WO2019180189A1

WO2019180189A1 - Aminopropoxyphenyl and benzyl 3,4-dihydro-2h-spiro[isoquinoline-1,4'-piperidin]-1'-yl derivatives having multimodal activity against pain

Info

Publication number: WO2019180189A1
Application number: PCT/EP2019/057186
Authority: WO
Inventors: Carmen ALMANSA-ROSALES; Marina VIRGILI-BERNADO; Monica Alonso-Xalma
Original assignee: Esteve Pharmaceuticals, S.A.
Priority date: 2018-03-23
Filing date: 2019-03-22
Publication date: 2019-09-26

Abstract

The present invention relates to aminopropoxyphenyl and benzyl 3,4-dihydro-2H- spiro[isoquinoline-1,4'-piperidin]-1'-ylderivatives having dual pharmacological activity towards both the α2δ-subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel and the µ-opioid receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

Description

AMINOPROPOXYPHENYL AND BENZYL 3,4-DIHYDRO-2H-

SPIRO[ISOQUINOLINE-1 ,4'-PIPERIDIN]-1 '-YL DERIVATIVES HAVING MULTIMODAL ACTIVITY AGAINST PAIN

FIELD OF THE INVENTION

The present invention relates to compounds having dual pharmacological activity towards both the a₂d subunit of the voltage-gated calcium channel, and the m-opioid receptor (MOR or mu-opioid receptor) and more particularly to aminopropoxyphenyl and benzyl 3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'-piperidin]-T-yl derivatives having this pharmacological activity, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

BACKGROUND OF THE INVENTION

The adequate management of pain constitutes an important challenge, since currently available treatments provide in many cases only modest improvements, leaving many patients unrelieved (Turk, D.C., Wilson, H.D., Cahana, A.; 201 1 ; Lancet ; 377; 2226-2235). Pain affects a big portion of the population with an estimated prevalence of 20 % and its incidence, particularly in the case of chronic pain, is increasing due to the population ageing. Additionally, pain is clearly related to comorbidities, such as depression, anxiety and insomnia, which leads to important productivity losses and socio-economical burden (Goldberg, D.S., McGee, S.J.; 2011 ; BMC Public Health ; 1 1 ; 770). Existing pain therapies include non-steroidal anti- inflammatory drugs (NSAIDs), opioid agonists, calcium channel blockers and antidepressants, but they are much less than optimal regarding their safety ratio. All of them show limited efficacy and a range of secondary effects that preclude their use, especially in chronic settings.

Voltage-gated calcium channels (VGCC) are required for many key functions in the body. Different subtypes of voltage-gated calcium channels have been described (Zamponi et al., Pharmacol Rev. 2015 67:821-70). The VGCC are assembled through interactions of different subunits, namely oti (Ca_voti), b (Ca_vp) a₂d (Ca_va₂6) and g (Ca_vy). The oti subunits are the key porous forming units of the channel complex, being responsible for the Ca²⁺ conduction and generation of Ca²⁺ influx. The a₂d, b, and g subunits are auxiliary, although very important for the regulation of the channel, since they increase the expression of the oti subunits in the plasma membrane as well as modulate their function, resulting in functional diversity in different cell types. Based on their physiological and pharmacological properties, VGCC can be subdivided into low voltage-activated T-type (Ca_v3.1 , Ca_v3.2, and Ca_v3.3), and high voltage-activated L- (Ca_v1.1 through Ca_v1.4), N-(Ca_v2.2), P/Q-(Ca_v2.1 ), and R- (Ca_v2.3) types, depending on the channel forming Cava subunits. All of these five subclasses are found in the central and peripheral nervous systems. Regulation of intracellular calcium through activation of these VGCC plays obligatory roles in: 1 ) neurotransmitter release, 2) membrane depolarization and hyperpolarization, 3) enzyme activation and inactivation, and 4) gene regulation (Perret and Luo, Neurotherapeutics. 2009 6:679-92; Zamponi et al., 2015 supra ; Neumaier et al., Prog Neurobiol. 2015 129:1-36.). A large body of data has clearly indicated that VGCC are implicated in mediating various disease states including pain processing. Drugs interacting with the different calcium channel subtypes and subunits have been developed. Current therapeutic agents include drugs targeting L-type Ca_v1.2 calcium channels, particularly 1 ,4-dihydropyridines, which are widely used in the treatment of hypertension. T-type (Ca_v3) channels are the target of ethosuximide, widely used in absence epilepsy. Ziconotide, a peptide blocker of N-type (Ca_v2.2) calcium channels, has been approved as a treatment of intractable pain. (Perret and Luo, 2009, supra, Vink and Alewood, Br J Pharmacol. 2012 167:970-89.).

The Ca_v1 and Ca_v2 subfamilies contain an auxiliary a d subunit, which is the therapeutic target of the gabapentinoid drugs of value in certain epilepsies and chronic neuropathic pain. To date, there are four known a d subunits, each encoded by a unique gene and all possessing splice variants. Each a d protein is encoded by a single messenger RNA and is post-translationally cleaved and then linked by disulfide bonds. Four genes encoding a2d subunits have now been cloned. a₂d-1 was initially cloned from skeletal muscle and shows a fairly ubiquitous distribution. The a₂d-2 and a₂d-3 subunits were subsequently cloned from brain. The most recently identified subunit, a₂d-4, is largely non-neuronal. The human a₂d-4 protein sequence shares 30, 32 and 61% identity with the human a₂d-1 , a₂d-2 and a₂d-3 subunits, respectively. The gene structure of all a₂d subunits is similar. All a₂d subunits show several splice variants (Davies et al., Trends Pharmacol Sci. 2007 28:220-8.; Dolphin AC, Nat Rev Neurosci. 2012 13:542-55., Biochim Biophys Acta. 2013 1828:1541-9.).

