RU2251546C1 - Substituted 3-oxo-1,2,3,4-tetrahydroxinoxalines, pharmaceutical compositions (variants), methods for production and uses thereof - Google Patents

Abstract

FIELD: organic chemistry, pharmaceutical compositions.

SUBSTANCE: invention relates to substituted 3-oxo-1,2,3,4-tetrahydroxinoxalines of general formula 1

, wherein R¹ represents substituted sulfanyl or substituted sulfonyl group, containing as substituent optionally substituted C1-C4-alkyl, optionally substituted C3-C8-cycloalkyl, aryl-(C1-C4)alkyl optionally substituted in aril or alkyl group, heterocyclyl-(C1-C4)alkyl optionally substituted in heterocycle or alkyl group; R² and R³ independently represent hydrogen, halogen, CN, NO₂, optionally substituted hydroxyl, optionally substituted amino group, optionally substituted carboxylic group, optionally substituted carbamoyl group, optionally substituted arylcarbonyl group or optionally substituted heterocyclylcarbonyl group; R⁴ and R⁵ independently represent hydrogen or inert substituent. Claimed compounds are high effective kaspase-3 inhibitors and are useful in production of pharmaceutical compositions for treatment of diseases associated with excess apoptosis activation, as well as for experimental investigations of apoptosis in vivo and in vitro. Also disclosed are pharmaceutical composition in form of tablets, capsules or injections in pharmaceutically acceptable package, as well as method for production thereof and therapy method.

EFFECT: pharmaceutical composition for apoptosis treatment and investigation.

6 cl, 3 dwg, 8 ex, 1 tbl

Description

This invention relates to new 1,2,3,4-tetrahydroquinoxalines having physiological activity. More specifically, the present invention relates to new substituted 3-oxo-1,2,3,4-tetrahydroquinoxalinecarboxylic acids, their esters and amides having physiological activity.

The present invention also relates to a new chemotype of substances, namely substituted 1,2,3,4-tetrahydroquinoxalines, which have specific physiological activity that allows them to be used as “molecular tools”, as well as active drug substances that selectively suppress programmed cell death (apoptosis - Apoptosis: Pharmacological Implications and Therapeutic Opportunities. Kaufmann, SH, Ed .; Academic Press: San Diego, 1997); as well as pharmaceutical compositions containing these compounds in the form of active substances; as well as a method of treating and preventing the development of various diseases associated with increased activation of apoptosis. This extremely wide range of diseases includes, in particular, cardiovascular diseases (for example, acute ischemic lesions - stroke, myocardial infarction); neurodegenerative, for example, Parkinson's and Alzheimer's diseases (Ryan C., Salvesen G. Caspases and neuronal development. Biol Chem. 2003, 384 (6): 855-861), viral diseases (for example, hepatitis C and AIDS), and t .d. (Cryns, VL; Yuan, J. The cutting edge: Caspases in apoptosis and disease. In When Cells Die; Lockshin, RA, Zakeri, Z., Tilly, JL, Eds .; Wiley-Liss: New York, 1998; p .177-210).

The pharmacological effect of substituted 1,2,3,4-tetrahydroquinoxalines is based on the highly effective apoptosis suppression realized through the inhibition of cysteine protease - caspase-3, which plays a key role in the development of apoptosis.

It is now very clear that the life of multicellular organisms is based on a balance of constantly occurring processes. Cell division and growth should be accompanied by an alternative process of removing old, damaged, mutated and other cells undesirable for the body. A controlled form of programmed cell death with characteristic morphological and biochemical characteristics is defined as apoptosis (the Greek word for Russian "leaf fall": aro - separation, ptosis - fall) (Apoptosis: Pharmacological Implications and Therapeutic Opportunities. Kauftnann, SH, Ed .; Academic Press : San Diego, 1997); (When Cells Die; Lockshin, R.A., Zakeri, Z., Tilly, J.L., Eds .; Wiley-Liss: New York, 1998). To date, it has been established that impaired cell death control leads to shifts in homeostasis and the development of various pathological conditions (Nicholson D.W. From bench to clinic with apoptosis-based therapeutic agents. Nature (London) 2000, 407: 810-816). In the case of increased activation of apoptosis, the most serious pathologies arise, related to cardiovascular, neurodegenerative, infectious, metabolic, etc. diseases (Cryns VL; Yuan J. The cutting edge: Caspases in apoptosis and disease. In When Cells Die; Lockshin, RA, Zakeri, Z., Tilly, JL, Eds .; Wiley-Liss: New York, 1998; p. 177-210). So, it has been shown that the course of AIDS and a number of serious diseases of the nervous system (parkinsonism, Alzheimer's disease) is characterized by increased activation of apoptosis (Hartmann A., Hunot S., Michel P., Muriel M.-P., Vyas S., Faucheux B. , Mouatt-Prigent P., Turmel H., Srinivasan A., Ruberg M., Evan G., Agid Y., Hirsch E. Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease. PNAS 2000, 97 (6): 2875-2880). With brain ischemia and stroke, a significant part of the cells of the affected area dies precisely by the mechanism of apoptosis. In animal and human cells, apoptosis in most cases is associated with proteolytic activation of the caspase cascade, a family of evolutionarily conserved cysteine proteases that specifically break down proteins after aspartic acid residues. Based on structural homology, caspases are divided into subfamilies a) caspase-1 (caspase 1, 4, 5), b) caspase-2 (caspase-2) and c) caspase-3 (caspase 3, 6-10) (Nicholson, DW ; Thornberry, NA Caspases: killer proteases. Trends Biochem. Sci. 1997, 22: 299-306); (Nicholson D.W. Caspase structure, proteolytic substrates and function during apoptotic cell death [Review]. Cell. Death. Diff. 1999, 6: 1028-1042).

Caspase-3 plays a particularly important role, which actually determines the life prospects of cells (Porter, A.G .; Janicke, R.U. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999, 6: 99-104).

Therefore, the search for highly effective casaz-3 inhibitors that can block the development of apoptosis is a very promising approach to the creation of fundamentally new cardioprotectors (Chapman J., Magee W., Stukenbrok H., Beckius G., Milici A., Tracey WA novel nonpeptidic caspase-3 / 7 inhibitor, (S) - (+) - 5- [1- (2-methoxymethylpyrrolidinyl) -sulfonyl] isatin reduces myocardial ischemic injury. Eur. J. Pharmacol. 2002, 456 (1-3): 59-68) Neuroprotective (Scott C., Sobotka-Briner C., Wilkins D., Jacobs R., Folmer J., Frazee W., Bhat R., Ghanekar S., Aharony D. Novel Small Molecule Inhibitors of Caspase-3 Block Cellular and Biochemical Features of Apoptosis. PharmacoI. Exp. Therap. 2003, 304 (1): 433-440), hepatoprotectors (Anselmo D., Katori M., Kaldas M., Hoglen N., Valentino K., Busuttil R., Kupiec-we glinski W., Farmer, D. Apoptosis targeted therapy with the caspase inhibitor IDN-6556, ameliorates ex-vivo liver ischemia reperfusion injury. Am J Transplant 2002, 2 (Suppl. 3): 920) for the treatment and protection against a wide range of diseases , the key link of which is apoptosis.

Numerous recent studies have led to the discovery of highly effective caspase-3 inhibitors in the peptide series (Garcia-Calvo M., Peterson E., Leiting B., Ruel R., Nicholson D., Thornberry N. Inhibition of human caspases by peptide-based and macromolecular inhibitors. J. Biol. Chem. 1998, 273: 32608-32613) and peptidomimetic compounds (Karanewsky D., Bai X., Linton S., Krebs J., Wu J., Pham B., Tomaselli K. Conformationally constrained inhibitors ofcaspase-1 and of the human CED-3 homologue caspase-3. Bioorg. Med. Chem. Lett. 1998, 8: 2757-2762). An example of such compounds is, for example, the following peptidomimetic derivatives developed by Idun Pharmaceuticals, Inc. (Tomaselli K.J., Gladstone P.L., Temansky R.J. WO 0179162 October 25, 2001) and Vertex Pharmaceuticals Inc. (Golec, J., Lang, P., Diu-Hercend, A., Knegtel, R., Weber, P., Miller, K., Hercend, T., Mortimore, M., Miller, A. WO 0285899 October 31, 2002).

However, such compounds have a very limited clinical use, due to their unsatisfactory pharmacokinetic and physicochemical properties (Scott C., Sobotka-Briner C., Wilkins D., Jacobs R., Folmer J., Frazee W., Bhat R. , Ghanekar S., Aharony D. Novel Small Molecule Inhibitors of Caspase-3 Block Cellular and Biochemical Features of Apoptosis Pharmaco I. Exp. Therap. 2003, 304 (1): 433-440). In this regard, the search continues for non-peptide low molecular weight caspase inhibitors. So, quite effective inhibitors (IC ₅₀ = 5-40 nM) of caspase-3 in a series of isatins were found, for example, (Chapman J., Magee W., Stukenbrok H., Beckius G., Milici A., Tracey W. A novel nonpeptidic caspase-3/7 inhibitor, (S) - (+) - 5- [l- (2-methoxymethylpyrrolidinyl) sulfonyl] isatin reduces myocardial ischemic injury. Eur J. Pharmacol. 2002, 456 (1-3): 59 -68) and (Lee, D., Long, SA, Murray, JH et al. Potent and selective nonpeptide inhibitors ofcaspases 3 and 7. J Med Chem 2001.44 (12): 2015-2026)

However, the low selectivity of compounds of this class stimulates further searches for caspase-3 inhibitors. Thus, caspase inhibitors in a series of quinazolines have recently been discovered, the substances have moderate activity and selectivity (Scott C., Sobotka-Briner C., Wilkins D., Jacobs R., Folmer J., Frazee W., Bhat R., Ghanekar S ., Aharony D. Novel Small Molecule Inhibitors of Caspase-3 Block Cellular and Biochemical Features of Apoptosis. Pharmaco L. Exp. Therap. 2003, 304 (1): 433-440).

Various 3-oxo-1,2,3,4-tetrahydroquinoxalines are known, including those having different types of biological activity (Riess, G .; Kleim, J.-P .; Rosner, M .; Paessens, A .; Blunck, M. Eur. Pat. EP 0655166 B1, 2003. Meichsner, C .; Riess, G .; Winkler, I. Eur. Pat. EP 0708093 B1, 2001. Billhardt, U.-M .; Rosner, M .; Riess , G .; Winkler, I .; Bender, R. Pat. EP 0 509 398 B1, 2001. Kleim, J.-P .; Bender, R .; Kirsch, R .; Meichsner, C .; Paessens, A. Antimicrob, Agents & Chemoter. 1995, 39 (10), 2253-2257).

However, in the scientific and patent literature to date, there has been no information on the antiprotease activity of substituted 1,2,3,4-tetrahydroquinoxalines and the biological activity of substituted 3-oxo-1,2,3,4-tetrahydroquinoxaline carboxylic acids of their esters and amides.

As a result of studies aimed at the search for new biologically active compounds, including selectively suppressing programmed cell death (apoptosis), the inventors found that substituted 3-oxo-1,2,3,4-tetrahydroquinoxalines are a new chemotype of non-peptide caspase inhibitors 3.

More specifically, this invention relates to “molecular tools” and active drug substances that selectively suppress programmed cell death (apoptosis); as well as pharmaceutical compositions containing substituted 3-oxo-1,2,3,4-tetrahydroquinoxalines as active substances, including new substituted 3-oxo-1,2,3,4-tetrahydroquinoxaline carboxylic acids, their esters and amides as well as the method of their preparation and the method of its use for treating and preventing the development of various diseases associated with increased activation of apoptosis, for example, acute ischemic lesions (for example, stroke, myocardial infarction), neurodegenerative (for example, Parkinson's and Alzheimer's disease), viral behind diseases (e.g., hepatitis C and AIDS), etc. The present invention also relates to new substituted 3-oxo-1,2,3,4-tetrahydroquinoxalinecarboxylic acids, their esters and amides.

