of myelin basic protein (MBP) or its neurogenic peptide derivatives and CFA. Acute diseases may be induced by the addition of bacterial toxins, e.g. bordetella pertussis. Relapsing / receding disease is induced by adoptive T-cell transfer from animals immunized with MBP / peptide.

CIA can be induced in DBA / 1 mice by immunization with type II collagen (J. Immunol: 142 (7): 2237-2243). In mice, this induces signs of arthritis as early as 10 days after antigen challenge, which may be evident ninety days after immunization. In both EAE and CIA models, the compound may be administered either prophylactically or at the time of disease outbreak. Effective drugs should reduce the strength and / or extent of the disease.

120

Certain compounds of the present invention that inhibit one or more angiogenic receptor PTKs and / or protein kinase, e.g. lck involved in mediating inflammatory responses can reduce the strength and extent of arthritis in these models.

Compounds can also be tested in mouse allograft models, either skin (reviewed in Ann. Rev. Immunol., 10: 333-58, 1992; Transplantation: 57 (12): 170117D6, 1994) or heart (Am. J. Anat. : 11: 273,1963). Complete epidermal grafts were transplanted from C57BL / 6 mice to BALB / c mice. The grafts can be monitored daily starting from day 6 for rejection. In a neonatal heart transplant mouse model, neonatal hearts are ectopically transplanted from C57BL / 6 mice into the ears of adult CBA / J mice. The heart begins to operate four to seven days after transplantation and rejection can be examined by a visually dissecting microscope to monitor cardiac interruption.

Cell receptor PTK assays

To determine the level of activity a. The following cellular assay was used for the effect of various compounds of the present invention on KDR / VEGFR2. Similar receptor PTK assays using specific ligand stimulation can be designed according to the same lines for other tyrosine kinases using standard techniques.

VEGF-induced KDR phosphorylation in human umbilical vein endothelial cells (HUVEC) can be measured by Western blotting:

1. HUVEC cells (from pool donors) were purchased from Clonetics (San Diego, CA) and cultured according to the supplier's instructions. Only early passages (3-8) were used for these tests. Cells were cultured in 100 mm flasks (Falcon for tissue culture; Becton Dickinson; Plymouth, England) with complete EBM medium (Clonetics).

2. To evaluate the inhibitory activity of the compounds, cells were trypsinized and seeded at 0.5-1.0 x 10 ⁵ cells per well into each well of clustered plates (6 wells each) (Costar; Cambridge, MA).

3. 3-4 days after seeding, a continuous increase was observed in 90-100% of the platelets. Medium was removed from all wells, cells were washed with 5-10 ml PBS and incubated for 18-24 hours with 5 ml EBM basal medium with no added supplements (i.e. lack of serum).

121

4. Serial dilutions of inhibitors in 1 ml EBM medium (25 μΜ, 5 μΜ or ΙμΜ final concentration) were added to the cells and the cells were incubated for 1 hour at 37 ° C. Human recombinant VEGFlu® (R & D Systems) in 2 ml EBM medium was then added to all wells at a final concentration of 50 ng / ml and incubation was continued at 37 ° C for 10 minutes. Control cells treated or untreated with VEGF were used to determine the background of phosphorylation and phosphorylation induction of VEGF. All wells were then washed with 5-10 ml cold PBS containing 1 mM sodium orthovanadate (Sigma). Cells were lysed and wiped in 200 μΐ of RIPA buffer (50 mM Tris-HCl) pH 7, 150 mM NaCl, 1% NP-40, 0.25% sodium deoxycholate, 1 mM EDTA containing protease inhibitors (PMSF 1 mM, aprotinin 1). µg / ml, pepstatin 1 µg / ml, leupeptin 1 µg / ml, Na vanadate 1 mM, Na fluoride 1 mM) and 1 µg / ml Yeast (all chemicals were from Sigma Chemical Company, St. Louis, MO). The lysate was centrifuged at 14,000 rpm to eliminate the nuclei. per min. for 30 minutes.

Equivalent amounts of proteins were then precipitated by addition of cold (-20 ° C) ethanol (2 volumes) for a minimum of 1 hour and a maximum of overnight. The pellets were reconstituted in Laemli sample buffer containing 5% mercaptoethanol (BioRad Hercules, CA) and heated for 5 minutes. Proteins were re-chromatographed by polyacrylamide gel electrophoresis ((6%, 1.5mm Novex, San Deigo, CA) and transferred to a nitrocellulose membrane using a Novex system. After blocking with bovine serum albumin (3%), the proteins were overnight at 4 ° C. labeled with polyclonal anti-KDR antibody (C20, Santa Cruz Biotechnology; Santa Cruz, CA) or monoclonal antibody antiphosphotyrosine (4G10, Upstate Biotechnology, Lake Placid, NY) After washing and incubating for 1 hour with HRP-conjugated F (ab) 2 goat anti-rabbit or goat anti-mouse IgG were individual bands visualized by emission chemiluminescence (ECL) (Amersham Life Sciences, Arlington Height, IL).

Certain compounds of the examples of the present invention significantly inhibit cellular VEGF-induced KDR tyrosine kinase phosphorylation at concentrations that are less than 50 µΜ.

122

In vivo model of uterine edema

In this assay, the capacity of the compounds to inhibit the acute increase in uterine weight in mice that occurred in the first few hours after estrogen stimulation was measured. This rapid increase in uterine weight is known to be caused by edema due to the increased permeability of uterine vascularity. Cullinan-Bove and Koss (Endocrinology (1993), 133: 829-837) demonstrated a close temporary relationship between estrogen-stimulated uterine edema and overexpression of VEGF mRNA in the uterus. These results were confirmed by the use of a neutralizing monoclonal antibody to VEGF, which significantly reduced the acute weight gain after estrogen stimulation (WO 97/42187). Therefore, this system can serve as a model for the in vivo inhibition of VEGF signaling and associated hyperpermeability and edema.

Substances: All hormones were purchased from Sigma (St. Louis, MO) or Cal Biochem (La Jolla, CA) as lyophilized powders and prepared according to the supplier's instructions.

Carrier components (DMSO, Cremaphor EL) were purchased from Sigma (St. Louis, MO).

Mice (Balb / c, 8-12 weeks of age) were purchased from Taconic (Germantown, NY) and housed with pathogen exclusion in a facility designated by the Institutional Animal Line and Use Committee Guidelines.

process:

Day 1: Balb / c mice were injected intraperitoneally (i.p.) with 12.5 units of gonadotropin from mare marrow serum (PMSG).

Day 3: mice were administered 15 units of human chorionic gonadotropin (hCG) i.p. ·

Day 4: mice were randomized into groups of 5-10 individuals. Test compounds were administered i.p., i.v. or p.o. routes depending on the solubility of the carrier at doses ranging from 1-100 mg / kg. The control group received only the vehicle and two groups were not treated.

After 30 minutes of the experiment, the control group and one of the untreated groups were administered i.p. injection of 17-estradiol (500 µg / kg). After 2-3 hours the animals were sacrificed by CO 2 inhalation. Each was isolated after the midline cut

123 uterus and removed by incision under the cervix and at the junction of the uterus and the fallopian tubes. The fatty and joint tissue has been carefully removed so that the uterine integrity is not impaired prior to weighing (wet weight). The fluid was removed from the uterus by pressure between two filter papers using a 1 liter water-filled bottle. Uterines were weighed after removal of fluid (balance after fluid removal). The difference in weight before and after fluid removal was determined as the amount of fluid in the uterus. The mean fluid content of the treated groups was compared to the untreated or control groups. Statistical parameters were determined by Student's test. A non-stimulated control group was used to monitor the response to estradiol.

The results show that certain compounds of the present invention inhibit edema formation when administered systemically by different routes.

Certain compounds of the present invention that are inhibitors of angiogenic receptor tyrosine kinases may also exhibit activity in a model of neovascularization of a Matrigel implant. The model of neovascularization of Matrigel involves the formation of new blood vessels within a pure "marble" extracellular matrix subcutaneously implanted, which is induced by the presence of a proangiogenic factor produced by tumor cells (see: Passaniti, A., et al. Lab. Investig. (1992), 67 (4)). (1997), 249 (1), 63-73, Int. J. Cancer (1995), 63 (5), 694-701, Vasc. Biol. (1995), 15 (11), 519528; , 1857-6). The model is preferably usable within 3-4 days and outputs include macroscopic optical / image evaluation of neovascularization, microscopic determination of microvessel density and determination of hemoglobin (Drabkin method) and subsequently removal of the implant against controls in animals not treated with inhibitors. Alternatively, bFGF or HGF may be used as a stimulant in a given model.

Certain compounds of the present invention that inhibit one or more oncogenic, proto-oncogenic or proliferative-dependent protein kinases or angiogenic receptor PTKs also inhibit the growth of primary mouse, rat, or human xenograft tumors in mice or inhibit metastasis in mouse models.

124

DETAILED DESCRIPTION OF THE INVENTION

The core structure of the compounds of the present invention was synthesized by basic catalyzed aldol condensation followed by elimination. Scheme I is a general illustration of this reaction. Appropriate starting materials, H and III, for the preparation of compounds of formula IV of the present invention that are synthesized in accordance with Scheme I are commercially available and / or can be prepared by standard methods and / or are available according to the method described herein.

+

m.

Scheme I; General Synthesis of 4 - [(substituted) methylene] -2-pyrazolin-5-one

I. 4 - [(Pyrol-2-yl) methylene] -2-pyrazolin-5-one (V).

Example 1

3-Cyclopropyl-4 - [(4,5-dimethyl-2-yl) methylene] -2-pyrazolin-5-one.

Reaction mixture of 3-cyclopropyl-2-pyrazolin-5-one (790 mg, 6.3 mmol), 4,5-dimethylpyrrole-2-carboxaldehyde (800 mg, 6.5 mmol) and piperidine (100 mg) in ethanol (50 mL) ) was stirred at 90 ° C for 3.5 hours. The solvent was removed under reduced pressure, the solid residue was purified by flash column chromatography in ethyl acetate: hexanes (3: 7), then purified by recrystallization from toluene.

125

Example 40

3-7 tert-Butylureido-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one.

The reaction mixture of 3-amino-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one (1.7 mmol) and tert-butyl isocyanate (1 mL) in ethyl acetate (5 mL) was stirred at 80 ° C for 2 hours. The product was collected by filtration and recrystallized from ethanol.

Example 88

4 - {[4- (2-Dimethylaminoethoxycarbonyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one.

A mixture of 4 - [(4-carboxy-3,5-dimethylpyrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5one (200 mg, 0.68 mmol) in dichloromethane (20 mL) and a drop of DMF was added. were reacted with oxalyldichloride (0.2 mL) and stirred for 24 hours. A solution of dimethylaminoethanol (0.6 g, 6.7 mmol) in dichloromethane (5 mL) was then added and stirring was continued for another 24 hours. The solvent was evaporated completely and the solid residue was treated with NaHCO 3 (5%) and extracted with dichloromethane. The solid obtained after solvent removal is recrystallized from n-heptane.

Example 194

4 - {[4- (2-diethylamino-ethyl) -3,5-dimethyl-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-oxide-ontv

A mixture of Example 176 (0.2 g, 0.54 mmol) and n-chloroperbenzoic acid (0.2 g, 1.1 mmol) in chloroform (50 mL) was stirred at room temperature for 48 hours. The solvent was removed completely and the residue was purified by flash chromatography (dichloromethane / ethanol 9: 1). Yield 30%, mp 192 ° C (ethanol).

Table 1 w

Other synthesized compounds having structural formula (V).

Pr. Substituent on circle A R ¹ Solvent for recrystallization Howl. % process 1 4,5-dimethyl cyclopropyl toluene 30 see example 1

126

2 no benzyl toluene: heptane 64 see example 1 3 no 4-methoxy- phenoxy-methyl methanol 36 see example 1 4 no phenoxy-methyl ON THE 33 see example 1 5 no 4-chloro- phenoxy-methyl ethanol 33 see example 1 6 no 4-methoxy- benzyl ethanol 21 see example 1 7 4- (2-carboxyethyl) - 3-methyl benzyl ON THE see example 1 8 3- (2-carboxyethyl) - 4-methyl benzyl isopropanol see example 1 9 no 4-methyl- phenoxy-methyl methanol 42 see example 1 10 no amino isopropanol 90 see example 1 11 no isopropoxy isopropanol 52 see example 1 12 no phenylethyl ON THE 86 see example 1 13 no phenylamino isopropanol 86 see example 1 14 no 4-methylbenzyl methanol 60 see example 1 15 no 4-methylphenyl amino methanol 86 see example 1 16 no 4-methoxy- phenylamino DMF: water 92 see example 1 17 no 4-chlorobenzyl ethanol 56 see example 1 18 no 4-chlorophenyl amino ethanol 90 see example 1 19 no 3-chlorophenyl oxymethyl ON THE 50 see example 1 20 no indol-3-yl ethanol 90 see example 1 21 no 3-methoxybenzyl methanol 21 see example 1 22 no 3,4- dimethoxy- benzyl ethanol 83 see example 1

127

23 no 4-methoxy- phenylethyl ethanol 91 see example 1 24 no 4-phenyl phenoxy-methyl methanol 72 see example 1 25 no 2-phenylpropyl heptane 10 see example 1 26 no 3-phenylpropyl toluén'.heptán 60 see example 1 27 no 4-hydroxy- phenylethyl methanol 76 see example 1 28 3,5-dimethyl phenylethyl methanol 51 see example 1 29 no 4-methyl- phenylethyl ethanol 53 see example 1 30 3,5-dimethyl isopropoxy heptane 55 see example 1 31 no ethoxy ethanol 76 see example 1 32 no 4-nitro- phenylethyl toluene 48 see example 1 33 no 4-fluoro- phenylamino isopropanol 66 see example 1 34 no 4-chloro- phenylethyl ethanol 60 see example 1 35 4,5-dimethyl isopropoxy methanol 55 see example 1 36 3,5-dimethyl-4-ethyl isopropoxy toluene 47 see example 1 37 3,5-dimethyl-4-ethyl phenylethyl heptane 49 see example 1 38 1- (4-Hydroxy-butyl) isopropoxy ON THE 80 see example 1 39 no cyclopentyloxy methanol 75 see example 1 40 no tert butylureido ethanol 87 see example 40 41 4-methyl isopropoxy toluene 34 see example 1 42 4-methyl 4-amino- phenylethyl ON THE 27 see example 1 43 1-methyl- isopropoxy toluene 55 see example 1 44 5-methyl isopropoxy metanokvoda 30 see example 1

128

45 3,5-dimethyl-4-ethyl 4-aminophenyl- ethyl toluene 50 see example 1 46 5-methyl ethoxy ethanol 58 see example 1 47 3,5-dimethyl-4-ethyl 4-carbamoyl- phenylethyl DMF: water 82 see example 1 48 3,5-dimethyl-4-ethyl 4-methoxy- carbonyl phenylethyl methanol 70 see example 1 49 3,5-dimethyl-4- ethoxycarbonyl isopropoxy ethanol 81 see example 1 50 3,5-dimethyl-4- ethoxycarbonyl 4-amino- phenylethyl ethanol 62 see example 1 51 5-ethyl isopropoxy heptane 48 see example 1 52 3,5-dimethyl-4-ethyl 4-hydroxy- phenylethyl isopropanol 35 see example 1 53 no ethoxycarbonyl- methyl ethanol 35 see example 1 54 no 4-methoxy- phenylamino carbonyl methyl methanol 46 see example 1 55 3- (2-carboxyethyl) - 4-methyl isopropyl ethanol 32 see example 1 56 no cyclopropyl ethanol 50 see example 1 57 no cyclobutyl ethanol 65 see example 1 58 no 3-pyridyl ethanol 50 see example 1 59 1- (3,5-dichloro- phenyl) cyclopropyl ethanol 30 see example 1 60 no 2,2,3,3- tetramethyl- cyclopropyl toluene 55 see example 1 61 3,5-dimethyl cyclopropyl toluene 33 see example 1 62 no cyclopentyl toluene 66 see example 1

129

63 no 2-methyl- cyclopropyl hexane 44 see example 1 64 no benzothiazol-2 yi DMF: water 60 see example 1 65 4,5-dimethyl 3-pyridyl ethanol 35 see example 1 66 3,5-dimethyl-4-ethyl cyclopropyl ethanol 50 see example 1 67 no pyrrol-2-yl methanol 88 see example 1 68 4-methyl cyclopropyl ethanol 35 see example 1 69 4-methyl benzothiazol-2 yi ethanol 48 see example 1 70 3,5-dimethyl 3-pyridyl ethanol 24 see example 1 71 ' 3,5-dimethyl-4-ethyl 3-pyridyl ethanol 51 see example 1 72 5-methyl cyclopropyl ethanol 50 see example 1 73 5-methyl. 3-pyridyl ethanol 47 see example 1 74 5-ethyl cyclopropyl ethanol: water 21 see example 1 75 3,5-dimethyl-4- ethoxycarbonyl cyclopropyl ethanol 83 see example 1 76 5-phenyl isopropoxy methanol 66 see example 1 77 no propyl ON THE 49 see example 1 78 no methyl ON THE 6 see example 1 79 no 4-isopropyl- phenylamino ON THE 50 see example 1 80 no Phenylamino-3 ON THE 80 see example 1 81 1- (4-Hydroxy-butyl) cyclopropyl ethanol 34 see example 1 82 4- (2-carboxyethyl) -3- methyl isopropoxy ethanol 46 see example 1 83 4-carboxy-3,5- dimethyl isopropoxy ON THE 41 see example 1 84 4,5-tetramethylene isopropoxy ethanol 77 see example 1 85 3,4-dimethyl-4- morpholino methyl isopropoxy ON THE 30 see example 1

130

86 3,5-dimethyl-4- dimethylamino-methyl isopropoxy heptane 30 see example 1 87 4-acetyl-3,5- dimethyl isopropoxy ethanol 62 see example 1 88 3,5-dimethyl-4- (2- d i-methyl-aminomethyl- oxy-carbonyl) isopropoxy heptane 40 see example 88 89 3,5-dimethyl-4- (2- dimethylaminoethyl aminocarbonyl) isopropoxy toluene: heptane 41 see example 88 90 5-ethoxycarbonyl isopropoxy methanol 79 see example 1 91 5-carboxylic acid isopropoxy toluene 83 see example 1 92 no 4-chloro- phenylamino carbonyl methyl DMF / water 50 see example 1 93 5-phenyl cyclopropyl ethanol 72 see example 1 94 3,5-dimethyl-4-ethyl tetrahydrofurane 3-yl toluene 44 see example 1 95 4-carboxy-3,5- dimethyl cyclopropyl ethanol 69 see example 1 96 3,5-dimethyl-4- ethoxycarbonyl 3-pyridyl ethanol 86 see example 1 97 3,5-dimethyl-4- morpholino methyl cyclopropyl ON THE 34 see example 1 98 3,4-dimethyl pyrazinyl methanol 60 see example 1 99 4- (2-carboxy-ethyl) - 3-methyl cyclopropyl methanol 51 see example 1 100 3,5-dimethyl-4- dimethylaminomethyl cyclopropyl ON THE 67 see example 1 101 5-ethoxycarbonyl cyclopropyl ethanol 91 see example 1 102 4,5-tetramethylene cyclopropyl ethanol 84 see example 1

131

103 no 2-methoxy- carbonylethyl ethanol 56 see example 1 104 no ethoxycarbonyl ON THE 40 see example 1 105 no isopropyl ON THE 44 see example 1 106 no trans-2-phenyl- cyclopropyl toluene 46 see example 1 107 no cyclohexyl toluene 32 see example 1 108 4,5-tetramethylene cyclopropyl- amino ethanol 50 see example 1 109 5-morpholino-methyl cyclopropyl acetate 72 see example 1 110 5-carboxylic acid cyclopropyl ethanol 50 see example 1 111 4-chloro ethoxy ethanol ⁸⁸ see example 1 112 4-bromo ethoxy ethanol 70 see example 1 113 5-chloro ethoxy ON THE 37 see example 1 114 4-chloro cyclopropyl ethanol 42 see example 1 115 4-bromo cyclopropyl ethanol 50 see example 1 116 4,5-tetramethylene pyrazinyl ethanol 85 see example 1 117 4,5-tetramethylene 3-pyridyl ethanol 84 see example 1 118 4-carboxy-3,5- dimethyl pyrazinyl DMF 66 see example 1 119 3,5-dimethyl-4- (2- dimethylaminoethyl oxycarbonyl) cyclopropyl ON THE 71 see example 88 120 3,5-Dimethyl-4- (2- dimethylaminoethyl oxycarbonyl pyrazinyl ON THE 20 see example 88 121 3,5-dimethyl-4- dimethylamino-methyl pyrazinyl toluene 76 see example 1 122 3,5-dimethyl-4- dimetylaminometyl- maleate pyrazinyl ethanol 98 maleate salt formed from the free base of the compound of Example 121 (see explanatory note)

132

123 3,5-dimethyl-4- (2- morpholinoethyl aminocarbonyl) pyrazinyl toluene 20 see example 1 124 3,5-dimethyl 2-pyridyl ethanol 36 see example 1 125 3,5-dimethyl-4-ethyl 2-pyridyl ethanol 50 see example 1 126 4,5-tetramethylene 2-pyridyl ethanol 58 see example 1 127 3,5-dimethyl 2-furyl ethanol 51 see example 1 128 3,5-dimethyl-4- morpholinomethyl pyrazinyl ON THE 28 see example 1 129 3,5-dimethyl 2-thienyl ethanol 25 see example 1 130 4-ethoxycarbonyl cyclopropyl ethanol 68 see example 1 131 3,5-dimethyl-4- trifluoro-acetamido- methyl cyclopropyl ethanol 70 see example 1 132 4-aminomethyl-3,5- dimethyl cyclopropyl ethanol 30 see example 1 133 3,5-dimethyl benzothiazol-2 yi ethanol 40 see example 1 134 3,5-dimethyl-4- morpholinomethyl benzothiazol-2 yi ethanol 40 see example 1 135 3,5-dimethyl-4-ethyl pyrazinyl ethanol 74 see example 1 136 4-ethoxycarbonyl pyrazinyl toluene 26 see example 1 137 4-carboxylic acid pyrazinyl methanol 70 see example 1 138 3,5-dimethyl-4- dietanolaminometyl pyrazinyl ethanol 50 see example 1 139 3,5-dimethyl-4- trifluóracetamido- methyl pyrazinyl ON THE 78 see example 1 140 4-ethoxycarbonyl-3- phenyl cyclopropyl ethanol 68 see example 1 141 3,5-Dimethyl-4- (1- pyrrolidinylmethyl) pyrazinyl toluene 23 see example 1

133

142 3,5-dimethyl-4- dimethyl-aminomethyl 2-furyl toluene 20 see example 1 143 3,5-dimethyl-4- dimethyl-aminomethyl 2-thienyl toluene 48 see example 1 144 3,5-dimethyl-4- dimethyl-aminomethyl 3-pyridyl toluene 51 see example 1 145 3,5-dimethyl-4- ethoxycarbonyl phenyl ethanol 89 see example 1 146 3,5-dimethyl-4-ethyl phenyl methanol 34 see example 1 147 3,4-di- (ethoxy carbonyl) ethoxy ethanol 54 see example 1 148 4-ethoxycarbonyl ethoxy methanol 30 see example 1 149 3,5-dimethyl-4- ethoxycarbonyl 2- (3- · pyridyl) ethyl ethanol 81 see example 1 150 3,5-dimethyl-4- ethoxycarbonyl l-methyl-2- phenylethyl ethanol 52nd see example 1 151 4-carboxy-3,5- dimethyl ethoxy DMF: water 81 see example 1 ¹⁵² 5-Nitro ethoxy ethanol 64 see example 1 153 4-nitro ethoxy toluene ·. 95 see example 1 154 4-carboxylic acid ethoxy ON THE 40 see example 1 155 3,5-dimethyl-4- (2- dimethylaminoethyl aminocarbonyl) ethoxy heptane 86 see example 88 156 , 5-chloro-3- methoxycarbonyl-4- methoxy carbonyl methyl ethoxy ' ethanol '46' see example 1 ' 157 3- (2-carboxyethyl) -4- methyl ethoxy 1 ON THE 54 see example 1 158 3,5-dimethyl-4- ethoxycarbonyl ethoxy ethanol 82 see example 1

134

159 4,5-tetramethylene ethoxy heptane 80 see example 1 160 3,5-dimethyl-4- ethoxycarbonyl trifluoromethyl ethanol 45 see example 1 161 3,5-dimethyl-4- ethoxycarbonyl 5-isoxazolyl DMF: water 74 see example 1 162 3,5-dimethyl-4- ethoxycarbonyl 3-Aminophenyl ethanol 76 see example 1 163 4-morpholino ethylaminocarbonyl ethoxy ON THE 30 see example 88 164 4-ethoxycarbonyl-3- phenyl pyrazinyl toluene 70 see example 1 165 4- (4-methyl- piperazinylmethyl) - 3,5-dimethyl pyrazinyl DMF 58 see example 1 166 4-diethylamino methyl-3,5-dimethyl- pyrazinyl ON THE 20 see example 1 167 3,5-dimethyl-4- piperidino-methyl pyrazinyl toluene 25 see example 1 168 3,5-dimethyl-4- piperidinomethyl 5-isoxazolyl ON THE 35 see example 1 169 3,5-dimethyl-4- dimethylamino- methyl 5-isoxazolyl ON THE 30 see example 1 170 5-methyl-4- dimethylamino-methyl pyrazinyl toluene-heptane 75 see example 1 171 3,5-Dimethyl-4- [N- (2-dimethyl- aminoethyl) - / V-methyl- aminomethyl] pyrazinyl methanol 40 see example 1 172 3-dimethylaminopropyl methyl-4,5- tetramethylene cyclopropyl ON THE 30 see example 1

135

173 3-dimethylaminopropyl methyl-4,5- tetramethylene pyrazinyl ON THE 30 see example 1 174 3,5-dimethyl-4- dimethylamino- Methyl maleate cyclopropyl ethanol 90 maleate salt formed from the free base of Example 100 (see explanatory note) 175 4- (3-chloro- propionyl) -3,5 dimethyl pyrazinyl toluene 88 see example 1 176 4- (2-diethylamino ethyl) -3,5-dimethyl pyrazinyl ethanol 95 see example 1 177 3,5-dimethyl-4- (dimethylamino- methyl) 5-methyl-3- isoxazolyl toluene / heptane 40 see example 1 178 3,5-Dimethyl-4- (4- hydroxypiperidino- methyl) pyrazinyl methanol 40 see example 1 179 4-Aminomethyl-3,5- dimethyl maleate pyrazinyl methanol 76 see example 1 180 4- (4- Benzylpiperidino- methyl) -3,5-dimethyl pyrazinyl toluene 80 see example 1 181 3,5-Dimethyl-4- (2- hydroxyethyl) pyrazinyl ON THE 80 see example 1 182 3,5-Dimethyl-4- [2- (1-pyrrolidinylethyl)] pyrazinyl toluene 67 see example 1 183 3,5-Dimethyl-4- [2- (1-pyrrolidinylethyl)] cyclopropyl toluene 20 see example 1 184 3,5-Dimethyl-4- (2- hydroxyethyl) cyclopropyl ON THE 23 see example 1

136

185 3,5-Dimethyl-4- (2- methylaminoethyl) pyrazinyl ON THE 35 see example 1 186 4- (3-diethylamino propyl) -3,5-dimethyl pyrazinyl ethanol 52 see example 1 187 3,5-Dimethyl-4- (3- hydroxypropyl) pyrazinyl ethanol 82 see example 1 188 3,5-Dimethyl-4- dimethyl aminoacetyl- hydrochloride pyrazinyl ethanol / ethyl ether 51 see example 1 189 3,5-Dimethyl-4- dimethylamino-acetyl ethoxy ethanol / ethyl ether 44 see example 1 190 4- (2- Diethylaminoethyl) - 3,5-dimethyl cyclopropyl heptane 54 see example 1 191 3,5-Dimethyl-4- (2- dimethyl-amino-ethyl) pyrazinyl toluene 48 see example 1 192 3,5-Dimethyl-4- (4- hydroxybutyl) pyrazinyl methanol 58 see example 1 193 4- (4-Diethyl aminobutyl) -3,5 dimethyl pyrazinyl toluene 60 see example 1 194 4- (2-diethylamino ethyl-N-oxide) -3,5 dimethyl pyrazinyl ethanol 30 T see example 194 195 3,5-Dimethyl-4- (l- pyrolidinylacetyl pyrazinyl ON THE 57 see example 1 196 4 Dietylaminoacetyl- 3,5-dimethyl pyrazinyl ON THE 52 see example 1 197 3-Isopropyl-5-methyl pyrazinyl ethanol 44 see example 1

137

198 3,5-Dimethyl-4- [3- (1-pyrrolidinyl propyl pyrazinyl ethanol 30 see example 1 199 4-dimethyl aminomethyl-3- isopropyl-5-methyl- pyrazinyl toluene 40 see example 1 200 4-Dimethyl- a.minometyl 3- isopropyl-5-methyl cyclopropyl toluene 40 see example 1 201 3,5-Dimethyl-4- (2- ethoxyoxalylamino) pyrazinyl ethanol 40 see example 1 202 3,5-Dimethyl-4- (2- methylaminoethyl) cyclopropyl ON THE 60 see example I 203 3,5-Dimethyl-4- (2- cyclopropyl- aminoethyl pyrazinyl toluene 40 see example 1 204 3,5-Dimethyl-4- [2- (4-pyridyl methylamino) ethyl pyrazinyl ON THE 40 see example 1 205 3,5-Dimethyl-4- (2- cyclopropylamino ethyl) cyclopropyl toluene 36 see example 1 206 3,5-Dimethyl-4- (2- diethylaminoethyl) 2-pyrimidinyl toluene 35 see example 1 207 3,5-Dimethyl-4- (2- diethylaminoethyl) 3-pyridazinyl toluene 40 see example 1 208 3,5-Dimethyl-4- (2- diethylaminoethyl 4-pyrimidinyl toluene 50 see example 1 209 3,5-Dimethyl-4- (2- diethylaminoethyl 4-pyridazinyl toluene 30 see example 1

138

Table ΙΑ

Physical data of synthesized compounds having structural formula V.