The Ca_vot₂8-1 subunit may play an important role in neuropathic pain development (Perret and Luo, 2009, supra ; Vink and Alewood, 2012, supra). Biochemical data have indicated a significant Ca_va,₂8-1 , but not Ca_va,₂8-2, subunit upregulation in the spinal dorsal horn, and DRG (dorsal root ganglia) after nerve injury that correlates with neuropathic pain development. In addition, blocking axonal transport of injury- induced DRG Ca_vot₂8-1 subunit to the central presynaptic terminals diminishes tactile allodynia in nerve injured animals, suggesting that elevated DRG Ca_vot₂8-1 subunit contributes to neuropathic allodynia.

The Ca_vot₂8-1 subunit (and the Ca_vot₂8-2, but not Ca_vot₂8-3 and Ca_vot₂8-4, subunits) is the binding site for gabapentin which has anti-allodynic/ hyperalgesic properties in patients and animal models. Because injury-induced Ca_vot₂8-1 expression correlates with neuropathic pain development and maintenance, and various calcium channels are known to contribute to spinal synaptic neurotransmission and DRG neuron excitability, injury-induced Ca_vot₂8-1 subunit upregulation may contribute to the initiation and maintenance of neuropathic pain by altering the properties and/or distribution of VGCC in the subpopulation of DRG neurons and their central terminals, therefore modulating excitability and/or synaptic neuroplasticity in the dorsal horn. Intrathecal antisense oligonucleotides against the Ca_vot₂8-1 subunit can block nerve injury-induced Ca_vot₂8-1 upregulation and prevent the onset of allodynia and reserve established allodynia.

As mentioned above, the 0,₂8 subunits of VGCC form the binding site for gabapentin and pregabalin, which are structural derivatives of the inhibitory neurotransmitter GABA although they do not bind to GABAA, GABAB, or benzodiazepine receptors, or alter GABA regulation in animal brain preparations. The binding of gabapentin and pregabalin to the Ca_vot₂8 subunit results in a reduction in the calcium-dependent release of multiple neurotransmitters, leading to efficacy and tolerability for neuropathic pain management. Gabapentinoids may also reduce excitability by inhibiting synaptogenesis (Perret and Luo, 2009, supra ; Vink and Alewood, 2012, supra, Zamponi et al., 2015, supra). As mentioned before, there are few available therapeutic classes for the treatment of pain, and opioids are among the most effective, especially when addressing severe pain states. They act through three different types of opioid receptors (mu, kappa and gamma) which are transmembrane G-protein coupled receptors (GPCRs). Still, the main analgesic action is attributed to the activation of the m-opioid receptor (MOR). However, the general administration of MOR agonists is limited due to their important side effects, such as constipation, respiratory depression, tolerance, emesis and physical dependence [Meldrum, M.L. (Ed.). Opioids and Pain Relief: A Historical Perspective. Progress in Pain Research and Management, Vol 25. IASP Press, Seattle, 2003]. Additionally, MOR agonists are not optimal for the treatment of chronic pain as indicated by the diminished effectiveness of morphine against chronic pain conditions. This is especially proven for the chronic pain conditions of neuropathic or inflammatory origin, in comparison to its high potency against acute pain. The finding that chronic pain can lead to MOR down-regulation may offer a molecular basis for the relative lack of efficacy of morphine in long-term treatment settings [Dickenson, A.H., Suzuki, R. Opioids in neuropathic pain: Clues from animal studies. Eur J Pain 9, 113-6 (2005)]. Moreover, prolonged treatment with morphine may result in tolerance to its analgesic effects, most likely due to treatment-induced MOR down-regulation, internalization and other regulatory mechanisms. As a consequence, long-term treatment can result in substantial increases in dosing in order to maintain a clinically satisfactory pain relief, but the narrow therapeutic window of MOR agonists finally results in unacceptable side effects and poor patient compliance.

Polypharmacology is a phenomenon in which a drug binds multiple rather than a single target with significant affinity. The effect of polypharmacology on therapy can be positive (effective therapy) and/or negative (side effects). Positive and/or negative effects can be caused by binding to the same or different subsets of targets; binding to some targets may have no effect. Multi-component drugs or multi-targeting drugs can overcome toxicity and other side effects associated with high doses of single drugs by countering biological compensation, allowing reduced dosage of each compound or accessing context-specific multitarget mechanisms. Because multitarget mechanisms require their targets to be available for coordinated action, one would expect synergies to occur in a narrower range of cellular phenotypes given differential expression of the drug targets than would the activities of single agents. In fact, it has been experimentally demonstrated that synergistic drug combinations are generally more specific to particular cellular contexts than are single agent activities, such selectivity is achieved through differential expression of the drugs’ targets in cell types associated with therapeutic, but not toxic, effects (Lehar et al., Nat Biotechnol 2009; 27: 659-666.)·

In the case of chronic pain, which is a multifactorial disease, multi-targeting drugs may produce concerted pharmacological intervention of multiple targets and signaling pathways that drive pain. Because they actually make use of biological complexity, multi-targeting (or multi-component drugs) approaches are among the most promising avenues toward treating multifactorial diseases such as pain (Gilron et al., Lancet Neurol. 2013 Nov;12(11 ):1084-95.). In fact, positive synergistic interaction for several compounds, including analgesics, has been described (Schroder et al., J Pharmacol Exp Ther. 201 1 ; 337:312-20. Erratum in: J Pharmacol Exp Ther. 2012; 342:232.; Zhang et al., Cell Death Dis. 2014; 5:e1 138.; Gilron et al., 2013, supra).