The following are definitions of terms that are used in the description of this invention:

“Combinatorial library” means a collection of compounds obtained by parallel synthesis designed to search for a leader or optimize the biological activity of a lead compound, each library compound corresponding to a common scaffold and the library is a collection of related homologues or analogues.

“Focused library” means a combinatorial library, or a collection of several combinatorial libraries, or a collection of libraries and substances, specially organized in order to increase the likelihood of finding hits and leaders or to increase the efficiency of their optimization. The design of focused libraries, as a rule, is associated with a directed search for effectors (inhibitors, activators, agonists, antagonists, etc.) of specific biological targets (enzymes, receptors, ion channels, etc.).

“Lead compound” means a compound with outstanding activity related to a particular disease.

“Scaffold” means the general structural formula or molecular framework or invariant region of compounds characteristic of all compounds included in the combinatorial library.

“Chemotype” means a series of compounds, united by a common structural formula, and having a certain common property, for example, some kind of physiological activity. You can say, for example, "a new chemotype of potassium channel activators," or "a known chemotype of kinase inhibitors," etc. As a rule, the presence of a common structural fragment in compounds within the same chemotype is a necessary and sufficient condition for their common property.

“Substituent" means a chemical radical that binds to a scaffold or intermediate in the synthesis process. The substituent may be a halogen atom, a hydroxyl group, a carboxyalkyl group, a carboxyl group, a carbamoyl group or an inert substituent.

“Non-interfering substituent” means a low or non-reactive radical including, but not limited to C ₁ -C ₇ alkyl, C ₂ -C ₇ alkenyl, C ₂ -C ₇ alkynyl, C ₁ -C ₇ alkoxy , C ₇ -C ₁₂ aralkyl, substituted aralkyl, C ₇ -C ₁₂ heterocyclylalkyl, substituted heterocyclylalkyl, C ₇ -C ₁₂ alkaryl, C ₃ -C ₁₀ cycloalkyl, C ₃ -C ₁₀ cycloalkenyl, phenyl, substituted phenyl, toluyl, xylene , biphenyl, C ₂ -C ₁₂ alkoxyalkyl, C ₂ -C ₁₀ alkylsulfinyl, C ₂ -C ₁₀ alkylsulfonyl, (CH ₂ ) _m -O- (C ₁ -C ₇ alkyl), - (CH ₂ ) _m -N ( C ₁ -C ₇ alkyl) _n, aryl, substituted aryl, substituted alkoxy, fluoroalkyl, aryloxy keel, heterocyclyl, substituted heterocyclyl, and nitroalkyl; where m and n are from 1 to 7. Preferred “inert substituents” are C ₁ -C ₇ alkyl, C ₂ -C ₇ alkenyl, C ₂ -C ₇ alkynyl, C ₁ -C ₇ alkoxy, C ₇ -C ₁₂ aralkyl, C ₇ -C ₁₂ alkaryl, C ₃ -C ₁₀ cycloalkyl, C ₃ -C ₁₀ cycloalkenyl, phenyl, substituted phenyl, (CH ₂ ) _m -O- (C ₁ -C ₇ alkyl), - (CH ₂ ) _m- N (C ₁ -C ₇ alkyl) _n , aryl, substituted aryl, heterocyclyl and substituted heterocyclyl.

“Substituted group, substituted radical or scaffold” means, respectively, a group, radical or scaffold that has a substituent, including but not limited to: an inert substituent, a halogen atom, a nitro group, a cyano group, a sulfo group, a hydroxyl group, an amino group, a carboxyalkyl group, a carboxyl group, carbamoyl group. For example, substituted alkyl means alkyl in which one or more substituents, for example, hydroxyalkyl or methoxycarbonylalkyl, aminomethoxycarbonylmethyl, dimethylaminoalkyl, 2-hydroxy-2-methoxycarbonyl-ethyl, etc .; substituted amino group means an amino group which has one or two substituents, for example, an acylamino group, an N, N-dialkylamino group, an N-acyl-N-aryl amino group, an acetyl-methoxycarbonylmethylamino group, etc .; substituted phenyl means phenyl which has one or more substituents, for example 2-methoxycarbonylphenyl, 4-amino-3-methoxycarbonylphenyl, 3,4-diaminophenyl, etc.

“Optionally substituted group, optionally substituted radical or scaffold” means, respectively, a group, radical or scaffold, including groups, radicals or scaffolds with and without substituents. For example, the term optionally substituted amino group includes: an unsubstituted amino group and amino groups containing any substituents not contradicting the chemistry, including but not limited to acylamino groups, N, N-dialkylamino groups, N-acyl-N-arylamino groups, acylmethoxycarbonylmethylamino groups, etc.

“Aryl” means one or more aromatic rings, each of which includes 5 or 6 carbon atoms. “Aryl” may be a condensed polycycle, for example, as naphthalene, or non-condensed, for example, as biphenyl. “Substituted aryl” has one or more “non-interfering” substituents.

“Halogen” means a fluorine, chlorine, bromine or iodine atom.

“Heterocycle” means one or more saturated or aromatic rings with 5, 6 or 7 atoms, at least one of which is a heteroatom. Preferred heteroatoms are sulfur, oxygen and nitrogen. A “heterocycle” may be a condensed polycycle, for example, benzimidazole, benzoxazole. benzthiazole, quinoline or non-condensed, such as bipyridyl.

“Azoheterocycle” means a heterocycle comprising at least one nitrogen atom, for example, benzimidazole, benzoxazole, benzthiazole, quinoline.

“Substituted heterocycle” means a heterocycle having one or more “non-interfering” substituents.

“Parallel synthesis” means a method for conducting chemical synthesis of a combinatorial library of individual compounds.

The aim of the present invention is to provide a new chemotype of biologically active compounds selectively suppressing programmed cell death (apoptosis).

The goal is achieved by physiologically active substituted 3-oxo-1,2,3,4-tetrahydroquinoxaline general formula 1

wherein:

R ¹ represents a substituted sulfanyl group or a substituted sulfonyl group containing, as substituents, optionally substituted C _1-4 alkyl, optionally substituted C _3-8 cycloalkyl, optionally substituted in the aryl and / or alkyl moiety of aryl C _1-4 alkyl, optionally substituted in heterocyclic and / or an alkyl fragment of heterocyclyl C _1-4 alkyl, optionally substituted aryl, optionally substituted heterocyclyl;

R ² and R ³ independently represent a hydrogen, halogen, CN, NO ₂ atom, an optionally substituted hydroxy group or an optionally substituted amino group, an optionally substituted carboxyl group, an optionally substituted carbamoyl, an optionally substituted aryloxycarbonyl group or an optionally substituted heterocyclylcarbonyl group;

R ⁴ and R ⁵ independently represent: a hydrogen atom or an inert substituent; possessing the properties of caspase-3 inhibitors for obtaining a pharmaceutical composition and for experimental (in vitro, in vivo) studies of apoptosis processes as pharmacological tools.

An object of the present invention is also to provide a new pharmaceutical composition in the form of tablets, capsules or injections in a pharmaceutically acceptable package.

The goal is achieved by a pharmaceutical composition having the properties of caspase-3 inhibitors in the form of tablets, capsules or injections, placed in a pharmaceutically acceptable package containing, as an active substance, a pharmaceutically effective amount of substituted 3-oxo-1,2,3,4-tetrahydroquinoxaline of the general formula 1.

The aim of the present invention is the creation of a new pharmaceutical composition for the treatment and prevention of various diseases of warm-blooded animals and people associated with increased activation of apoptosis in the form of tablets, capsules or injections placed in a pharmaceutically acceptable package.

The goal is achieved by the pharmaceutical composition for the treatment and prevention of various diseases of warm-blooded animals and humans associated with increased activation of apoptosis in the form of tablets, capsules or injections placed in a pharmaceutically acceptable package containing a pharmaceutically effective amount of 3-oxo-1,2 as an active substance , 3,4-tetrahydroquinoxaline of the general formula 1.

The aim of the present invention is also to provide a method for producing a new pharmaceutical composition.

The goal is achieved by a method of obtaining a pharmaceutical composition having the properties of caspase-3 inhibitors by mixing the active substance with an inert filler, diluent and / or solvent, the distinguishing feature of which is that a pharmaceutically effective amount of 3-oxo-1 is used as the active substance, 2,3,4-tetrahydroquinoxaline of the general formula 1.

The aim of the present invention is also a method of treating and preventing the development of various diseases of warm-blooded animals and people associated with increased activation of apoptosis.

This goal is achieved by introducing to a warm-blooded animal or human a pharmaceutical composition containing, as an active substance, a pharmaceutically effective amount of 3-oxo-1,2,3,4-tetrahydroquinoxaline of the general formula 1.

The aim of the present invention is the creation of new biologically active 3-oxo1,2,3,4-tetrahydroquinoxaline.

The goal is achieved by substituted 3-oxo-1,2,3,4-tetrahydroquinoxalinecarboxylic acids with their esters or amides of the general formula 2

in which:

R ¹ , R ² , R ⁴ and R ⁵ are as defined above for the compounds of general formula 1, and R ⁶ is an optionally substituted hydroxy group, an optionally substituted amino, an optionally substituted aryloxy or an optionally substituted heterocyclyl group.

The synthesis scheme of 3-oxo-1,2,3,4-tetrahydroquinoxalines of the general formula 1 and 2 is presented below and is based on known reactions.

Published methods (Riess, G .; Kleim, J.-P .; Rosner, M .; Paessens, A .; can also be used to obtain 3-oxo-1,2,3,4-tetrahydroquinoxaline of general formula 1 and 2. Blunck, M. Eur. Pat. EP 0655166 B1, 2003. Meichsner, C .; Riess, G .; Winkler, I. Eur. Pat. EP 0708093 Bl, 2001. Billhardt, U.-M .; Rosner, M. ; Riess, G .; Winkler, I .; Bender, R. Pat. EP 0 509 398 Bl, 2001. Kleim, J.-P .; Bender, R .; Kirsch, R .; Meichsner, C .; Paessens, A. Antimicrob, Agents & Chemoter. 1995, 39 (10), 2253-2257).

Reagents used as starting materials are commercially available. The invention is described below using specific examples of the preparation of specific compounds and a combinatorial library. The structures of the compounds obtained were confirmed by chemical, chromatographic and spectral analysis. Liquid-phase parallel synthesis of new compounds and a combinatorial library was carried out using special synthesizers "CombiSyn-012-3000" [M. Baru, A. Ivaschenko, Russian Patent 2180609, 2002; PCT WO 02/087740 A1, 2002.] and equipment [Technology Platform. In Custom Chemistry; Chemical Diversity Labs, Inc .; San Diego, CA, 2002; p.5.].

The biological (antiprotease) activity of the compounds was determined on a serine protease (Caspase 3), which is involved in the regulation of programmed cell death (apoptosis). Caspase 3 activity was determined by the rate of cleavage of the peptide substrate containing the fluorescent molecule (methylcoumarin) in accordance with the protocol described in the Sigma-Aldrich Technical Bulletin [www.sigmaaldrich.com/sigma/bulletin/casp3fbul.pdf].

The invention is illustrated, but not limited to the following examples. All solvents and reagents were obtained from commercial sources such as Acros (Acros) (Belgium), Sigma-Aldrich (Sigma-Aldrich) (USA), Lancaster (Lancaster) (UK) and KemDiv (ChemDiv) (USA). Melting points (mp.) Were obtained on a device from Buchi (Switzerland) model B-520. ¹ H and ¹³ C NMR spectra were obtained on a Gemini-300 spectrometer (300 and 75 MHz, respectively) from Varian (USA) in CDCl ₃ or dimethyl sulfoxide-d ₆ . Chemical shifts are given on a scale of 6 (ppm). Internal standard tetramethylsilane.

The content of the main substance was monitored using HPLC on a Shimadzu 10-AV instrument (Luna-C18 column, Phenomenex, 25 cm (4.6 mm, UV detection at 215 and 254 nm) and LC-MS (HPLC-MS) on an Applied instrument Biosystems (Shimadzu 10-AV LC, Gilson-215 automatic sample feeding, API 150EX mass spectrometer, UV (215 and 254 nm) and ELS detectors, Luna-C18 column, Phenomenex, 5 cm (2 mm).