Example temperature mp (° C) Elemental analysis carbon hydrogen nitrogen Off. U.S. Off. U.S. Off. U.S. 1 220-222 68.10 68.27 6.59 6.61 18.32 18,30 2 182-184 71.69 72,00 5.21 5.40 16.72 16.47 3 177-180 64.63 64.06 5.08 5.02 14.13 14,00 4 163-165 67.40 66.88 4.90 4.88 15.72 15.53 5 218-222 59.71 59.87 4.00 4.24 13.92 13.85 6 179-180 68.55 68.45 5.03 5.44 14.99 14.99 7 270-272 67.64 67.17 5.67 5.82 12.45 12.38 8 (0.3 H ₂ O) - 226-228 66.58 66.10 5.72 5.65 12.26 12.27 9 207-210 68.31 68.20 5.37 5.44 14.93 14.96 10 265-270 54.53 55.07 4.57 4.47 31.80 31.98 11 172-174 60,26 60,37 5.97 5.80 19.16 18.97 12 145-147 72.43 72.29 5.69 5.70 15.83 16.17 13 285-287 66.65 66,66 4.79 4.71 22.20 22,12 14 254-255 72.43 72,36 5.69 5.53 15.83 15.84 15 256-258 67.65 67.31 5.29 5.12 21.03 20.96 16 288-290 63.81 63.90 4.99 4.53 19.84 19.75 17 178-180 63.05 63.26 4.23 4.10 14.70 14.59 18 (0.25 H ₂ O) ' 245-247 57.74 57,69 3.97 3.81 19,23 18.95 19 165-167 59.71 59.69 4.00 4.05 13.92 13.80 20 300-305 69.55 69.67 4.37 4.61 20.27 20.39 21 169-171 68.31 68.27 5.37 5.36 14.93 14.92 22 164-165 65.58 65.58 5.50 5.63 13.49 13.44 23 137-139 69,13 69.15 5.80 5.69 14.22 14,30

139

24 (0.25 H ₂ O) - 192-194 72.50 72.56 5.07 5.36 12.07 12.02 25 130-131 73.09 73.16 6.13 6.25 15.04 14.83 26 169-170 73.09 73.46 6.13 6.32 15.04 14.42 27 253-255 68.31 68.48 5.37 5.01 14.93 14.74 ' 28 186-187 73.69 73.89 6.52 6.49 14.32 14.25 29 153-154 73.09 73.38 6.13 5.95 15.04 14.85 30 176-177 63.14 63,20 6.93 6.77 16.99 16.98 31 211-213 58.53 58.81 5.40 5.27 20.48 20.52 32 224-226 61.92 62,02 4.54 4.75 18.05 18.31 33 272-273 62.21 62.45 4.10 4.33 20.73 20.81 34 193-194 64,11 64.27 4.71 4.85 14.02 14,07 35 195-197 63.14 63.26 6.93 6.76 16.99 17.04 36 188-190 65,43 65,59 7.68 7.00 15.26 15.29 37 168-170 74.73 74,40 7.21 7.10 13.07 13,11 38 138-140 61,84 61,87 7.27 7.17 14.42 14.31 39 201-203 63.65 63.65 6.16 6.19 17.13 17.24 40 266-268 56.71 57.04 6.22 6.06 25.43 25.69 41 215-217 61.78 61.77 6.48 6.40 18.01 17.96 42 (0.75 H ₂ O) ' 178-180 66.32 66.78 6.33 6.01 18.19 17.85 43 199-201 61.78 61.97 6.48 6.36 18.01 17.91 44 128-130 61.78 . 61.42 6.48 6.32 18.01 17.78 45 183-185 71.40 7lj38 7.19 7.28 16.65 16.62 46 197-199 64.35 64.69 7.33 6.96 16.08. 16.03 47 297-299 69.21 69.08 6.64 6.68 15.37 15.31 48 177-179 69,64 69.70 6.64 6.57 11.07 11,10 49 226-228 60.18 60.06 6.63 6.46 13.16 13.02 50 186-188 66.30 66.20 6.36 6.25 14.73 14.68 51 119-121 63.14 63.14 6.93 6.95 16.99 17,00 52 260-262 71.19 71.01 6.87 6.96 12.45 12.36 53 124-126 58.29 58,49 5.29 5.04 16.99 16.99

140

54 240-242 62.95 62,96 4.97 5.00 17.27 17,11 55 229-231 62,26 62.20 6.62 6.37 14.52 14.36 56 158-160 65.65 65,78 5.51 5.50 20.88 20.78 57 150-152 66.95 67.09 6.08 5.76 19.52 19.45 58 222-224 65.53 65.57 4.23 4.29 25.51 23.62 59 188-190 58.97 59.06 3.78 3.92 12,13 11.98 60 160-162 70.01 70.28 7.44 7.35 16.33 16.22 61 193-195 68,09 68.34 6.59 6.39 18.32 18,18 62 (0,2 toluene) * 127-129 69,82 69.73 6.75 6.64 16.96 17.20 63 132-133 66.95 67.11 6.08 6.03 19.52 19.73 64 340-342 61,20 61.38 3.42 3.70 19.03 19.19 65 220 (d) 67.65 67.47 5.29 5.30 21.04 20.94 66 206-210 70.01 69.65 7.44 7.46 16.33 16.23 67 245-247 63.70 63.76 4.45 4.64 24.76 24.64 68 212-215 66.95 66,72 6.08 5.63 19.52 19.29 69 (0.5 H ₂ O) * 327-329 60.55 60.90 4.12 4.09 17.65 17.42 70 235-238 67.65 67.66 5.29 5.40 21.04 20.98 71 270-272 69.36 69.41 6.16 6.21 19.03 18.98 72 170-172 66.95 67.05 6.08 6.08 19.52 19.42 73 210-212 66.65 66.73 4.79 4.82 22.21 22,10 74 163-165 68.10 68.15 6.59 6.63 18.32 18.27 75 240-242 63.77 63.77 6.35 6.35 13.94 13.90 76 212-214 69,14 69.27 , 5.80 5.88 14,23 ' 14.20 77-80 ¹³ C and 1 H NMR and analytical data from LC / MS were consistent with the given structure 81 134-136 65.91 65.60 7.00 6.99 15.37 15.03 82 267-269 59.01 59,12 6.27 6.22 13.76 13.66 83 > 300 57,72 57.81 5.88 5.84 14.42 14.25 84 206-207 65.91 66.04 7.01 6.78 15.37 15.34 85 162-164 62.41 62.36 7.56 7.46 16.17 15.94 86 173-175 63.13 63.27 7.95 7.73 18.41 18.34

141

87 209-210 62.27 61.86 6.62 6.58 14.52 14.25 88 165-167 59.65 59.82 7.23 7.05 15.46 15.34 89 192-194 59.82 59.92 7.53 7.26 19.38 19.21 90 205-207 57,72 57.96 5.88 5.62 14.42 14.43 91 235-237 51,24 51.78 5.38 5.49 14.94 14.95 ' 92 240-242 58.45 58.07 3.98 3.96 17.04 16.64 93 208-210 73,62 73.60 5.45 5.62 15,15 15.14 94 163-165 66.87 66.70 7.36 7.10 14.62 14.59 95 312 (d) 61.53 61.08 5.53 5.38 15.37 15,11 96 247-249 63.89 64.05 5.36 5.48 16.56 16.70 97 175-177 65.82 65.62 7.36 7.43 17,06 16.75 98 245-250 62.91 63.30 4.90 5.10 26.20 26.29 99 290 d 62,70 62.66 5.96 5.83 14.62 14.47 100 176-178 67.10 67.21 7.74 7.49 19.56 19.53 101 250-152 61.52 61.73 5.53 5.46 15.37 15.40 102 227-230 70.56 70.62 6.71 6.61 16.46 16.52 103 134-136 58.29 58.71 5.29 5.44 16.99 17.03 104 177-179 56,64 56.85 4.75 4.56 18.01 17.56 105 120-122 65.01 65,12 6.44 6.44 20.67 20.59 106 173-175 74,42 74.20 5.60 5.77 14.46 14.77 107 176-178 69,11 69.21 7.04 7.08 17.27 17.24 108 240-243 66.64 66.62 6.71 6.39 20.72 20.80 109 184-186 63.98 64.21 6.71 6.69 18.65 18.74 110 220 (d) 54.75 55,17 4.97 4.90 15.96 : 16.2 111 237-239 50,12 ' • 50.54 4,21, 3.90 17,53 ' 17.59 112 242-244 42,28 42.45 3.55 3.39 14.79 14.58 113 170-172 50.12 49.98 4.21 4.21 17.53 18.10 114 220 (d) 56,06 56.46 4.27 4.37 17.83 17.54 115 210 (d) 47.16 47.60 3.59 3.85 15,00 14.57 116 253-255 65.51 65.83 5.15 5.25 23.87 23.86 117 264-267 69.84 69.61 5.51 5.53 19.16 19.13 118 225-228 56.71 56.59 4.94 4.79 22,00 21.94

142

119 172-174 62.77 62,61 7.02 6.71 16.26 16,06 120 223-225 58.30 58.79 5.92 6.10 21.47 20.89 121 220-222 63.50 63.57 6.26 6.25 25.39 25.55 122 206-210 55.01 54.51 5.71 5.64 18.32 18,30 123 178-180 59.56 60.03 5.95 5.82 23.15 22.87 124 228-230 67.65 68,00 5.29 5.46 21.04 21.12 125 184-186 69.36 69,19 6.16 6.09 19.03 19.33 126 214-216 69.84 69.94 5.51 5.41 19.16 19.33 127 235-237 65.87 65.88 5.13 5.24 16.46 16.51 128 274-277 62.28 62,26 6.05 5.90 22.93 22.94 129 235-237 61.96 62,01 4.82 4.91 15.48 15.44 130 192-194 61.52 61.73 5.53 5.53 15.37 15.43 131 278-280 54,23 54,40 4.83 4.92 15.81 15.68 132 217-219 63.61 63.84 7.11 6.90 21.19 21.22 133 295-297 63,33 63.55 4.37 4.45 17.38 17.44 134 285 (d) 62.15 62,03 5.54 6.02 16.47 16.91 135 264-267 65,06 65.10 5.80 5.71 23.71 23.51 136 155-157 59.74 59.30 4.46 4.40 21.24 21.20 137 230-232 54.26 54.58 3.77 3.34 24.34 23.99 138 242-244 58.44 58.81 6.36 6.28 21.52 21.84 139 302-305 51,45 51.30 3.93 4.26 21.17 20.88 140 218-220 68,75 69,07 5.48 5.53 12.02 11.96 141 235-237 64.02 64,11 6.41 6.54 23.58 23.01 142 209-211 65.36 65.37 6.45 6.89 17.93 16.53 143 208-210 61.32 61.43 6.20 ' 6.18 16.83 16.64 144 220-224 66.85 67.24 6.54 6.54 21.65 21,11 145 216-217 67.64 67,71 5.68 5.80 12.45 12.53 146 274-275 73.70 73.80 6.53 6.53 14.32 14.39 147 132-134 55.01 55.24 5.48 5.32 12,03 12,03 148 212-216 56.31 56,25 5.45 5.20 15,15 15.02 149 180-182 65.56 65.10 6.05 5.96 15.29 15.20 150 168-170 69,64 69.91 6.64 6.43 11.07 11,10

143

151 310-312 56.31 56.30 5.45 5.15 15,15 15.17 152 208-210 48,00 48,37 4.03 4.19 22.39 22.65 153 287-289 48,00 48,37 4.03 4.04 22.39 22.64 154 290-293 53,01 52,63 4.45 4.47 16.86 16.59 155 158-160 58.61 58,82 6.94 6.48 16.08 16.05 ' 156 225-227 48,72 49,00 4.36 4.18 11.36 11.35 157 255-257 57,72 57.65 5.88 5.97 14.42 14.32 158 232-234 59.01 59.06 6.27 6.30 13.76 13.68 159 178-180 64.85 64.61 6.61 6.95 16.20 15.99 160 252-254 51.07 51,17 4.29 4.34 12.76 12,60 161 255-257 58.53 58.63 4.91 5.08 17,06 16.96 162 214-216 64,76, 64.91 5.72 5.74 15.90 15.74 163 197-199 56.50 56.22 6.41 6.37 19.38 18.96 164 255-257 65,11 65.37 4.42 4.49 18,08 18,11 165 295-297 63,31 63.62 6.64 6.66 25.84. 25.96 166 242-244 64.75 64.66 6.86 6.73 23.85 23.74 167 240-242 65.91 65.61 6.64 6.74 23,06 22.69 168 215-217 63.79 63.57 6.44 6.56 19.38 19.82 169 161-163 56.45 56,96 6.51 6.45 20.57 20.29 170 193-195 61.92 62.18 5.85 - 5.74 27,08 26.80 171 205-207 62,96 62.48 7.13 6.73 25.70 25.40 172 182-185 69.20 69.21 7.74 7.82 17.93 17.41 173 210-212 65,12 64.66 6.33 6.02 23.98 23.50 174 199-201 59,68 59.31 6.51 6.37 13.92 14.42 175 213 d 57.92 58.32 4.61 4.82 19.08 19.26. 176 210-212 65,55 65.24 7.15 7.18 22.93 22.94 177 242-244 62.37 61,87 6.47 6.55 21.39 21.06 178 (0.5 Η ₂ Ο) ' 255-257 61.68 61.48 6.47 6.45 21.58 21.68 179 (0.5 Η ₂ Ο) 205-208 54,15 54,27 5.02 4.97 19.94 19.63 180 (0.25) 211-214 70.64 70.56 6.69 7.06 18,30 17.93

144

181 306-308 61.72 61,64 5.50 5.45 22.49 22.41 182 (0.17 Η ₂ 0) 190-192 65.36 64.97 6.67 6.55 22.86 23.20 183 197-200 69.90 69,87 8.02 8.12 17.16 16.86 184 244-246 65.91 65,52 7.00 6.98 15.37 15,05 185 192-194 HRMF data and EM correspond to the structure 186 (3 Η ₂ Ο) 208.10 58.05 58,21 7.88 7.39 19.73 19.47 187 273-275 62.75 63.01 5.88 5.76 21.52 21,33 188 (C 1H. 2Η Ο ₂₎ > 300 d 50,83 51,14 5.88 5.70 19.76 20,10 189 198 60.36 59.86 6.97 6.90 17.60 17.36 190 133 69.48 69,19 8.59 8.47 17,06 16.74 191 216 60.60 60.43 6.73 6.32 23.56 23.14 192 222 63.70 63.85 6.24 6.23 20.63 20.53 193 184 66,98 66.70 7.66 7.40 21,30 20.85 194 192 62.75 62.46 6.79 6.73 21.96 21.64 195 (0.5 Η ₂ Ο) 220 61.94 61.66 5.93 5.72 21.68 21.54 196 (0.5Η ₂ Θ) 199 61,62 61.78 6.41 6.13 21.56 22,06 197 244 65,07 65.02 5.80 5.79 23.71 23.99 198 202-204 66.64 66.24 6.92 6.99 22.20 22,00 199 227 64.75 64.90 6.86 6.99 23.85 23.88 .200 190-192 68,75 68.86 8.33. 8.46 17.82 . 17.51 201 223 58.85 58.96 4.66 4.73 19.06 19.03 202 (0.4 Η ₂ Ο) 150 66.37 66.46 8.12 7.90 18.21 17.80 203 210-218 63.81 63.95 6.42 6.45 23.50 23,12 204 (0.2 Η ₂ Ο) 203-205 65.23 65.05 5.82 5.84 24.20 23.77

145

205 (0.4 H ₂ O) 158-160 67.64 67.93 7.81 7.74 17.53 17.40 206 (0.2 H ₂ O) 144-146 64.91 64.87 7.19 7.30 22.71 22.53 207 (0.2 H ₂ O) 218-220 64.91 64,79 7.19 7.00 22.71 22.78 208 220 65,55 65.45 7.15 7.13 22.93 22.53 209 212-216 65,55 65.49 7.15 7.38 22.93 22.31

The molecular weight calculated for elemental analysis includes the solvent in the indicated amount.

(d) means (decomposition, decomposition)

Explanatory note: The maleate salts were prepared by adding an ethanolic solution of maleic acid to the free base in ethanol at room temperature, cooling and filtering the crystalline product.

II. 4 - [(Indol-3-yl) methylene] -2-pyrazolin-5-one (VI)

Example 210

3-benzyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one

The reaction mixture of 3-benzyl-2-pyrazolin-5-one (905 mg, 5.2 mmol), 3-indolecarboxaldehyde (800 µg, 5.6 mmol) and piperidine (100 mg) in ethanol (50 mL) was stirred at the temperature

90 ° C for 3 hours. After cooling overnight, the product was collected by filtration and purified by recrystallization from ethanol.

146

Table 2

Other synthesized compounds having Structural Formula (VI).

Pr. Substituent on indole R ¹ Solvent for recrystallization Howl. % Method ₍ Preparations) 210 no benzyl ethanol 76 see example 210 211 l- (4-hydroxy-butyl) benzyl methanol 51 see example 210 212 no 4-methoxy- phenoxymethyl isopropanol 67 see example 210 213 no phenoxymethyl isopropanol 94 see example 210 214 no 4-chloro- phenoxymethyl ethanol 65 see example 210 215 no 4-methoxybenzyl ethanol 90 see example 210 216 no 4-methyl- phenoxymethyl ethanol 93 see example 210 217 no phenylethyl ethanol 84 see example 210 218 no isopropoxy methanol 81 see example 210 219 no 4-methylbenzyl ethanol 95th see example 210 220 no phenylamino isopropanol 52 see example 210 221 no 4-methylphenyl amino methanol 60 see example 210 222 no 4-methoxyphenyl amino ethanol 96 see example 210

147

223 no 4-chlorobenzyl ethanol 77 see example 210 224 l- (4-hydroxybutyl) 4-methoxybenzyl DMF: water 89 see example 210 225 no 4-chloro-phenyl-amino DMF: water 86 see example 210 226 no 3-methoxybenzyl DMF: water 99 see example 210 227 no 3,4-dimethoxy- benzyl DMF: water 88 see example 210 228 no 4-hydroxybenzyl DMF: water 56 see example 210 229 no 3-chloro- phenoxymethyl isopropanol 89 see example 210 230 no indol-3-yl methanol 58 see example 210 231 no 4-methoxy-phenylethyl isopropanol 88 see example 210 232 no 4-phenyl phenoxymethyl ON THE 91 see example 210 233 no 2-phenyl-propyl methanol 60 see example 210 234 no 3-fepylpropyl ethanol 76 see example 210 235 no 4-hydroxy- phenylethyl methanol 51 see example 210 236 no Methyl-4-phenylethyl ethanol 86 see example 210 237 no ethoxy ethanol 90 see example 210 238 l- (4-hydroxy-butyl) isopropoxy toluene: heptane 43 see example 210

148

239 l- (4-hydroxy-butyl) phenylethyl methanol 80 see example 210 240 no 4-nitro-phenyl-ethyl isopropanol 83 see example 210 241 no propoxy DMF: water 43 see example 210 242 no 4-fluoro-phenylamino acetate 65 see example 210 243 no 4-amino-phenylethyl methanol: water 74 see example 210 244 2-methyl- isopropoxy methanol 40 see example 210 245 7-methyl isopropoxy ethanol 98 see example 210 246 7-methyl phenylethyl DMF: water 97 see example 210 247 no cyclopentyl ethanol 56 see example 210 248 1-methyl isopropoxy ethanol 81 see example 210 249 no 4-methoxy- carbonyl-phenylethyl ethanol 77 see example 210 250 1-Isopropyl isopropoxy toluene: heptane 71 see example 210 251 1-methyl 4-hydroxy- phenylethyl ethanol 50 ' see example 210 252 no isopropyl ethanol 76 see example 210 253 no 4-chlorophenyl aminocarbonyl methyl DMF: water 40 see example 210

149

254 no ethoxycarbonyl- methyl methanol 40 see example 210 255 no 4-methoxy- phenylamino carbonylmethyl DMF: water 40 see example 210 256 no cyclopropyl DMF: water 50 see example 210 257 no 3-pyridyl ethanol 50 see example 210 258 no 2-amino- carbonylethyl methanol 55 see example 210 259 no cyclobutyl ethanol 79 see example 210 260 no 2- (dimethylamino carbonyl) ethyl ethanol 97 see example 210 261 l- (4-hydroxy-butyl) cyclopropyl ethanol 80 see example 210 262 no 4-pyridyl ethanol 91 see example 210 263 no cyclopentyl ethanol 75 see example 210 264 no 2,2,3,3 -tetramethyl- cyclopropyl ethanol 32 see example 210 265 no 2-methyl - cyclopropyl ethanol 34 see example 210 266 l- (4-hydroxy-butyl) cyclohexyl toluene 41 see example 210 267 l- (4-hydroxy-butyl) 4-pyridyl ethanol 50 see example 210 268 no benzothiazol-2-yl ethanol 50 see example 210

150

269 no 2-pyridyl 67 see example 210 270 no dimethylamino ethanol 77 see example 210 271 no pyrrol-2-yl ethanol 83 see example 210 272 no 6-methoxybenzoic thiazol-2-yl ethanol 60 see example 210 273 1-methyl- cyclopropyl ethanol 76 see example 210 274 7-methyl cyclopropyl ethanol 60 see example 210 275 1-methyl- 3-pyridyl ethanol 64 see example 210 276 no propyl ON THE 63 see example 210 277 no methyl ON THE 68 see example 210 278 no trifluoromethyl ON THE 14 see example 210 279 l- (4-hydroxy-butyl) hydrogen atom ON THE 62 see example 210 280 l- (4-hydroxy-butyl) methyl ON THE 36 see example 210 281 I- (4-hydroxy-butyl) trifluoromethyl ' ON THE · 7 see example 210 282 l- (4-hydroxy-butyl) 7erc-butyl ON THE 50 see example 210 283 no ethoxycarbonyl ethanol 74 see example 210 284 no 2-methoxy- carbonylethyl ethanol 79 see example 210

151

285 no trans-2-phenyl-l- cyclopropyl ethanol 92 see example 210 286 l- (4-hydroxy-butyl cyclobutyl ethanol 26 see example 210 287 6-carboxy-l-methyl- cyclopropyl ethanol 26 see example 210 288 5-methoxy-1-methyl- cyclopropyl ethanol 75 see example 210 289 1-methyl- pyrazinyl ethanol 82 see example 210 290 1,7-dimethyl cyclopropyl ethanol 97 see example 210 291 1-methyl- tetrahydrofuran-3 - yi ethanol 78 see example 210 292 1-methyl- cyclopropylamine ethanol 54 see example 210 293 6-carboxy-l-methyl- isopropoxy DMF: water 45 see example 210 294 1,7-dimethyl isopropoxy methanol 53 see example 210 295 5-methoxy-l-methyl- isopropoxy ethanol 72 see example 210 296 1-methyl- 4-fluoro-phenyl-amino methanol 80 see example 210 297 1-methyl trifluoroacetamide methanol 70 see example 210 298 1-methyl- 4-amino-phenyl-ethyl toluene 64 see example 210 299 1-methyl- amino ethanol 80 see example 210 300 no 4-chlorophenyl-ethyl ethanol 85 see example 210

152

301 1-methyl- ethoxy ethanol 80 see example 210 302 1-methyl- 5-isoxazolyl DMF: water 83 see example 210 303 I methyl fe / 's-butyl ethanol 92 see example 210 304 6-carboxy-1-methyl pyrazinyl DMF 98 see example 210 305 l-Methyl-6- [2- (4- morpholino) ethylcarbonyl pyrazinyl ON THE 20 see example 210

Table 2A

Physical data of synthesized compounds having Structural Formula VI.