Given the significant differences in pharmacokinetics, metabolisms and bioavailability, reformulation of drug combinations (multi-component drugs) is challenging. Further, two drugs that are generally safe when dosed individually cannot be assumed to be safe in combination. In addition to the possibility of adverse drug-drug interactions, if the theory of network pharmacology indicates that an effect on phenotype may derive from hitting multiple targets, then that combined phenotypic perturbation may be efficacious or deleterious. The major challenge to both drug combination strategies is the regulatory requirement for each individual drug to be shown to be safe as an individual agent and in combination (Hopkins, Nat Chem Biol. 2008; 4:682-90.).

An alternative strategy for multitarget therapy is to design a single compound with selective polypharmacology (multi-targeting drug). It has been shown that many approved drugs act on multiple targets. Dosing with a single compound may have advantages over a drug combination in terms of equitable pharmacokinetics and biodistribution. Indeed, troughs in drug exposure due to incompatible pharmacokinetics between components of a combination therapy may create a low- dose window of opportunity where a reduced selection pressure can lead to drug resistance. In terms of drug registration, approval of a single compound acting on multiple targets faces significantly lower regulatory barriers than approval of a combination of new drugs (Hopkins, 2008, supra). Thus, the present application, relates to the advantages of having dual activity, for m- receptor and the a₂d-1 subunit of voltage-gated calcium channels, in the same molecule to treat chronic pain.

In this way, the present invention relates to compounds having a complementary dual mechanism of action (m-receptor agonist and blocker of the a₂d subunit, in particular the a₂d-1 subunit, of voltage-gated calcium channels) which implies a better profile of tolerability than the strong opioids (morphine, oxycodone, fentanyl etc) and/or better efficacy and tolerability than gabapentinoids (pregabalin and gabapentin).

Pain is multimodal in nature, since in nearly all pain states several mediators, signaling pathways and molecular mechanisms are implicated. Consequently, monomodal therapies fail to provide complete pain relief. Currently, combining existing therapies is a common clinical practice and many efforts are directed to assess the best combination of available drugs in clinical studies (Mao, J., Gold, M.S., Backonja, M.; 201 1 ; J. Pain; 12; 157-166).

Accordingly, there is still a need to find compounds that have an alternative or improved pharmacological activity in the treatment of pain, being both effective and showing the desired selectivity, and having good “drugability” properties, i.e. good pharmaceutical properties related to administration, distribution, metabolism and excretion.

The authors of the present invention, have found a serie of compounds that show dual pharmacological activity towards both the a₂d subunit, in particular the a₂d-1 subunit, of the voltage-gated calcium channel, and the m-opioid receptor (MOR or mu- opioid receptor) resulting in an innovative, effective and alternative solution for the treatment of pain.

In view of the existing results of the currently available therapies and clinical practices, the present invention offers a solution by combining in a single compound binding to two different targets relevant for the treatment of pain. This was mainly achieved by providing the compounds according to the invention that bind both to the m-opioid receptor and to the a₂d subunit, in particular the a₂d-1 subunit, of the voltage- gated calcium channel. SUMMARY OF THE INVENTION

In this invention a family of structurally distinct aminopropoxyphenyl and benzyl 3,4- dihydro-2H-spiro[isoquinoline-1 ,4'-piperidin]-T-yl derivatives, encompassed by formula (I), which have a dual pharmacological activity towards both the a₂d subunit, in particular the a₂d-1 subunit, of the voltage-gated calcium channel, and the m-opioid receptor, was identified thus solving the above problem of identifying alternative or improved pain treatments by offering such dual compounds.

The main object of the invention is directed to a compound having a dual activity binding to the a₂d subunit, in particular the a₂d-1 subunit, of the voltage-gated calcium channel and the m-opioid receptor for use in the treatment of pain.

As this invention is aimed at providing a compound or a chemically related series of compounds which act as dual ligands of the a₂d subunit, in particular the a₂d-1 subunit, of the voltage-gated calcium channel and the m-opioid receptor it is a very preferred embodiment if the compound has a binding expressed as K, responding to the following scales:

K_ί(m) is preferably < 1000 nM, more preferably < 500 nM, even more preferably < 100 nM.

K,(a₂d-1 ) is preferably < 10000 nM, more preferably < 5000 nM, even more preferably < 500 nM or even more preferably < 100 nM.

The invention is directed in a main aspect to a compound of general Formula (I),

wherein Ri, R₂, R3, R3', R₄, R₄·, X, Ui, Y2 and n are as defined below in the detailed description.

A further object of the invention refers to the processes for preparation of compounds of general formula (I). A still further object of the invention refers to the use of intermediate compounds for the preparation of a compound of general formula (I).

It is also an object of the invention a pharmaceutical composition comprising a compound of formula (I).

Finally, it is an object of the invention the use of compound as a medicament and more particularly for the treatment of pain and pain related conditions.

DETAILED DESCRIPTION OF THE INVENTION

In this invention a family of structurally distinct aminopropoxyphenyl and benzyl 3,4- dihydro-2H-spiro[isoquinoline-1 ,4'-piperidin]-1 '-yl derivatives, encompassed by formula (I), which have a dual pharmacological activity towards both the a₂d subunit, in particular the a₂d-1 subunit, of the voltage-gated calcium channel, and the m-opioid receptor was identified, thus solving the above problem of identifying alternative or improved pain treatments by offering such dual compounds.