Analytical TLC was performed on silica gel on Silufol UV254 aluminum plates (5 cm (15 cm) (Kavalier, Czech Republic) or on glass plates with a 0.25 mm layer of silica gel 60 F ₂₅₄ (Merck, Germany). Visualization was carried out using UV light at a long 254 nm waves. Silica gel 5-40 μm (Chemapol, Czech Republic) and 63 μm (EM Science, USA) were used for chromatographic purification. According to LC / MS data, all synthesized compounds had a basic substance content higher than 95% (unless indicated) otherwise).

Examples 1

General method for producing 1,2,3,4-tetrahydroquinoxalines of general formula 1 and 2.

A. General method for producing 2-amino-3-sulfonylpropionic acids 5. In a 2 L flask equipped with a magnetic stirrer and reflux condenser, 1 mol of D, L-cysteine, 3.1.1 mol of the corresponding alkylating reagent 4, 2.2 mol of NaOH and 500 ml of water. The reaction mixture is heated at 80-90 ° C and stirring for 2-12 hours. The reaction mass is gradually cooled with stirring at 10 ° C and acidified with 2% hydrochloric acid to pH 5. The resulting product is separated, washed 5 times with 100 ml of water and dried. Receive acid 5, which is used in further synthesis without further purification. Yield 85-95%.

B. General method for producing 2- (2-nitroanilino) -3-sulfanylpropionic acids 7. Into a 2 L flask equipped with a magnetic stirrer and reflux condenser, 1 mol of the corresponding 2-halogen-nitrobenzene 6, 1.1 mol of the corresponding 2-amino -3-sulfonylpropionic acids 5, 2 mol NaOH and 500 ml of water. The reaction mixture is heated at 80-90 ° C and stirring for 8-14 hours. The reaction mass is gradually cooled with stirring at 10 ° C and acidified with 10% hydrochloric acid to pH 3-4. The resulting product is separated, washed 5 times with 100 ml of water and dried. Receive acid 7, which is used in further synthesis without further purification. The yield is 70-90%.

Example 2. General method for producing 2-sulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline 1.1. Dissolve 1 mol of 2- (2-nitroanilino) -3-sulfanylpropionic acid 7 in 500 ml of aqueous ammonia in a 4 L flask. To the resulting solution, 4 moles of sodium dithionite are added in portions at 50-60 ° C. The reaction mass is heated to boiling with stirring and boiled for 1 h. The reaction mass is cooled to room temperature and carefully acidified with 6 N hydrochloric acid. The resulting mass containing, according to LC MS 2 (-2-aminophenylamino) -3-sulfonylpropionic acid 8, was incubated for 4 hours with stirring and 60-70 ° C. And then cooled to room temperature. The precipitate is filtered off and washed on a filter to neutral wash water in Congo Red. The resulting product is dried to constant weight. Get 1.1 with a yield of 60-85%, including:

2- (2-Methylbenzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {1}: ¹ H-NMR (DMSO-d ₆ ) 2.35 (s, 3H, CH3 -Ar); 2.85 (s, 2H, -S-CH2-CH); 3.88 (t, 2H, S-CH2-Ar); 4.38 (ws, 1H, -CH-NH); 5.31 (ws, 1H, -NH-CH-); 6.99 (d, 1H, Ar); 7.27-7.64 (m, 6H, Ar); 11.36 (s, 1H, -NH-CO); 13.42 (ws, 1H, -COOH).

2- (2-Chloro-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {2}: ¹ H-NMR (DMSO-d ₆ ) 2.94 (s, 2H, - S-CH2-CH); 3.88 (t, 2H, S-CH2-Ar);

4.42 (ws, 1H, -CH-NH); 5.35 (ws, 1H, -NH-CH-); 7.21 (d, 1H, Ar); 7.27-7.99 (m, 6H, Ar);

11.38 (s, 1H, -NH-CO); 12.66 (ws, 1H, -COOH).

2- (3-Fluoro-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {3}: ¹ H-NMR (DMSO-d ₆ ) 2.78 (s, 2H, - S-CH2-CH); 3.22 (t, 2H, S-CH2-Ar); 4.09 (ws, 1H, -CH-NH); 6.44 (s, 1H, -CH-NH); 6.71 (d, 1H, Ar); 6.85-7.88 (m, 6H, Ar); 11.40 (s, 1H, -NH-CO); 13.84 (ws, 1H, -COOH).

2- (2-Fluoro-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {4}: ¹ H-NMR (DMSO-d ₆ ) 2.76 (s, 2H, - S-CH2-CH); 3.99 (t, 2H, S-CH2-Ar); 4.27 (ws, 1H, -CH-NH); 5.99 (s, 1H, -CH-NH); 6.71 (d, 1H, Ar); 6.66-7.08 (m, 3H, Ar); 7.29-8.08 (m, 3H, Ar); 10.94 (s, 1H, -NH-CO); 13.84 (ws, 1H, -COOH).

2- (3-Bromo-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {5}: Mol. weight 497.29, LC MS, m / z 408 (M + 1).

2- (2,5-Dimethyl-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {6}: ¹ H-NMR (DMSO-d ₆ ) 2.12 (s, 3H , CH3-Ar); 2.65 (s, 3H, CH3-Ar); 2.85 (s, 2H, -S-CH2-CH); 3.67 (t, 2H, S-CH2-Ar); 4.21 (ws, 1H, -CH-NH); 5.12 (ws, 1H, -NH-CH-); 6.85 (d, 1H, Ar); 7.17-7.75 (m, 5H, Ar); 10.24 (s, 1H, -NH-CO); 12.42 (ws, 1H, -COOH).

2- (2-Chloro-4-fluoro-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {7}: ¹ H-NMR (DMSO-d ₆ ) H-NMR 5 2.78 (s, 2H, -S-CH2-CH); 3.60 (t, 2H, S-CH2-Ar); 4.59 (ws, 1H, -CH-NH); 5.92 (ws, 1H, -NH-CH-); 6.64 (d, 1H, Ar); 7.45-8.02 (m, 5H, Ar); 11.39 (s, 1H, -NH-CO); 13.35 (ws, 1H, -COOH).

2- (4-Fluoro-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {8}

2- (2-Chloro-6-fluoro-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1 {9}

2- (4-Methyl-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {10}

2- (4-Chloro-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {11}

2- (3-Chloro-benzylsulfanylmethyl) -oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {12}

2-Methylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {13}

2 - ([1,3] dioxolan-2-ylmethylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {14}

3-oxo-2- (pyridin-3-ylmethylsulfanylmethyl) -1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {15}

3-Oxo-2- (pyridin-2-ylmethylsulfanylmethyl) -1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {16}

2- (Octahydroquinolisin-1-ylmethylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {17}

2- (5-Methoxycarbonyl-thiophen-2-ylmethylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {18}

2- (Adamantan-1-ylmethylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.1 {19}.

6-Methyl-2-methylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline 1.1 {20}: Mol. weight 222.31, LC MS, m / z 223 (M + 1).

8-Fluoro-2-methylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline 1.1 {21}: Mol. weight 226.27, LC MS, m / z 227 (M + 1).

7-Acetylamino-2-methylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline 1.1 {22}: Mol. weight 265.34, LC MS, m / z 266 (M + 1).

2-Benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline 1.1 {23}: Mol. weight 284.38, LC MS, m / z 285 (M + 1).

2-Benzylsulfanylmethyl-7-trifluoromethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline 1.1 {23}: Mol. weight 358.38, LC MS, m / z 359 (M + 1).

Example 3. General method for producing 2-sulfonylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline 1.2.

In a three-necked 1 L flask equipped with a reflux condenser, a thermometer and a dropping funnel, 0.1 mol of the corresponding 2-sulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline 1.1 and 300 ml of glacial acetic acid are placed. 2.5 mol of 20% aqueous hydrogen peroxide is added dropwise to the resulting solution over 1 h, maintaining the temperature of the reaction mass at 70-80 ° С (intensive cooling).

The reaction mass is boiled for 4 hours, then slowly cooled with stirring to 15 ° C. The precipitate is filtered off, washed five times with 60 ml portions of cold water, and then three times with 100 ml portions of cold ethanol. The resulting precipitate is dried over phosphorus pentoxide to constant weight, 1.2 is obtained with a yield of 70-80%, including:

2- (3-Bromo-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.2 {7} 3.38 (m, 1H, CH-CH2-SO2); 3.71 (d, 1H, CH-CH2-SO2, J = 6.8 Hz); 4.43-4.62 (m, 3H, Alk); 6.29 (ws, 1H, -NH-CH-); 6.78-8.65 (t, 7H, Ar); 10.58 (ws, 1H, -NH-CO); 13.55 (ws, 1H, -COOH).

2- (2-Fluoro-benzylsulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.2 {2}

3-Oxo-2-n-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.2 {3} 2.26 (s, 3H, CH3-Ar); 3.21 (m, 1H, CH-CH2-SO2); 3.64 (d, 1H, CH-CH 2 -SO 2, J = 7.3 Hz); 4.26-4.44 (m, 3H, Alk); 6.00 (ws, 1H, -NH-CH-); 6.62 (d, 1H, Ar); 7.15-7.55 (m, 6H, Ar); 10.12 (ws, 1H, -NH-CO); 12.44 (ws, 1H, -COOH).

2- (4-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.2 {4}

2- (3-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.2 (5}

2- (2-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.2 {6}

2- (3-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.2 {7}

2- (2,5-Dimethyl-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.2 {8}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.2 {9} 3.92 (m, 1H, CH-CH2-SO2); 4.04 (d, 1H, CH-CH 2 -SO 2, J = 6.5 Hz); 4.55-4.71 (m, 3H, Alk); 6.02 (ws, 1H, -NH-CH-); 6.62-8.31 (t, 6H, Ar); 10.29 (ws, 1H, -NH-CO); 13.65 (ws, 1H, -COOH).

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.2 {10} 2.28 (s, 3H, CH3-Ar); 3.25 (t, 1H, CH-CH2-SO2); 3.34 (d, 1H, CH-CH2-SO2, J = 7.1 Hz); 4.00-4.13 (t, 3H, Alk); 6.32 (ws, 1H, -NH-CH-); 6.44 (d, 1H, Ar); 7.01-7.48 (t, 6H, Ar); 11.07 (ws, 1H, -NH-CO); 13.14 (ws, 1H, -COOH).

2- (4-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.2 {11} 3.36 (t, 1H, CH-CH2-SO2); 3.85 (d, 1H, CH-CH2-SO2, J = 7.1 Hz); 4.48-4.65 (m, 3H, Alk); 6.12 (ws, 1H, -NH-CH-); 6.68 (d, 1H, Ar); 7.18-7.62 (m, 6H, Ar); 11.26 (ws, 1H, -NH-CO); 13.32 (ws, 1H, -COOH).

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 1.2 {12} 2.31 (s, 3H, CH3-Ar); 3.16 (m, 1H, CH-CH 2 -SO 2); 3.28 (d, 1H, CH-CH2-SO2, J = 7.3 Hz); 4.11-4.19 (m, 3H, Alk); 6.40 (ws. 1H, -NH-CH-); 6.58 (d, 1H, Ar); 7.12-7.51 (m, 6H, Ar); 10.96 (ws, 1H, -NH-CO); 14.00 (ws, 1H, -COOH).

2-Benzylsulfonylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline 1.2 {13}: Mol. weight 316.38, LC MS, m / z 317 (M + 1).

2-Benzylsulfonylmethyl-7-trifluoromethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline 1.2 {14}: Mol. weight 384.38, LC MS, m / z 385 (M + 1).