Example temperature mp (° C) Elemental analysis carbon hydrogen nitrogen Off. U.S. Off. U.S. Off. U.S. 210 292-295 75.73 75.74 5.02 5.28 13.94 13.85 211 217-220 73.97 73.93 6.20 6.14 11.25 11.18 212 266-268 69.35 69,23 4.65 5.05 12,13 12,03 213 284-286 71.91 71.86 4.76 4.78 13.24 13.34 214 264-267 64.87 64.78 4.01 4.12 11.94 11.93 215 265-270 72,49 72.64 5.17 5.21 12.68 12.72 216 288-291 72,49 72,52 5.17 5.36 12.68 12.74 217 268-270 76,17 76.12 5.43 5.55 13.32 13.59 218 263-265 66.90 66.75 5.61 5.46 15.60 15.48 219 280-282 76,17 76.34 5.43 5.23 13.32 13,30 220 265-267 71.50 71.48 4.66 4.62 18.53 18.35 221 (0.75 H ₂ O) * 255-257 69,11 69.30 5.30 5.07 16.98 16.99 222 265-267 68.66 68.65 4.85 4.98 16.85 16,67

153

223 274-277 67,96 67.77 4.20 4.39 12.51 12.33 224 204-206 71.44 71.39 6.24 6.14 10.41 10.32 225 248-250 64.19 64.01 3.89 4.15 16.63 16.59 226 288-290 72,49 72.46 5.17 5.16 12.68 12.81 227 282-284 69.79 69.68 5.29 5.29 11.62 11.75 228 295-300 71.91 71.20 4.76 4.76 13.24 13.44 229 265-268 64.87 64.91 4.01 4.16 11.94 11.92 230 (0.5 CH 3 OH) * 288-292 71.91 71.45 4.71 4.69 16.36 13.36 231 266-268 73.02 72.78 5.54 5.70 12.16 12.09 232 (0.75 H ₂ O) * 295-296 73.78 73.58 5.07 5.21 10.32 10.20 233 253-255 76.57 76,06 5.81 6.09 12.75 • 12.60 234 218-220 76.57 76.52 5.81 5.93 12.75 12.62 235 (1.0 CH ₃ OH) * 271-275 69.40 69.40 5.82 5.72 .11,56 11.38 236 244-245 76.57 76.73 5.81 5.72 12.75 12.64 237 248-250 65.87 65.94 5.13 5.01 16.46 16,45 238 210-212 66.84 66,76 6.79 6.83 12,30 12.21 239 205-207 74.39 74.32 6.50 6.58 10.84 10.92 240 295-297 66.65 66.65 4.47 4.85 15.54 15.75 241 246-247 66.90 66.95 5.61 5.56 15.60 15.61 242 (0.75 EtOAc) * 251-252 65.28 64.88 4.92 4.91 14.50 14.53 243 244-246 72.70 72,45 5.49 5.67 16.95 16.71 244 (0.25 CH ₃ OH) * 262-264 66.99 66.78 6.22 6.09 14.42 14.46 245 254-256 67.82 67,78 6.04 5.76 14.83 14.82 246 302-304 76.57 75,96 5.81 5.59 12.75 12.84 247 277-279 69,13 68.95 5.80 5.79 14.22 14.36 248 239-240 67.82 67.75 6.04 6.10 14.83 14,77 249 259-260 70.76 70.62 5.13 5.43 11.25 11.24

154

250 161-163 69.43 69.40 6.75 6.80 13.49 13.48 251 255-257 73,04 72.89 5.50. 5.72 12.17 12.11 252 264-266 71.12 71,17 5.96 5.87 16.58 16.65 253 305-307 63.41 63,17 3.99 4.07 14.79 14.57 254 235-237 64.63 64,81 5.08 5.04 14.13 14.22 255 (0.5 Η ₂ Ο) * > 300 65,78 65.64 4.99 4.81 14.61 14.61 256 300-305 71.69 71.39 5.21 5.22 16.72 16.75 257 305-307 70.82 70,71 4.36 4.36 19.43 19.50 258 280-281 61.58 61.86 5.29 5.44 18.36 18,12 259 > 300 72.43 72.30 5.69 5.71 15.84 15.85 260 258-260 65.79 65,66 5.84 5.50 18.05 17.82 261 215-216 70.56 70.29 6.54 6.45 12.99 12.99 262 > 300 70.82 70.76 4.19 4.78 19.43 19.29 263 300-304 73.09 72.79 6.13 6.06 15.04 14.98 264 (0.25 Η ₂ Ο) * 296-298 73.16 73.43 6.86 6.89 13.47 13.36 265 294-296 72.43 72.57 5.69 5.73 15.84 15.85 266 226-227 72.29 72.10 7.44 7.56 11.49 11.54 267 224-225 68.27 68.65 5.73 5.91 15,16 15.25 268 > 300 66.26 65.96 3.51 3.64 16.27 16.25 269 278-280 70.82 71.07 4.19 4.35 19.43 19.53 270 258-260 66,12 66.26 5.54 5.50 22,03 21.87 271 300-302 69.55 68.91 4.37 4.54. 20.28 20.23 272 > 300 64.16 64.20 3.77 3.94 14.96 14.69 273 245-247 72.43 72.34 5.69 5.72 15.83 15.78 274 286-288 72,73 72.14 5.69 5.91 15.83 15.60 275 (0.5 Η ₂ Ο) * 230-232 69.44 69,89 4.85 4.84 17.99 18.10 276-282 ¹³ C and Η NMR and analytical data from LC / structures The VIS corresponds to the above

155

283 250 (d) 63.59 63.42 4.62 5.00 14.83 14.83 284 267-269 64.63 64.58 5.08 5.29 14.13 14.14 285 280-282 75.99 76,11 5.31 5.32 12.66 12.65 286 220-222 71.19 71,16 6.87 6.85 12.45 12.46 287 237- 240 (d) 66.00 66.00 4.88 4.85 13.58 13.43 288 236-238 67.09 67,48 5.96 6.00 13.80 13.76 289 263-265 67.31 67.58 4.32 4.48 23,09 23.31 290 258-260 72.15 72.33 6.22 6.06 14.85 15,11 291 208-210 69,13 69.18 5.80 5.85 14.23 14.25 292 160- 164 (d) 68.55 68.25 5.75 5.86 19.98 19.71 293 330-332 62,38 62.37 5,23 ' 5.31 12.84 12.87 294 245-247 68.67 68.86 6.44 6.21 14.13 14.14 295 238-239 65.16 65.31 6.11 6.10 13.41 13.46 296 218-219 67.09 66.65 4.82 4.99 16.12 16,10 297 252-253 53,58 53.80 3.30 3.51 16.66 16,67 298 192-193 74.29 74.26 5.98 5.85 15.27 15,38 299 246-247 63.73 63.51 5.10 5.32 22.88 22.54 300 271-272 68.67 68.59 4.61 5.04 12.01 11.81 301 194-196 66.90 66.94 5.61 5.72 15.60 15.62 302 271-272 65.75 66.02 4.14 4.34 19.17 19,00 303 201-203 70.28 70.02 7.44 7.41 13.29 13.17 304 > 300 60.47 60.96 4.54 4.33 20.02 19.85 305 240-241 61.52 61.67 5.59 5.67 20.92 20.91

The molecular weight calculated for elemental analysis includes the solvent in the indicated amount.

(d) means (decomposition, decomposition)

Explanatory note: The maleate salts were prepared by adding an ethanolic solution of maleic acid to the free base in ethanol at room temperature, cooling and filtering the crystalline product.

156

III. 4 - [(Indol-2-yl) methylene] -2-pyrazolin-5-one (VII).

Table 3

Synthesized compounds having the structural formula VU.

Example Substituent on indole R ¹ Solvent for recrystallization Howl. % Method of preparation 306 no isopropoxy ethanol 81 see example 210 307 no 4-hydroxy- phenylethyl ethanol 45 see example 210 308 no 4-amino-phenylethyl ON THE 20 see example 210 309 no 4-methoxy- carbonyl-phenylethyl toluene 75 see example 210 310 no 4-carbamoyl- phenylethyl DMF .water 90 see example 210 311 no cyclopropyl ethanol 35 see example 210 312 3-dimethyl- aminomethyl cyclopropyl ON THE 20 1 see example 210 313 no 3-pyridyl ethanol 62 see example 210 314 5-methoxy isopropoxy methanol 78 see example 210 315 1-methyl- isopropoxy DMF: water 89 see example 210 316 no tetrahydrofuran-3 yi acetate 30 see example 210 317 5-methoxy cyclopropyl ethanol 33 see example 210 318 5-Nitro cyclopropyl DMF 84 see example 210

157

319 no isopropylamino methanol 80 see example 210 320 no 4-carboxyphenyl ethyl DMF: water 65 see example 210 321 no phenyl ethanol 55 see example 210 322 3-methyl isopropoxy methanol 76 see example 210 323 3- (2-methoxycarbonylamino carbonyl-2-acetami- to ethyl) isopropoxy toluene: heptane 40 see example 210 324 no ethoxy ethanol 55 see example 210 325 3- (4-morpholino methyl) ethoxy ethanol 65 see example 210 326 3- (4-morpholino methyl) cyclopropyl acetate 46 see example 210 327 5-methoxy pyrazinyl ON THE 91 see example 210 328 5-methoxy 2-pyridyl ON THE 90 see example 210 329 4-chloro-6,7- dihydro- ethoxy ethanol 54 see example 210 330 4-chloro-6,7- dihydro- pyrazinyl toluene 83 see example 210 331 4-oxo-5,6,7 tetrahydro- pyrazinyl toluene 40 see example 210 332 3-dimethyl- aminomethyl ethoxy toluene-heptane 41 see example 210

ι

Table 3A

Physical data of synthesized compounds having the structural formula VII.

Example temperature mp (° C) Elemental analysis carbon hydrogen nitrogen Off. U.S. Off. U.S. Off. U.S. 306 221-223 66.90 67.11 5.61 5.53 15.60 15.68 307 242-245 72,49 72.34 5.17 5.15 12.68 12.36

158

308 187-189 72.71 72.99 5.49 5.48 16.96 16.35 309 210-212 70.76 70.99 5.13 5.00 11.25 11,11 310 (0.25 Η ₂ Ο) * 263-265 69.44 69.51 5.09 5.05 15.43 15.21 311 (0.75 Η ₂ Ο) * 238-240 68.04 67,68 5.55 5.11 15.87 15.75 312 (0.25 Η ₂ Ο) * 202 (d) 69.10 69,13 6.60 6.46 17.91 17.56 313 (0.5 Η ₂ Ο) * 155-157 68.67 68.68 4.40 4.48 18.84 of 18.56 314 219-220 64.20 64.48 5.72 5.76 14.04 14.08 315 254-255 67.83 67.89 6.05 6.09 14.83 14,83 ' 316 180-183 68.31 68,49 5.37 5.57 14.94 14.80 317 221-224 68.31 68.34 5.37 5.35 14.94 14.82 318 316-320 60.80 60.70 4.08 4.35 18.91 19.01 319 245-247 67.14 67.08 6.01 6.03 20.88 20.94 320 > 300 70,18 69,87 4.77 4.87 11.69 11.76 321 210-211 75.25 75.17 4.56 4.75 14.62 14.62 322 241-243 67.83 67.97 6.05 6.05 14.83 14.89 323 205-206 61.16 61,51 5.87 5.93 13.58 13.27 324 265-267 65.87 65.91 5.13 5.27 16.46 16.52 325 205-206 64.39 64.64 6.26 6.35 15.81 15.82 326 203-180 68.55 68.53 6.32 6.31 15.99 15.80 327 272-274 63,94 64.29 4.10 4.00 21.93 22,10 328 170-172 67.91 68.06 4.43 4.43 17.60 17.74 329 177-203 57.64 57.87 4.84 4.79 14.40 14.35 330 (0.4 toluene) * 206-209 62.27 62.20 4.22 4.47 19.31 19.27 331 (0,1 toluene) * 300-303 63.36 63.49 4.36 4.41 22,12 21.96 332 185-187 65.37 65.13 6.45 6.35 17.94 17.70

159

The molecular weight calculated for elemental analysis includes the solvent in the indicated amount.

(d) means (decomposition, decomposition)

IV. 4 - [(7-Azaindol-3-yl) methylene] -2-pyrazolin-5-one (VIII).

Table 4

Synthesized compounds having the structural formula VIII.

Example Substituent on azaindole R ¹ Solvent for recrystallization Howl. % Method of preparation 333 no benzyl DMF: water 71 see example 210 334 l- (4-hydroxy- butyl) benzyl acetate 30 see example 210 335 no 4-methoxy- phenoxymethyl DMF: water 80 see example 210 336 no isopropoxy methanol 61 see example 210 337 none ' amino · DMF: water 92 see example 210 338 no 4-methoxybenzyl DMF: water 96 see example 210 339 no phenylamino DMF: water 77 see example 210 340 no 4-methylbenzyl ethanol 95 see example 210 341 no 4-hydroxy- phenylethyl ethanol 84 see example 210 342 1- (4-hydroxy- butyl) 4-hydroxy- phenylethyl methanol 80 see example 210

160

343 no isopropyl ethanol 30 see example 210 344 no cyclopropyl ethanol 50 see example 210 345 no cyclobutyl ethanol 74 see example 210 346 no 3-pyridyl ethanol 40 see example 210 347 no phenyl ON THE 56 see example 210 348 no 4-fluoro-phenylamino ON THE 14 see example 210 349 no propyl ON THE 24 see example 210 350 no methyl ON THE 77 see example 210 351 no trifluoromethyl ON THE 17 see example 210 352 no / Tert-butyl ON THE 80 see example 210 353 l- (4-hydroxy- butyl) trifluoromethyl ON THE 6 see example 210 354 no 4-isopropyl- phenylamino ON THE 30 see example 210 355 no 3-methyl phenylamino ON THE 70 see example 210 356 l- (4-hydroxy- butyl) 3-methyl phenylamino ON THE 30 see example 210 357 no phenylethyl DMF: water 63 see example 210

Table 4A

Physical data of synthesized compounds having Structural Formula VIII.

Example temperature mp (° C) Elemental analysis carbon hydrogen nitrogen Off. U.S. Off. U.S. Off. U.S. 333 274-277 71.50 71.63 4.66 4.88 18.53 18.17 334 176-179 70.56 70.67 5.92 5.87 14.96 14.78 335 300-302 65,69 65.62 4.35 4.85 16.12 15.77 336 258-260 62.21 61.57 5.22 5.12 20.72 20.57 337 (1H ₂ O) * > 300 53,82 53.92 4.48 4.34 28.54 28.22

161

338 273-276 68.66 68.05 4.85 4.89 16.85 16,67 339 (1H ₂ O) * 249-252 63.54 63.45 4.70 4.75 21.79 21.68 340 (0.5 H ₂ O) * > 300 70.07 70.54 5.22 5.07 17.21 17.24 341 270-272 68.66 68.25 4.85 5.04 16.86 16.71 342 211-212 68.30 67.97 5.98 6.11 13.85 13.80 343 300 (d) 66,12 65.91 5.54 5.57 22,03 21.89 344 (0.25 H ₂ O) * 245-246 65,48 65.20 4.90 4.76 21.82 21.47 345 300-302 66.52 66,51 5.39 5.22 20.69 20.88 346 212-215 66,50 65.84 3.83 4.07. 24.20 23.93 347 280-282 70,80 70.50 4.20 4.10 19.40 19.10 348-356 ¹³ C and 1 H NMR and analytical data from LC / MS correspond to the above structure 357 317-319 72.13 71.69 5.09 5.04 17.70 17.65

The molecular weight calculated for elemental analysis includes the solvent in the indicated amount.

(d) means (decomposition, decomposition)

Explanatory note: The maleate salts were prepared by adding an ethanolic solution of maleic acid to the free base in ethanol at room temperature, cooling and filtering the crystalline product.

ABOUT

IX.

162

Table 5 ‘

Synthesized compounds having structural formula IX.

Example Substituent on Circle A R ¹ Solvent for recrystallization Howl. % Method of preparation 358 4-dimethylamino benzyl ethanol 32 see example 210 359 4-dimethylamino isopropoxy toluene: heptane 51 see example 210 360 4-dimethylamino phenylethyl ON THE 45 see example 210 361 4-dimethyl-amino cyclopropyl ethanol 77 see example 210

Table 5A

Physical data of synthesized compounds having structural formula IX.

Example temperature mp (° C) Elemental analysis carbon hydrogen nitrogen Off. U.S. Off. U.S. Off. U.S. 358 253-255 74.73 74.20 6.27 6.13 13.75 13.34 359 197-198 65.91 66,33 7.01 6.86 15.37 15.27 360 224-225 75,20 75.08 6.62 6.56 13.15 13.19 361 280-289 70.56 70.33 6.71 6.80 16.46 16.20

VI. 4 - [(Pyrazol-4-yl) methylene] -2-pyrazolin-5-one (X).

N

H

X.

163

Table 6

Synthesized compounds having structural formula X.

Example Substituent on Circle A R ¹ Solvent for recrystallization Howl.% process 362 3-methyl isopropoxy ' acetate 80 see example 210 363 3-methyl cyclopropyl toluene 51 see example 210

Table 6A

Physical data of synthesized compounds having the structural formula X.

Example temperature mp (° C) Elemental analysis carbon hydrogen nitrogen Off. U.S. Off. U.S. Off. U.S. 362 228-230 56.39 56,06 6.02 5.91 23.91 23.77 363 265-267 61,09 61.30 5.59 5.83 25.91 25.71

VII. 4 - [(Imidazol-2-yl) methylene] -2-pyrazolin-5-one (XI).

Table 7

Synthesized compounds having the structural formula XI.

Example Substituent on Circle A R ¹ Solvent for recrystallization Howl. % Method of preparation 364 no isopropoxy toluene 45 see example 210 365 no cyclopropyl ethanol 42 see example 210

164

Table 7A

Physical data of synthesized compounds having Structural Formula XI.

Example temperature mp (° C) Elemental analysis carbon hydrogen nitrogen Off. U.S. Off. U.S. Off. U.S. 364 212-214 54.53 54.96 5.49 4.61 25.43 25.67 365 264-266 59.39 59.52 4.98 5.00 27.71 27.37

VIII. 4 - [(Imidazol-4-yl) methylene] -2-pyrazolin-5-one (XII).

IX.

Table 8

A synthesized compound having Structural Formula XII.

Example substituent Circle A on the R ¹ Solvent for recrystallization Howl. % Method of preparation 366 no isopropoxy ethanol 81 see example 210

Table 8A

Physical data of synthesized compounds having structural formula XII.

Example temperature mp (° C) Elemental analysis carbon hydrogen nitrogen Off. U.S. Off. U.S. Off. U.S. 366 259-260 54.53 54.84 5.49 5.68 25.43 25.37

165

IX. 4 - [(Thien-2-yl) methylene] -2-pyrazolin-5-one (XIII).

Table 9

A synthesized compound having the structural formula ΧΙΠ.

Example Substituent on Circle A R ¹ Solvent for recrystallization Howl. % Method of preparation 367 no cyclopropyl ethanol 20 see example 210

Table 9A

Physical data of synthesized compounds having the structural formula XIII.

Example temperature mp (° C) Elemental analysis carbon hydrogen nitrogen Off. U.S. off- U.S. Off. U.S. 367 275-277 60,53 60.68 4.61 4.74 12.83 12.50

X. 4 - [(Indol-3-yl) methylene] -1-methyl-2-pyrazolin-5-one (XIV).

166

Table 10

A synthesized compound having Structural Formula XIV.

Example substituent Circle A on the R ¹ Solvent for recrystallization Howl. % Method of preparation 368 no isopropyl ethanol 54 see example 210

Tabuľka10A

Physical data of synthesized compounds having Structural Formula XIV.

Example temperature mp (° C) Elemental analysis carbon hydrogen nitrogen Off. U.S. Off. U.S. Off. U.S. 368 241-242 71,88 71,73 6.41 6.47 15.72 15.71

XI. 4 - [(Pyrol-3-yl) methylene] -2-pyrazolin-5-one (XV).

Table 11

A synthesized compound having the structural formula XV.

Example Substituent on pyrrole R ¹ Solvent for recrystallization Howl. % Method of preparation 369 no isopropoxy methanol 70 see example 210

167

Table 11A

Physical data of synthesized compounds having Structural Formula XV.

Example temperature mp (° C) Elemental analysis carbon hydrogen nitrogen Off. U.S. Off. U.S. Off. U.S. 369 252-255 60,26 60.35 5.98 5.82 19.17 19.13

XII. 4 - [(Quinolin-5-yl) methylene] -2-pyrazolin-5-one (XVI).

Table 12

A synthesized compound having Structural Formula XVI.

Example Substituent on quinoline R ¹ Solvent for recrystallization Howl. % Method of preparation 370 8-hydroxy isopropoxy methanol 40 see. Example 210

Table 12A

Physical data of synthesized compounds having Structural Formula XVI.

Example temperature mp CC) Elemental analysis carbon hydrogen nitrogen Off. U.S. Off. U.S. Off. U.S. 370 > 300 64.64 64.43 5.09 5.01 14.13 13.98

168

X. Synthesis of starting materials.

A. Synthesis of 3-ketoesters (XIX).

The general method used in the synthesis of 3-ketoesters is shown in Scheme II.

Scheme Π

Synthesis of 3-ketoesters

+ ct ^ r ’

Base 1

2. 3% HCl ³ · anhydrous ethanol + Δ

XVIII.

h ₃ ch ₂ c.

XIX.

Example 371

Ethyl 3- (2,2,3,3-tetramethylcyclopropyl) -3-oxopropionate

Pyridine (5 g, 0.063 mol) and 2,2,3,3-tetramethylcyclopropylcarbonyl chloride (5 g, 0.031 mol) were added to an ice-cold solution of 2,2-dimethyl-1,3-dioxane-4,7-dione (4 g). , 7 g, 0.032 mol) in anhydrous dichloromethane (37 mL) under a nitrogen atmosphere. The temperature was maintained at 0 ° C for 1 hour, then allowed to warm to room temperature overnight. The mixture was then poured into a separatory funnel, washed twice with 3% hydrochloric acid and twice with water. The organic layer was dried over magnesium sulfate, then filtered and concentrated under reduced pressure to give 5 g of a dark red oil, which was refluxed for 3 hours in anhydrous ethanol (60 mL). The solvent was evaporated and the product purified by distillation.

169

Example 377

Ethyl 3- (6-methoxy-benzothiazol-2-yl) -3-oxopropionate.

Ethyl acetate (7.2 g, 0.082 mol) was added to sodium hydride (1.5 g of 50% dispersion in oil, 0.032 mol) maintaining the temperature below 25 ° C, then 2-ethoxycarbony-2 (6- methoxy) benzothiazole (5.25 g, 0.022 mol). The mixture was heated at gentle reflux and then stirred at room temperature overnight. Quench the reaction with ice water (50 mL) and adjust the pH to 7.7 with concentrated hydrochloric acid. After precipitation, the product was collected by filtration, washed with water and dried.

Example 378

Ethyl 4- (4-fenylfenyloxy) -3-oxobutanoate.

Sodium hydride (5.0 g, 0.114 mol) and 4-phenylphenol (15.3 g, 0.09 mol) were stirred at 0 ° C in 75 mL of dimethylformamide (DMF) for 2 hours. Ethyl 4-chloroacetoacetate (5.0 g, 0.03 mol) in DMF (75 mL) was then added. The mixture was stirred for 1 hour at 0 ° C and for 12 hours at room temperature, then neutralized with 50% phosphoric acid and extracted with dichloromethane. The product obtained is purified by chromatography on a silica gel column using toluene: ethanol (8: 2) as the eluent.

Table 13

Synthesized compounds having the structural formula XIX.

Example R ¹ Howl. % Boiling point (° C) temperature Melting point (° C) process 371 2,2,3,3-tetramethyl- cyclopropyl 67 68 (0.2 mmHg) ON THE see example 371 372 2-methylcyclopropyl 50 62-4 (0.2 mmHg) ON THE see example 371 373 trans-2-phenyl- cyclopropyl 64 138-40 (0.2 mmHg) ON THE see example 371 374 tetrahydrofuran-3-yl 60 82-6 (0.2 mmHg ON THE see example 371 375 3-Methoxyphenyl methyl 62 132 (0.2 mmHg) ON THE see example 371 376 phenylethyl 55 110 (0.2 mmHg ON THE see example 371

170

377 6-methoxy- benzothiazol-2-yl 65 ON THE 160 see example 377 378 4-methyl-phenylphenoxy 33 ON THE 83 see example 378 379 3-chloro-phenoxymethyl 32 147 (8mmHg) ON THE see example 378 380 pyrazinyl 71 ON THE 82 see example 377

B. Synthesis of ethyl-cyclopentyloxy-thiocarbonyl acetate.

XX. XXI. xxn.

Scheme III. Synthesis of ethylalkyloxy or aryloxycarbonimidoylacetate hydrochloride (R ⁹ is a substituted or unsubstituted aliphatic or aromatic group).

Example 381

Synthesis of ethyl cyclopentyloxycarbonimidoylacetate hydrochloride (XXII).