The main object of the invention is directed to a compound having a dual activity binding to the a₂d subunit, in particular the a₂d-1 subunit, of the voltage-gated calcium channel and the m-opioid receptor, for use in the treatment of pain.

As this invention is aimed at providing a compound or a chemically related series of compounds which act as dual ligands of the a₂d subunit, in particular the a₂d-1 subunit, of the voltage-gated calcium channel and the m-opioid receptor, it is a very preferred embodiment if the compound has a binding expressed as K, responding to the following scales:

K_ί(m) is preferably < 1000 nM, more preferably < 500 nM, even more preferably < 100 nM. K,(a₂d-1 ) is preferably < 10000 nM, more preferably < 5000 nM, even more preferably < 500 nM or even more preferably < 100 nM.

The applicant has surprisingly found that the problem of providing a new effective and alternative for treating pain and pain related disorders can be solved by using a multimodal balanced analgesic approach combining two different synergistic activities in a single drug (i.e., dual ligands which are bifunctional and bind to m-opioid receptor and to a₂d subunit, in particular the a₂d-1 subunit, of the voltage-gated calcium channel), thereby enhancing through the a₂d blockade without increasing the undesirable side effects. This supports the therapeutic value of a dual agent, whereby the a₂d binding component acts as an intrinsic adjuvant of the MOR binding component.

A dual compound that possess binding to both the m-opioid receptor and to the a₂d subunit of the voltage-gated calcium channel shows a highly valuable therapeutic potential by achieving an outstanding analgesia (enhanced in respect to the potency of the opioid component alone) with a reduced side-effect profile (safety margin increased compared to that of the opioid component alone) versus existing opioid therapies.

Advantageously, the dual compounds according to the present invention would in addition show one or more the following functionalities: blockade of the a₂d subunit, in particular the a₂d-1 subunit, of the voltage-gated calcium channel and m-opioid receptor agonism

It has to be noted, though, that functionalities“antagonism” and“agonism” are also sub-divided in their effect into subfunctionalities like partial agonism or inverse agonism. Accordingly, the functionalities of the compound should be considered within a relatively broad bandwidth.

An antagonist blocks or dampens agonist-mediated responses. Known subfunctionalities are neutral antagonists or inverse agonists.

An agonist increases the activity of the receptor above its basal level. Known subfunctionalities are full agonists, or partial agonists. In addition, the two mechanisms complement each other since MOR agonists are only marginally effective in the treatment of neuropathic pain, while the blockers of the a₂d subunit, in particular the a₂d-1 subunit, of voltage-gated calcium channels show outstanding effects in preclinical neuropathic pain models. Thus, the a₂d component, in particular the a₂d-1 component, adds unique analgesic actions in opioid-resistant pain. Finally, the dual approach has clear advantages over MOR agonists in the treatment of chronic pain as lower and better tolerated doses would be needed based on the potentiation of analgesia but not of the adverse events of MOR agonists.

A further advantage of using designed multiple ligands is a lower risk of drug-drug interactions compared to cocktails or multi-component drugs, thus involving simpler pharmacokinetics and less variability among patients. Additionally, this approach may improve patient compliance and broaden the therapeutic application in relation to monomechanistic drugs, by addressing more complex aetiologies. It is also seen as a way of improving the R&D output obtained using the“one drug-one target” approach, which has been questioned over the last years [Bornot A, Bauer U, Brown A, Firth M, Hellawell C, Engkvist O. Systematic Exploration of Dual-Acting Modulators from a Combined Medicinal Chemistry and Biology Perspective. J. Med. Chem, 56, 1197- 1210 (2013)].

In its broader aspect, the present invention is directed to compounds of general Formula (I):

wherein Ri, R₂, R3, R3', R₄, R₄·, X, Yi, Y₂, and n are as defined in the detailed description, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (I)

wherein

X is selected from a bond, -[C(R_aRb)]_P-, -[CH₂]pC(0)[CH₂]_q-, -[CH₂]_pC(0)N(R_z)[CH₂]_q-, - [CH₂]_pN(R_z)C(0)[CH₂]_q- and -[CH₂]_pN(R_z)[CH₂]_q-;

R_a is selected from hydrogen, halogen, substituted or unsubstituted C alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; Rb is selected from hydrogen, halogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R_a and R_b, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl;

R_z is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and -C(0)-Ci-6 alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5;

n is 0 or 1 ;

Yi is -C(RioRio')-; wherein R₁₀ and Rio· are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R₁₀ and Re form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

Y₂ is -C(Rio”Rio )-; wherein Rio- and R-io- are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R_10” and Rio- form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

wherein m is 0, 1 or 2; r is 0 , 1 or 2;

Y is -CH₂- or C=0;

R₅ and R_5' are independently selected from halogen, -R₅₁, -OR₅₁, -NO₂, - NR₅₁R_{51 '}, -NR_5iC(0)R_5r, -NR_5iS(0)₂R₅r, -S(0)₂NR_5iR₅r, - NR_5iC(0)NR₅rR_5i ·, -

SR51 , -S(0)R5i, -S(0)₂R5i, -CN, haloalkyl, haloalkoxy, -C(0)0Rsi, - C(0)NR_5iR₅r, -OCH₂CH₂OR_5I , -NR_5iS(0)₂NR₅rR_5i and -C(CH₃)₂OR_5I ; wherein R₅₁, Rsr and Rsr are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

R₆ is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7;

R₇ is selected from substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl;