Example 4. General method for the synthesis of substituted amides of 3-oxo-1,2,3,4-tetrahydroquinoxaline-7-carboxylic acids 2. Dissolve 300 mmol of the corresponding acid 1.1, 1.2 or 1.3 and 305 mmol carbonyl diimidazole, 100 ml of anhydrous dimethylformamide can withstand 10 min at room temperature, and then 3 hours, the resulting solution was maintained at 80-90 ° C. The resulting solution was diluted with 500 ml of anhydrous dimethylformamide, then distributed into 120 combinatorial synthesizer reactors (5 ml into the reactor, approximately 3 mmol of imidazolid acid). 3.2 mmol of the corresponding primary or secondary amine in 3 ml of anhydrous dimethylformamide are added to each reactor. The reaction mass is kept for 8 hours with stirring and 75-80 ° C, after which 50 ml of cold water are added to each reactor. The precipitates are filtered off and recrystallized from ethanol-dimethylformamide. Amides 2 are obtained with a yield of 60-80%, including:

2- (2-Methylbenzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid propylamide 2.1 {1}: ¹ H-NMR (DMSO-d ₆ ) 0.91 (t, 3H, CH3 -CH2); 1.52 (q, 2H, CH3-CH2-); 2.29 (s, 3H, CH3-Ar); 2.78 (s, 2H, -S-CH2-CH); 3.17 (d, 2H, -CH2- NH); 3.75 (t, 2H, S-CH2-Ar); 4.13 (s, 1H, -CH-NH); 6.44 (s, 1H, -NH-CH-); 6.65 (d, 1H, Ar); 7.01-7.31 (m, 6H, Ar); 7.92 (t, 1H, CH2-NH-CO-); 10.42 (s, 1H, -NH-CO).

2- (2-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid phenethylamide 2.1 {2}: ¹ H-NMR (DMSO-d ₆ ) 2., 72- 2.93 (m, 4H, Alk); 3.45 (q, 2H, RP-CH2-CH2); 3.86 (t, 2H, S-CH2-Ar); 4.12 (s, 1H, -CH-NH); 6.28 (s , 1H, -CH-NH); 6.65 (d, 1H, Ar); 7.11-7.42 (m, 11H, Ar); 7.93 (t, 1H, CH2-NH-CO-); 10.42 (s, 1H, - NH-CO).

4- [2- (2-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carbonyl] piperazine-1-carboxylic acid ethyl ester 2.1 {3}: H-NMR (DMSO- d ₆ ) 1.29 (t, 3H, CH3-CH2O); 2.84 (m, 1H, CH-CH2-S); 3.45, 3.53 (s, s, 8H, 4CH2-piperazine); 3.87 (t, 2H, S- CH2-Ar); 4.03-4.18 (m, 3H, Alk); 6.31 (s, 1H, -CH-NH); 6.70 (d, 1H, Ar); 6.85 (s, 2H, Ar); 7.22 (s, 2H, Ar); 7.36 (s, 2H, Ar); 10.42 (s, 1H, -NH-CO).

3- (2-Chloro-benzylsulfanylmethyl) -7- (4-phenylpiperazin-1-carbonyl) -3,4-dihydro-1H-quinoxalin-2-one 2.1 {4}: ¹ H-NMR (DMSO-d ₆ ) 2.85 (m, 2H, -S-CH2-CH); 3.2 (s, 4H, (CH2) 2N-Ar); 3.70 (s, 4H, (CH2) 2N-CO); 3.86 (t, 2H, S-CH2-Ar); 4.10 (s, 1H, -CH-NH); 6.31 (s, 1H, -CH-NH); 6.67-6.94 (m, 6H, Ar); 7.15-7.42 (m, 6H, Ar); 10.42 (s, 1H, -NH-CO).

2- (2-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid [2- (4-chlorophenyl) ethyl] -amide 2.1 {5}: ¹ H-NMR ( DMSO-d ₆ ) 2.74-2.91 (m, 4H, Alk); 3.43 (d, 2H, Ph-CH2-CH2); 3.86 (t, 2H, S-CH2-Ar); 4.11 (s, 1H, -CH -NH); 6.30 (s, 1H, -CH-NH); 6.68 (d, 1H, Ar); 7.12-7.45 (m, 11H, Ar); 7.96 (t, 1H, CH2-NH-CO-); 10.43 (s, 1H, -NH-CO).

3- (2-Chloro-benzylsulfanylmethyl) -7- [4- (2-fluoro-phenyl) -piperazin-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.1 {6}: ¹ H -NMR (DMSO-d ₆ ) 2.83 (m, 2H, -S-CH2-CH); 3.07 (s, 4H, (CH2) 2N-Ar); 3.52 (s, 4H, (CH2) 2N-CO); 3.86 (t, 2H, S-CH2-Ar); 4.10 (s, 1H, -CH-NH); 6.28 (s, 1H, -CH-NH); 6.70 (d, 1H, Ar); 6.84-7.14 (m, 6H, Ar); 7.17-7.43 (m, 4H, Ar); 10.43 (s, 1H, -NH-CO).

2- (3-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid [2- (4-chloro-phenyl) -ethyl] -amide 2.1 {7}: ¹ H- NMR (DMSO-d ₆ ) 2.69-2.87 (m, 4H, Alk); 3.42 (m, 2H, Ph-CH2-CH2); 3.74 (t, 2H, S-CH2-Ar); 4.09 (s, 1H, -CH-NH); 6.33 (s, 1H, -CH-NH); 6.65 (d, 1H, Ar); 6.91 (t, 1H, Ar); 7.03-7.33 (m, 9H, Ar); 7.93 (t , 1H, CH2-NH-CO-); 10.40 (s, 1H, -NH-CO).

2- (3-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methyl-benzylamide 2.1 {8}: ¹ H-NMR (DMSO-d ₆ ) 2.31 (s , 3H, CH3-Ar); 2.74 (m, 2H, CH-CH2-S); 3.72 (t, 2H, S-CH2-Ar); 4.08 (s, 1H, -CH-NH); 4.4 (d, 2H, -CH2-NH-CO); 6.33 (s, 1H, -CH-NH); 6.69 (d, 1H, Ar); 6.93 (t, 1H, Ar); 7.03-7.37 (m, 9H, Ar) ; 8.37 (t, 1H, CH2-NH-CO-); 10.41 (s, 1H, -NH-CO).

7- (3,4-Dihydro-1H-isoquinolin-2-carbonyl) -3- (3-fluorobenzylsulfanylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {9}: ¹ H-NMR (DMSO -d ₆ ) 2.75 (m, 2H, CH-CH 2 -S); 2.90 (t, 2H, Ar-CH2-CH2); 3.74 (m, 4H, Alk); 4.06 (s, 1H, -CH-NH); 4.65 (s, 2H, Ar-CH 2 -NH); 6.24 (s, 1H, -CH-NH); 6.69 (d, 1H, Ar); 6.88 (m, 3H, Ar); 7.02-7.15 (m, 6H, Ar); 7.22 (q, 1H, Ar); 10.40 (s, 1H, -NH-CO).

2- (3-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 2-methoxybenzylamide 2.1 {10}: ¹ H-NMR (DMSO-d ₆ ) 2.75 (m , 2H, CH-CH2-S); 3.64 (t, 2H, S-CH2-Ar); 3.88 (s, 3H, CH3O); 4.11 (s, 1H, -CH-NH); 4.43 (d, 2H, -CH2-NH-CO); 6.37 (s, 1H, -CH-NH); 6.70 (d, 1H, Ar); 6.82-7.42 (m, 10H, Ar); 8.17 (t, 1H, CH2-NH- CO-); 10.45 (s, 1H, -NH-CO).

2- (2-Chloro-4-fluoro-benzenesulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (furan-2-ylmethyl) -amide 2.1 {11} 2.81 (m, 2H CH-CH2-S); 3.81 (t, 2H, S-CH2-Ar); 4.12 (s, 1H, -CH-NH); 4.42 (d, 2H, -CH2-NH-CO); 6.17 (s, 1H, -CH-NH); 6.30 (s, 1H, C-H Furyl); 6.37 (s, 1H, C-H Furyl); 6.65 (d, 1H, Ar); 7.00 (t, 1H, Ar); 7.17 (d, 1H, Ar); 7.25-7.43 (m, 4H, Ar); 8.35 (t, 1H, CH2-NH-CO-); 10.42 (s, 1H, -NH-CO).

3- (3-Fluoro-benzylsulfanylmethyl) -7- (3-methyl-4-m-tolyl-piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {12}

3- (2-Methylbenzylsulfanylmethyl) -7- (4-phenylpiperazin-1-carbonyl) -3,4-dihydro-1H-quinoxalin-2-one 2.1 {13}

3- (2-Methyl-benzylsulfanylmethyl) -7- (4-phenylpiperazin-1-carbonyl) -3,4-dihydro-1H-quinoxalin-2-one 2.1 {14}

2- (2-Methyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 2-chloro-benzylamide 2.1 {15}

2- (2-Methyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid [2- (4-chloro-phenyl) -ethyl] -amide 2.1 {16}

7- [4- (2-Fluoro-phenyl) piperazin-1-carbonyl] -3- (2-methyl-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {17}

2- (2-Methylbenzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid phenethylamide 2.1 {18}

2- (2-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 2-methoxybenzylamide 2.1 {19}

4- [2- (2-Fluoro-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carbonyl] piperazine-1-carboxylic acid ethyl ester 2.1 {20}

3- (2-Fluoro-benzylsulfanylmethyl) -7 piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {21}

2- (2-Fluoro-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid phenethylamide 2.1 {22}

7- (1,4-dioxa-8-aza-spiro [4.5] decan-8-carbonyl) -3- (2-fluoro-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {23 }

3- (2-Fluoro-benzylsulfanylmethyl) -7- (4-phenyl-piperazine-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {24}

7- [4- (2-Chlorophenyl) piperazine-1-carbonyl] -3- (2-fluoro-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {25}

3- (2-Fluoro-benzylsulfanylmethyl) -7- (4-pyridin-2-yl-piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {26}

3- (2-Fluoro-benzylsulfanylmethyl) -7- [4- (4-methoxy-phenyl) -piperazin-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.1 {27}

3- (2-Fluoro-benzylsulfanylmethyl) -7- [4- (2-fluoro-phenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.1 {28}

7- (4-Benzyl-piperazin-1-carbonyl) -3- (2-fluoro-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {29}

7- (2,3-dihydro-indol-1-carbonyl) -3- (2-methyl-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {30}

7- (1,4-dioxa-8-aza-spiro [4.5] decan-8-carbonyl) -3- (2-methyl-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {31 }

4 - {[2- (2-Methyl-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-carbonyl] amino} -piperidin-1-carboxylic acid ethyl ester 2.1 {32}

2- (2-Methyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-dipropylamino-propyl) -amide 2.1 {33}

7- [4- (2-Methyl-phenyl) -piperazin-1-carbonyl] -3- (2-methyl-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxalin-2-one 2.1 {34}

2- (2-Methylbenzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) -amide 2.1 {35}

2- (2-Methyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid hexylamide 2.1 {36}

2- (2-Methyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid heptylamide 2.1 {37}

2- (2-Methylbenzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-morpholin-4-yl-ethyl) -amide 2.1 {38}

3- (2-Methyl-benzylsulfanylmethyl) -7- (3-methyl-n-tolyl-piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {39}

2- (3-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid acid (pyridin-3-ylmethyl) -amide 2.1 {40}

2- (3-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-methoxyethyl) -amide 2.1 {41}

2- (3-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid heptylamide 2.1 {42}

2- (3-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid octylamide 2.1 {43}

2- (3-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid hexylamide 2.1 {44}

4- [2- (2-Methyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carbonyl] piperazine-1-carboxylic acid ethyl ester 2.1 {45}

2- (2-Chloro-4-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2,2-diethoxyethyl) -amide 2.1 {46}

2- (3-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid allylamide 2.1 {47)

2- (2,5-Dimethyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (pyridin-3-ylmethyl) -amide 2.1 {48}

3- (2,5-Dimethyl-benzylsulfanylmethyl) -7- (1,4-dioxa-8-aza-spiro [4.5] decan-8-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {49}

2- (2,5-Dimethyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2,2-diethoxyethyl) -amide 2.1 {50}

2- (2,5-Dimethyl-benzylsulfanylmethyl-3-oxo-1,2,3.4-tetrahydroquinoxaline-6-carboxylic acid (3-dimethylamino-propyl) -amide 2.1 {51}