A mixture of dry ethyl cyanoacetate (14 g, 0.12 mol) and dry cyclopentanol (12 g,

0.15 mol) was saturated at 0 ° C with hydrogen chloride gas for 3 hours, kept at 0 ° C overnight, then diluted with diethyl ether. After precipitation, the product was collected by filtration and washed with ether.

Yield 22.4 g (77%), mp 110-112 ° C.

Scheme IV: Synthesis of ethyl-alkyloxy-thio or aryloxy-thiocarbonylacetate.

171

Example 382

Ethyl-cyclopentyloxy-thiocarbonylacetate (XXIV)

A mixture of ethyl cyclopentyloxycarbonimidoylacetate hydrochloride (22 g, 0.09 mol) in anhydrous pyridine (150 mL) was treated with hydrogen sulfide for 8 hours and maintained at room temperature for 48 hours. The reaction mixture was acidified with concentrated hydrochloric acid and extracted with diethyl ether. The ether phase is washed with water, dried and purified by distillation. Yield 15 g, (75%), b.p. 140-142 ° C (15 mmHg).

C.

XXV.

XXVI.

Scheme V; Synthesis of 2-pyrazolin-5-ones according to Method 1.

h ₃ ch ₃ c

Q-Et h ₂ n — n h ₂

H _and C

XXIX.

Scheme VII; Synthesis of 2-pyrazolin-5-ones according to Method 3.

\

_N-CH3

172

Scheme VIII: Synthesis of 2-pyrazolin-5-ones according to Method 4.

Example 383

3- (2,2,3,3-tetramethylcyclopropyl) -2-pyrazolin-5-one.

Hydrazine hydrate (1.1 g, 0.024 mol) was added to a solution of ethyl 3- (2,2,3,3-tetramethylcyclopropyl-3-oxopropionate (4.41 g, 0.020 mol) in anhydrous ethanol (60 mL). refluxed for 3 hours, cooled, the solvent was evaporated and the residue triturated with hexanes to give a white solid.

Example 411

3- (4-hydroxybenzyl) -2-pyrazolin-5-one.

A stirred suspension of 3- (4-methoxybenzyl) -2-pyrazolin-5-one (2.5 mmol) in dichloromethane (100 mL) cooled to -78 ° C was treated with boron tribromide 7.5 mL (1 M in dichloromethane). ). After 1 hour at -78 ° C, the reaction mixture was stirred at room temperature for 12 hours. Quench the mixture with water (50 mL), then separate the aqueous phase and basify with 5% sodium bicarbonate solution. The precipitate formed is filtered and crystallized from methanol. '

Example 413

3- (4-Karbarmoylfenyletyl) -2-pyrazolin-5-one.

A mixture of 3- (4-methoxycarbonylphenylethyl) -2-pyrazolin-5-one (7.7 mmol) in 25% ammonium hydroxide solution (30 mL) was stirred at room temperature for 12 hours. The solvent was concentrated in vacuo and the resulting solid product was filtered and dried.

173

Example 414

3- (2-aminocarbonylethyl) -2-pyrazolin-5-one.

A mixture of 3- (ethoxycarbonylmethyl) -2-pyrazolin-5-one (1 g, 5.8 mmol) and NaCN (28 mg,

0.58 mmol) in 30 mL 9M ammonia in MeOH was heated at 45 ° C in a sealed flask for 3 days. After cooling, the solvent was evaporated and the residue was suspended in water. The precipitated solid was collected by filtration.

Example 416

3- (4-methoxy-phenylamino) -2-pyrazolin-5-one.

A mixture of 3-amino-2-pyrazolin-5-one (20 mmol), 4-methoxyaniline (25 mol) in 50 mL acetic acid was refluxed for 4 hours. The solvent was evaporated and the residue was suspended in water. The solid was filtered and crystallized from methanol.

Table 14

Synthesized compounds having the structural formula XXVI.

Example R ¹ ť % T. melting (° C) Solvent for recrystallization process 383 2,2,3,3-tetramethyl- cyclopropyl 44 195-7 ON THE see example 383 384 ethoxycarbonylmethyl 44 115-6 toluene see example 383 385 pyrrol-2-yl 30 205-8 ON THE see example 383 386 indol-3-yl 69 250-3 ON THE see example 383 387 ' 6-methoxy-benzothiazol-2-yl 40 269-70 ON THE see example 383 388 2-metylcyklopropyI 70 196-7 Water see example 383 389 trans-2-phenyl-cyclopropyl 65 194-5 ethanol see example 383 390 tetrahydrofuran-3-yl 36 204-5 ethanol see example 383 391 4-methoxybenzyl 73 192-5 ON THE see example 383 392 4-methylbenzyl 80 212-4 etanokvoda see example 383 393 4-chlorobenzyl 67 206-8 ethanol see example 383 394 3-methoxybenzyl 72 163-5 ON THE see example 383

174

395 3,4-dimethoxybenzyl 69 193-5 ON THE see example 383 396 phenylethyl 72 204-7 ON THE see example 383 397 2-phenyl-propyl 72 215 ON THE see example 383 398 3-phenylpropyl 76 200-1 ethanol see example 383 399 4-methoxyphenylethyl 85 230 ethanol see example 383 400 4-methylphenylethyl 90 251-2 ON THE see example 383 401 4-chlorophenylethyl 63 243 ON THE see example 383 402 4-nitrofenyletyI 69 247 DMF: water see example 383 403 4-aminophenylethyl 61 220-2 ON THE see example 383 404 4-methoxy-karbonylfenyletyl 77 259-60 ethanol see example 383 405 4-methyl-fenyIfenyloxy 50 250 ethanol see example 383 406 4-methoxy-phenoxymethyl 70 216-8 ethanol see example 383 407 4-chloro-phenoxymethyl 38 224-6 ethanol see example 383 408 3-chloro-phenyloxymethyl 40 232-4 ethanol see example 383 409 4-metylfenyloxymetyl 77 207-10 methanol see example 383 410 cyclopentyloxy 75 180-1 toluene see example 383 411 4-hydroxybenzyl 75 233 methanol see example 411 412 4-hydroxyphenylethyl 70 205-6 Water see example 411 413 4-karbamoylfenyletyl 90 > 270 DMF: water see example 413 414 2-aminocarbonylethyl 66 193-6 ON THE see example 414 415 2-dimethylamino carbonylethyl 38 203-9 ON THE see example 414 416 4-methoxy-phenylamino 30 232-4 methanol see example 416 417 4-chlorophenylamino 28 262-4 ethanol see example 416 418 4-fluorophenyl amino 35 259-60 ON THE see example 416 419 cyclopropyl amino 82 155-158 ON THE see example 383 420 pyrazinyl 86 193 (d) ethanol see example 383 421 isopropylamino 20 123-25 ethanol see example 383 422 2-pyrimidinyl 55 278-80 ethanol see example 383 423 3-pyridazinyl 83 294-95 ethanol see example 383 424 4-pyrimidinyl 72 290-300 ethanol see example 383 425 4-pyrimidinyl 60 288-291 ethanol see example 383

175

D. Synthesis of aldehydes

Example 426 1- (4-Acetoxybutyl) -azaindole-3-carboxaldehyde

A solution of 7-azaindole-3-carboxaldehyde (4.19 g, 28 mmol) in dry N-γ-dimethylformamide (50 mL) was added dropwise to a stirred suspension of 60% sodium hydride (oil dispersion) (1.2 g, 30 mL). mmol) in dry DMF (65 mL) under a nitrogen atmosphere, maintaining the temperature at 5-10 ° C. After the addition was complete, stirring was continued at the same temperature for 30 minutes, then a solution of 4-bromobutyl acetate (6.16 g, 31 mmol) in dry MTV-dimethylformamide (15 mL) was added dropwise. The mixture was allowed to warm to room temperature and stirred at room temperature for 137 hours. Water (100 mL) was then added and the mixture was extracted with dichloromethane (2 x 100 mL). The organic phase was washed with water (3 x 100 mL), dried over anhydrous magnesium sulfate, filtered and the solvent was removed under reduced pressure to give an oil (6.8 g, 93%) which was used further without purification.

Example 427 1- (4-Hydroxybutyl) -7-azaindole-3-carboxaldehyde

To a solution of 1- (4-acetoxybutyl) -7-azaindole-3-carboxaldehyde (2.3 g, 8.8 mmol) in methanol (40 mL) was added sodium hydroxide solution (0.2 g, 17.5 mmol). in water (35 mL). The mixture is heated at 60 ° C for 0.5 hour, then the solvent is completely evaporated. The residue was dissolved in a mixture of ethyl acetate and water (50 mL: 50 mL) and the aqueous layer was separated. The organic phase is washed with water, dried over magnesium sulphate, filtered and evaporated to dryness. The residue is used without purification. Yield 78%, mp 90 ° C.

Example 428 1- (4-Hydroxybutyl) pyrrole-2-carboxaldehyde.

The product was obtained by the procedure of Example 51, but using pyrrole-2-carboxaldehyde instead of 7-azaindole-3-carboxaldehyde. The product was purified by chromatography on a silica gel column (5: 5) ethyl acetate: hexanes. Yield 67%.

176

Example 429

3-Isopropyl-5-methylpyrrole-2-carboxaldehyde.

To a solution of anhydrous DMF (2.1 mL, 27 mmol) in anhydrous dichloroethane (50 mL) at 0 ° C under a nitrogen atmosphere was added POCl 3 (2.1 mL, 23 mmol). The solution was allowed to warm to room temperature over 1 hour. The suspension was then cooled to 0 ° C and a solution of 3-isopropyl-5-methylpyrrole (2g, 16 mmol) in dichloroethane (20 mL) was added dropwise over 20 minutes. After stirring at room temperature for 24 hours, water and NaOH were added to adjust the pH to 8. The organic layer was extracted, dried and the solvent was removed completely. The residue was purified by flash chromatography. Yield 67%, mp 90-93 ° C.

Example 430

3,5-Dimethyl-4-morpholino-methylpyrrole-2-carboxaldehyde.

3,5-Dimethylpyrrole-2-carboxaldehyde (0.5g, 4 mmol) was added to a solution of morpholine (0.35 g, 4 mmol), 37% formaldehyde (0.32 g, 4 mmol) and acetic acid (2 mL) ). The mixture was stirred overnight at room temperature under a nitrogen atmosphere, then the reaction was diluted with NaHCO 3 to pH = 8. The aqueous solution was extracted with ethyl acetate and the organic layer was dried over MgSO 4. The ethyl acetate was evaporated in vacuo to give 0.4 g of pure solid.

The following compounds were synthesized in a manner analogous to that described in Example 430:

3,5-dimethyl-4-dimethylaminomethylpyrrole-2-carboxaldehyde,

3- (4-morpholino) methyl-indole-2-carboxaldehyde,

3,5-dimethyl-4-diethylaminomethylpyrrole-2-carboxaldehyde,

3,5-dimethyl-4-piperidinomethylpyrrole-2-carboxaldehyde,

3,5-dimethyl-4 - [(4-methyl-1-piperazinyl) methyl] pyrrole-2-carboxaldehyde,

3,5-dimethyl-4- (1-pyrrolidinylmethyl) pyrrole-2-carboxaldehyde,

5-methyl-4-dimetylaminometylpyrol-2-carboxaldehyde,

3.5- dimethyl-4 - [/ ^V-methyl-N - (2-dimethylaminoethyl) aminomethyl] pyrrole-2-carboxaldehyde,

3,5-dimethyl-4-diethanolaminomethylpyrrole-2-carboxaldehyde,

4- (4-benzylpiperidinomethyl) -3,5-dimethylpyrrole-2-carboxaldehyde,

4-dimethylaminomethyl-3-isopropyl-5-iTietylpyrol-2-carboxaldehyde,

177

3,5-dimethyl-4- (4-hydroxypiperidinomethyl) pyrrole-2-carboxaldehyde a

3-dimethylaminomethyl-4,5-tetrametylénpyrol-2-carboxaldehyde.

Example 431

3,5-Dimethyl-4-trifluoroacetamidomethylpyrrole-2-carboxaldehyde.

A mixture of 3,5-dimethylpyrrole-2-carboxaldehyde (2.6 g, 0.02 mol) and N - (hydroxymethyl) trifluoroacetamide (3 g, 0.02 mol) was added portionwise to sulfuric acid (15 mL), whereupon the temperature is kept below 10 ° C. The reaction mixture was allowed to warm to room temperature over 4 hours, poured into ice water (100 mL). The precipitated solid was filtered and washed with water. The white solid (78% yield) was used without purification. Melting point 200 ° C.

Example 432

4-Aminomethyl-3,5-dimethyl-2-carboxaldehyde.

A mixture of 3,5-dimethyl-4-trifluoroacetamidomethylpyrrole-2-carboxaldehyde (3.9 g, 15.7 mmol), 10% NaOH (19 mL) and methanol (100 mL) was heated to reflux for 1 hour, then the solution was concentrated under reduced pressure to half the original volume. Water was added and the precipitated solid was filtered. Yield 72%, mp 210-220 ° C (dec.).

Example 433

3-Acetyl-4-oxopentylacetát.

Mechanically stirred mixture of pentane-2,4-dione (60 g, 0.6 mol), 2-bromoacetate (100 g, 0.6 mol), anhydrous potassium carbonate (83 g, 0.6 mol), IK (99, 6 g, 0.6 mol) and dry acetone (500 mL) were heated at reflux for 24 hours. The mixture was concentrated under reduced pressure and poured into hydrochloric acid (1.7 M, 400 mL). The product is isolated by sequential extraction with ether, ethyl acetate and dichloromethane. The combined organic extracts were washed with brine, the solvent was completely removed and the residue was distilled to give 38 g of acetate. The boiling point is 75-80 ° C (0.1 mm Hg).

178

4-Acetyl-5-oxohexyl acetate [yield 60%, temperature warns 110 ° C (0.2 mm Hg)] and

5-acetyl-6-oxoheptylacetate [77% yield, boiling point 102 ° C (0.2 mm Hg)] was prepared according to the method of Example 433.

Example 434

Tert-Butyl 4- (2-acetoxyethyl) -3,5-dimethylpyrrole-2-carboxylate.

A stirred solution of tert-butyl acetoacetate (26 g, 0.165 mol) in acetic acid (48 mL) was treated dropwise at below 20 ° C with sodium metabisulfite (11.3 g, 0.165 mol) in water (17 mL). The reaction mixture was allowed to stand overnight. A solution of 3-acetyl-4-oxopentylacetate (30 g, 0.161 mol) in acetic acid (56 mL) was heated to 80 ° C, then a mixture of zinc powder (26.2 g, 0.40 mol) and sodium acetate was added portionwise. (26.3 g, 0.32 mol), while the hydroxy imine derivative (97 mL, 0.165 mol) was added dropwise. The reaction mixture is vigorously stirred during the addition, which is controlled so that the zinc is always in excess and the temperature is maintained at 90-100 ° C. After the addition, the mixture was gently heated for 15 minutes and stirred at room temperature overnight. The reaction mixture was poured into ice water and allowed to stand for over 2 hours. The solid was filtered and washed with water and recrystallized from aqueous ethanol. Yield 78%, mp 92 ° C.

Tert-Butyl 4- (3-acetoxypropyl) -3,5-dimethylpyrrole-2-carboxylate [yield 60%, mp 73 ° C (hexane)] and tert-butyl-4- (4-acetoxybutyl) - 3,5-dimethylpyrrole-2-carboxylate (yield 52%, mp 62 ° C (hexane)) was prepared according to the method of example 434.

Example 435 I

3,5-Dimethyl-4- (2-hydroxyethyl) pyrrole-2-carboxaldehyde.

Tert-Butyl 4- (2-acetoxyethyl) -3,5-dimethylpyrrole-2-carboxylate (15 g, 53 mmol) was dissolved in TFA (40 mL) and the solution was stirred at 40 ° C under nitrogen for 10 min. minutes. The reaction mixture was then cooled to 0 ° C and 5-triethylorthoformate (9.6 mL, 58 mmol) was added dropwise. The mixture was then allowed to warm to 20 ° C and stirred for 1 hour before being poured into ice water, then extracted with dichloromethane and the extracts washed successively with 10% aqueous ammonia and water and dried over MgSO 4.

179

4- (2-Acetoxyethyl) -3,5-dimethylpyrrole-2-carboxaldehyde was purified by silica gel column chromatography eluting with ethyl acetate: hexanes (7: 3). Yield 45%, mp 125127 ° C (water).

To a solution of the above compound (5g, 23 mmol) in ethanol (20 mL) was added 10% NaOH solution (10 mL). The mixture was stirred at room temperature for 30 minutes and the final solution was concentrated, diluted with water and extracted with dichloromethane. The organic extracts were dried and the solvent was removed completely. Yield 98%, mp 100 ° C (ethyl acetate).

3,5-Dimethyl-4- (3-hydroxypropyl) pyrrole-2-carboxaldehyde [yield 60%, melting point 85 ° C (ethyl acetate / hexane)] and 3,5-dimethyl-4- (4-hydroxybutyl) pyrrole-2-carboxaldehyde (yield 38%, mp 99 ° C (hexane)) was prepared according to the method of Example 435.

Example 436

4- (2-diethylamino-ethyl) -3,5-dimethyl-2-carboxaldehyde.

Methanesulfonyl chloride (4 mL, 51 mmol) in anhydrous THF (4 mL) was added to a stirred solution of 3,5-dimethyl-4- (2-hydroxyethyl) pyrrole-2-carboxaldehyde (4.3 g, 25.7 mmol) and triethylamine (5.2 g, 51 mmol) in anhydrous THF (60 mL) at 0-5 ° C and stirred for 1 h at room temperature. Water was then added to the mixture and the precipitated solid was filtered. Yield 89%, mp 142-44 ° C.

A mixture of the above mesylate (23 mmol), K 2 CO 3 (23 mmol), diethylamine (90 mmol) and 2-propanol (70 mL) was heated at 100 ° C for 0.5 h. The solvent was removed completely and the residue was treated with water and extracted with methylene chloride. The organic extracts were dried and the solvent was evaporated completely. Yield 70%, mp 70 ° C (rt-heptane).

3,5-Dimethyl-4- [2- (1-pyrrolidinylethyl)] pyrrole-2-carboxaldehyde, 3,5-dimethyl-4- (2-ethylaminoethyl) pyrrole-2-carboxaldehyde, 4- (3-diethylaminopropyl) -3, 5-dimethylpyrrole-2-carboxaldehyde, 4- (4-diethylaminobutyl) -3,5-dimethylpyrrole-2-carboxaldehyde, 3,5-dimethyl-4- [3- (1-pyrrolidinylpropyl)] pyrrole-2-carboxaldehyde isolated as an oil and were prepared in a manner analogous to that described in Example 436.

180

Example 437

4- (2-chloroacetyl) -3,5-dimethyl-2-carboxaldehyde.

Anhydrous aluminum chloride (42 g, 315 mmol) was added dropwise over 30 minutes to a solution of 3,5-dimethylpyrrole-2-carboxaldehyde (5 g, 40 mmol) in 1,2-dichloroethane (50 mL) under a nitrogen atmosphere and at room temperature. After stirring for 15 minutes, chloroacetyl chloride (17 g, 150 mmol) was added dropwise over 1 hour. After the addition, the mixture was stirred at room temperature for 16 hours. The mixture was poured into crushed ice and the organic layer was separated, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Yield 57%, mp 205-209 ° C (toluene).

Example 438

3,5-dimethyl-4- (2-dietylaminoacetyl) pyrrole-2-carboxaldehyde

Diethylamine (5 mL) was added to a solution of 4- (2-chloroacetyl) -3,5-dimethylpyrrole-2-carboxaldehyde (1 g, 5 mmol) in THF (20 mL). The mixture was stirred at room temperature for 24 hours. The solvent was removed under reduced pressure and the residue was treated with water, NaHCO 3 (5%) and extracted with dichloromethane. After drying and filtering, the solvent is removed and the residue is used without further purification.

3,5-Dimethyl-4- (2-dimethylaminoacetyl) pyrrole-2-carboxaldehyde, 3,5-dimethyl-4- [2- (1-pyrrolidinyl) acetyl] pyrrole-2-carboxaldehyde were prepared in a manner analogous to that described above in Example 438.

Example 439

3,5-Dimethyl-4-etoxyoxalylpyrol-2-carboxaldehyde.

Anhydrous aluminum chloride (37 g, 277 mmol) was added dropwise over 30 minutes to a solution of 3,5-dimethylpyrrole-2-carboxaldehyde (7.6 g, 62 mmol) in 1,2-dichloroethane (140 mL) under an atmosphere. nitrogen at room temperature. After stirring for 30 min, nitromethane (11.2 mL, 179 mmol) was added and the mixture was cooled to 0 ° C and ethyl chlorooxoacetate (12.8 g, 94 mmol) was added dropwise over 1 h. After the addition, the mixture was stirred at room temperature for 4 hours, poured into crushed ice and the organic layer was separated, dried and evaporated to give a white solid. Yield 45%, mp 125-127 ° C (toluene).

181

All compounds of the above examples had NMR spectra that matched their chemical structures.

While the present invention has been detailed and described with reference to preferred embodiments, it is to be understood that various changes may be made without departing from the scope and characteristics of the present invention, which is fully defined in the appended claims.

Claims (44)