R₂ is selected from substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl,

R₃ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

R_3' is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

R₄ and R_4' are independently selected from halogen, -R₄I , -OR₄I , -NO2, - NR_4iR₄r, -NR_4iC(0)R₄r, -NR_4iS(0)₂R₄r, -S(0)₂NR_4iR₄r, -NR_4iC(0)NR₄rR₄-r, - SR₄I , -S(0)R₄I , -S(0)₂R₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R_4i, - C(0)NR_4iR₄r, -0CH₂CH₂0R₄I , -NR_4iS(0)₂NR₄ R_4i” and -C(CH₃)₂0R₄I ; wherein R₄I , R₄r and R₄r are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl and substituted or unsubstituted cycloalkyl;

These compounds according to the invention are optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another embodiment, these compounds according to the invention are optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof. Please note that “or a corresponding salt thereof” does also mean “or a corresponding pharmaceutically acceptable salt thereof. This does apply to all below described embodiments and uses of“salt” being thus equivalent to“pharmaceutically acceptable salt”.

In a particular embodiment the following proviso applies: when Y is CO, then R₆ is not -C(0)R₇.

In a particular embodiment the following proviso applies: when R₆ is -C(0)R₇, then Y is not CO.

In a particular embodiment the following proviso applies: when R6 is -C(0)R7, then Y is -CH2-. In a further embodiment the compound according to the invention is a compound of general Formula (I)

wherein

R_a is selected from hydrogen, halogen, substituted or unsubstituted C alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl;

R_b is selected from hydrogen, halogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R_a and R_b, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl;

R_z is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and -C(0)-Ci-₆ alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5; n is 0 or 1 ;

Yi is -C(RioRio')-; wherein R₁₀ and Rio· are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R₁₀ and R-io form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

Y2 is -C(Rio”Rio'”)-; wherein Rio- and R₁₀ - are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R_10” and Rio- form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH2- or C=0;

R5 and R5' are independently selected from halogen, -R51, -OR51, -NO2, - NR51R51', -NR_5iC(0)R_5r, -NR_5iS(0)₂R₅r, -S(0)₂NR_5iR₅-r, - NR_5iC(0)NR_5i R_5i”, - SR51 , -S(0)R5i, -S(0)2R5i, -CN, haloalkyl, haloalkoxy, -C(0)ORsi, - C(0)NR_5iR₅ , -OCH₂CH₂OR_5I , -NR_5iS(0)₂NR₅rR₅r and -C(CH₃)₂OR_5I ; wherein R₅₁, Rsr and R₅r are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

R₆ is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7; wherein the alkyl, alkenyl or alkynyl defined in R₆, if substituted, is substituted with one or more substituent/s selected from -OR61, halogen, -CN, haloalkyl, haloalkoxy and -NReiRer; wherein the cycloalkyl, aryl and heterocyclyl defined in R₆, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R61, -OR61, -NO2, -NR6iR6r, - NR_6iC(0)R₆r, -NR6iS(0)2R6r, -S(0)2NR6iR6r, - NR6iC(0)NR6i R6i”, -SR61 , - S(0)R6i, -S(0)2R6i, -CN, haloalkyl, haloalkoxy, -C(0)0R6i, -C(0)NR6iR6r, - OCH2CH2OR61, -NR6iS(0)₂NR₆rR6r and -C(CH3)20R6i; preferably selected from halogen, -R61, -OR61, -NR_6iR₆r, -CN, haloalkyl and haloalkoxy; wherein R₆₁, Rer and R_6i” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl;

R₇ is selected from substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl; wherein the alkyl, alkenyl or alkynyl defined in R₇, if substituted, is substituted with one or more substituent/s selected from -OR71, halogen, -CN, haloalkyl, haloalkoxy and -NR71R71'; wherein the cycloalkyl, aryl and heterocyclyl, as defined in R₇, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R71, -OR71, -NO2, -NR_7iR₇r, - NR_7iC(0)R₇r, -NR7iS(0)2R7 , -S(0)2NR7iR7r, - NR7iC(0)NR7-rR7-r, -SR71 , - S(0)R7i, -S(0)2R7i, -CN, haloalkyl, haloalkoxy, -C(0)0R7i, -C(0)NR_7iR7r, - OCH2CH2OR71, -NR7iS(0)₂NR₇rR7r' and -C(CH3)20R7i; preferably selected from halogen, -R71, -OR71, -NR71R71', -CN, haloalkyl and haloalkoxy; wherein R₇₁, R₇r and R₇r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; R₂ is selected from substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, wherein the aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R21, -OR21, -NO2, -NR21R21', -

NR_2iC(0)R₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2r, - NR2iC(0)NR2i R2i”, -SR21 , - S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, -C(0)NR2iR2r, - OCH2CH2OR21, -NR2iS(0)₂NR₂rR2r' and -C(CH₃)₂OR₂I ; wherein R₂₁, R_21' and R_21” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

R₃ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; wherein, the alkyl, alkenyl or alkynyl defined in R₃, is substituted with one or more substituent/s selected from -OR₃₁, halogen, -CN, haloalkyl, haloalkoxy and -NR31R31'; wherein the cycloalkyl in R3, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, - R31, -OR31, -NO2, -NR31R31', -NR_3iC(0)R₃r, -NR3iS(0)2R3r,

S(0)₂NR_3iR3r, - NR_3iC(0)NR₃rR₃r', -SR31 , -S(0)R₃₁, -S(0)₂R₃₁, -CN, haloalkyl, haloalkoxy, -C(0)0R3i, -C(0)NR3iR3r, -OCH2CH2OR31, -