2- (2,5-Dimethyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-morpholin-4-yl-propyl) -amide 2.1 {52}

2- (2,5-Dimethyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2,2-dimethoxyethyl) -amide 2.1 {53}

2- (2-Chloro-4-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 2-methoxybenzylamide 2.1 {54}

2- (2-Chloro-4-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-b-carboxylic acid (3-morpholin-4-yl-propyl) -amide 2.1 {55}

2- (2-Chloro-4-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 2-chloro-benzylamide 2.1 {56}

2- (4-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-methoxy-propyl) -amide 2.1 {57}

2- (4-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid hexylamide 2.1 {58}

2- (4-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid propylamide 2.1 {59}

2- (2,5-Dimethyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid heptylamide 2.1 {60}

2- (2,5-Dimethyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-morpholin-4-yl-ethyl) -amide 2.1 {61}

4- [2- (2,5-Dimethyl-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carbonyl] piperazine-1-carboxylic acid ethyl ester 2.1 {62}

2- (2-Chloro-4-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (pyridin-3-ylmethyl) -amide 2.1 {63}

7- (1,4-dioxa-8-aza-spiro [4.5] decane-8-carbonyl) -3- (3-fluoro-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {64 }

2- (3-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-methoxy-propyl) -amide 2.1 {65}

2- (3-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-morpholin-4-yl-propyl) -amide 2.1 {66}

2- (3-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid hexylamide 2.1 {67}

2- (2-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid allylamide 2.1 {68}

2- (2-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid propylamide 2.1 {69}

2- (2-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid hexylamide 2.1 {70}

2- (2-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-methoxyethyl) -amide 2.1 {71}

2- (2-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid octylamide 2.1 {72}

2- (2,5-Dimethyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-ethoxy-propyl) -amide 2.1 {73}

2- (4-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-methoxyethyl) -amide 2.1 {74}

3- (2-Chloro-6-fluoro-benzylsulfanylmethyl) -7- (1,4-dioxa-8-aza-spiro [4.5] decan-8-carbonyl) -3,4-dihydro-1H-quinoxaline-2- he is 2.1 {75}

2- (2-Chloro-6-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid hexylamide 2.1 {76}

2- (2-Chloro-6-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-methoxyethyl) -amide 2.1 {77}

3- (2-Chloro-6-fluoro-benzylsulfanylmethyl) -7- (4-phenyl-piperidin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {78}

2- (3-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid octylamide 2.1 {79}

2- (3-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid allylamide 2.1 {80}

2- (4-Methylbenzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid hexylamide 2.1 {81}

2- (4-Methylbenzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (pyridin-3-ylmethyl) -amide 2.1 {82}

2- (4-Methyl-benzisulfanylmethyl-3-oxo -], 2,3,4-tetrahydroquinoxaline-6-carboxylic acid allylamide 2.1 {83}

2- (4-Methylbenzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid octylamide 2.1 {84}

2- (4-Methyl-benzylsulanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-methoxy-propyl) -amide 2.1 {85}

2- (4-Methyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid propylamide 2.1 {86}

7- (1,4-dioxa-8-aza-spiro [4,5] decan-8-carbonyl) -3- (4-methyl-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {87}

2- (4-Methyl-benzylsulfanylmethyl-2-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-morpholin-4-yl-propyl) -amide 2.1 {88}

7- (Azepan-1-carbonyl) -3- (2,5-dimethyl-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {89}

2- (4-Methyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) -amide 2.1 {90}

2- (4-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-morpholin-4-yl-propyl) -amide 2.1 {91}

2- (4-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid hexylamide 2.1 {92}

2- (4-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid allylamide 2.1 {93}

2- (4-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid octylamide 2.1 {94}

2- (4-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-methoxy-propyl) -amide 2.1 {95}

3- (2-Chloro-benzylsulfanylmethyl) -7- (4-methyl-piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {96}

3- (2-Chloro-benzylsulfanylmethyl) -7- (4-pyridin-2-yl-piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {97}

3- (2-Chloro-benzylsulfanylmethyl) -7- [4- (4-fluoro-phenyl) -piperazin-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.1 {98}

2- (2-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopentylamide 2.1 {99}

2- (2-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methoxybenzylamide 2.1 {100}

2- (2-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methyl-benzylamide 2.1 {101}

2- (2-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 3-methyl-benzylamide 2.1 {102}

2- (2-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-cyclohex-1-enyl-ethyl) -amide 2.1 {103}

2- (2-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclohexylamide 2.1 {104}

7- [4- (2,3-Dimethyl-phenyl) piperazin-1-carbonyl] -3- (3-fluoro-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {105}

7- [4- (2,5-Dimethyl-phenyl) piperazine-1-carbonyl] -3- (3-fluoro-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxalin-2-one 2.1 {106}

7- [4- (5-Chloro-2-methyl-phenyl) piperazine-1-carbonyl] -3- (3-fluoro-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxalin-2-one 2.1 {107 }

3- (3-Fluoro-benzylsulfanylmethyl) -7- (4-methyl-piperisin-1-carbonyl) -3,4-dihydro-1H-quinoxalin-2-one 2.1 {108}

3- (3-Fluoro-benzylsulfanylmethyl) -7- [4- (4-fluoro-phenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.1 {109}

3- (3-Fluoro-benzylsulfanylmethyl) -7- [4- (4-methoxy-phenyl) piperazin-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.1 {110}

2- (3-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid sec-butylamide 2.1 {111}

2- (3-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-chloro-benzylamide 2.1 {112}

2- (3-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopentylamide 2.1 {113}

2- (3-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid isopropylamide 2.1 {114}

2- (3-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid phenethylamide 2.1 {115}

2- (3-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (tetrahydro-furan-2-ylmethyl) -amide 2.1 {116}

2- (3-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (furan-2-ylmethyl) -amide 2.1 {117}

2- (3-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid butylamide 2.1 {118}

3- (2-Methylbenzylsulfanylmethyl) -7- (piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {119}

7- [4- (2,3-Dimethyl-phenyl) piperazin-1-carbonyl] -3- (2-methyl-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {120}

3- (2-Methylbenzylsulfanylmethyl) -7- (3-methyl-4-m-tolyl-piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {121}

3- (2-Methyl-benzylsulfanylmethyl) -7- [4- (3-trifluoromethyl-phenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.1 {122}

2- (2-Methylbenzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid sec-butylamide 2.1 {123}

2- (2-Methylbenzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-chlorobenzylamide 2.1 {124}

2- (2-Methyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid [2- (3,4-dimethoxy-phenyl) -ethyl] -amide 2.1 {125}

2- (2-Methylbenzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methoxybenzylamide 2.1 {126}

2- (2-Methyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methyl-benzylamide 2.1 {127}

2- (2-Methylbenzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 3-methoxybenzylamide 2.1 {128}

2- (2-Methyl-benzylsulfanylmethyl-3-oxo-], 2,3,4-tetrahydroquinoxaline-6-carboxylic acid butylamide 2.1 {129}

7- [4- (2,5-Dimethyl-phenyl) piperazin-1-carbonyl] -3- (4-methyl-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {130}

3- (4-Methylbenzylsulfanylmethyl) -7- (3-methyl-4-m-tolyl-piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {131}

3- (4-Methyl-benzylsulfanylmethyl) -7- (4-pyridin-2-yl-piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {132}

7- [4- (4-Fluoro-phenyl) piperazin-1-carbonyl] -3- (4-methyl-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxalin-2-one 2.1 {133}

7- [4- (4-Methoxy-phenyl) piperazin-1-carbonyl] -3- (4-methyl-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {134}

3- (4-Methylbenzylsulfanylmethyl) -7- (morpholine-4-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 1.1 {135}

2- (4-Methyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopentylamine 2.1 {136}

2- (4-Methylbenzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methylbenzylamide 2.1 {137}

2- (4-Methylbenzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-methyl-butyl) -amide 2.1 {138}

2- (4-Methyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid phenethyl-amide 2.1 {139}

2- (4-Methyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-cyclohex-1-enyl-ethyl) -amide 2.1 {140}

2- (4-Methyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (furan-2-ylmethyl) -amide 2.1 {141}

2- (4-Methyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid benzylamide 2.1 {142}

2- (4-Methylbenzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid butylamide 2.1 {143}

7- [4- (2,5-Dimethyl-phenyl) piperazin-1-carbonyl] -3- (4-fluoro-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {144}

7- [4- (5-Chloro-2-methyl-phenyl) piperazine-1-carbonyl] -3- (4-fluoro-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {145 }

3- (4-Fluoro-benzylsulfanylmethyl) -7- (3-methyl-4-m-tolyl-piperazine-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-oi 2.1 {146}

3- (4-Fluoro-benzylsulfanyllmethyl) -7- (4-methyl-piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {147}

3- (4-Fluoro-benzylsulfanylmethyl) -7- [4- (4-fluoro-phenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.1 {148}

7- (4-Benzo [1,3] dioxol-5-ylmethyl-piperazin-1-carbonyl) -3- (4-fluoro-benzylsulfanylmethyl) -3,4-dihydro-1H-quinoxalin-2-one 1.1 {149 }

2- (4-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-chloro-butylamide 2.1 {150}

2- (4-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopentylamide 2.1 {151}

2- (4-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methoxybenzylamide 2.1 {152}

2- (4-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methyl-benzylamide 2.1 {153}

2- (4-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 3-methoxybenzylamide 2.1 {154}

2- (4-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (1,2,3,4-tetrahydro-naphthalen-1-yl) -amide 1.1 {155}

2- (4-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-ethyl-hexyl) -amide 2.1 {156}

2- (4-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (furan-2-ylmethyl) -amide 2.1 {157}

2- (4-Fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid butylamide 1.1 {158}

3- (4-Chloro-benzylsulfanylmethyl) -7- [4- (2,3-dimethyl-phenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.1 {159}

3- (4-Chloro-benzylsulfanylmethyl) -7- (3-methyl-4-m-tolyl-piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {160}

2- (4-Chloro-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid benzylamide 2.1 {161}

2- (4-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopentylamide 2.1 {162}

2- (4-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopropylamide 2.1 {163}

2- (4-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 3-methoxybenzylamide 2.1 {164}

2- (4-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (furan-2-ylmethyl) -amide 2.1 {165}

2- (4-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid butylamide 2.1 {166}

2- (3-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-methyl-butyl) -amide 2.1 {167}

2- (3-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid phenethylamide 2.1 {168}

2- (3-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-cyclohex-1-enyl-ethyl) -amide 2.1 {169}

2- (3-Chloro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (furan-2-ylmethyl) -amide 2.1 {170}

3- (2,5-Dimethyl-benzylsulfanylmethyl) -7- (pyrrolidin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {171}

3- (2,5-Dimethyl-benzylsulfanylmethyl) -7- (4-pyridin-2-yl-piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {172}

2- (2,5-Dimethyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid [2- (3,4-dimethoxyphenyl) ethyl] amide 2.1 {173}

2- (2,5-Dimetip-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid phenethylamide 2.1 {174}

2- (2,5-Dimethyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid benzylamide 2.1 {175}

3- (2-Chloro-6-fluoro-benzylsulfanylmethyl) -7- [4- (2,3-dimethyl-phenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.1 {176}

3- (2-Chloro-6-fluoro-benzylsulfanylmethyl) -7- [4- (2,5-dimethyl-phenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.1 {177}

3- (2-Chloro-6-fluoro-benzylsulfanylmethyl) -7- [4- (5-chloro-2-methyl-phenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2- he is 2.1 {178}

3- (2-Chloro-6-fluoro-benzylsulfanylmethyl) -7- (3,4-dihydro-1H-isoquinoline-2-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {179}

3- (2-Chloro-6-fluoro-benzylsulfanylmethyl) -7- [4- (3-trifluoromethyl-phenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-chitoxalin-2-one 2.1 {180 }

3- (2-Chloro-6-fluoro-benzylsulfanylmethyl) -7- (4-pyridin-2-yl-piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 1.1 {181}