PATENT CLAIMS A method for inhibiting the activity of one or more protein kinases, comprising administering a compound of the formula and its physiologically acceptable salts and biologically active metabolites, wherein R is selected from the group consisting of substituted or unsubstituted: an aliphatic group, an aromatic group, a (C3-C6) cycloalkyl group, a heterocyclic group, an aralkyl group, a (C3-C6) cycloalkyl-alkyl group and a heterocyclyl-alkyl group; R &lt; ¹ & gt ^; is hydrogen or -AZ; R ² is hydrogen or is selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 5 -C 6) cycloalkyl-alkyl and heterocyclyl-alkyl ; A is - (CH ₂ ) _n -, - (CH ₂ ) n NH-, - (CH ₂ ) n O -, - (CH ₂ ) n S -,> - (CH ₂ ) _n S (O) -. or - (CH ₂ ) n S (O) ₂ -; Z is hydrogen, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring a system selected from the group consisting of (C3-C6) cycloalkyl, isoxazole, isothiazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, pyrazole, pyrazole, pyrazole , thiazole and N -oxides thereof, said The 183 ring system may be optionally substituted with one or more moieties selected from the group consisting of halogens, lower alkyl, R ³ O-, HO-, HOC (O) -, R ³ OC (O) -, trihalomethyl, nitro, aryl , -CN, -C (O) NR ⁴ R ⁵ and -NR ⁴ R ⁵ ; R ³ in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic, (C 1 -C 8) cycloalkyl, heterocyclic, aralkyl, (C 3 -C 6) cycloalkyl-alkyl and heterocyclyl-alkyl; R ⁴ and R ⁵ in each case are independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C3-C6) cycloalkyl, heterocyclic, aralkyl, (C3-C6) cycloalkyl-alkyl and heterocyclyl-alkyl; optionally, R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl, wherein each is optionally substituted with one or more moieties selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic, (C3-C6) cycloalkyl, heterocyclic, aralkyl, (C3-C6) cycloalkyl-alkyl and heterocyclyl-alkyl; and n is an integer ranging from 0 to 3. The method of claim 1, wherein the inhibition of said protein kinase is performed in a recipient in need thereof. The method of claim 2, wherein the compound is a mixture of stereoisomers. 184 The method of claim 3, wherein the stereoisomers are enantiomers. The method of claim 3, wherein the stereoisomers are E and Z isomers. The method of claim 2, wherein the compound is a mixture of structural isomers. The method of claim 6, wherein the structural isomers are tautomers. The method of claim 2, wherein said protein kinase is either a receptor tyrosine kinase or a non-receptor tyrosine kinase. The method of claim 8, wherein said tyrosine kinase is selected from the group consisting of DRC, Flt-1, TIE-2, FGFR, PDGFR, IGF-1R, c-Met, Lck, Src, fyn, Lyn, Blk. and yes. 10. A method of treating or significantly inhibiting hyperproliferative disorders or inflammatory diseases in a recipient in need thereof, comprising administering to said recipient a compound of formula (I) a physiologically acceptable salt thereof and a biologically active metabolite, wherein: R 185 is selected from the group consisting of substituted or unsubstituted: an aliphatic group, an aromatic group, a (C3-C6) cycloalkyl group, a heterocyclic group, an aralkyl group, a (C3-C6) cycloalkyl-alkyl group and a heterocyclyl-alkyl group; R &lt; ¹ & gt ^; is hydrogen or -AZ; ^R2 is H or is selected from the group consisting of substituted or unsubstituted: lower alkyl group, an aromatic group, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C3-C6) cycloalkyl-alkyl and heterocyclyl- an alkyl group; A is - (CH ₂ ) _n -, - (CH ₂ ) n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) n S (O) - or - (CH ₂ ) _n S (O) ₂ -; Z is hydrogen, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring a system selected from the group consisting of C 3 -C 6 cycloalkyl, isoxazole, isothiazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole their A-oxides, wherein said ring system may be optionally substituted with one or more moieties selected from the group consisting of halogens, lower alkyl, R ³ O-, HO-, HOC (O) -, R ³ OC (O) -, trihalomethyl, nitro, aryl, -CN, -C (O) NR ⁴ R ⁵ and -NR ⁴ R ⁵ ; R ³ in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 -C ₆ ) cycloalkyl-alkyl and heterocyclyl-alkyl; R ⁴ and R ⁵ in each case are independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C ₃ -C 6) cycloalkyl, 186 heterocyclic group, aralkyl group, (C3-C6) cycloalkyl-alkyl group and heterocyclyl-alkyl group; optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl, wherein each is optionally substituted with one or more moieties selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic, (C 5 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 6 -C 6) cycloalkyl, and heterocyclyl- and n is an integer ranging from 0 to 3. A method of treating or inhibiting angiogenesis in a recipient in need thereof, comprising administering to said recipient a compound of formula (I), its physiologically acceptable salts and biologically active metabolites, wherein R is selected from the group consisting of substituted or unsubstituted: aliphatic, aromatic, (C 1 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 -C 6) cycloalkyl-alkyl and heterocyclyl-alkyl; R &lt; ¹ & gt ^; is hydrogen or -AZ; R ² is hydrogen or is selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic 187 groups, a (C3-C6) cycloalkyl group, a heterocyclic group, an aralkyl group, a (C3-C8) cycloalkyl-alkyl group and a heterocyclyl-alkyl group; A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) _n S (O) -, or - (CH ₂ ) _n S (O) ₂ -; Z is hydrogen, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring a system selected from the group consisting of (C 3 -C ₆ ) cycloalkyl, isoxazole, isothiazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole, thiazole and their A-oxides, wherein said ring system may be optionally substituted with one or more moieties selected from the group consisting of halogens, lower alkyl, R ³ O-, HO-, HOC (O) -, R ³ OC ( O) -, trihalomethyl, nitro, aryl, -CN, -C (O) NR ⁴ R ⁵ and -NR ⁴ R ⁵ ; R ³ in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic, (C 3 -C 8) cycloalkyl, heterocyclic, aralkyl, (C 1 -C 6 -cycloalkyl-alkyl) and heterocyclyl-alkyl; R ⁴ and R ⁵ in each case are each independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C 3 -C 8) cycloalkyl, heterocyclic, aralkyl, (C 5 -) C 6-6 cycloalkyl-alkyl and heterocyclyl-alkyl; optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl, wherein each optionally substituted with one or more moieties selected from the group consisting of lower alkyl, hydroxy, lower alkoxy of lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, 188 heterocyclic group, aralkyl group, (C 3 -C 6) cycloalkyl-alkyl group and heterocyclyl-alkyl group; and n is an integer ranging from 0 to 3. 12. A method of inducing an anti-angiogenic effect in a recipient in need thereof, comprising administering to said recipient a compound of the formula EMI2.1 its physiologically acceptable salts and biologically active metabolites, wherein R is selected from the group consisting of substituted or unsubstituted: an aliphatic group, an aromatic group, a (C 3 -C 6) cycloalkyl group, a heterocyclic group, an aralkyl group, a (C 5 -C 6 cycloalkyl-alkyl group and a heterocyclyl-alkyl group; R &lt; ¹ & gt ^; is hydrogen or -AZ; ^R2 is H or is selected from the group consisting of substituted or unsubstituted: lower alkyl group, an aromatic group, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C3-C6) cycloalkyl-alkyl and heterocyclyl- an alkyl group; A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) n S (O) - or - (CH ₂ ) n S (O) ₂ -; Z is hydrogen, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring a system selected from the group consisting of (C 3 -C 6) cycloalkyl, isoxazole, isothiazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine. 189 benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole, thiazole and their A-oxides, said ring system may optionally be substituted with one or more moieties selected from the group consisting of halogens, lower alkyl, R ³ O-, HO-, HOC (O) -, R ³ OC (O) -, trihalomethyl, nitro, aryl, -CN, -C (O) NR ⁴ R ⁵ and-NR ⁴ R ⁵ ; R ³ in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic, (C 6 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 -C 6) cycloalkyl- alkyl and heterocyclyl-alkyl; R ⁴ and R ⁵ in each case are each independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 5 -C 6 -cycloalkyl) -alkyl and heterocyclyl-alkyl; optionally, R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl, wherein each optionally substituted with one or more moieties selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl group, an aromatic group, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C ₃ -C 6) cycloalkyl- alkyl and heterocyclyl-alkyl; and n is an integer ranging from 0 to 3. 13. A method of treating or inhibiting the progression of a disease or condition in a recipient in need thereof, comprising administering a compound of formula 190 of its physiologically acceptable salts and biologically active metabolites, said recipient wherein R is selected from the group consisting of substituted or unsubstituted: an aliphatic group, an aromatic group, a (C3-C6) cycloalkyl group, a heterocyclic group, an aralkyl group, a (C3-C6) cycloalkyl-alkyl group and a heterocyclyl-alkyl group; R &lt; ¹ & gt ^; is hydrogen or -AZ; ^R2 is H or is selected from the group consisting of substituted or unsubstituted: lower alkyl group, an aromatic group, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C3-C <>) cycloalkyl-alkyl, and heterocyclyl-alkyl; A is - (CH ₂ ) _n -, - (CH ₂ ) n NH-, - (CH ₂ ) n O-, - (CH ₂ ) n S -, - (CH ₂ ) _n S (O) -, or - (CH ₂ ) _n S (O) ₂ -; Z is hydrogen, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring a system selected from the group consisting of (C 3 -C 8) cycloalkyl, isoxazole, isothiazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole, thiazole and their A-oxides, wherein said ring system may be optionally substituted with one or more moieties selected from the group consisting of halogens, lower alkyl, R ³ O-, HO-, HOC (O) -, R ³ OC ( O) -, trihalomethyl, nitro, aryl, -CN, -C (O) NR ⁴ R ⁵ and -NR ⁴ R ⁵ ; 191 R ³ in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic, (C3-C8) cycloalkyl, heterocyclic, aralkyl, (C3-C6) cycloalkyl-alkyl and heterocyclyl-alkyl; R ⁴ and R ⁵ in each case are each independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C 5 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 -C 6) cycloalkyl -alkyl and heterocyclyl-alkyl; optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl, wherein each is optionally substituted with one or more moieties selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic, (C3-C6) cycloalkyl, heterocyclic, aralkyl, (C3-C6) cycloalkyl-alkyl and heterocyclyl-alkyl; and n is an integer of 0 to 3; wherein said disease or condition is selected from the group consisting of cancer, arthritis, atherosclerosis, restenosis, psoriasis, hemangioma, myocardial angiogenesis, coronary and cerebral collaterals, ischemic limb angiogenesis, corneal disease, rubeosis, neovascular glaucoma, neovascular glaucoma, ulcer, Helicobacter-related diseases, viral. induced angiogenic disorders, fractures, diabetic retinopathy, Crohn's disease, inflammatory bowel disorder, feline scratch fever, retinopathy of prematurity, ulcers, thyroid hyperplasia, burns, trauma, acute lung injury, chronic lung disease, chronic lung disease, chronic lung disease, chronic lung disease, chronic lung disease and allergic inflammation, ovarian hyperstimulation syndrome, pulmonary and cerebral edema, keloid, fibrosis, cirrhosis, carpal tunnel syndrome, sepsis, adult respiratory distress syndrome, multi-organ dysfunction syndrome, ascites, and tumor-related effusions. 192 14. A method of affecting vascular hyperpermeability or edema formation in a recipient in need thereof, comprising administering to said recipient a compound of the formula EMI3.1 physiologically acceptable salts and biologically active metabolites thereof, wherein R is selected from the group consisting of substituted or unsubstituted: an aliphatic group, an aromatic group, a (C3-C6) cycloalkyl group, a heterocyclic group, an aralkyl group, a (C3-C6) cycloalkyl-alkyl group and a heterocyclyl-alkyl group; R &lt; ¹ & gt ^; is hydrogen or -AZ; ^R2 is H or is selected from the group consisting of substituted or unsubstituted: lower alkyl group, an aromatic group, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C3-C6) cycloalkyl-alkyl and heterocyclyl- an alkyl group; Z is hydrogen, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring a system selected from the group consisting of (TX-C 6 cycloalkyl, isoxazole, isothiazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, thrazole, oxazole, thrazole, oxazole) and the N -oxides thereof, wherein said ring system may be optionally substituted with one or more moieties selected from the group consisting of halogens, lower alkyl, R ³ O-, 193 ΗO-, HOC (O) -, R ³ OC (O) -, trihalomethyl, nitro, aryl, -CN, -C (O) NR ⁴ R ⁵ and-NR ⁴ R ⁵ ; R ³ in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 6 -C 6 -cycloalkyl-alkyl) and heterocyclyl-alkyl; R ⁴ and R ⁵ in each case are each independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower alkyl, aromatic, (C 6 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 -C 6) cycloalkyl -alkyl and heterocyclyl-alkyl; optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl, wherein each is optionally substituted with one or more moieties selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 -C 6) cycloalkyl- alkyl and heterocyclyl-alkyl; and n is an integer ranging from 0 to 3. The method of claim 14, wherein the effect on edema formation ¹ is anti-oedematous. 16. The method of claim 2 wherein said protein kinase is a serine kinase. 17. The method of claim 2 wherein said protein kinase is a threonine kinase. 194 18. A compound represented by the following structural formula: and physiologically acceptable salts thereof, wherein R is selected from the group consisting of substituted or unsubstituted: indole, imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, 4,5,6,7-tetrahydroindole, benzoindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrrole, pyrazole, oxazole and thiazole; R &lt; ¹ & gt ^; is hydrogen or -AZ; A is - (CH ₂ ) _n -, - (CH ₂ ) _n NH-, - (CH ₂ ) _n O-, - (CH ₂ ) _n S-, - (CH ₂ ) n S (O) - or - (CH ₂ ) _n S (O) ₂ -; Z is hydrogen, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC (O) -, -NR ⁴ R ⁵ , -C (O) NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring a system selected from the group consisting of (C 3 -C 6) cycloalkane, isoxazole, isothiazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, pyrazole, oxrazole, oxrazole , thiazole and N -oxides thereof, wherein said ring system may be optionally substituted with one or more moieties selected from the group consisting of halogens, lower alkyl, R ³ O-, HO-, HOC (O) -, R ³ OC (O) -, trihalomethyl, nitro, aromatic, (C 3 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 -C 6) cycloalkyl-alkyl, heterocyclyl-alkyl, -CN, -C (O) NR ⁴ R ⁵ or -NR ⁴ R ⁵ ; R ³ in each case is independently selected from the group consisting of substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic, (C 3 -C 6) cycloalkyl, 195 heterocyclic group, aralkyl group, (C 1 -C 6 cycloalkyl-alkyl group and heterocyclyl-alkyl group; R ⁴ and R ⁵ in each case are each independently hydrogen or selected from the group consisting of substituted or unsubstituted: lower; An alkyl group, an aromatic group, a (C3-C6) cycloalkyl group, a heterocyclic group, an aralkyl group, a (C3-C6) cycloalkyl-group and a heterocyclyl-alkyl group; optionally R ⁴ and R ⁵ together with the nitrogen atom to which they are attached represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiamorpholino, azepino or perhydro-1,4-diazepin-1-yl, wherein each is optionally substituted with one or more moieties selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic, (C 5 -C 6) cycloalkyl, heterocyclic, aralkyl, (C 3 -C 6) cycloalkyl-alkyl, and and the index n is an integer ranging from 0 to 3; provided that when R is unsubstituted indol-3-yl, then R ¹ is not -NH ₂ . The compound of claim 18, wherein: A is -NH-, -O-, -S-, -S (O) - or -S (O) ₂ and Z is cyclopropyl, 3-pyridyl or pyrazinyl. The compound of claim 18, wherein: A is -O-; and Z is ethyl, n-propyl or isopropyl. 196 The compound of claim 18, wherein: A is -CH ₂ -; and Z is phenyl, wherein said phenyl is optionally substituted with one or more moieties selected from the group consisting of halogens, trihalomethyl, hydroxy, -NR ⁴ R ⁵ , nitro, -CONR ⁴ R ⁵ , lower alkyl, R ³ O-, -C ( O) OR ⁴ and -OC (O) R ⁴ . 22. A compound selected from the group consisting of: 3-Cyclopropyl-4 - {[(3,5-dimethyl-4- (4-methyl-l-piperazinylmethyl) pyrrol-2-yl] methylene} 2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3,5-dimethyl-4- (l-pyrolidinylmetylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3,5-dimethyl-4-piperidinometylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-dietanolaminometyl-3,5-dimethyl-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3-dimethylaminomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3-morpholinomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3-diethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[3- (4-methyl-1-piperazinylmethyl) -4,5-tetramethylenopyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [{3- (1-pyrrolidinyl) methyl-4,5-tetramethylenopyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3-piperidinomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-diethylamino-3,5-dimethyl-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4- (3,5-dibromo-4-hydroxy-benzylidene) -2-pyrazolin-5-one, 197 3-Cyclopropyl-4 - [(4-oxo-l, 5,6,7-tetrahydro-indole-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(5-Chloro-pyrrol-2-yl) -methylene] -3-cyclopropyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(5-trifluoromethylpyrrole-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4- [4- (2-dimetylaminoetoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one 3-Cyclopropyl-4- [4- (2-dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3-ethoxycarbonylindol-2-yl) methylene] -2-pyrazoIin-5-one, 3-Cyclopropyl-4- [3- (2-dimetylaminoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin-5-one 3-Cyclopropyl-4- [3- (2-dimethylaminoethylaminocarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4- [4- (4-morfolinoetoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4- [4- (4-morfolinoetylaminokarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4- [3- (4-morfolinoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4- [3- (4-morfolinoetylaminokarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3,4-diethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3-cyclopropyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(5-ethoxy-4- methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(5-chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] 2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morpholinomethyl-pyrrol-2-yl) -methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - {[(3,5-Dimethyl-4 - [(4-methyl-l-piperazinylrnetyl) pyrrol-2-yl] methylene} -3- (3-pyridyl) 2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - [(l-pyrolidinyImetylpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-pipendinometylpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(4-Dietanolaminometyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 198 4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(3-MorfolinometyI-4,5-tetrametylénpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(3-diethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - {[3- (4-Methyl-1-piperazinylmethyl) -4,5-tetramethylenepyrrol-2-yl] methylene} -3- (3-pyridyl) -2-pyrazolin-5-one, 3- (3-Pyridyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylene-pyrrol-2-yl] -methylene} -2-pyrazolin-5-one, 4 - [(3-Piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(4-diethylamino-ethyl-3,5-dimethyl-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(4-oxo-l, 5,6,7-tetrahydro-indole-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(4-dimethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(4-bromopyridin-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(4-chloropyridin-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(5-chloropyridin-2-yl) methylene] -3- (3-pyridyl-2-pyrazolin-5-one, 3- (3-Pyridyl) -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- [4- (2-DimetylaminoetoxykarbonylpyroI-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- [4- (2-Dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(3-EtoxykarbonyIindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- [3- (2-Dimetylaminoetylaminokarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- [4- (4-MorfoIinoetoxykarbonylpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- [4- (4-Morfolinoetylaminokarbonylpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- [3- (4-Morfolinoetoxykarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 199 4- [3- (4-Morfolinoetylarninokarbonylindol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(3,4-Dietoxykarbonylpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3- (3-pyridyl) 2-pyrazolin-5-one, 4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - {[(4-methyl-l-piperazinylmethyl) pyrrol-2-yl] methylene} -3-isopropoxy-2pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - [(l-pyrolidinylmetylpyroÍ-2-yl) methylene-] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (piperidinometylpyrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(4-Dietanolaminometyl'3,5 dimetyIpyroI-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(3-Dimethylaminomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3-Isopropoxy-4 - [(3-morpholinomethyl-4,5-tetramethylene-pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(3-Diethylaminomethyl-4,5-tetrarnethylene-pyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3-Isopropoxy-4 - {[3- (4-methyl-1-piperazinyl) methyl-4,5-tetramethylenopyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-isopropoxy-4 - {[3- (l-pyrrolidinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} 2-pyrazolin-5-one, 3-Isopropoxy-4 - [(3-piperidinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(4-diethylamino-ethyl-3,5-dimetylpyroi-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 200 4- (3,5-Dibromo-4-hydroxy-benzylidene) -3-isopropoxy-2-pyrazolin-5-one, 3-Isopropoxy-4 - [(4-oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(4-Bromopyrrol-2-yl) methylene] -3-isopropoxy- 2-pyrazolin-5-one, 4 - [(4-Chloro-pyrrol-2-yl) -methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(5-Chloro-pyrrol-2-yl) -methylene] - 3-isopropoxy-2-pyrazolin-5-one, 3-Isopropoxy-4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4- [4- (2-Dimetylaminoetoxykarbonylpyrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4- [4- (2-DÍmetylaminoetylaminokarbonylpyrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4- [3- (2-Dimétylaminoetoxykarbonylindol-2-yl) methylene-] -3-isopropoxy-2-pyrazolin-5-one, 4- [3- (2-Dimetylaminoetylaminokarbonylindol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3-isopropoxy-4- [4- (4-morfolinoetoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-isopropoxy-4- [4- (4-morfolinoetylaminokarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-isopropoxy-4- [3- (4-morfolinoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3-Isopropoxy-4- [3- (4-morpholinoethylaminocarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [[3,4-Diethoxycarbonylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - {[(4-methyl-l-piperazinylmethyl) pyrrol-2-yl] methylene} -3-ethoxy-2pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - [(l-pyrolidinylmetylpyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (piperidinometylpyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 - [(4-Dietanolaminometyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 - [(3-dimethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 201 3-Ethoxy-4 - [(3-morpholinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(3-Diethylaminomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 3-Ethoxy-4 - {[3- (4-methyl ~ l-piperazinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} 2-pyrazolin-5-one, 3-Ethoxy-4 - {[3- (I-pyrrolidinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Ethoxy-4 - [(3-piperidinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3-ethoxy 2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimetylaminometylpyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 3-Ethoxy-4 - [(4-oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 3-Ethoxy-4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethoxycarbonylpyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one; 4- [4- (2-Dimethylaminoethylaminocarbonylpyrol-2-yl) methylene] -3-ethoxy- 2-pyrazolin-5-one, 4 - [(3-Ethoxycarbonylindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4- [3- (2-Dimetylaminoetylaminokarbonylindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 3-Ethoxy-4- [4- (4-morfolinoetoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxy-4- [4- (4-morfolinoetylaminokarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxy-4- [3- (4-morfolinoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxy-4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3-ethoxy-2-pyrazolin-5-one,, 3-Ethoxy-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one; 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3-ethoxy-2-pyrazolin-5-one, 4 - {[3- (2-amino-2-carboxyethyl) indol-2-yl] methylene} -3-ethoxy-2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3-ethoxy-2pyrazolin-5-one, 4 - [(3-Dimethylaminomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 202 4 - [(3-morpholinomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3-Dietylarninometyl-4,5-tetrametylénpyrol-2-yl) methylene] -3-pyrazinyl "2-pyrazolin-5-one, 4 - {[3- (4-methyl-l-piperazinylmethyl) -4,5-tetrametyIénpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 3-Pyrazinyl-4 - {[3- (1-pyridinyl) methyl-4,5-tetramethylene-pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4 - [(3-Piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindole) -2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one; 4 - [(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5 -one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-bromopyridin-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-chloropyridin-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(5-chloropyridin-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 3-Pyrazinyl-4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4- [4- (2-Dimetylaminoetoxykarbonylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4- [4- (2-Dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4- [3- (2-Dimetylaminoetylaminokarbonylindol-2-yl) methylene] -3-pyrazinyl'2-pyrazoline-5-one, 4- [4- (4-MorfolinoetoxykarbonylpyroI-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4- [4- (4-MorfolinoetylaminokarbonylpyroI-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one ,. 4- [3- (4-MorfolinoetoxykarbonyIindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4- [3- (4-Morfolinoetylaminokarbonylindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-etoxykarbonylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrol-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(l-methyl-indol-3-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 3-Pyrazinyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 203 4 - [(Indol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,4-Dietoxykarbonylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazoIin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3- (2-amino-2-carboxyethyl) indol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-õhu, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3-pyrazinyl-2 pyrazolin-5-one, 4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) p-ethylene] -3-pyrazinyl-2 pyrazolin-5-one, 4 - [(4-BrómpyroI-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4 - [(4-chloropyridin-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4 - [(5-chloropyridin-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 3- (imidazol-2-yl) -4 - [(5-trifluoromethylpyrrole-2-yl) methylene] -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4 - [(4-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4- [4- (2-Dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] -3- (imidazol-2-yl) 2-pyrazolin-5-one, 4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4- [3- (2-Dimetylaminoetylaininokarbonylindol-2-yl) methylene] -3- (imidazol-2-yl) 2-pyrazolin-5-one, 3- (imidazol-2-yl) -4- [4- (4-morfolinoetoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (imidazol-2-yl) -4- [4- (4-morfolinoetylaminokarbonylpyrol-2-yl) methylene] -2-pyrazoline ₁ 5-one, 3- (imidazol-2-yl) -4- [3- (4-morfblinoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4- [3- (4-morpholinoethylaminocarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4- [(5-m.etoxyindol-2-yl) methylene] -2-pyrazolin-5-one, 204 3- (Imidazol-2-yl) -4 - [(4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3 (imidazol-2-yl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 3- (imidazol-2-yl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (imidazol-2-yl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (Imidazol-2-yl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one; 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) -4- [(3,4-diethoxycarbonylpyrrol-2-yl) methylene] -3- (imidazol-2-yl)] - 2-pyrazolin-5-one ) indol-2-yl] methylene-} -3- (imidazol-2-yl) 2-pyrazolin-5-one, 4 - {[3- (2-amino-2-carboxyethyl) indol-2-yl] methylene} -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3- (imidazol-2-yl) -2-pyrazolin-5-one, 4 - [(4-bromopyridin-2-yl) methylene] -3- (l-methylcyclopropyl) -2-pyrazolin-5-one, 4 - [(4-chloropyridin-2-yl) methylene] -3- (l-methylcyclopropyl) -2-pyrazolin-5-one, 4 - [(5-ChIórpyrol-2-yl) methylene] -3- (l-methylcyclopropyl) -2-pyrazolin-5-one, 3- (1-Methylcyclopropyl) -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one; 4- [4- (2-Dimethylaminoethoxycarbonylpyrol-2-yl) methylene] -3- (l-methylcyclopropyl) 2-pyrazolin-5-one, 4- [4- (2-Dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] -3- (l-metylcyklopiOpyI) 2-pyrazolin-5-one, 4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3- (l-methylcyclopropyl) -2-pyrazolin-5-one, 4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3- (l-methylcyclopropyl) 2-pyrazolin-5-one, 4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 3- (1-Methylcyclopropyl) -4- [4- (4-morpholinoethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 205 3- (l-methylcyclopropyl) -4- [4- (4-morfolinoetylaminokarbonylpyrol-2-yl) methylene] 2-pyrazolin-5-one, 3- (l-methylcyclopropyl) -4- [3- (4-morfolinoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin5-one, 3- (1-methylcyclopropyl) -4- [3- (4-morpholinoethylaminocarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 3- (1-Methylcyclopropyl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 4 - [(5-methoxy-indol-2-yl) methylene] -3- (l-methylcyclopropyl) -2-pyrazolin-5-one, 3- (1-Methylcyclopropyl) -4 - [(4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrol-2-yl) methylene] -3- (lmetylcyklopropyl) -2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3- (l-methylcyclopropyl) -2-pyrazolin-5-one, 4 - [(pyrrol-2-yl) methylene] -3- (l-methylcyclopropyl) -2-pyrazolin-5-one, 4 - [(Indol-2-yl) methylene] -3- (l-methylcyclopropyl) -2-pyrazolin-5-one, 4 - [(3,4-Dietoxykarbonylpyrol-2-yl) methylene] -3- (l-methylcyclopropyl)) - 2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene-} -3 (l-methylcyclopropyl) 2-pyrazolin-5-one, 4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrol-2-yl) methylene] -3- (1-methylcyclopropyl) -2-pyrazolin-5-one, 