NR3iS(0)₂NR₃rR3r' and -C(CH3)20R3i; preferably selected from halogen, -R31, -OR31, -NR31R31', -CN, haloalkyl and haloalkoxy; wherein R₃₁, R_31' and R_31” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl;

R_3' is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; wherein, the alkyl, alkenyl or alkynyl defined in R_3', if substituted, is substituted with one or more substituent/s selected from -OR₃₂, halogen, -CN, haloalkyl, haloalkoxy and -NR32R32'; wherein R₃₂ and R_32' are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

R₄ and R_4' are independently selected from halogen, -R₄I , -OR₄I , -NO₂, - NR_4iR₄r, -NR_4iC(0)R₄r, -NR_4iS(0)₂R₄r, -S(0)₂NR_4iR₄r, -NR_4iC(0)NR₄rR₄-r, - SR₄I , -S(0)R₄I , -S(0)₂R₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R_4i, - C(0)NR_4iR₄r, -0CH₂CH₂0R₄I , -NR_4iS(0)₂NR₄ R_4i” and -C(CH₃)₂0R₄I ; wherein R₄I , R₄r and R₄r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl and substituted or unsubstituted cycloalkyl;

the alkyl, alkenyl or alkynyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, - OR13, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13'; wherein R13 and R13' are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C2-6 alkynyl;

the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, halogen, -R-u, -OR-u, -NO2, -NR-uR-u', -NRi4C(0)Ri4’, -NRi4S(0)2Ri4’, - S(0)₂NRi₄Ri4', - NRi₄C(0)NRi4'Ri4”, -SR14 , -S(0)Ri4, -S(0)2Ri4, — CN, haloalkyl, haloalkoxy, -C(0)0Ri4, -C(0)NRi4Ri4·, -OCH2CH2OR14,

NRi₄S(0)₂NRi4'Ri4” and -C(CH3)20R-i4; wherein R14, Ru· and R-u- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the following proviso applies: when Y is C=0-, then R₆ is not -C(0)R₇;

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (I )

O^’) wherein Ri, R₂, R3, R3', R₄, R₄·, X and n are as defined in the detailed description, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

O^’) wherein

X is selected from a bond, -[C(R_aRb)]_P-, -[CH₂]pC(0)[CH₂]_q-, -[CH₂]_pC(0)N(R_z)[CH₂]_q-, - [CH₂]_pN(R_z)C(0)[CH₂]_q- and -[CH₂]_pN(R_z)[CH₂]_q-; R_a is selected from hydrogen, halogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;

Rb is selected from hydrogen, halogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R_a and R_b, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl;

R_z is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and -C(0)-Ci-6 alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5;

n is 0 or 1 ;

R1 is

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH2- or C=0;

R₅ and R_5' are independently selected from halogen, -R₅₁, -OR₅₁, -NO₂, - NR₅₁R_{51 '}, -NR_5iC(0)R_5r, -NR_5iS(0)₂R₅r, -S(0)₂NR_5iR₅-r, - NR_5iC(0)NR_5i R_5i”, - SR51 , -S(0)R5i, -S(0)2R5i, -CN, haloalkyl, haloalkoxy, -C(0)0Rsi, - C(0)NR_5iR₅r, -OCH₂CH₂OR₅I , -NR_5iS(0)₂NR₅rR_5i and -C(CH₃)₂OR₅I ; wherein R₅₁, Rsr and R₅r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

R₆ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7;

R₇ is selected from substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl;

R₃ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

R3' is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

O^’) wherein

R_a is selected from hydrogen, halogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl;

R_z is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and -C(0)-Ci-₆ alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5;

n is 0 or 1 ;

wherein m is 0, 1 or 2; r is 0 , 1 or 2;

Y is -CH2- or C=0;

R5 and R5' are independently selected from halogen, -R51, -OR51, -NO2, - NR51R51', -NR_5iC(0)R_5r, -NR_5iS(0)₂R₅r, -S(0)₂NR_5iR₅-r, - NR_5iC(0)NR_5i R_5i”, - SR51 , -S(0)R5i, -S(0)2R5i, -CN, haloalkyl, haloalkoxy, -C(0)0Rsi, -

C(0)NR_5iR₅r, -OCH₂CH₂OR_5I , -NR_5iS(0)₂NR₅rR_5i and -C(CH₃)₂OR_5I ; wherein R51, Rsr and Rsr are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

R₆ is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7; wherein the alkyl, alkenyl or alkynyl defined in R₆, if substituted, is substituted with one or more substituent/s selected from -OR₆₁, halogen, -CN, haloalkyl, haloalkoxy and -NRei Rer; wherein the cycloalkyl, aryl and heterocyclyl defined in R₆, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R61, -OR61, -NO2, -NReiRer, -

NR_6iC(0)R₆r, -NR6iS(0)2R6r, -S(0)2NR6iR6r, - NR6iC(0)NRerR6i”, -SR61 , - S(0)R6i, -S(0)2R6i, -CN, haloalkyl, haloalkoxy, -C(0)0R6i, -C(0)NR6iR6r, - OCH2CH2OR61, -NR6iS(0)₂NR₆rR6r and -C(CH3)20R6i; preferably selected from halogen, -R61, -OR61, -NReiRer, -CN, haloalkyl and haloalkoxy; wherein R₆₁, Rer and Rer are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl;