3- (2-Chloro-6-fluoro-benzylsulfanylmethyl) -7- [4- (4-methoxy-phenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.1 {182 }

2- (2-Chloro-6-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid sec-butylamide 2.1 {183}

2- (2-Chloro-6-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid tert-butylamide 2.1 {184}

2- (2-Chloro-6-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-chloro-benzylamide 2.1 {185}

2- (2-Chloro-6-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopentylamide 2.1 {186}

2- (2-Chloro-6-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid isopropylamide 2.1 {187}

2- (2-Chloro-6-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid phenethyl amide 2.1 {188}

2- (2-Chloro-6-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 3-methoxybenzylamide 2.1 {189}

2- (2-Chloro-6-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-cyclohex-1-anyl-ethyl) -amide 2.1 {190}

2- (2-Chloro-6-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carbolic acid (furan-2-ylmethyl) -amide 2.1 {191}

3- (2-Chloro-6-fluoro-benzylsulfanylmethyl) -7- (4-pyridin-2-yl-piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {192}

2- (2-Chloro-6-fluoro-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methyl-benzylamide 2.1 {193}

2- (2,5-Dimethyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid tert-butyl ester 2.1 {194}

3- (2,5-Dimethyl-benzylsulfanylmethyl) -7- (morpholine-4-carboline) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {195}

3- (2,5-Dimethyl-benzylsulfanylmethyl) -7- (2-hydroxymethyl-pyrrolidin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {196}

3- (2,5-Dimethyl-benzylsulfanylmethyl) -7- (7-hydroxy-6-methoxy-3,4-dihydro-1H-isoquinoline-2-carbonyl) -3,4-dihydro-1H-quinoxaline-2- he is 2.1 {197}

2- (2,5-Dimethyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2,2-diethoxyethyl) -methyl-amide 2.1 {198}

2- (2,5-Dimethyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-hydroxyethyl) -methyl amide 2.1 {199}

2- (2,5-Dimethyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid furan-2-ylmethyl- (tetrahydro-furan-2-ylmethyl) -amide 2.1 {200}

2- (2,5-Dimethyl-benzylsulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid dimethylamide 2.1 {201}

2-Methanesulfanylmethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2,2-diethoxyethyl) -amide 2.1 {202}

2 - ([1.3] dioxolan-2-ylmethylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2,2-diethoxyethyl) -amide 2.1 {203}

3-Oxa-2- (pyridin-3-ylmethylsulfanylmethyl) -1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2,2-diethoxyethyl) -amide 2.1 {204}

3-Oxa-2- (pyridin-3-ylmethylsulfanylmethyl) -1,2,3,4-tetrahydroquinazoline-6-carboxylic acid (2,2-diethoxyethyl) -amide 2.1 {205}

2- (Octahydroquinolin-1-ylmethylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2,2-diethoxyethyl) -amide 2.1 {206}

5- [6- (2,2-Diethoxyethylcarbonyl) -3-oxo-1,2,3,4-tetrahydroquinoxalin-2-ylmethylsulfanylmethyl] thiophene-2-carboxylic acid methyl ester 2.1 {207}

2- (Adamantan-1-ylmethylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2,2-diethoxyethyl) amide 2.1 {208}

3- (3-Fluoro-benzylsulfanylmethyl) -7- (4-phenyl-piperazine-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.1 {209}

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 2-chloro-benzylamide 2.2 {1}: ¹ H-NMR (DMSO-d ₆ ) 2.42 (s, 3H, CH3-Ar); 3.36 (m, 1H, CH-CH 2 -SO 2); 3.79 (d, 1H, CH-CH2-SO2, J = 7.5 Hz); 4.45-4.65 (m, 5H, Alk); 6.17 (s, 1H, -NH-CH-); 6.78 (d, 1H, Ar); 7.11-7.49 (m, 10H, Ar); 8.50 (t, 1H, CH2-NH-CO-); 10.64 (s, 1H, -NH-CO).

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclooctylamide 2.2 {2} ¹ H-NMR (DMSO-d ₆ ) 1.47-1.83 (m, 12H, - (CH2 ) 7-); 2.40 (s, 3H, CH3-Ar); 3.34 (m, 1H, CH-CH 2 -SO 2); 3.79 (d, 1H, CH-CH2-SO2, J = 7.1 Hz); 4.00 (m, 1H, -CH2-CH-CH2-); 4.44-4.68 (m, 3H, Alk); 6.04 (s, 1H, -NH-CH-); 6.72 (d, 1H, Ar); 7.14-7.40 (m, 6H, Ar); 7.58 (d, 1H, CH-NH-CO-); 10.58 (s, 1H, -NH-CO).

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (thiophen-2-ylmethyl) -amide 2.2 {3} ¹ H-NMR (DMSO-d ₆ ) 2.4 (s , 3H, CH3-Ar); 3.35 (m, 1H, CH-CH 2 -SO 2); 3.77 (d, 1H, CH-CH2-SO2, J = 7.5 Hz); 4.45-4.79 (m, 5H, Alk); 6.14 (s, 1H, -NH-CH-); 6.75 (d, 1H, Ar); 6.9 (t, 1H (Ar)); 6.96 (s, 1H, Ar); 7.14-7.25 (m, 4H, Ar); 7.35 (m, 3H, Ar); 8.56 (t, 1H, CH2-NH-CO-); 10.53 (s, 1H, -NH-CO),

3-Oxo-2-methylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (thiophen-2-ylmethyl) -amide 2.2 {4} ¹ H-NMR (DMSO-d ₆ ) 2.36 (s, 3H , CH3-Ag); 3.22 (m, 1H, CH-CH2-SO2); 3.57 (d, 1H, CH-CH2-SO2, J = 7.5 Hz); 4.42 (m, 1H, -CH-); 4.47 (dd, 2H, SO2-CH2-Ar, J = 6.5 Hz); 4.58 (d, 2H, -CH2-NH-CO-, J = 3.1 Hz); 6.14 (s, 1H, -NH-CH-); 6.75 (d, 1H, Ar); 6.9 (t, 1H (Ar)); 6.96 (d, 1H, Ar); 7.11-7.27 (m, 5H, Ar); 7.35 (m, 2H, Ar); 8.6 (t, 1H. CH2-NH-CO-); 10.53 (s, 1H, -NH-CO).

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclooctylamide 2.2 {5} ¹ H-NMR (DMSO-d ₆ ) 1.43-1.81 (m, 12H, - (CH2 ) 7-); 2.36 (s, 3H, CH3-Ar); 3.18 (m, 1H, CH-CH 2 -SO 2); 3.6 (d, 1H, CH-CH2-SO2, J = 7.5 Hz); 3.95 (m, 1H, -CH2-CH-CH2-); 4.38-4.57 (m, 3H, Alk); 6.03 (s, 1H, -NH-CH-); 6.72 (d, 1H, Ar); 7.10-7.37 (m, 6H, Ar); 7.57 (d, 1H, CH-NH-CO-); 10.55 (s, 1H, -NH-CO).

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 2-chloro-benzylamide 2.2 {6} ¹ H-NMR (DMSO-d ₆ ) 2.37 (s, 3H, CH3 -Ar); 3.22 (m, 1H, CH-CH2-SO2); 3.59 (d, 1H, CH-CH2-SO2, J = 7.1 Hz); 4.35-4.62 (m, 5H, Alk); 6.16 (s, 1H, -NH-CH-); 6.78 (d, 1H, Ar); 7.06-7.52 (m, 10H, Ar); 8.49 (t, 1H, CH2-NH-CO-); 10.62 (s, 1H, -NH-CO).

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 2-chloro-benzylamide 2.2 {7} ¹ H-NMR (DMSO-d ₆ ) 3.37-3.85 (dd, dd 2H, CH-CH2-SO2); 4.45 (m, 1H, -CH-); 4.5 (d, 2H, -CH2-NH-CO); 4.68 (s, 2H, -CH2-Ar); 6.23 (s, 1H, -NH-CH-); 6.77 (d, 1H, Ar); 7.09-7.45 (m, 8H, Ar); 7.62 (t, 1H, Ar); 8.51 (t, 1H, CH2-NH-CO-); 10.69 (s, 1H, -NH-CO),

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (thiophen-2-ylmethyl) -amide 2.2 {8} ¹ H-NMR ( DMSO-d ₆ ) 3.35-3.42, 3.72-3.81 (dd, dd 2H, CH-CH2-SO2); 4.47 (d, 1H, -CH-); 4.63 (d, 2H, -CH2-NH-CO-, J = 2.9 Hz); 4.71 (s, 2H, -CH2-Ar); 6.15 (s, 1H, -NH-CH-); 6.74 (d, 1H, Ar); J = 5.75 Hz); 6.9 (t, 1H, Ar); 6.96 (s, 1H, Ar); 7.09 (m, 5H, Ar); 7.61 (t, 1H, Ar); 8.57 (t, 1H, CH2-NH-CO-); 10.65 (s, 1H, -NH-CO).

2- (3-Bromo-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclooctylamide 2.2 {9} ¹ H-NMR (DMSO-d ₆ ) 1.43-1.85 (m, 12H , - (CH2) 7-); 3.25 (m, 1H, CH-CH 2 -SO 2); 3.67 (d, 1H, CH-CH 2 -SO 2, J = 7 Hz); 3.97 (m, 1H, -CH2-CH-CH2-); 6 4.43-4.62 (m, 3H, Alk); 6.08 (s, 1H, -NH-CH-); 6.74 (d, 1H, Ar); 7.25-7.65 (m, 7H, Ar); 10.58 (s, 1H, -NH-CO).

2- (3-Bromo-phenylmethanesulfonylmethyl) -3-oxo-1,2,3.4-tetrahydroquinoxaline-6-carboxylic acid (thiophen-2-ylmethyl) -amide 2.2 {10} ¹ H-NMR (DMSO-d ₆ ) 3.24 -3.7 (dd, 2H, CH-CH2-SO2); 4.42-4.72 (m, 5H, Alk); 6.21 (s, 1H, -NH-CH-); 6.77 (d, 1H, Ar); 6.84-7.06 (m, 3H, Ar); 7.15-7.91 (m, 7H, Ar); 8.59 (t, 1H, CH2-NH-CO-); 10.64 (s. 1H, -NH-CO).

2- (3-Bromo-phenylmethanesulfonylmethyl) -3-oxo, 1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-methyl-butyl) -amide 2.2 {11} ¹ H-NMR (DMSO-d ₆ ) 0.94 (d, 6H, (CH3) 2CH); 1.45 (q, 2H, CH-CH2-CH2); 1.64 (m, 1H, (CH3) 2CH); 3.27 (m, 3H, Alk); 3.67 (d, 1H, -CH2-CH-CH2-, J = 7.5 Hz); 4.45-4.62 (m, 3H, Alk); 6.1 (s, 1H, -NH-CH-); 6.75 (d, 1H, Ar); 7.31 (s, 4H, Ar); 7.43 (d, 1H, Ar); 7.51 (d, 1H, Ar); 7.62 (s, 1H, Ar); 7.78 (t, 1H, CH2-NH-CO-); 10.57 (s, 1H, -NH-CO).