4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3- (lmetylcyklopropyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (4-methyl-l-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (2-furyl) 2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (l-pyrrolidinylmethyl) pyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 206 4 - [(3,5-Dimethyl-4-piperidinometylpyrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(4-Dietanolaminometyl-3,5-dimethyl-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(3-dimethylaminomethyl-4,5-tetrametyIénpyrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 3- (2-Furyl) -4 - [(3-morpholinomethyl-4,5-tetramethylene-pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(3-Diethylaminoethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 3- (2-Furyl) -4 - {[3 - (4-methyl-l-piperazinylmethyl) -4,5-tetrametylénpyrol-2-yl] methylene} 2-pyrazolin-5-one, 3- (2-Furyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylene-pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3- (2-Furyl) -4 - [(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminoethyl-3) 5'-dimethylpyrrol-2-yl) methylene] -3- (2-phthyl) -2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxybenzylidene) -3- (2-furyl) - 2-pyrazolin-5-one, 3- (2-furyl) -4 - [(4-oxo-l, 5,6,7-tetrahydro-indole-2-yl) methylene] -2-pyrazolin-5-one, 3- (2-Furyl) -4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Bromopyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(4-chloropyridin-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(5-chloropyridin-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 3- (2-Furyl) -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4- [4- (2-Dimetylaminoetoxykarbonylpyrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4- [4- (2-Dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4- [3- (2-Dimetylaminoetylaminokarbonylindol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 3- (2-furyl) -4- [4- (4-morfolinoetoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2-furyl) -4- [4- (4-morfolinoetylaminokarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2-furyl) -4- [3- (4-morfolinoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2-Furyl) -4- [3- (4-morpholinoethylaminocarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 207 3- (2-Furyl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 3- (2-Furyl) -4 - [(5- methoxyindole-2-yl) methylene] -2-pyrazolin-5-one, 3- (2-Furyl) -4 - [(4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrol-2-yl) methylene] -3- (2-furyl) 2-pyrazolin-5-όηιι, 3- (2-furyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (2-furyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2-Furyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-) 4 - [(3,4-diethoxycarbonylpyrrol-2-yl) methylene] -3- (3- (2-furyl)) - 2-pyrazolin-5-one methoxycarbonylethyl) indol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[3- (2-amino-2-carboxyethyl) indol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3- (2-furyl) 2-pyrazolin-5-one, 4 - [(5-chloro-4-metoxykarbonyImetyl-3-methoxycarbonylpyridin-2-yl) methylene] -3- (2-furyl) 2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - [(morfolinometylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (4-methyl-l-piperazinyl) methyl-pyrrole-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (l-pyrolidinylmetylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazoIin-5-one, 4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-piperidinometylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-Dietanolaminometyl-3,5-dimethyl-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3-dimethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3-morpholinomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3-diethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[3- (4-methyl-l-piperazinylmethyl) -4,5-tetrametylénpyrol-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one, 208 4 - {[3- (1-Pyrrolidinylmethyl) -4,5-tetramethylenopyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3-piperidinomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-diethylamino-ethyl-3,5-dimethyl-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-Oxo-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-dimethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-bromopyridin-2-yl) methylene] -3- (2-ttenyl) -2-pyrazolin-5-one, 4 - [(4-chloropyridin-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(5-chloropyridin-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 3- (2-Thienyl) -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- [4- (2-Dimetylaminoetoxykarbonylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- [4- (2-Dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- [3- (2-Dimetylaminoetylaminokarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- [4- (4-Morfolinoetoxykarbonylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- [4- (4-Morfolinoetylaminokarbonylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- [3- (4-Morfolinoetoxykarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- [3- (4-Morfolinoetylaminokarbonylindol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethyl pyrrole-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(l-methyl-indol-3-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4- [3,5-dimethyl-4-etoxykarbonylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(5-methoxy-indol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4,5-TetrametyIénpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimetylaminoetoxykarbonyl) pyrrol-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrol-2-yl] methylene} -3- (2-thienyl) -2pyrazoIin-5-one, 209 4 - [(indol-3-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(pyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(Indol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3,4-Dietoxykarbonylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[3- (2-amino-2-carboxyethyl) indol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-bromopyridin-2-yl) methylene] -3-cyclopropoxy-2-pyrazolin-5-one, 4 - [(4-chloropyridin-2-yl) methylene] -3-cyclopropoxy-2-pyrazolin-5-one, 4 - [(5-Chloro-pyrrol-2-yl) -methylene] -3-cyclopropoxy-2-pyrazolin-5-one, 3-cyclopropyloxy-4 - [(5-trifluoromethylpyrrole-2-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropyloxy-4 - [(4-etoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropoxy-4- [4- (2-dimetylaminoetoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropoxy-4- [4- (2-dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] -2-pyrazolin 5th, ’ 3-cyclopropyloxy-4 - [(3-ethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropoxy-4- [3- (2-dimetylaminoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropoxy-4- [3- (2-dimetylaminoetylaminokarbonylindol-2-yl) methylene] -2-pyrazolin 5-one, · 3-cyclopropoxy-4- [4- (4-morfolinoetoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropoxy-4- [4- (4-morfolinoetylaminokarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropoxy-4- [3- (4-morfolinoetoxykarb'onylindol-2-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropoxy-4- [3- (4-morfolinoetylaminokarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropyloxy-4 - [(3,5-dimethyl-4-ethyl pyrrole-2-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropyloxy-4 - [(l-methyl-indol-3-yl) methylene] -2-pyrazolin-5-one, 210 3-cyclopropoxy-4- [3,5-dimethyl-4-etoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-CykIopropoxy-4 - [(5-methoxyindol-2-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropyloxy-4 - [(4,5-tetrametylénpyrol-2-yl) rnetylén] -2-pyrazolin-5-one, 3-Cyclopioxy-4 - {[3,5-dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-cyclopropyloxy-4 - {[3,5-Dimethyl-4- (2-dimetylaminoetylamÍnokarbonyl) pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropyloxy-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropyloxy-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropyloxy-4 - [(Indol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropoxy-4 - [(3,4-diethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3-cyclopropoxy-2-pyrazolin-5-one, 4 - {[3- (2-amino-2-carboxyethyl) indol-2-yl] methylene} -3-cyclopropoxy-2-pyrazolin-5-one, 3-Cyclopropoxy-4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3-cyclopropoxy-2-pyrazolin-5-one, 4 - [(4-bromopyridin-2-yl) methylene] -3- [2- (5-pyrimidinyletyI)] - 2-pyrazolin-5-one, 4 - [(4-chloropyridin-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one, 4 - [(5-chloropyridin-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one, 3- [2- (5-pyrimidinylethyl)] - 4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one; 4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene ] -3- [2- (5-pyrimidinylethyl)] - 2pyrazolin-5-one, 4- [4- (2-Dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2pyrazolin-5-one, 4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one, 4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2pyrazolin-5-one, 4- [3- (2-Dimetylaminoetylaminokarbonylindol-2-yl) methylene] -3- [2- (5-pyriniidinyletyI)] - 2pyrazolin-5-one, 211 4- [4- (4-Morfolinoetoxykarbonylpyrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2pyrazolin-5-one, 4- [4- (4-Morfolinoetylaminokarbonylpyrol-2-yl) methylene] -3- [2- (5-pyrimidinyIetyl)] - 2pyrazolin-5-one, 4- [3- (4-Morpholinoethoxycarbonylindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazoline 5th zone, 4- [3- (4-MorfblinoetylaminokarbonyIindol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethyl pyrrole-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one, 4 - [(l-methyl-indol-3-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one, 4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazoline 5th zone, 4 - [(5-methoxy-indol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one, 3- [2- (5-pyrimidinylethyl)] - 4 - [(4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrol-2-yl) methylene] -3- [2- (5pyrimidinyletyl)] - 2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one, 3- [2- (5-pyrimidinylethyl)] - 4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(Indol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one, 4 - [(3,4-Dietoxykarbonylpyrol-2-yl) methylene] -3- [2- (5-pyrimidinylethyl)] - 2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- [2- (5-pyrimidinylethyl)] 2-pyrazolin-5-one, 4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- [2- (5-pyrimidinylethyl)] - 2-pyrazoline · 5th zone, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3- [2- (5pyrimidinyletyl)] - 2-pyrazolin-5-one, 4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3- [2- (5pyrimidinyletyl)] - 2-pyrazolin-5-one, 4 - [(4-bromopyridin-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - [(4-chloropyridin-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - [(5-chloropyridin-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 212 3- (2-Phenylethyl) -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4- [4- (2-Dimetylaminoetoxykarbonylpyrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazoline 5th zone, 4 - [(3-EtoxykarbonylindoI-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4- [3- (2-Dimetylaminoetoxykarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazoline 5th zone, 4- [4- (4-Morfolinoetoxykarbonylpyrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4- [4- (4-Morfolinoetylaminokarbonylpyrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4- [3- (4-Morfolinoetoxykarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4- [3- (4-Morfolinoetylaminokarbonylindol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - [(l-methyl-indol-3-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4- [3,5-dimethyl-4-etoxykarbonylpyrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - [(5-methoxy-indol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 3- (2-Phenylethyl) -4 - [(4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimethylaminoethylaminocarbonyl) pyrrol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one,> 4 - [(Indol-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - [(3,4-DiétoxykarbonyIpyroI-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- (2-phenylethyl) 2-pyrazolin-5-one, 4 - {[3- (2-amino-2-carboxyethyl) indol-2-yl] methylene} -3- (2-phenylethyl) -2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-metoxykarbonylmetyI-3-methoxycarbonylpyridin-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazolin-5-one, 213 4 - [(5-chloro-4-metoxykarbonylrnetyl-3-methoxycarbonylpyridin-2-yl) methylene] -3- (2-phenylethyl) -2-pyrazol-in-5-one, 4 - [(4-bromopyridin-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4 - [(4-chloropyridin-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4 - [(5-chloropyridin-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 3- [2- (4-hydroxyphenyl) ethyl] -4 - [(5-trifluoromethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Ethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] 2-pyrazolin-5-one, 4- [4- (2-Dimethylaminoethylaminocarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4 - [(3-ethoxycarbonylindol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4- [3- (2-DimetyIaminoetoxykarbonylindol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] 2-pyrazolin-5-one, 4- [3- (2-Dimethylaminoethylaminocarbonylindol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 3- [2- (4-hydroxyphenyl) ethyl] -4- [4- (4-morpholinoethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-hydroxyphenyl) ethyl] -4- [4- (4-morfolinoetylaminokarbonylpyrol-2-yl) methylene] 2-pyrazolin-5-one, 3- [2- (4-hydroxyphenyl) ethyl] -4- [3- (4-morfolinoetoxykarbonylindol-2-yl) methylene] 2-pyrazolin-5-one, 3- [2- (4-hydroxyphenyl) ethyl] -4- [3- (4-morpholinoethylaminocarbonylindol-2-yl) methylene] -2-pyrazolin-5-one; ·, Í · 4- [3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) phenyl] -2-pyrazolin-5-one, 3- [2- (4-hydroxyphenyl) ethyl] -4 - [(5-methoxy-indol-2-yl) methylethyl] -2-pyrazolin-5-one, 3- [2- (4-hydroxyphenyl) ethyl] -4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4 - {[3,5-dimethyl] -4- (2-dimetylaminoetylaminokarbonyl) pyiOl-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 214 4 - [(3,4-Dietoxykarbonylpyrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4 - {[3- (2-amino-2-carboxyethyl) indol-2-yl] methylene} -3- [2- (4-hydroxyphenyl) ethyl] 2-pyrazolin-5-one, 4 - [(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyridin-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 4 - [(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -3- [2- (4-hydroxyphenyl) ethyl] -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4 - [(4-Bromo-pyrrol-2-yl) nietylén] -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4 - [(4-chloropyrrole-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4 - [(5-chloropyrrole-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4 - [(5-trifluórmetylpyroI-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4 - [(4-etoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4- [4- (2-dimetylaminoetoxykarbonylpyrol-2-yl) methylene] 2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4- [4- (2-dimetylaminoetylaminokarbonylpyrol-2-yl) methylene] 2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4 - [(3-ethoxycarbonylindol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4- [3- (2-dimetylaminoetoxykarbonylindol-2-yl) methylene] 2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4- [3- (2-dimetylaminoetylaminokarbonylindol-2-yl) methylene] 2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4- [4- (4-morpholinoethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4- [4- (4-morfolinoetylaminokarbonylpyrol-2-yl) methylene] 2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4- [3- (4-morfolinoetoxykarbonylindol-2-yl) methylene] -2-pyrazolin5-one, 3- [2- (4-aminophenyl) ethyl] -4- [3- (4-morfolinoetylaminokarbonylindol-2-yl) methylene] 2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4 - [(5-methoxy-indol-2-yl) methylene] -2-pyrazolin-5-one, 215 3- [2- (4-aminophenyl) ethyl] -4 - [(4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] 4 - {[3,5-dimethyl-4- (2-dimethylaminoethoxycarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4 - {[3,5-dimethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4 - [(3,4-diethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - {[3- (2-Acetamido-2-methoxycarbonylethyl) indol-2-yl] methylene} -3- [2- (4-aminophenyl) ethyl] -2-pyrazolin-5-one, 4 - {[3- (2-Amino-2-carboxyethyl) indol-2-yl] methylene} -3- [2- (4-aminophenyl) ethyl] -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4 - [(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- [2- (4-aminophenyl) ethyl] -4 - [(5-chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morpholinomethyl-pyrrol-2-yl) -methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - {[(4-methyl-l-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (4-pyrimidinyl) 2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (piperidinometylpyrol-2-yl) methylene] -3- (4-pyrimidinyl-2-pyrazolin-5-one, 4 - [(4-Dietanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3-dimethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (4-pyrimidinyl) 2-pyrazolin-5-one, 4 - [(3-Morpholinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one. 216 4 - [(3-diethylaminomethyl-4,5-tetrametyIénpyrol-2-yl) methylene] -3- (4-pyrimidinyl) 2-pyrazolin-5-one, 4 - {[3- (4-methyl-l-piperazinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 3- (4-Pyrimidinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenepyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4 - [(3-Piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazoline 5th zone, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (4-pyrimidyl) pyrazolin-5-one, 4 - [(4-diethylamino-ethyl-3,5-dimethyl-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazoIin-5-one, 4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-oxo-l, 5,6,7-tetrahydro-indole-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-dimethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-dimethyl-4-morfblinometylpyrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one; 4 - [(3,5-Dimethyl-4-dÍetylaminometylpyrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (piperidinometylpyrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Dietanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one. 217 4 - [(3-Morpholinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazoline 5th zone, 4 - [(3-diethylaminomethyl-4,5-tetrametylénpyroI-2-yl) methylene] -3- (5-pyrimidinyl) 2-pyrazolin-5-one, 4 - {[3- (4-methyl-l-piperazinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} -3- (5pyrimidinyl) -2-pyrazolin-5-one, 3- (5-Pyrimidinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenepyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4 - [(3-Piperidinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazoline 5th zone, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazoline 5th zone, 4 - [(4-diethylamino-ethyl-3,5-dimethyl-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-oxo-l, 5,6,7-tetrahydro-indole-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-dimethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - {[(4-methyl-l-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (2-pyrimidinyl) 2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3,5-dimetylpyroI-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (piperidinometylpyrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Dietanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazoline Of the 5th zone. 218 4 - [(3-Dimethylaminomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3-Morpholinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazoline 5th zone, 4 - [(3-diethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (2-pyrimidinyl) 2-pyrazolin-5-one, 4 - {[3- (4-methyl-l-piperazinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 3- (2-Pyrimidinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenopyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4 - [(3-Piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazoline 5th zone, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazoline 5th zone, 4 - [(4-diethylamino-ethyl-3,5-dimethyl-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimethylaminomethyl-pyrrol-2-yl) -methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-oxo-l, 5,6,7-tetrahydroindoI-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-dimethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (3 pyridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (l-pyrolidinylmetylpyrol-2-yl) methylene] -3- (3-pyridazinyl) 2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-piperidinometylpyrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 219 4 - [(4-Dietanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3-dimethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (3-pyridazinyl) 2-pyrazolin-5-one, 4 - [(3-Morpholinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3-diethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (3-pyridazinyl) 2-pyrazolin-5-one, 4 - {[3- (4-methyl-l-piperazinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} -3- (3pyridazinyl) -2-pyrazolin-5-one, 3- (3-Pyridazinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenopyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4 - [(3-Piperidinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-diethylamino-ethyl-3,5-dimethyl-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-oxo-l, 5,6,7-tetrahydro-indole-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-dimethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-Dietylaminornetyl-3,5-dimethyl-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one. 220 4 - [(3,5-Dimethyl-4- (piperidinometylpyrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-Dietanolaminomethyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3-dimethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (4-pyridazinyl) 2-pyrazolin-5-one, 4 - [(3-Morpholinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3-diethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (4-pyridazinyl) 2-pyrazolin-5-one, 4 - {[3- (4-Methyl-1-piperazinyl) methyl-4,5-tetramethylenepyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 3- (4-Pyridazinyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenopyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4 - [(3-Piperidinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-diethylamino-ethyl-3,5-dimethyl-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-oxo-l, 5,6,7-tetrahydro-indole-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-dimethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - {[(4-methyl-l-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (5-isoxazolyl) 2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - [(l-pyrolidinylmetylpyrol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (5-izoxazoIyl) -2-pyrazolin-5-one. 221 4 - [(4-Dietanolaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one, 4 - [(3-dimethylaminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] -3- (5-isoxazolyl) 2-pyrazolin-5-one, 3- (5-isoxazolyl) -4 - [(3-morpholin] aminomethyl-4,5-tetrametylénpyrol-2-yl) methylene] ^{-2-pyrazolin-5-one-one,} 4 - [(3-Diethylaminomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one, 3- (5-Isoxazolyl) -4 - {[3- (4-methyl-1-piperazinyl) methyl-4,5-tetramethylene-pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3- (5-isoxazolyl) -4 - {[3- (1-pyrrolidinyl) methyl-4,5-tetramethylenopyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3- (5-isoxazolyl) -4 - [(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one, 4 - [(4-diethylamino-ethyl-3,5-dimethyl-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (5-isoxazolyl) -2-pyrazolin-5-one, 4 - [(4-oxo-l, 5,6,7-tetrahydro-indole-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one, 4 - [(4-dimethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (5-izoxazoIyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) 2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - {[(4-methyl-1-piperazinylmethyl) pyrrol-2-yl] methylene} -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4 - [(1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) 2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-piperidinometylpyrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) 2-pyrazolin-5-one, 4 - [(4-Dietanolaminometyl-3,5-dimethyl-pyrrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) 2-pyrazolin-5-one. 222 4 - [(3-Dimethylamino-n-methyl-4,5-tetrarnethylene-pyrrol-2-yl) -methylene] -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one, 3- (5-Methyl-3-isoxazolyl) -4 - [(3-morpholinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one, 3- (5-methyl-3-isoxazolyl) -4 - {[3- (4-methyl-l-piperazinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} -2-pyrazolin-5-one, 3- (5-methyl-3-isoxazolyl) -4 - {[3- (l-pyrrolidinyl) methyl-4,5-tetrametylénpyrol-2-yl] methylene} 2-pyrazolin-5-one, 3- (5-Methyl-3-isoxazolyl) 4 - [(3-piperidinomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one, 4 - [(4-diethylamino-ethyl-3,5-dimethyl-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) 2-pyrazolin-5-one, 4- (3,5-Dibromo-4-hydroxy-benzylidene) -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimetylaminometylpyrc> l-2-yl) methylene] -3- (5-methyl-3-izoxazoIyl) 2-pyrazolin-5-one, 3- (5-Methyl-3-isoxazolyl) -4 - [(4-oxo-1,5,6,7-tetrahydroindol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Dimethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (5-methyl-3-isoxazolyl) -2-pyrazolin-5-one, 3-cyclopropyl-4- (1-3-[(dimethylamino) methyl] -4,5,6,7-tetrahydro-1H-2-indolylmethylidene) 4,5-dihydro-1H-5-pyrazolone, . . 3-cyclopropyl-4- (1-4 - [(1,1-dimethylammonio) methyl] -3,5-dimethyl-1H-2-pyrrolylmethylidene) -4,5-dihydro-1H-5-pyrazolone maleate salt . 4- [1- (4 - [[2- (dimethylamino) ethyl] (methyl) amino] methyl-3,5-dimethyl-1H-2-pyrrolyl) methylidene] 3- (2-pyrazinyl) -4, 5-dihydro-l // - 5-pyrazolone, 4- (1- 4- [2- (diethylamino) ethyl] -3,5-dimethyl-1H-2-pyrrolylmethylidene) -3- (2-pyrazinyl) -4,5-dihydro-1H-pyrazolone . 4- 1- [4- (3-chloropropanoyl) -3,5-dimethyl-1H-2-pyrrolyl] methylidene-3- (2-pyrazinyl) -4,5-dihydro-1H-5-pyrazolone, 223 4- (1-3 - [(dimethylamino) methyl] -4,5,6,7-tetrahydro-l // - 2-indolylmetylidén) -3- (2-pyrazinyl) -4,5-dihydro-5-IA pyrazolone, 4- (l-4 - [(dimethylamino) methyl] -3,5-dimethyl-l // - 2-pyrolylmetylidén) -3- (5-methyl-3izoxazolyl) -4,5-dihydro-177-5-pyrazolone . 3-Cyclopropyl-4 - [(4,5-dimethyl-2-yl) methylene] -2-pyrazolin-5-one, 3-benzyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-MetoxyfenyloxymetyI) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Phenyloxymethyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Chlórfenyloxymetyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-methoxybenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Benzyl-4 - {[4- (2-carboxyethyl) -3-methylpyrrole-2-yl] methylene} -2-pyrazolin-5-one, 3-Benzyl-4 - {[3- (2-carboxyethyl) -4-methylpyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3- (4-Methylphenyloxymethyl) -4 - [(pyrrole-2) yl) methylene] -2-pyrazoIin-5-one, 2-Amino-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Isopropoxy-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-phenyl-ethyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-phenylamino-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-methylbenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-methyl-phenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-methoxy-phenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-chlorobenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Chlórfenylamind) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (3-Chlórfenyloxymetyl) -4 - [(pyrrol-2-yl) methylene-] -2-pyrazolin-5-one, 3- (indol-3-yl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (3-methoxybenzyl) -4 -. [(Pyrrol-2-yl) methylene-] -2-pyrazolin-5-one, 3- (3,4-dimethoxybenzyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-methoxyphenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Fenylfenyloxymetyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2-phenyl-propyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (3-phenyl-propyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Hydroxyphenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(3,5-Dimethylpyrrol-2-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one, 3- (4-methylphenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 224 4 - [(3,5-Dimethyl-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3-Ethoxy-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-nitrophenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-fluoro-phenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Chloro-phenylethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4,5-Dimethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethyl pyrrole-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethyl pyrrole-2-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one, 4 - {[1- (4-Hydroxybutyl) pyrrol-2-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one, 3-Cyclopentyloxy-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-7erc-Butyl-ureido-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-isopropoxy-4 - [(4-methylpyrrole-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-aminophenylethyl) -4 - [(4-methylpyrrolidin-2-yl) methylene] -2-pyrazolin-5-one, 3-isopropoxy-4 - [(l-methylpyrrole-2-yl) methylene] -2-pyrazolin-5-one, 3-isopropoxy-4 - [(5-methylpyrrole-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-aminophenylethyl) -4 - [(3,5-dimethyl-4-ethyl pyrrole-2-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxy-4 - [(5-methylpyrrole-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Carbamoyl-phenylethyl) -4 - [(3,5-dimethyl-4-ethylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (4-methoxycarbonylphenylethyl-2-pyrazolin-5-one), 4 - [(3,5-Dimethyl-4-etoxykarbonylpyrol-2-yl) methylene] -3-isopropoxy-2-pyrazoIin-5-one, 3- (4-Aminophenylethyl) -4 - [(3,5-dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolinone, 4 - [(5-Ethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-etyIpyrol-2-yl) rnetylén] -3- (4-hydroxyphenylethyl) -2-pyrazolin-5-one, 3- (ethoxycarbonylmethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Methoxyphenylaminocarbonylmethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - {(3- (2-Carboxyethyl) -4-methylpyrrol-2-yl] methylene} -3-isopropyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(pyrrol-2-yl) methylene 2-Pyrazolin-5-one, 3-Cyclobutyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (3-Pyridyl) -4 - [(pyrrol-2) yl) methylene] -2-pyrazolin-5-one, 3- Cyclopropyl-4 - [[1- (3,5-dichlorophenyl) pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(Pyrol-2-yl) methylene] -3- (2,2,3,3-tetramethylcyclopropyl) -2-pyrazolin-5-one, 225 3-Cyclopropyl-4 - [(3,5-dimethyl-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopentyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2-Methylcyclopropyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4- (Benzothiazol-2-yl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4,5-Dimethyl-2-yl) methylene] -4- (3-pyridyl)] - 2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3,5-dimethyl-4-ethyl pyrrole-2-yl) methylene] -2-pyrazolin-5-one, 3- (pyrrol-2-yl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-methylpyrrole-2-yl) methylene] -2-pyrazolin-5-one, 3- (Benzothiazol-2-yl) -4 - [(4-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(3,5-Dimethylpyrrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4- [3,5-dimethyl-4-ethyl pyrrole-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-onii, 3-Cyclopropyl-4 - [(5-methylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(5-Methylpyrrol-2-yl) methyl] -3- (3-pyridyl) -2-pyrazolin-5-one, 3-C'yklopropyl-4 - [(5-ethyl pyrrole-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3,5-dimethyl-4-etoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-isopropoxy-4 - [(5-phenyl-pyrrol-2-yl) methylene] -2-pyrazoIin-5-one, 