R₇ is selected from substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl; wherein the alkyl, alkenyl or alkynyl defined in R₇, if substituted, is substituted with one or more substituent/s selected from -OR₇₁, halogen, -CN, haloalkyl, haloalkoxy and -NR71R71'; wherein the cycloalkyl, aryl and heterocyclyl, as defined in R₇, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R71, -OR₇I , -NO2, -NR_7iR₇r, - NR_7iC(0)R₇r, -NR_7iS(0)₂R₇r, -S(0)₂NR_7iR₇r, - NR_7iC(0)NR₇-rR₇-r, -SR₇I , -

S(0)R₇I , -S(0)₂R₇I , -CN, haloalkyl, haloalkoxy, -C(0)0R_7i, -C(0)NR_7iR₇r, - 0CH₂CH₂0R₇I , -NR₇IS(0)₂NR₇I R₇I” and -C(CH₃)₂0R₇I ; preferably selected from halogen, -R₇I , -OR₇I , -NR_7iR₇r, -CN, haloalkyl and haloalkoxy; wherein R₇I , R₇r and R₇r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

R₂ is selected from substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, wherein the aryl or heterocyclyl in R₂, if substituted, is substituted with one or more substituent/s selected from halogen, -R21, -OR21, -NO2, -NR21R21', - NR_2iC(0)R₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2r, - NR2iC(0)NR2i R2i”, -SR21 , - S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, -C(0)NR2iR2r, - OCH2CH2OR21, -NR2iS(0)₂NR₂rR2r' and -C(CH₃)₂OR₂I ; wherein R₂₁, R_21' and R_21” are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

R₃ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; wherein, the alkyl, alkenyl or alkynyl defined in R3, is substituted with one or more substituent/s selected from -OR₃₁, halogen, -CN, haloalkyl, haloalkoxy and -NR31R31'; wherein the cycloalkyl in R₃, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, - R31, -OR31, -NO2, -NR31R31', -NR_3iC(0)R₃r, -NR3iS(0)2R3r,

S(0)₂NR_3iR3r, - NR_3iC(0)NR₃rR₃r', -SR31 , -S(0)R₃₁, -S(0)₂R₃₁, -CN, haloalkyl, haloalkoxy, -C(0)0R3i, -C(0)NR3iR3r, -OCH2CH2OR31, - NR3iS(0)₂NR₃rR3r' and -C(CH3)20R3i; preferably selected from halogen, -R31, -OR31, -NR31R31', -CN, haloalkyl and haloalkoxy; wherein R31, R31' and R31” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl;

R3' is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; wherein, the alkyl, alkenyl or alkynyl defined in R3', if substituted, is substituted with one or more substituent/s selected from -OR₃₂, halogen, -CN, haloalkyl, haloalkoxy and -NR32R32'; wherein R₃₂ and R_32' are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

R₄ and R_4' are independently selected from halogen, -R_4I , -OR_4I , -NO₂, - NR_4iR₄r, -NR_4iC(0)R₄r, -NR_4iS(0)₂R₄r, -S(0)₂NR_4iR₄r, -NR_4iC(0)NR₄rR₄-r, - SR_4I , -S(0)R_4I , -S(0)₂R_4I , -CN, haloalkyl, haloalkoxy, -C(0)0R_4i, - C(0)NR_4iR₄r, -0CH₂CH₂0R_4I , -NR_4iS(0)₂NR₄ R_4i” and -C(CH₃)₂0R_4I ; wherein R₄₁, R_41' and R_41” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl and substituted or unsubstituted cycloalkyl;

the alkyl, alkenyl or alkynyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, - OR₁₃, halogen, -CN, haloalkyl, haloalkoxy and -NR₁₃R_13'; wherein R₁₃ and R_13' are independently selected from hydrogen, unsubstituted C_1-6 alkyl, unsubstituted C_2-6 alkenyl, and unsubstituted C_2-6 alkynyl;

the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, halogen, -R-u, -OR-u, -NO2, -NR-uR-u', -NRi4C(0)Ri4’, -NRi4S(0)2Ri4’, - S(0)₂NRi₄Ri4', - NRi₄C(0)NRi4'Ri4”, -SR14 , -S(0)Ri4, -S(0)2Ri4, — CN, haloalkyl, haloalkoxy, -C(0)0Ri4, -C(0)NRi4Ri4·, -OCH2CH2OR14, NRi₄S(0)₂NRi4'Ri4” and -C(CH3)20R-i4; wherein R₁₄, Ru· and R-u- are independently selected from hydrogen, unsubstituted C_1-6 alkyl, unsubstituted C_2-6 alkenyl, unsubstituted C_2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l^a)

wherein Ri, R3, R3', R₄, R₄·, R9, R9', X, Ui, Y2 and n are as defined in the detailed description, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l^a)

wherein

R_a is selected from hydrogen, halogen, substituted or unsubstituted C alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; R_b is selected from hydrogen, halogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R_a and R_b, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl; R_z is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and -C(0)-Ci-₆ alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5; n is 0 or 1 ;

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH2- or C=0;

R5 and R5' are independently selected from halogen, -R51, -OR51, -NO2, - NR51R51', -NR_5iC(0)R_5r, -NR_5iS(0)₂R₅r, -S(0)₂NR_5iR₅-r, - NR_5iC(0)NR_5i R_5i”, - SR51 , -S(0)R5i, -S(0)2R5i, -CN, haloalkyl, haloalkoxy, -C(0)0Rsi, - C(0)NR_5iR₅r, -OCH₂CH₂OR₅I , -NR_5iS(0)₂NR₅rR_5i and -C(CH₃)₂OR₅I ; wherein R51, Rsr and R₅r are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

R₇ is selected from substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl; R₃ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