2- (4-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (thiophen-2-ylmethyl) -amide 2.2 {12}

2- (4-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 2-chloro-benzylamide 2.2 {13}

2- (4-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclooctylamide 2.2 {14}

2- (4-Chlorophenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-piperidin-1-yl-propyl) -amide 2.2 {15}

2- (4-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-dimethylaminoethyl) -amide 2.2 {16}

2- (4-Chlorophenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-piperidin-1-yl-propyl) -amide 2.2 {17}

2- (4-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-diisobutylamino-propyl) -amide 2.2 {18}

2- (3-Bromo-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-morpholin-4-yl-propyl) -amide 2.2 {19}

2- (3-Bromo-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-morpholin-4-yl-propyl) -amide 2.2 {20}

3- (3-Bromo-phenylmethanesulfonylmethyl) -7- (1,4-dioxa-8-aza-spiro [4.5] decan-8-carbonyl1) -3,4-dihydro-1H-quinoxalin-2-one 2.2 {21 }

2- (3-Bromo-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-diethylamino-propyl) -amide 2.2 {22}

2- (3-Bromo-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-piperidin-1-yl-propyl) -amide 2.2 {23}

2- (3-Bromo-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-ethoxy-propyl) -amide 2.2 {24}

2- (3-Bromo-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid [3- (2-methyl-piperidin-1-yl) -propyl] -amide 2.2 {25 }

2- (3-Bromo-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-azepan-1-yl-ethyl) -amide 2.2 {26}

2- (3-Bromo-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid [3- (3,5-dimethyl-piperidin-1-yl) -propyl] -amide 2.2 {27}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid acid (3-pyrrolidin-1-yl-propyl) -amide 2.2 {28}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-morpholin-4-yl-ethyl) -amide 2.2 {29}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid [3- (2-methyl-piperidin-1-yl) -propyl] - amide 2.2 {30}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-methoxyethyl) amide 2.2 {31}

3- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -7- (1,4-dioxa-8-aza-spiro [4.5] ilecane-8-сarbonyl) -3,4-dihydro-1H-quinoxaline-2- he is 2.2 {32}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid [2- (4-methyl-piperidin-1-yl) -propyl] - amide 2.2 {33}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-diethylamino-propyl) -amide 2.2 {34}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-ethoxy-propyl) -amide 2.2 {35}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid [3- (3,5-dimethyl-piperidin-1-yl) -propyl ] -amide 2.2 {36}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-diethylaminoethyl) -amide 2.2 {37}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-piperidin-1-yl-propyl) -amide 2.2 {38}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-methoxy-propyl) -amide 2.2 {39}

7- (1,4-Dioxa-8-aza-spiro [4.5] desane-8-carbonyl) -3-m-tolylmethanesulfonylmethyl-3,4-dihydro-1H-quinoxaline-2-one 2.2 {40}

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-diethylamino-ethyl) -amide 2.2 {41}

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-morpholin-4-yl-ethyl) -amide 2.2 {42}

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-ethoxy-propyl) -amide 2.2 {43}

7- (1,4-Dioxa-8-aza-siro [4.5] desane-8-сarbonyl) -3-o-tolylmethanesulfonylmethyl-3,4-dihydro-1H-quinoxaline-2-one 2.2 {44}

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-morpholin-4-yl-propyl) -amide 2.2 {45}

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2,3-dihydro-benzo [1,4] dioxin-2-ylmethyl) -amide 2.2 {46}

2- (2-Chlorophenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid benzyl methyl amide 2.2 {47}

1- [2- (2-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carbonyl] piperidine-4-carboxylic acid ethyl ester 2.2 {48}

3- (2-Chloro-phenylmethanesulfonylmethyl) -7- (4-cyclohexyl-piperazine-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {49}

3- (2-Chloro-phenylmethanesulfonylmetype) -7- [4- (3-trifluoromethyl-phenyl) piperazin-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.2 {50}

3- (2-Chloro-phenylmethanesulfonylmethyl) -7- [4- (4-fluoro-phenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.2 {51}

7- (4-Benzo [1,3] dioxol-5-ylmethyl-piperazin-1-carbonyl) -3- (2-chloro-phenylmethane-sulfonylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {52}

3- (2-Chloro-phenylmethanesulfonylmethyl) -7- [4- (4-methoxy-phenyl) piperazin-1-carbonyl] -3,4-dihydro-1H-quinoxalin-2-one 2.2 {53}

3- (2-Chloro-phenylmethanesulfonylmethyl) -7- (morpholine-4-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {54}

2- (2-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid sec-butylamide 2.2 {55}

2- (2-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-chloro-benzylamide 2.2 {56}

2- (2-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopentylamide 2.1 {57}

2- (2-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methoxybenzylamide 2.2 {58}

2- (2-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopropylamide 2.2 {59}

2- (2-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid phenethyl amide 2.2 {60}

2- (2-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (tetrahydro-furan-2-ylmethyl) -amide 2.2 {61}

2- (2-Chlorophenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 3-methoxybenzylamide 2.2 {62}

2- (2-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-cyclohex-1-enyl-ethyl) -amide 2.2 {63}

2- (2-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (furan-2-ylmethyl) -amide 2.2 {64}

2- (2-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid butylamide 2.2 {65}

7- (4-Cyclohexyl-piperazin-1-carbonyl) -3- (3-fluoro-phenylmethanesulfonylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {66}

7- (3,4-Dihydro-1H-isoquinolin-2-carbonyl) -3- (3-fluoro-phenylmethanesulfonylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {67}

3- (3-Fluoro-phenylmethanesulfonylmethyl) -7- (4-pyridin-2-yl-piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {68}

3- (3-Fluoro-phenylmethanesulfonylmethyl) -7- [4- (4-fluoro-phenyl) piperazin-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.2 {69}

2- (3-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methoxybenzylamide 2.2 {70}

2- (3-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methylbenzylamide 2.2 {71}

2- (3-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-methyl-butyl) -amide 2.2 {72}

2- (3-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid phenethylamide 2.1 {73}

2- (3-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (tetrahydro-furan-2-ylmethyl) -amide 2.2 {74}

2- (3-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 3-methoxybenzylamide 2.2 {75}

2- (3-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (furan-2-ylmethyl) -amide 2.2 {76}

2- (3-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid benzylamide 2.2 {77}

2- (3-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid butylamide 2.2 {78}

7- (Pyrrolidin-1-carbonyl) -3-o-tolylmethanesulfonylmethyl-3,4-dihydro-1H-quinoxaline-2-one 2.2 {79}

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-chloro-benzylamide 2.2 {80}

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopentylamide 2.2 {81}

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid [2- (3,4-dimethyl-phenyl) -ethyl] -amide 2.2 {82}

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-methyl-butyl) -amide 2.2 {83}

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-cyclohex-1-enyl-ethyl) -amide 2.2 {84}

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (furan-2-ylmethyl) -amide 2.2 {85}

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid benzylamide 2.2 {86}

3-Oxo-2-o-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid butylamide 2.2 {87}

7- (3,4-Dihydro-1H-isoquinolin-2-carbonyl) -3-m-tolylmethanesulfonylmethyl-3,4-dihydro-1H-quinoxaline-2-one 2.2 {88}

3-m-Tolylmethanesulfonylmethyl-7- [4- (3-trifluoromethyl-phenyl) piperazyl-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.2 {89}

7- [4- (4-Fluoro-phenyl) piperazine-1-carbonyl] -3-m-tolylmethanesulfonylmethyl-3,4-dihydro-1H-quinoxaline-2-one 2.2 {90}

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid sec-butylamide 2.2 {91}

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-chloro-benzylamide 2.2 {92}

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopentylamide 2.2 {93}

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid [2- (3,4-dimethoxy-phenyl) -ethyl] -amide 2.2 {94}

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methoxybenzylamide 2.2 {95}

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methyl-benzylamide 2.2 {96}

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (1-phenyl-ethyl) -amide 2.2 {97}

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopropylamide 2.2 {98}

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-methyl-butyl) -amide 2.2 {99}

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid phenethylamide 2.2 {100}

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (tetrahydro-furan-2-ylmethyl) -amide 2.2 {101}

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 3-methoxybenzylamide 2.2 {102}

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-cyclohex-1-enyl-ethyl) -amide 2.2 {103}

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (furan-2-ylmethyl) -amide 2.2 {104}

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid benzylamide 2.2 {105}

3-Oxo-2-m-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid butylamide 2.2 {106}

3-p-Tolylmethanesulfonylmethyl-7- [4- (3-trifluoromethylphenyl) piperazin-1-carbonyl] -3,4-dihydro-1H-quinoxalin-2-one 2.21 {107}

7- (Piperidin-1-carbonyl) -3-p-tolylmethanesulfonylmethyl-3,4-dihydro-1H-quinoxaline-2-one 2.2 {108}

3-Oxo-2-p-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopentylamide 2.2 {109}

3-Oxo-2-p-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-methyl-butyl) -amide 2.2 {110}

3-Oxo-2-p-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid phenethylamide 2.2 {111}

3-Oxo-2-p-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (tetrahydrofuran-2-ylmethyl) -amide 2.2 {112}

3-Oxo-2-p-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-ethyl-hexyl) -amide 2.2 {113}

3-Oxo-2-p-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (furan-2-ylmethyl) -amide 2.2 {114}

3-Oxo-2-p-tolylmethanesulfonylmethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid butylamide 2.2 {115}

3- (4-Fluoro-phenylmethanesulfonylmethyl) -7- (3-methyl-piperidin-1-carbonyl) -3,4-dihydro-1H-quinoxalin-2-one 2.2 {116}

3- (4-Fluoro-phenylmethanesulfonylmethyl) -7- (pyrrolidin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {117}

7- (4-Cyclohexyl-piperazin-1-carbonyl) -3- (4-fluoro-phenylmethanesulfonylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {118}

7- [4- (2,5-Dimethyl-phenyl) piperazine-1-carbonyl] -3- (4-fluoro-phenylmethanesulfonyl-methyl) -3,4-dihydro-1H-quinoxalin-2-one 2.2 {119 }

7- [4- (5-Chloro-2-methyl-phenyl) piperazine-1-carbonyl] -3- (4-fluoro-phenylmethanesulfonyl-methyl) -3,4-dihydro-1H-quinoxalin-2-one 2.2 {120}

3- (4-Fluoro-phenylmethanesulfonylmethyl) -7- (4-pyridin-2-yl-piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {121}

3- (4-Fluoro-phenylmethanesulfonylmethyl) -7- [4- (4-fluoro-phenyl) piperazin-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.2 {122}

7- (4-Benzo [1,3] dioxol-5-ylmethyl-piperazin-1-carbonyl) -3- (4-fluoro-phenylmethanesulfonylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {123}

3- (4-Fluoro-phenylmethanesulfonylmethyl) -7- [4- (4-methoxy-phenyl) piperazin-1-carbonyl] -3.4-dihydro-1H-quinoxaline-2-one 2.2 {124}

2- (4-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid sec-butylamide 2.2 {125}

2- (4-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-chloro-benzylamide 2.2 {126}

2- (4-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopentylamide 2.2 {127}

2- (4-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methoxybenzylamide 2.2 {128}

2- (4-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3.4-tetrahydroquinoxaline-6-carboxylic acid 4-methyl-benzylamide 2.2 {129}

2- (4-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (1-phenyl-ethyl) -amide 2.2 {130}

2- (4-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopropylamide 2.2 {131}

2- (4-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-methyl-butyl) -amide 2.2 {132}

2- (4-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid phenethylamide 2.2 {133}

2- (4-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (tetrahydrofuran-2-ylmethyl) -amide 2.2 {134}

2- (4-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (1,2,3,4-tetrahydronaphthalen-1-yl) -amide 2.2 {135}

2- (4-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-cyclohex-1-enyl-ethyl) -amide 2.2 {136}

2- (4-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclohexylamide 2.2 {137}

2- (4-Fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid butylamide 2.2 {138}

2- (4-Chlorophenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopropylamide 2.2 {139}

2- (4-Chloro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-methyl-butyl) -amide 2.2 {140}

3- (3-Chloro-phenylmethanesulfonylmethyl) -7- (3-methyl-piperidin-1-carbonyl) -3,4-dihydro-1H-quinoxalin-2-one 2.2 {141}

3- (3-Chloro-phenylmethanesulfonylmethyl) -7- (3,4-dihydro-1H-isoquinoline-2-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {142}

3- (3-Chlorophenylmethanesulfonylmethyl) -7- [4- (3-trifluoromethylphenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.2 {143}

3- (3-Chloro-phenylmethanesulfonylmethyl) -7- (4-pyridin-2-yl-piperazin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {144}

3- (3-Chloro-phenylmethanesulfonylmethyl) -7- [4- (4-fluoro-phenyl) piperazin-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.2 {145}

7- (4-Benzo [1,3] dioxol-5-ylmethyl-piperazin-1-carbonyl) -3- (3-chloro-phenylmethanesulfonylmethyl) -3,4-dihydro-1H-quinoxalin-2-one 2.2 {146 }