3-Propyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-methyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-isopropyl-phenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (3-phenylamino) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[1- (4-hydroxybutyl) pyrrol-2-yl] methylene] -2-pyrazolin-5-one, 4 - [[4- (2-Carboxyethyl) -3-methylpyrrol-2-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one, 4 - [(4-Carboxy-3,5-dimethylpyrol-2-yl) ) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3-Isopropoxy-4 - [(4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) ) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(4-Acetyl-3,5-dimethyl-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimetylaminoetyloxykarbonyl) pyrrol-2-yl] methylene} -3-isopropoxy-2pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrol-2-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one, 4 - [(5-Etoxykarbonylpyrol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 226 4 - [(5-carboxypyrrol-2-yl) methylene] -3-isopropoxy-2-pyrazoIin-5-one, 3- (4-Chlórfenylaminokarbonylmetyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(5-phenylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethylpyrrol-2-yl) methylene] -3- (tetrahydrofuran-3-yl) -2-pyrazolin-5-one, 4 - [(4-Carboxy-3,5) -dimethylpyrol-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one, 4 - [(3,5-dimethyl-4-ethoxycarbonylpyrol-2-yl) methylene] -3- (3-pyridyl) 2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3,5-dimethyl-4-morpholinomethyl-pyrrol-2-yl) -methylene] -2-pyrazolin-5-one, 4 - [(3,4-dimethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-carboxyethyl) -3-methylpyrrole-2-yl] methylene} -3-cyclopropyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3,5-dimethyl-4-dimetylaminometylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(5-etoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4,5-tetrametylénpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (2-methoxycarbonyl-ethyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-ethoxycarbonyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Isopropyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (trans-2-phenylcyclopropyl) -4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclohexyl-4 - [(pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-cyclopropylamino-4 - [(4,5-tetrametylénpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(5-morpholinomethyl-pyrrol-2-yl) -methylene] -2-pyrazolin-5-one, 4 - [(5-Carboxypyrol-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one, 4 - [(4-chloropyridin-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 - [(4-bromopyridin-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 - [(5-chloropyridin-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 [(4-chloropyridin-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one, 4 - [(4-bromopyridin-2-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one, 3-Pyrazinyl-4 - [(4,5-tetrametylénpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3- (3-Pyridyl) -4 - [(4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Carboxy-3,5-dimethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[3,5-dimethyl-4- (2-dimethylaminoethyloxycarbonyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimethylaminoethyloxycarbonyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 227 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one maleate salt of 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2) yl) methylene] -3-pyrazinyl-2pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-morfolinoetylaminokarbonyl) pyrrol-2-yl] methylene-3-pyrazinyl-2pyrazolin-5-one, 4 - [(3,5-Dimethyl-2-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethyl pyrrole-2-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5-one, 4 - [(4,5-tetrametylénpyrol-2-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5-one, 4 - [(3,5-dimethyl-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(3,5-dimethyl-4-morfolinometylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-dimethylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-etoxykarbonylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3,5-dimethyl-4-trifluoroacetamidomethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-aminomethyl-3,5-dirnetylpyroI-2-yl) methylene] -2-pyrazoIin-5-one, 3- (benzothiazol-2-yl) -4 - [(3,5-dimethyl-2-yl) methylene] -2-pyrazolin-5-one, 3- (Benzothiazol-2-yl) -4 - [(3,5-dimethyl-4-morpholinomethylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-Etoxykarbonylpyrol-2-yl) methylene-] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-carboxypyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dietanolaminometylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-trifluóracetamidometyIpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazoIin-5-one, 3-Cyclopropyl-4 - [(4-ethoxycarbonyl-3-phenylpyrrol-2-yl) methylene] -2 'pyrazolin-5-one, ¹ 4 - {[3,5-Dimethyl-4- (1-pyrrolidinylmethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimetylamÍnometylpyrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimetylaminometylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimetylaminometylpyrol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-etoxykarbonylpyrol-2-yl) methylene] -3-phenyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethyl pyrrole-2-yl) methylene] -3-phenyl-2-pyrazolin-5-one, 228 4 - [(3,4-di (ethoxycarbonyl) pyrrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 3-Ethoxy-4 - [(4-ethoxycarbonylpyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (2-pyridylethyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3- (1-methyl-2-phenylethyl) -2-pyrazolin-5-one, 4 - [(4-Carboxy-3,5-dimethyl-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 3-Ethoxy-4 - [(5-nitro-pyrrol-2-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxy-4 - [(4-nitropyrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(4-Carboxypyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimetylaminoetylaminokarbonyl) pyrrol-2-yl) methylene} -3-ethoxy-2pyrazolin-5-one, 4 - [(5-chloro-3-methoxycarbonyl-4-metoxykarbonylmetylpyrol-2-yl) methylene] -3-ethoxy-2pyrazolin-5-one, 4 - {[3- (2-carboxyethyl) -4-methylpyrrol-2-yl] methylene} -3-ethoxy-2-pyrazolin-5-one, 4 - {[(3,5-Dimethyl-4-ethoxycarbonylpyrrole) 2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 3-Ethoxy-4 - [(4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) methylene] -3-trifluoromethyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl) Methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one; 3- (3-Aminophenyl) -4 - [(3,5-Dimethyl-4-ethoxycarbonylpyrol-2-yl) methylene] -2 pyrazoline-5-one, 3-Ethoxy-4 - {[2- (4-morpholinoethyl) aminocarbonylpyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4 - {[4- (4-Methyl-1-piperazinylmethyl) -3,5] - [(4-ethoxycarbonyl-3-phenylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one Dimethylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-piperidinometylpyról-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-piperidinometylpyrol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimetyIaminometylpyrol-2-yl) methylene] -3- (5-isoxazolyl) -2-pyrazolin-5-one, 4 - [(5-methyl-4-dimetylaminometylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazoIin-5-one, 4 - {{3,5-Dimethyl-4- [N- (2-dimethylaminoethyl) - N -methylaminomethylpyrrol-2-yl} -methylene} -3-pyrazinyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3-dimethylaminomethyl-4,5-tetramethylenopyrrol-2-yl) methylene] -2-pyrazolin-5-one, 229 4 - [(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3,5-dimethyl-4-dimethylaminomethylpyrrole) maleate salt -2-yl) methylene] -2-pyrazolin-5-one, 4 - {[4- (3-Chloropropionyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -3] 5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl) methylene] -3- (5- methyl-3-isoxazolyl) 2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (4-hydroxypiperidinomethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-Aminomethyl-3,5-) -, maleate salt dimethyl-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (4-Benzyl) methylpyrrole-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-hydroxyethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - {{3,5-dimethyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[3,5-dimethyl-4- (2-hydroxyethyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-ethylaminoethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (3-Diethylaminopropyl) - 3,5-dimethyl-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (3-hydroxypropyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-dimethyl-4) hydrochloride -dimethylaminoacetylpyrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4-dimetylaminoacetylpyrol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[(2-diethylaminoethyl) -3,5-dimethyl-4-pyrrol- _2'- yl] methylene} -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-dimethylaminoethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (4-hydroxybutyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (4-diethylamino-butyl) -3,5-dimethyl-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one. 230 4 - {[4- (2-diethylaminoethyl, / V-oxide) -3,5-dinnetylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[3,5-dimethyl-4- (l-pyrolidinylacetyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-Dietylaminoacetyl-3,5-dimethyl-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3-Isopropyl-5-methylpyrrole-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- [3- (1-pyrrolidinylpropyl)] pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(Dimethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(dimethylaminomethyl-3-isopropyl-5-methylpyrol-2-yl) methylene] -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-ethoxyoxalyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 3-Benzyl-4 - [(indol-3- yl) methylene] -2-pyrazolin-5-one, 3-Benzyl-4 - {[1- (4-hydroxybutyl) indol-3-yl] methylene} -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (4-methoxyphenyloxymethyl) -2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3-phenoxymethyl-2-pyrazolin-5-one, 3- (4-Chloro-phenyloxymethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (4-methoxybenzyl) -2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3- (4-metylfenyloxymetyl) -2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3- (4-methylbenzyl) -2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3-phenylamino-2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3- (4-methylphenylamino) -2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3- (4-methoxy-phenylamino) -2-pyrazolin-5-one, 3- (4-Chlorobenzyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4 - {[1- (4-hydroxybutyl) indol-3-yl] methylene) -3- (4-methoxybenzyl) -2-pyrazolin-5-one, 3- (4-Chloro-phenylamino) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (3-methoxybenzyl) -2-pyrazolin-5-one, 3- (3,4-dimethoxybenzyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (4-hydroxybenzyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (3-Chlórfenyloxymetyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (indol-3-yl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 231 4 - [(indol-3-yl) methylene] -3- (4-methoxyphenylethyl) -2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3- (4-fenyIfenyloxymetyl) -2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3- (2-phenylpropyl) -2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3- (3-phenylpropyl) -2-pyrazolin-5-one, 3- (4-Hydroxyphenylethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (4-methylphenylethyl) -2-pyrazolin-5-one, 3-Ethoxy-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one; 4 - {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -3-isopropoxy-2-pyrazolin-5-one, 4 - {[1- (4-Hydroxybutyl) indol-3-yl] methylene 3-Phenylethyl-2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (4-nitrophenylethyl) -2-pyrazolin-5-one, 4 - [(Indol-3) yl) methylene] -3-propoxy-2-pyrazolin-5-one, 3- (4-fluoro-phenylamino) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (4-aminophenylethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3-isopropoxy-4 - [(2-methyl-indol-3-yl) methylene] -2-pyrazolin-5-one, 3-Isopropoxy-4 - [(7-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 4 - [(7-Methylindol-3-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one, 3-Cyclopentyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3-Isopropoxy-4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (4-methoxycarbonylphenylethyl) -2-pyrazolin-5-one, 3-Isopropoxy-4 - [(1-isopropylindol-3-yl) methylene] -2- pyrazolin-5-one, 3- (4-Hydroxyphenylethyl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 3-Isopropyl-4 - [(indol-3-yl) (methylene) -2-pyrazolin-5-one, 3- (4-Chlorophenylaminocarbonylmethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxycarbonylmethyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (4-methoxyphenylaminocarbonylmethyl) -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one; 4 - [(Indol-3-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 3- (2-aminocarbonylethyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3-cyclobutyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (2-dimethylaminocarbonyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[1- (4-hydroxybutyl) indol-3-yl] methylene) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (4-pyridyl) -2-pyrazolin-5-one, 3-Cyclopentyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 232 4 - [(indol-3-yl) rnetylén] -3- (2,2,3,3-tetramethylcyclopropyl) -2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3- (2-methylcyclopropyl) -2-pyrazolin-5-one, 3-Cyclohexyl-4 - {[1- (4-hydroxybutyl) indol-3-yl] methylene} -2-pyrazolin-5-one, 4 - {[1- (4-Hydroxybutyl) indol-3-yl] methylene} -3- (4-pyridyl) -2-pyrazolin-5-one, 3- (Benzothiazol-2-yl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5-one, 3-Dimethylamino-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (pyrrol-2-yl) -2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3- (6-methoxy-benzothiazol-2-yl) -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(l-methyl-indol-3-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(7-methylindol-3-yl) methylene] -2-pyrazolin-5-one; 4 - [(1-Methylindol-3-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3-propyl-2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3-methyl-2-pyrazolin-5-one, 4 - [(indol-3-yl) methylene] -3-trifluoromethyl-2-pyrazolin-5-one, 4 - {[l- (4-hydroxybutyl) indol-3-yl] methylene} -2-pyrazolin-5-one, 4 - {[l- (4-hydroxybutyl) indol-3-yl] methylene} -3-methyl-2-pyrazolin-5-one, 4 - {[l- (4-HydiOxybutyl) indol-3-yl] methylene} -3-trifluoromethyl-2-pyrazolin-5-one 4 - {[l- (4-hydroxybutyl) indol-3-yl] methylene} -3- (tert-butyl) -2-pyrazolin-5-one, 3-Ethoxycarbonyl-4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (2-methoxycarbonylethyl) -2-pyrazolin-5-one, 4 - [(Indol-3-yl) methylene] -3- (trans-2-phenyl) -l-cyclopropyl) -2-pyrazolin-5-one, 3-Cyclobutyl-4 - {[1- (4-hydroxybutyl) indol-3-yl] methylene} -2-pyrazolin-5-one, 4 - [(6-Carboxy-1-methylindol-3-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(5-methoxy-1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 4 - [(1-Methylindol-3-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(1,7-dimethylindol-3-yl) methylene] -2-pyrazolin-5-one, 4 - [(1-Methylindol-3-yl) methylene] -3- (tetrahydrofuran-3-yl) -2-pyrazolin-5-one, 3-Cyclopropylamino-4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 4 - [(6-Carboxy-1-methylindol-3-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(1,7-Dimethylindol-3-yl) methylene] -3- izopiOpoxy-2-pyrazolin-5-one, 3-Isopropoxy-4 - [(5-methoxy-1-methylindol-3-yl) methylene] -2-pyrazolin-5-one; 3- (4-Fluorophenylamino) -4 - [(1-methylindol-3-yl) ) methylene] -2-pyrazolin-5-one, 233 4 - [(l-methyl-indol-3-yl) methylene] -3-trifluoroacetamido-2-pyrazolin-5-one, 3- (4-aminophenylethyl) -4 - [(l-methyl-indol-3-yl) methylene] -2-pyrazolin-5-one, 3-Amino-4 - [(l-methyl-indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (4-ChIórfenyletyl) -4 - [(indol-3-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxy-4 - [(l-methyl-indol-3-yl) methylene] -2-pyrazolin-5-one, 3- (5-Isoxazolyl) -4 - [(1-methylindol-3-yl) methylene] -2-pyrazolin-5-one, 4 - [(1-Methylindol-3-yl) methylene] -3- tert -butyl-2-pyrazolin-5-one, 4 - [(6-carboxy-l-methyl-indol-3-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{1-Methyl-6- [2- (4-morpholino) ethyl] aminocarbonylindol-3-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(Indol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3- (4-hydroxyphenylethyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-aminophenylethyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Metoxykarbonylfenyletyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 3- (4-Karbamoylfenyletyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3-dimethylaminomethylindol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(Indol-2-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 3-isopropoxy-4 - [(5-methoxy-indol-2-yl) methylene] -2-pyrazolin-5-one, 3-Isopropoxy-4 - [(1-methylindol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(Indol-2-yl) methylene] -3- (tetrahydrofuran-3-yl) -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(5-methoxy-indol-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(5-nitroindol-2-yl) methylene] -2-pyrazolin-5-one; 4 - [(Indol-2-yl) methylene] -3-isopropylamino-2-pyrazolin-5-one, 3- (4-Carboxyphenylethyl) -4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 4 - [(Indol-2-yl) methylene] -3-phenyl-2-pyrazolin-5-one, 3-isopropoxy-4 - [(3-methyl-indol-2-yl) methylene] -2-pyrazolin-5-one, 3-Isopropoxy-4 - {[3- (2-methoxycarbonyl-2-acetamidoethyl) indol-2-yl] methylene} -2-pyrazolin-5-one, 3-Ethoxy-4 - [(indol-2-yl) methylene] -2-pyrazolin-5-one, 3-Ethoxy-4 - {[3- (4-morpholinomethyl) indol-2-yl] methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[3- (4-morpholinomethyl) indol-2-yl] methylene} -2-pyrazolin-5-one, 4 - [(5-Methoxyindol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 234 4 - [(5-methoxy-indol-2-yl) methylene] -3- (2-pyridyl) -2-pyrazolin-5-one, 4 - [(4-chloro-6,7-dihydro-indol-2-yl) methylene-] -3-ethoxy-2-pyrazolin-5-one, 4 - [(4-chloro-6,7-dihydro-indol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-oxo-l, 5,6,7-dihydro-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3-Dimetylaminometylindol-2-yl) methylene] -3-ethoxy-2-pyrazolin-5-one, 4 - [(7-azaindole-3-yl) methylene] -3-benzyl-2-pyrazolin-5-one, 3-Benzyl-4 - {[1- (4-hydroxybutyl) -7-azaindol-3-yl] methylene} -2-pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) methylene] -3- (4-methoxyphenyloxymethyl) -2-pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) methylene] -3-isopropoxy- 2-pyrazolin-5-one, 3-Amino-4 - [(7-azaindol-3-yl) methylene] -2-pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) methylene] -3- (4-methoxybenzyl) -2-pyrazolin-5-one, 4 - [(7-azaindole-3-yl) methylene-] -3-phenylamino-2-pyrazolin-5-one, 4 - [(7-azaindole-3-yl) methylene] -3- (4-methylbenzyl) -2-pyrazoIin-5-one, 4 - [(7-azaindole-3-yl) methylene] -3- (4-hydroxyphenylethyl) -2-pyrazolin-5-one, 4 - {[1- (4-Hydroxybutyl) -7-azaindol-3-yl] methylene} -3- (4-hydroxyphenylethyl) -2-pyrazolin-5-one, 4 - [(7-azaindole-3-yl) methylene] -3-isopropyl-2-pyrazolin-5-one, 4 - [(7-azaindole-3-yl) methylene] -3-cyclopropyl-2-pyrazolin-5-one, 4 - [(7-azaindole-3-yl) methylene] -3-cyclobutyl-2-pyrazolin-5-one, 4 - [(7-azaindole-3-yl) methylene] -3- (3-pyridyl) -2-pyrazolin-5-one, 4 - [(7-azaindol-3-yl) methylene] -3-phenyl-2-pyrazolin-5-one, 4 - [(7-azaindole-3-yl) methylene] -3- (4-fluoro-phenylamino) -2-pyrazolin-5-one, 4 - [(7-azaindole-3-yl) methylene] -3-propyl-2-pyrazolin-5-one, 4 - [(7-Azaindol-3-yl) methylene] -3-methyl-2-pyrazolin-5-one; . 4 - [(7-azaindole-3-yl) methylene] -3-trifluoromethyl-2-pyrazolin-5-one, 4 - [(7-azaindole-3-yl) methylene] -3- (tert-butyl) -2-pyrazolin-5-one, 4 - {[l- (4-hydroxybutyl) -7-azaindole-3-yl] methylene} -3-trifluoromethyl-2-pyrazolin-5-one, 4 - [(7-azaindole-3-yl) methylene] -3- (4, isopropylphenylamino) -2-pyrazolin-5-one, 4 - [(7-azaindole-3-yl) methylene] -3- (3-methylphenylamino) -2-pyrazolin-5-one, 4 - {[l- (4-hydroxybutyl) -7-azaindole-3-yl] methylene} -3- (3-methylphenylamino) -2-pyrazolin-5-one, 4 - [(7-azaindole-3-yl) methylene] -3-phenylethyl-2-pyrazolin-5-one, 3-benzyl-4 - [(4-dimethylaminophenyl) methylene] -2-pyrazolin-5-one, 235 4 - [(4-dimethylaminophenyl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - [(4-dimethylaminophenyl) methylene] -3-phenylethyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-dimethylaminophenyl) methylene] -2-pyrazolin-5-one, 3-isopropoxy-4 - [(3-methyl-pyrazol-4-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3-methylpyrazol-4-yl) methylene] -2-pyrazolin-5-one; 4 - [(Imidazol-2-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(imidazol-2-yl) methylene] -2-pyrazolin-5-one; 4 - [(Imidazol-4-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(thien-2-yl) methylene] -2-pyrazolin-5-one; 4 - [(Indo-3-yl) methylene] -3-isopropyl-1-methyl-2-pyrazolin-5-one, 3-Isopropoxy-4 - [(pyrrol-3-yl) methylene] -2-pyrazolin-5-one, 4 - [(8-Hydroxyquinolin-5-yl) methylene] -3-isopropoxy-2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {[4- (2-diethylamino-ethyl) -3,5-dimethyl-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[4- (2-diethylamino-ethyl) -3,5-dimethyl-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3,5-dimethyl-4- (l-pyrolidinylmetylpyroI-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[4- (2-cyklopropylaminoetyl) -3,5-dimethyl-2-yl] methylene} 2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[3,5-dimethyl-4- (2-Phenylaminoethyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {{3,5-dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -2-pyrazolin-5-one, 236 4 - {[4- (2-carboxyethyl) -3,5-dimethyl-2-yl] methylene} -3-cyclopropyl-2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(4-diethylaminomethyl-3-isopropyl-5-methylpyrrole-2-yl) methylene] 2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[4- (l-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene- 2-pyrazolin-5}-one, 3-Cyclopropyl-4 - {{3-isopropyl-5-methyl-4- [2- (l-pyrrolidinylethyl)] pyrrol-2-yl) methylene} 2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[4- (2-cyclopropylaminoethyl) -3-isopropyl-5-methylpyrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrol-2-yl} methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[3-isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4- {{4- [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[4- (4-dimethylamino-butyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} 2-pyrazolin-5-one, 3-Cyclopropyl-4 - [(3-cyclopropyl-4-diethylaminomethyl-5-methylpyrrole-2-yl) methylene] 2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[3-cyclopropyl-4- (l-pyrrolidinylmethyl) -5-methylpyrrole-2-yl] methylene} 2-pyrazolin-5-one, 3-Cyclopropyl-4 - {{3-cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {{3-cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[3-cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrole-2-yl] methylene} 2-pyrazolin-5-one, 3-Cyclopropyl-4 - {{3-cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {[3-cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 3-Cyclopropyl-4 - {(3-cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2-yl} methylene} -2-pyrazolin-5-one, 23Ί 3-Cyclopropyl-4 - {[3-cyclopropyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2-yl] methylene} -2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4- [4- (2-carboxyethyl) -3,5-dimethyl-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (l-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyklopropylaminoetyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 3-Pyrazinyl-4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 4 - {[3-Isopropyl-5-methyl-4- (4-piperidino-butyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 3-Pyrazinyl-4 - {{4- [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrole-2-yl} methylene} -2pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 238 4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (l-pyrolidinylmetylpyrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-ethylamino-ethyl) pyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-Phenylaminoethyl) pyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3- (2-furyl) 2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[4- (l-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (2-furyl) 2-pyrazolin-5-one, 4 - {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3- (2-fluorophenyl) -2-pyrazolin-5-one, 3- (2-Furyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl) -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 3- (2-furyl) -4 - {[3-isopropyl-5-methyl-4- (4-piperidino-butyl) pyrrol-2-yl] methylene} 2-pyrazolin 5th zone, 3- (2-Furyl) -4 - {{4- [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 239 4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (2-furyl) 2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyro-1-2-yl} methylene} -3- (2-furyl) -2-pyrazolin-5 -one 4- {3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrole-2-yl} methylene} -3- (2-fi.iryl) 2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrole-2-yl] methylene} -3- (2-furyl) 2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene} 3- (2-furyl) -2-pyrazoline 5-one, 4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene} -3- (2-furyl) 2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2-yl} methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2-yl] methylene} -3- (2-furyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (l-pyrolidinylmetylpyrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazoline 5th zone, 4 - {[3,5-Dimethyl-4- (2-ethylamino-ethyl) pyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-Phenylaminoethyl) pyrrole-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3- (2-thienyl) 2-pyrazolin-5-one, 4 - {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (2-thienyl) -2-pyrazolin-5-one, ¹ 4 - [(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl) methylene] -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[4- (l-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one, 4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[4- (2-Cyklopropylaminoetyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one, 240 4 - {{4- [3- (1-Pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[3-Isopropyl-5-methyl-4- (4-piperidino-butyl) pyrrol-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one, 4 - {(4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrol-2-yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[4- (4-dimethylamino-butyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one, 4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (2-thienyl) 2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2-yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrole-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene} -3 (2-thienyl) -2-pyrazoline-5 -one 4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2-yl} methylene} -3- (2-thienyl) -2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2-yl] methylene} -3- (2-thienyl) 2-pyrazolin-5-one; 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-Cyklopropylaminoetyl) -3,5-dimethyl-2-yl] methylene} -3- (4-pyrimidinyl) 2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-ethylamino-ethyl) pyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 241 {4- [3 ₁ 5-Dimethyl-4- (2-Phenylaminoethyl) pyrrol-2-yl] methylene) -3- (4-pyrimidinyl) -2-pyrazolin5- one, 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-carboxyethyl) -3,5-dimethyl-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3-isopropyl-5-methylpyrrole-2-yl) methylene] -3- (4-pyrimidinyl) 2-pyrazolin-5-one, 4 - {[4- (l-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (4-pyrimidinyl) 2-pyrazolin-5-one, 4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene) -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-cyklopropylaminoetyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazoIin-5-one, 3- (4-Pyrimidinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 4 - {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{4- [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrole-2-yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (4-dimethylamino-butyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (4-pyrimidinyl) 2-pyrazolin-5-one, 4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (4-pyrimidinyl) 2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene} -3- (4-pyrimidinyl) -2-pyrazoline 5-one, 4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrole-2-yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrole-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazol-in-5-one, 4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene} -3 (4-pyrimidinyl) -2-pyrazoline-5 -one 242 4 - {[3-Cyclopropyl-5-methyl-4- (3-fenylmetylaminopropyl) pyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2-yl} methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4- [3-Cyclopropyl-5-methyl-4- (4-cyklobutylaminobutyl) pyrrol-2-yl] methylene} -3- (4-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-Cyklopropylaminoetyl) -3,5-dimethyl-2-yl] methylene} -3- (5-pyrimidinyl) 2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-ethylamino-ethyl) pyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3- (5-pyrimidinyl) 2-pyrazolin-5-one, 4 - {[4- (2-carboxyethyl) -3,5-dimethyl-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3-isopropyl-5-methylpyrrole-2-yl) methylene] -3- (5-pyrimidinyl) 2-pyrazolin-5-one, 4 - {[4- (l-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (5-pyrimidinyl) 2-pyrazolin-5-one, 4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (2-cyklopropylaminoetyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (5pyrimidinyl) -2-pyrazolin-5-one, 3- (5-Pyrimidinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 4 - {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 243 4 - {{4- [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrole-2-yl) methylene} -3- (5pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (4-Dimethylaminobutyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3-Cyclopropyl-4-diethyl] aminomethyl-5-methylpyrrole-2-yl) methylene] -3- (5-pyrimidinyl) 2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2-yl} methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[3-cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrole-2-yl] methylene} -3- (5pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene} 3- (5-pyrimidinyl) -2-pyrazoline-5 -one 4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene} -3- (5-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [4- (l-pyrrolidinyl) butyl] pyrrol-2-yl} methylene} -3- (5pyrimidinyl) -2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-5-methyl-4- (4-cyklobutylaminobutyl) pyrrol-2-yl] methylene} -3- (5pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (2-pyrimidinyl) -2-pyrazolin-5-one, _m.p. 4 - {[4- (2-Cyklopropylaminoetyl) -3,5-dimethyl-2-yl] methylene} -3- (2-pyrimidinyl) 2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-ethylaminoethyl) pyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3- (2-pyrimidinyl) 2-pyrazolin-5-one, 244 4 - {[4- (2-carboxyethyl) -3,5-dimethyl-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3-isopropyl-5-methylpyrrole-2-yl) methylene] -3- (2-pyrimidinyl) 2-pyrazolin-5-one, 4 - {[4- (l-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (2-pyrimidinyl) 2-pyrazolin-5-one, 4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3- (2-pyrimidinyl) 2-pyrazolin-5-one, 4 - {[4- (2-cyklopropylaminoetyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 3- (2-Pyrimidinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 4 - {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{4- [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrole-2-yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[4- (4-DimetyIaminobutyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (2-pyrimidinyl) 2-pyrazolin-5-one, 4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (2-pyrimidinyl) 2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrole-2-yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrole-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene} 3- (2-pyrimidinyl) -2-pyrazolin-5-one 4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2-yl} methylene} -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 245 4- [3-Cyclopropyl-5-methyl-4- (4-cyclobutylaminobutyl) pyrrol-2-yl] methylene) -3- (2-pyrimidinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {[4- (2-Cyklopropylaminoetyl) -3,5-dimethyl-2-yl] methylene) -3- (3-pyridazinyl) 2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-ethylaminoethyl) pyrrol-2-yl] methylene) -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene) -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl} methylene} -3- (3-pyridazinyl) pyrazolin-5-one, 4 - {[4- (2-carboxyethyl) -3,5-dimethyl-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3-isopropyl-5-methylpyrrole-2-yl) methylene] -3- (3-pyridazinyl) 2-pyrazolin-5-one, 4 - {[4- (l-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene) -3- (3-pyridazinyl) 2-pyrazolin-5-one, 4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {[4- (2-cyklopropylaminoetyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene) -3- (3pyridazinyl) -2-pyrazolin-5-one, 3- (3-Pyridazinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl) methylene} -2-pyrazolin-5-one, 4 - {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene) -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {(4- [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrole-2-yl) methylene} -3- (3pyridazinyl) -2-pyrazolin-5-one ,,. 