3- (3-Chloro-phenylmethanesulfonylmethyl) -7- [4- (4-methoxy-phenyl) piperazin-1-carbonyl] -3,4-dihydro-1H-quinoxalin-2-one 2.2 {147}

2- (2,5-Dimethyl-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid benzyl methyl amide 2.2 {148}

7- (4-Cyclohexyl-piperazine-1-carbonyl) -3- (2,5-dimethyl-phenylmethanesulfonylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {149}

7- (3,4-Dihydro-1H-isoquinoline-2-carbonyl) -3- (2,5-dimethyl-phenylmethanesulfonylmethyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {150}

3- (2,5-Dimethyl-phenylmethanesulfonylmethyl) -7- [4- (3-trifluoromethyl-phenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-quinoxylin-2-one 2.2 {151}

3- (2,5-Dimethyl-phenylmethanesulfonylmethyl) -7- [4- (4-fluoro-phenyl) -piperisin-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.2 {152}

3- (2,5-Dimethyl-phenylmethanesulfonylmethyl) -7- [4- (4-methoxyphenyl) piperisin-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.2 {153}

2- (2,5-Dimethyl-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-ethyl-hexyl) -amide 2.2 {154}

2- (2,5-Dimethyl-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid benzylamide 2.2 {155}

2- (2,5-Dimethyl-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid butylamide 2.2 {156}

1- [2- (2-Chloro-6-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carbonyl] piperidine-4-carboxylic acid ethyl ester 2.2 {157}

3- (2-Chloro-6-fluoro-phenylmethanesulfonylmethyl) -7- (pyrrolidin-1-carbonyl) -3,4-dihydro-1H-quinoxalin-2-one 2.2 {158}

3- (2-Chloro-6-fluoro-phenylmethanesulfonylmethyl) -7- [4- (2,3-dimethyl-phenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.2 {159}

3- (2-Chloro-6-fluoro-phenylmethanesulfonylmethyl) -7- [4- (5-chloro-2-methyl-phenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2- he is 2.2 {160}

3- (2-Chloro-6-fluoro-phenylmethanesulfonylmethyl) -7- [4- (3-trifluoromethyl-phenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.2 {161 }

3- (2-Chloro-6-fluoro-phenylmethanesulfonylmethyl) -7- (morpholine-4-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {162}

2- (2-Chloro-6-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-chloro-benzylamide 2.2 {163}

2- (2-Chloro-6-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopentylamide 2.2 {164}

2- (2-Chloro-6-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methoxybenzylamide 2.2 {165}

2- (2-Chloro-6-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopropylamide 2.2 {166}

2- (2-Chloro-6-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (tetrahydrofuran-2-ylmethyl) -amide 2.2 {167}

3- (2-Chloro-6-fluoro-phenylmethanesulfonylmethyl) -7- (pyrrolidin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {168}

3- (2-Chloro-6-fluoro-phenylmethanesulfonylmethyl) -7- [4- (2,5-dimethyl-phenyl) piperazine-1-carbonyl] -3,4-dihydro-1H-quinoxaline-2-one 2.2 {169}

7- (4-Benzo [1,3] dioxol-5-ylmethyl) piperazine-1-carbonyl) -3- (2-chloro-6-fluoro-phenylmethanesulfonylmethyl) -3,4-dihydro-1H-quinoxaline-2 -on 2.2 {170}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-chloro-benzylamide 2.2 {171}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid cyclopentylamide 2.2 {172}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-methoxybenzylamide 2.2 {173}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (1-phenyl-ethyl) -amide 2.2 {174}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (3-methyl-butyl) -amide 2.2 {175}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2-cyclohex-1-enyl-ethyl) -amide 2.2 {176}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-carboxylic acid (furan-2-ylmethyl) -amide 2.2 {177}

2- (2-Chloro-4-fluoro-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid butylamide 2.2 {178}

3- (3-Bromo-phenylmethanesulfonylmethyl) -7- (pyrrolidin-1-carbonyl) -3,4-dihydro-1H-quinoxaline-2-one 2.2 {179}

2- (3-Bromo-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 4-chloro-benzylamide 2.2 {180}

2- (3-Bromo-phenylmethanesulfonylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid 2-mercapto-benzylamide 2.2 {181}

. Для коррекции на собственную флуоресценцию тестируемых соединений, флуоресцентные измерения (F $\genfrac{}{}{0ex}{}{\text{0}}{\text{i}}$ ) проводили в отдельных платах, не содержащих энзимные реагенты (фермент плюс субстрат). Полная активность фермента измерялась по флуоресценции в реакционных лунках, содержащих все реакционные компоненты кроме тестируемых соединений (F₁₀₀), а нулевая активность определялась по флуоресценции лунок, содержащих соответствующие тестируемые соединения и все реакционные реагенты за исключением фермента (F₀).Example 5. A focused library was compiled, including 880 compounds, including 408 substituted 3-oxo-1,2,3,4-tetrahydroquinoxaline 1 and 2, and tested for antiprotease activity. Antiprotease activity was determined on a serine protease (Caspase 3), which is involved in the regulation of programmed cell death (apoptosis). Caspase 3 activity was determined by the rate of cleavage of a peptide substrate containing a fluorescent molecule (methylcoumarin). The cleavage of methylcoumarin from the peptide molecule as a result of the proteolytic reaction of the enzyme is accompanied by an increase in the fluorescence intensity measured using a VICTOR ² V fluorescence parallel reader (PerkinElmer, USA) at an excitation wavelength of 355 nm and an emission wavelength of 460 nm. For the reactions, optical 96-well microplates were used. Caspase 3 and a fluorescent substrate from Sigma (USA) were used in the experiments. The reaction conditions and composition of the medium were used in accordance with the recommendation of the manufacturer. Stock solutions of the test compounds were prepared by dissolving them in DMSO (dimethyl sulfoxide) to a concentration of 10 mM. Stock solutions of the compounds were added to the enzyme solution in such a volume as to obtain a final concentration of the compound of 10 μM. After 10 minutes of incubation of the enzyme with the test compound, an enzyme substrate was added to the solution and fluorescence measurements were carried out 1 hour after the addition of the substrate

. To correct for intrinsic fluorescence of test compounds, fluorescence measurements (F $\genfrac{}{}{0ex}{}{\text{0}}{\text{i}}$ ) was carried out in separate boards not containing enzyme reagents (enzyme plus substrate). The full activity of the enzyme was measured by fluorescence in the reaction wells containing all the reaction components except the test compounds (F ₁₀₀ ), and the zero activity was determined by the fluorescence of the wells containing the corresponding test compounds and all reaction reagents except the enzyme (F ₀ ).

The calculation of inhibition was carried out according to the following formula:

where F _i = F $\genfrac{}{}{0ex}{}{\text{e}}{\text{i}}$ -F $\genfrac{}{}{0ex}{}{\text{0}}{\text{i}}$ , the subscript corresponds to the test compound in the presence of which fluorescence is measured, and the superscripts (e) and (0) indicate the presence or absence of enzymatic reagents, respectively.

Some examples of the tested compounds that showed high activity during screening of the library are shown in the following table, and the concentration dependences of inhibition are shown in the figure.

Table
Protease activity of certain substituted 1,2,3,4-tetrahydro-quinoxalines ID Compound structure IC50, nM Activity 1.2 {10}

3800 Inhibition 1.2 {14}

780 Inhibition 2.1 {46}

360 Inhibition 2.1 {50}

240 Inhibition

Concentration dependences of caspase 3 inhibition

2- (2-chloro-4-fluoro-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2,2-diethoxyethyl) -amide 2.1 {46} (curve 1 ) and 2- (2,5-dimethyl-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2,2-diethoxyethyl) -amide 2.1 {50} (curve 2 ) are presented in figure 1.

Example 6. The example illustrates the preparation of tablets containing 50 mg of the active ingredient. 800 mg of starch, 800 mg of ground lactose, 200 mg of talc and 500 mg of 2- (2,5-dimethyl-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2.2- diethoxy-ethyl) -amide 2.1 {50} and pressed into a bar. The resulting bar is crushed into granules and sieved through sieves, collecting granules with a size of 14-16 mesh. The granules obtained are tabletted into a suitable tablet form weighing 280 mg each. According to the invention, pharmaceutical compositions in the form of tablets are likewise prepared containing other compounds of the general formula 1 or 2 as the active ingredient.

Example 7. Capsules containing 200 mg of 2- (2,5-dimethyl-benzylsulfanylmethyl) -3-oxo-1,2,3,4-tetrahydroquinoxaline-6-carboxylic acid (2,2-diethoxyethyl) amide 2.1 {50}, according to the invention can be obtained by thoroughly mixing compound 2.1 {50} with lactose powder in a ratio of 2: 1. The resulting powdery mixture is packaged in 300 mg in a suitable size gelatin capsule.

Example 8. Injectable compositions for intramuscular, intraperitoneal or subcutaneous injection can be prepared by mixing 500 mg of the active ingredient with a suitable solubility, for example, 2- (2,5-dimethyl-benzylsulfanylmethyl) -3-oxo-1,2,3,4- tetrahydroquinoxaline-6-carboxylic acid (2,2-diethoxy-ethyl) -amide 2.1 {50}, with 300 mg of chlorobutanol, 2 ml of propylene glycol and 100 ml of injection water. The resulting solution is filtered and placed in 1 ml ampoules, which are sealed and sterilized in an autoclave.

Claims (6)

1. The use of physiologically active substituted 3-oxo-1,2,3,4-tetrahydroquinoxaline general formula 1

in which R ¹ represents a substituted sulfanyl group or a substituted sulfonyl group containing optionally substituted C _1-4 alkyl, optionally substituted C _3-8 cycloalkyl, optionally substituted in the aryl and / or alkyl moiety, aryl C _1-4 alkyl, optionally substituted in the heterocyclic and / or alkyl fragment of heterocyclyl C _1-4 alkyl, optionally substituted aryl, optionally substituted heterocyclyl; R ² and R ³ independently represent a hydrogen, halogen, CN, NO ₂ atom, an optionally substituted hydroxy group or an optionally substituted amino group, an optionally substituted carboxyl group, an optionally substituted carbamoyl, an optionally substituted aryloxycarbonyl group or an optionally substituted heterocyclylcarbonyl group; R ⁴ and R ⁵ independently of one another represent a hydrogen atom or an inert substituent having caspase-3 inhibitor properties, to obtain a pharmaceutical composition and for experimental (in vitro, in vivo) studies of apoptosis processes as pharmacological tools. 2. A pharmaceutical composition having the properties of caspase-3 inhibitors in the form of tablets, capsules or injections in a pharmaceutically acceptable package containing, as an active substance, a pharmaceutically effective amount of substituted 3-oxo-1,2,3,4-tetrahydroquinoxaline of the general formula 1 according to claim 1. 3. A pharmaceutical composition for treating and preventing the development of various diseases of warm-blooded animals and people associated with increased activation of apoptosis, in the form of tablets, capsules or injections, placed in a pharmaceutically acceptable package containing, as an active substance, a pharmaceutically effective amount of substituted 3-oxo- 1,2,3,4-tetrahydroquinoxaline of general formula 1 according to claim 1. 4. A method of obtaining a pharmaceutical composition according to claim 2 or 3 by mixing the active substance with an inert filler, diluent and / or solvent, characterized in that a pharmaceutically effective amount of substituted 3-oxo-1,2,3,4- is used as the active substance. tetrahydroquinoxaline of general formula 1 according to claim 1. 5. A method of treating and preventing the development of various diseases of warm-blooded animals and people associated with increased activation of apoptosis by administering to the warm-blooded animal or human a pharmaceutical composition according to claim 2 or 3. 6. Substituted 3-oxo-1,2,3,4-tetrahydroquinoxalinecarboxylic acids and their derivatives of the general formula 2

in which R ¹ , R ³ , R ⁴ and R ⁵ have the above meaning for compounds of general formula 1 according to claim 1, R ⁶ represents an optionally substituted hydroxy group, an optionally substituted amino, an optionally substituted aryloxy or an optionally substituted heterocyclyl group.