4 - {[4- (4-dimethylamino-butyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene) -3- (3-pyridazinyl) · 2-pyrazolin-5-one, 246 4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrole-2-yl) methylene] -3- (3-pyridazinyl) 2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl) methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrole-2-yl) methylene} -3- (3pyridazinyl) -2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrole-2-yl] methylene} -3- (3pyridazinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl) methylene} 3- (3-pyridazinyl) -2-pyrazoline-5 -one 4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene} -3- (3-pyridazinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [4- (l-pyrrolidinyl) butyl] pyrrol-2-yl) methylene} -3- (3pyridazinyl) -2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-5-methyl-4- (4-cyklobutylamÍnobutyl) pyrrol-2-yl] methylene} -3- (3pyridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (1-pyrrolidinylmethylpyrrol-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3,5-dimethyl-2-yl) methylene] -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {[4- (2-Cyklopropylaminoetyl) -3,5-dimethyl-2-yl] methylene) -3- (4-pyridazinyl) 2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-ethylaminoethyl) pyrrol-2-yl] methylene) -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-phenylaminoethyl) pyrrol-2-yl] methylene) -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl) methylene) -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(4-diethylaminomethyl-3-isopropyl-5-methylpyrrole-2-yl) methylene] -3- (4-pyridazinyl) 2-pyrazolin-5-one, 4 - {[4- (l-pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene) -3- (4-pyridazinyl) 2-pyrazolin-5-one, 247 4 - {[4- (2-carboxyethyl) -3,5-dimethyl-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {[4- (2-cyklopropylaminoetyl) -3-isopropyl-5-methylpyrrole-2-yl] methylene} -3- (4pyridazinyl) -2-pyrazolin-5-one, 3- (4-Pyridazinyl) -4 - {{4- [3- (1-pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl} methylene} -2-pyrazolin-5-one, 4 - ([3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {{4- [3- (4-pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrolidin-2-yl} methylene} -3- (4pyridazinyl) -2-pyrazolin-5-one, 4 - {[4- (4-Dimethylamino-butyl) -3-isopropyl-5-methyl-pyrrol-2-yl] -methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrolidin-2-yl) methylene] -3- (4-pyridazinyl) 2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2-yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrole-2-yl] methylene} -3- (4pyridazinyl) -2-pyrazolin-5-one, 4- {{3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl} methylene} 3- (4-pyridazinyl) -2-pyrazoline-5 -one 4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2-yl} methylene} -3- (4-pyridazinyl) -2-pyrazolin-5-chloro, 4 - {[3-Cyclopropyl-5-methyl-4- (4-cyclobutyl aminobutyl) pyrrol-2-yl] methyl en} -3- (4-pyridazinyl) -2-pyrazolin-5-one, 4 - [(3,5-Dimethyl-4- (l-pyrolidinylmetylpyrol-2-yl) methylene] -3- (l, 2,4-triazin-3-yl) 2-pyrazolin-5-one, 248 4 - [(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl) methylene] -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminoethyl) -3,5-dimethylpyrrol-2-yl] methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-ethylamino-ethyl) pyrrol-2-yl] methylene) -3- (l, 2,4-triazin-3-yl) 2-pyrazolin-5-one, 4 - {[3,5-Dimethyl-4- (2-Phenylaminoethyl) pyrrol-2-yl] methylene} -3- (l, 2,4-triazin-3-yl) 2-pyrazolin-5-one, 4 - {{3,5-Dimethyl-4- [2- (4-pyridylmethylamino) ethyl] pyrrol-2-yl) methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazoline-5 -one 4 - {[4- (2-Carboxyethyl) -3,5-dimethylpyrrol-2-yl] methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one, 4 - [(4-DietylaminometyI-3-isopropyl-5-methylpyrrole-2-yl) methylene] -3- (l, 2,4-triazin-3-yl) 2-pyrazolin-5-one, 4 - {[4- (1-Pyrrolidinylmethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one, 4 - {{3-Isopropyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazoline- 5-one, 4 - {[4- (2-cyclopropylaminoethyl) -3-isopropyl-5-methylpyrrol-2-yl] methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one, 4 - {{4- [3- (1-Pyrrolidinyl) propyl] -3-isopropyl-5-methylpyrrol-2-yl) methylene} -3- (1,2,4-triazin-3-yl) -2-pyrazoline- 5-one, 4 - {[3-Isopropyl-5-methyl-4- (4-piperidinobutyl) pyrrol-2-yl] methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one . 4 - {{4- [3- (4-Pyridylmethylamino) propyl] -3-isopropyl-5-methylpyrrol-2-yl) methylene} -3- (1,2,4 triazin-3-yl) -2-pyrazoline 5-one, 4 - {[4- (4-DimetylaminobutyI) -3-isopropyl-5-methylpyrrole-2-yl] methylene) -3- (l, 2,4-triazin-3-yl) -2-pyrazolin-5-one, 4 - [(3-Cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl) methylene] -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [2- (1-pyrrolidinyl) ethyl] pyrrol-2-yl} methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazoline 5-one, 249 4 - {{3-Cyclopropyl-4- [2-di (methoxyethyl) aminoethyl] -5-methylpyrrol-2-yl} methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazoline-5 -one 4 - {[3-Cyclopropyl-4- (3-diethylaminopropyl) -5-methylpyrrol-2-yl] methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one, 4 - {(3-Cyclopropyl-4- [3- (2,5-dimethyl-1-pyrrolidinyl) propyl] -5-methylpyrrol-2-yl) methylene} 3- (1,2,4-triazine-3- yl) -2-pyrazolin-5-one, 4 - {[3-Cyclopropyl-5-methyl-4- (3-phenylmethylaminopropyl) pyrrol-2-yl] methylene) -3- (1,2,4-triazin-3-yl) -2-pyrazolin-5-one, 4 - {{3-Cyclopropyl-5-methyl-4- [4- (1-pyrrolidinyl) butyl] pyrrol-2-yl} methylene) -3- (1,2,4-triazin-3-yl) -2- pyrazolin-5-one, 4 - {[3-Cyclopropyl-5-methyl-4- (4-cyklobutylaminobutyl) pyrrol-2-yl] methylene) -3- (l, 2,4triazín-3-yl) -2-pyrazolin-5-one, 4 - {[4- (2-diethylamino-ethyl) -5-methyl-3-trifluoromethylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-4- [2- (l-pyrrolidinylethyl)] - 3-trifluoromethylpyrrole-2-yl) methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-ethylamino-ethyl) -5-methyl-3-trifluoromethylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-4- [2- (4-pyridylmethylaminomethyl)] - 3-tnfluórmetylpyrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-trifluoromethylpyrrol-2-yl) methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminoethyl) -5-methyl-3-trifluoromethylpyrrol-2-yl] methylene) -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-diethylamino-ethyl) -5-methyl-3- / tert butylpyrol-2-yl] methylene) -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-4- [2- (1-pyrrolidinyl-ethyl)] - 3-tert-butyl-pyrrol-2-yl) -methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminoethyl) -5-methyl-3- tert -butylpyrrol-2-yl] methylene) -3-pyrazinyl-2-pyrazoline 5th zone, 4- {5-Methyl-4- [2- (4-pyridylmethylaminomethyl)] - 3 / tert butylpyrol-2-yl] methylene) -3-pyrazinyl · 2-pyrazolin-5-one, 250 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-tert-butylpyrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminoethyl) -5-methyl-3- / e / c-butylpyrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-diethylamino-ethyl) -3-ethyl-5-methylpyrrole-2-yl] methylene-} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Ethyl-5-methyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-ethyl-4- (2-ethylamino-ethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Ethyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-ethylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminoethyl) -5-methyl-3-ethyl pyrrole-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-cyclobutyl-4- (2-diethylamino-ethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{3-Cyclobutyl-5-methyl-4- [2- (1-pyrrolidinyl-1-yl)] pyrrol-2-yl} methylene} -3-pyrazines . 4 - {[3-Cyclobutyl-4- (2-ethylaminoethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{3-cyclobutyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-cyclobutylpyrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, ... '. ' 4 - {[4- (2-Aminoethyl) -5-methyl-3-cyclobutylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclopentyl-4- (2-diethylamino-ethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{3-Cyclopentyl-5-methyl-4- [2- (l-pyrrolidinylethyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[3-Cyclopentyl-4- (2-ethylamino-ethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 251 4 - ({3-Cyclopentyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (l-imidazolyl) ethyl] -5-methyl-3-cyklopentylpyrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-Aminoethyl) -5-methyl-3-cyclopentylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclohexyl-4- (2-diethylamino-ethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{3-Cyclohexyl-5-methyl-4- [2- (l-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[3-Cyclohexyl-4- (2-ethylamino-ethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{3-Cyclohexyl-5-methyl-4- [2- (4-pyridylnietylaminoetyl)] pyrrol-2-yl} methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazolyl) ethyl] -5-methyl-3-cyclohexylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminoethyl) -5-methyl-3-cyklohexylpyrol-2-yl] methylene} -3-pyrazinyl-2-pyrazoIin-5-one, 4 - {[4- (2-diethylamino-ethyl) -5-methyl-3-phenyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3-phenyl-4- [2- (l-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-ethylamino-ethyl) -5-methyl-3-phenyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3-phenyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-phenylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminoethyl) -5-methyl-3-phenyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-diethylamino-ethyl) -5-methyl-3- (4-methoxyphenyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (4-methoxyphenyl) -4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 252 4 - {[4- (2-ethylamino-ethyl) -5-methyl-3- (4-methoxyphenyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (4-methoxyphenyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3- (4-methoxyphenyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminoethyl) -5-methyl-3- (4-methoxyphenyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-DietyIaminoetyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (2-pyridyl) -4- [2- (l-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-ethylamino-ethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (2-pyridyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3- (2-pyridyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminoethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-diethylamino-ethyl) -5-methyl-3-pyrazinylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3-pyrazinyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminoethyl) -5-methyl-3-pyrazinylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one; 4 - {{5-Methyl-3-pyrazinyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3pyrazinyl-2-pyrazoIin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3-pyrazinylpyrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyklopropylaminoetyl) -5-methyl-3-pyrazinylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 253 4 - {[4- (2-Diethylaminoethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (2-imidazoyl) -4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, i 4 - {[4- (2-ethylamino-ethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2-yl] metyléri} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (2-imidazolyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3- (2-imidazoyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyklopropylaminoetyl) -5-methyl-3- (2-imidazoyl) pyrrol-2-yl] methylene} -3-pyrazinyl 2-pyrazolin-5-one, 4 - ([4- (2-diethylamino-ethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (2-pyrimidinyl) -4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - ([4- (2-ethylamino-ethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (2-pyrimidinyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl) methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (l-imidazolyl) ethyl] -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-Cyklopropylaminoetyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one, 4- [4- (2-diethylamino-ethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (3-isoxazolyl) -4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl (methylene} -3-pyrazinyl-2 pyrazolin-5-one, 4 - {[4- (2-ethylamino-ethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (3-isoxazolyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl (methylene (-3-pyrazinyl-2-pyrazolin-5-one), 254 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyklopropylaminoetyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl] methylene} 3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -5-methyl-3- (2-furyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (2-furyl) -4- [2- (l-pyrrolidinylethyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-Ethylaminoethyl) -5-methyl-3- (2-furyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (2-furyl) -4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl) methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (l-imidazolyl) ethyl] -5-methyl-3- (2-furyl) pyrrole-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-Cyklopropylaminoetyl) -5-methyl-3- (2-furyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-Diethylaminoethyl) -5-hydroxymethyl-3-isopropylpyrrol-2-yl] methylene} -3-pyrazinyl-2 pyrazolin-5-one, 4 - {{5-Hydroxymethyl-3-isopropyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-ethylamino-ethyl) -5-hydroxymethyl-3-isopropyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Hydroxymethyl-3-isopropyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -5-hydroxymethyl-3-isopropylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyklopropylaminoetyl) -5-hydroxymethyl-3-isopropyl-pyrrol-2-yl] methylene) -3pyrazinyl-2-pyrazolin-5-one, 4- [4- (2-Diethylaminoethyl) -3,5-dicyclopropylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3,5-Dicyclopropyl-4- [2- (1-pyrrolidinylethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 255 4 - {[4- (2-Ethylaminoethyl) -3,5-dicyclopropylpyrrol-2-yl] methylene (-3-pyrazinyl-2-pyrazolin-5-one), 4 - {{3,5-Dicyclopropyl-4- [2- (4-pyridylmethylaminoethyl)] pyrrol-2-yl (methylene} 3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) ethyl] -3,5-dicyclopropylpyrrol-2-yl (methylene) -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyklopropylaminoetyl) -3,5-dicyklopropylpyrol-2-yl] methylene (3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-diethylaminomethyl) -5-methyl-3-trifIuórmetylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-dimethylaminomethyl) -5-methyl-3-trifluoromethylpyrrole-2-yl] methylene (3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-4- [2- (l-pyrrolidinylmethyl)] - 3-trifluoromethylpyrrole-2-yl (methylene (3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3-trifluoromethylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-4- [2- (4-pyridylmethylaminomethyl)] - 3-trifluoromethylpyrrole-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (l-imidazolyl) methyl] -5-methyl-3-trifluoromethylpyrrole-2-yl} methylene (3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-Aminomethyl) -5-methyl-3-trifIuórmetylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-diethylaminomethyl) -5-methyl-3- / erc'-butylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-dimethylaminomethyl) -5-methyl-3-zerc butylpýrol-2-yl] methylene (3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-4- [2- (1-pyrrolidinylmethyl)] - 3-tert-butylpyrol-2-yl (methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- / No ?? c-butylpyrol-2-yl] methylene (3-pyrazinyl-2pyrazolin-5-one, 4- {5-Methyl-4- [2- (4-pyridylmetylaminoinetyl)] - 3-Zr, n-butylpyrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one, 256 4 - {{4- [2- (l-imidazolyl) methyl] -5-methyl-3-t-butyl] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-Aminomethyl) -5-methyl-3- tert -butyllpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-diethylaminomethyl) -3-ethyl-5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Dimethylaminomethyl) -3-ethyl-5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Ethyl-5-methyl-4- [2- (l-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[3-ethyl-4- (2-ethylaminomethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3-Ethyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3-ethylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminomethyl) -5-methyl-3-etyIpyrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-cyclobutyl-4- (2-diethylaminomethyl) -5-methylpyrrolidin-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[3-cyclobutyl-4- (2-dimethylaminomethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{3-Cyclobutyl-5-methyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclobutyl-4- (2-ethylaminomethyl) -5-methylpyrrol-2-yl] methylene} -3-pyrazinyl-2H-pyrazolin-5-one, 4 - {{3-Cyclobutyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (l-imidazolyl) methyl] -5-methyl-3-cyklobutylpyrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-Aminomethyl) -5-methyl-3-cyclobutylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclopentyl-4- (2-diethylaminomethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 257 4 - {[3-Cyclopentyl-4- (2-dimethylaminomethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{3-Cyclopentyl-5-methyl-4- [2- (l-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[3-Cyclopentyl-4- (2-ethylaminomethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{3-Cyclopentyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one, 4- {4- [2- (l-imidazolyl) methyl] -5-methyl-3-cyklopentylpyrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-Aminomethyl) -5-methyl-3-cyclopentylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclohexyl-4- (2-diethylaminomethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[3-Cyclohexyl-4- (2-dimethylaminomethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{3-Cyclohexyl-5-methyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclohexyl-4- (2-ethylaminomethyl) -5-methylpyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{3-Cyclohexyl-5-methyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (l-imidazolyl) methyl] -5-methyl-3-cyklohexylpyrol-2-yl} methylene} -3-pyrazinyl-2pyrazoIin-5-one, 4 - {[4- (2-Aminomethyl) -5-methyl-3-cyclohexylpyrrol-2-yl] methylene}; 3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminomethyl) -5-methyl-3-phenylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-dimethylaminomethyl) -5-methyl-3-phenyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3-phenyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 258 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3-phenyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3-phenyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3-phenylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminomethyl) -5-methyl-3-phenyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-diethylaminomethyl) -5-methyl-3- (4-methoxyphenyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-dimethylaminomethyl) -5-methyl-3- (4-methoxyphenyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (4-methoxyphenyl) -4- [2- (l-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (4-methoxyphenyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazoIin-5-one, 4 - {{5-Methyl-3- (4-methoxyphenyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl) methylene} -3 pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (l-imidazolyl) methyl] -5-methyl-3- (4-methoxyphenyl) pyrrole-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Aminomethyl) -5-methyl-3- (4-methoxyphenyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-diethylaminomethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazoIin-5-one, 4 - {[4- (2-dimethylaminomethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (2-pyridyl 4- [2- (l-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (2-pyridyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3pyrazinyI-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (2-pyridyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 259 4 - {[4- (2-Aminomethyl) -5-methyl-3- (2-pyridyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-diethylaminomethyl) -5-methyl-3-pyrazinylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-dimethylaminomethyl) -5-methyl-3-pyrazinylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3-pyrazinyl-4- [2- (l-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3-pyrazinylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3-pyrazinyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3-pyrazinylpyrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminomethyl) -5-methyl-3-pyrazinylpyrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-diethylaminomethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-dimethylaminomethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (2-imidazolyl) -4- [2- (l-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (2-imidazoyl) pyrrol-2-yl] methylene-} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (2-imidazoyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrole-2ryl} methylene} -3 '^; pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (2-imidazoyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-CykIopropylaminometyl) -5-methyl-3- (2-imidazoyl) pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-diethylaminomethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 260 4 - {[4- (2-dimethylaminomethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Methyl-3- (2-pyrimidinyl) -4- [2- (l-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (2-pyrimidinyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (l-imidazolyl) methyl] -5-methyl-3- (2-pyrimidinyl) pyrrol-2'-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminomethyl) -5-methyl-3- (2-pyrimidinyl) pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-diethylamino-ethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-dimethylaminoethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (3-isoxazolyl) -4- [2- (l-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (3-isoxazolyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3 pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminomethyl) -5-methyl-3- (3-isoxazolyl) pyrrol-2-yl] methylene} -31 pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-diethylaminomethyl) -5-methyl-3- (2-furyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-dimethylaminomethyl) -5-methyl-3- (2-furyl) pyrrole-2-yl] methylene-} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (2-furyl) -4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 261 4 - {[4- (2-Ethylaminomethyl) -5-methyl-3- (2-furyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Methyl-3- (2-furyl) -4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) methyl] -5-methyl-3- (2-furyl) pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Cyclopropylaminomethyl) -5-methyl-3- (2-furyl) pyrrole-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-Diethylaminomethyl) -5-hydroxymethyl-3-isopropylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Dimethylaminomethyl) -5-hydroxymethyl-3-isopropyl-pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {{5-Hydroxymethyl-3-isopropyl-4- [2- (1-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3 pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -5-hydroxymethyl-3-isopropyl-pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {{5-Hydroxymethyl-3-isopropyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{4- [2- (1-Imidazoyl) methyl] -5-hydroxymethyl-3-isopropylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 5 - {[4- (2-Cyclopropylaminomethyl) -5-hydroxymethyl-3-isopropylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Diethylaminomethyl) -3,5-dicyclopropylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {[4- (2-Dimethylaminomethyl) ethyl] - 3,5-dicyclopropyl-pyrrol-2-yl] methylene} -3'-pyrazinyl-2-pyrazolin-5-one, 4 - {{3,5-Dicyclopropyl-4- [2- (l-pyrrolidinylmethyl)] pyrrol-2-yl} methylene} -3-pyrazinyl-2pyrazolin-5-one, 4 - {[4- (2-Ethylaminomethyl) -3,5-dicyclopropylpyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - {{3,5-Dicyclopropyl-4- [2- (4-pyridylmethylaminomethyl)] pyrrol-2-yl} methylene} -3pyrazinyl-2-pyrazolin-5-one, 262 4 - {{4- [2- (1-Imidazoyl) methyl] -3,5-dicyclopropylpyrrol-2-yl} methylene} -3-pyrazinyl-2-pyrazolin-5-one, 4 - [(4-Cyclopropylaminomethyl-3,5-dicykIopropylpyrol-2-yl) methylene] -3-pyrazinyl-2pyrazolin-5-one, 4 - {[3-Cyclopropylaminomethyl-5-methyl-4- (2-diethylamino-ethyl) pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {[3-Cyclopropylaminomethyl-5-methyl-4- (2-hydroxyethyl) pyrrol-2-yl] methylene} -3pyrazinyl-2-pyrazolin-5-one, 4 - {[3-dimethylaminomethyl-5-methyl-4- (2-diethylaminoethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2-pyrazolin-5-one and 4 - {[3-hydroxymethyl-5-methyl-4- (2-diethylamino-ethyl) pyrrol-2-yl] methylene} -3-pyrazinyl-2pyrazolín-5-one. The compound of claim 18, wherein the compound is a mixture of stereoisomers. The compound of claim 23, wherein the stereoisomers are enantiomers. The compound of claim 24, wherein the stereoisomers are E and Z isomers. The compound of claim 18, wherein the compound is a mixture of structural isomers. The compound of claim 26, wherein the structural isomers are tautomers. 28. A method of inhibiting the activity of one or more protein kinases comprising administering a compound of claim 18. 29. The method of claim 28, wherein said compound is administered to a recipient in need of inhibition of one or more protein kinases. 263 The method of claim 29, wherein the compound is a mixture of stereoisomers. 31. The method of claim 30, wherein the stereoisomers are enantiomers. The method of claim 30, wherein the stereoisomers are E and Z isomers. 33. The method of claim 29, wherein the compound is a mixture of structural isomers. 34. The method of claim 29, wherein the structural isomers are tautomers. 35. The method of claim 29, wherein said protein kinase is a tyrosine kinase. 36. The method of claim 35, wherein said tyrosine kinase is selected from the group consisting of KDR, Flt-1, TIE-2, Lck, Src, Fyn, Lyn, Blk and yes. 37. A method of treating hyperproliferative disorders in a recipient comprising administering to said recipient a compound of claim 18. 38. A method of affecting angiogenesis in a recipient comprising administering to said recipient a compound of claim 18. 39. A pharmaceutical composition comprising a compound according to claim 1 18 and a pharmaceutically acceptable carrier or diluent. 264 40. A pharmaceutical composition comprising the compound of claim 22 and a pharmaceutically acceptable carrier or diluent. The compound of claim 18, wherein R is substituted with one or more substituents each independently selected from the group consisting of halogens, lower alkyl, R ³ O-, hydroxy, HOC (O) -, R ³ OC ( O) -, R ³ OC (O) R ⁶ -, R ³ OR ⁶ -, trihalomethyl, trihalomethylcarbonyl, nitro, -C (O) NR ⁴ R ⁵ , -NR ⁴ R ⁵ , R ³ CO-, - (CH 2) ) n R ⁷ , -O (CH 2) n R ⁷ , -C (O) NR ⁴ (CH 2) n R ⁷ , -C (O) (CH 2) _n -R ⁷ , -C (O) - (CH 2) n C (O) -R ⁷ , -C (O) O ( CH 2) _n R ⁷ , -OC (O) (CH 2) n R ⁷ , -NR ⁴ C (O) (CH 2) _n R ⁷ , -R ⁶ NR ⁴ R ⁵ , -R 6 R ⁷ -R ⁷ -R ⁷ . -R ⁶ C (O) O (CH 2) n R ⁷ , -R ⁶ OC (O) (CH 2) _n R ⁷ , -R ⁶ N (R ⁶ -R ⁷ ) 2, -R ⁶ C (O) NR ⁴ (CH ₂ ) _n R ⁷ , R ⁶ NR ⁴ C (O) (CH ₂ ) _n R ⁷ , -R ⁶ CH (C (O) OR ⁴ ) (NR ⁵ C (O) R ⁴ ), an optionally substituted aryl group and optionally substituted aralkyl; wherein optionally substituted aryl groups and optionally substituted aralkyl groups are optionally substituted with one or more substituents selected from the group consisting of halogen, trihalomethyl, hydroxy, -NR ⁴ R ⁵ , nitro, -CONR ⁴ R ⁵ , lower alkyl, R ³ O- , -C (O) OR ⁴ and -OC (O) R ³ ; R ⁶ is lower alkyl or aryl; and R ⁷ is alkoxy, haloalkyl, lower alkyl piperazine, hydroxy, R ³ O-, R ³ C (O) - or -NR ⁴ R ⁵ . The compound of claim 41, wherein R is pyrrolyl, indolyl, azaindolyl, phenyl, pyrazolyl, imidazolyl, thienyl, 4,5,6,7-tetrahydroindolyl or quinolinyl. The compound of claim 42 wherein R is pyrrol-2-yl, pyrrol-3-yl, indol-2yl, indol-3-yl, azaindol-3-yl, pyrazol-4-yl, imidazol-2- yl, imidazol-4-yl, thien-2-yl or quinolin-5-yl. A compound according to claim 18 or 43, wherein R ¹ is trifluoromethyl, amino, cyclopropylamino, methyl, ethyl, propyl, isopropyl, 265 cyclopropyl, 2-methylcyclopropyl, 2,2,3,3-tetramethylcyclopropyl, 2-phenylcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, - (CH ₂ ) _p -O-phenyl, - (CH ₂ ) _p -O- (4-methoxyphenyl) - (CH ₂ ) _p -O- (4-chlorophenyl), - (CH ₂ ) _p -O- (4-methylphenyl), - (CH ₂ ) _p -O- (3-methylphenyl), - (CH ₂ ) _p -O- (4-phenylphenyl), - (CH ₂ ) _p -O- (4-hydroxyphenyl), - (CH ₂ ) _p -O- (4-nitrophenyl), - (CH ₂ ) _p -O- (4-aminophenyl) -, - (CH ₂ ) _p -O- (4-carbamoylphenyl), - (CH ₂ ) _p -O (4-methoxycarbonylphenyl), -NH-phenyl, -NH- (4-methoxyphenyl), -NH- (4 -chlorophenyl), -NH- (4-fluorophenyl), -NH- (4-isopropylphenyl), isopropoxy, ethoxy, cyclopentyloxy, - (CH ₂ ) _p -indolyl, - (CH ₂ ) _p -pyridyl, - (CH ₂₎ - _p -benzothiazolyl, - (CH ₂ ) _p -pyrolyl, - (CH ₂ ) _p -tetrahydrofuryl, - (CH ₂ ) _p pyrazinyl, - (CH ₂ ) _p -furyl, - (CH ₂ ) _p -thienyl, - (CH ₂ ) _p -phenyl, - (CH ₂ ) _p - (5-methylisoxazolyl), - (CH ₂ ) _p -isoxazolyl, - (CH ₂ ) _p -pyridazinyl, - (CH ₂ ) _p -pyrimidinyl, - ( CH ₂ ) _n -C (O) -OMe, - (CH ₂ ) _n -C (O) -OEt and benzyl optionally substituted is g or more Cl, F, OMe, methyl or amino groups; where index p is an integer ranging from 1 to 3. The compound of claim 44, wherein R is optionally substituted with one or more moieties selected from the group consisting of Br, Cl, F, aminomethyl, α,-dimethylaminomethyl, carboxy, carboxymethyl, carboxyethyl, carbonylmethyl, carbonylethyl, methoxycarbonyl, ethoxycarbonyl , phenyl, 4-morpholinomethyl, -C (O) -O- _{(CH2) 2-N} (Me) _2, -C (O) -O- _{(CH2) 2-N} (Et) _2, -C (O) -O-CH ₂ -N (Me) ₂ , -C (O) -O- (CH ₂ ) ₂ -N (Me) ₂ , -C (O) -NH- (CH ₂ ) ₂ -N (Me) ₂ , -CH ₂ -NH-C (O) -CF 3 and an optionally substituted moiety selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl and phenyl, wherein said optionally substituted moiety is optionally substituted with one or more groups selected from Br, Cl, F, hydroxy, nitro, amino or lower alkyl.