R_3' is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

Rg and Rg· are independently selected from halogen, -R₂₁, -OR₂₁, -NO₂, -

NR21R21’, -NR_2iC(0)R₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2 , - NR2iC(0)NR2i R2i”, -SR21 , -S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, - C(0)NR_2iR₂r, -OCH2CH2OR21, -NR2iS(0)₂NR₂rR2r' and -C(CH₃)₂OR₂I ; wherein R₂₁, R_21' and R_21” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

wherein

R_a is selected from hydrogen, halogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; R_b is selected from hydrogen, halogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R_a and R_b, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl; R_z is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and -C(0)-Ci-₆ alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5;

n is 0 or 1 ;

wherein m is 0, 1 or 2; r is 0 , 1 or 2;

Y is -CH2- or C=0;

S(0)R₇I , -S(0)₂R₇I , -CN, haloalkyl, haloalkoxy, -C(0)0R_7i, -C(0)NR_7iR₇r, - 0CH₂CH₂0R_7I , -NR_7IS(0)₂NR_7I R_7I” and -C(CH₃)₂0R_7I ; preferably selected from halogen, -R₇I , -OR₇I , -NR_7iR₇r, -CN, haloalkyl and haloalkoxy; wherein R₇I , R₇r and R₇r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

R₃ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; wherein, the alkyl, alkenyl or alkynyl defined in R₃, is substituted with one or more substituent/s selected from -OR₃1 , halogen, -CN, haloalkyl, haloalkoxy and -NR31 R31'; wherein the cycloalkyl in R₃, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, - R31 , -OR31 , -NO2, -NR31 R31', -NR_3iC(0)R₃r, -NR3iS(0)2R3r, S(0)₂NR_3i R3r, - NR_3iC(0)NR₃rR3r, -SR31 , -S(0)R₃1 , -S(0)₂R₃1 , -CN, haloalkyl, haloalkoxy, -C(0)0R3i , -C(0)NR3iR3r, -OCH2CH2OR31 , - NR3iS(0)₂NR₃rR3r' and -C(CH3)20R3i; preferably selected from halogen, -R31 , -OR31 , -NR31 R31', -CN, haloalkyl and haloalkoxy; wherein R₃₁, R_31' and R_31” are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;

R_3' is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; wherein, the alkyl, alkenyl or alkynyl defined in R_3', if substituted, is substituted with one or more substituent/s selected from -OR32, halogen, -CN, haloalkyl, haloalkoxy and -NR32R32'; wherein R32 and R32' are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

Rg and Rg· are independently selected from halogen, -R21, -OR21, -NO2, - NR21R21’, -NR_2iC(0)R₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2 , - NR2iC(0)NR2i R2i”, -SR21 , -S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, - C(0)NR_2iR₂r, -OCH2CH2OR21, -NR2iS(0)₂NR₂rR2r' and -C(CH₃)₂OR₂I ; wherein R₂₁, R_21' and R_21” are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

the alkyl, alkenyl or alkynyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, - OR13, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13'; wherein R₁₃ and R_13' are independently selected from hydrogen, unsubstituted C_1-6 alkyl, unsubstituted C_2-6 alkenyl, and unsubstituted C_2-6 alkynyl;

the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, halogen, -R14, -OR14, -NO2, -NR-uR-u', -NRi4C(0)Ri4’, -NRi4S(0)2Ri4’, -

S(0)₂NRi₄Ri4', - NRi₄C(0)NRi4'Ri4”, -SR14 , -S(0)Ri4, -S(0)2Ri4, — CN, haloalkyl, haloalkoxy, -C(0)0Ri4, -C(0)NRi4Ri4·, -OCH2CH2OR14,

NRi₄S(0)₂NRi4'Ri4” and -C(CH3)20Ri4; wherein R₁₄, Ru· and R-u- are independently selected from hydrogen, unsubstituted C_1-6 alkyl, unsubstituted C_2-6 alkenyl, unsubstituted C_2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l^a’)

wherein Ri, R3, R3', R₄, R₄·, R9, RET, X and n are as defined in the detailed description, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

(P wherein

X is selected from a bond, -[C(R_aRb)]_P-, -[CH₂]pC(0)[CH₂]_q-, -[CH₂]_pC(0)N(R_z)[CH₂]_q-, - [CH₂]_pN(R_z)C(0)[CH₂]_q- and -[CH₂]_pN(R_z)[CH₂]_q-; R_a is selected from hydrogen, halogen, substituted or unsubstituted C alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl;

R_b is selected from hydrogen, halogen, substituted or unsubstituted C alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R_a and R_b, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl;

n is 0 or 1 ;

wherein m is 0, 1 or 2; r is 0 , 1 or 2;

Y is -CH2- or C=0;

R₆ is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7;

R₄ and R_4' are independently selected from halogen, -R₄I , -OR₄I , -NO₂, - NR_4iR₄r, -NR_4iC(0)R₄r, -NR_4iS(0)₂R₄r, -S(0)₂NR_4iR₄r, -NR_4iC(0)NR₄rR₄-r, - SR₄I , -S(0)R₄I , -S(0)₂R₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R_4i, - C(0)NR_4iR₄r, -0CH₂CH₂0R₄I , -NR_4iS(0)₂NR₄ R_4i” and -C(CH₃)₂0R₄I ; wherein R₄I , R₄r and R₄r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl and substituted or unsubstituted cycloalkyl; Rg and Rg· are independently selected from halogen, -R21, -OR21, -NO2, - NR21R21’, -NR_2iC(0)R₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2 , - NR2iC(0)NR2i R2i”, -SR21 , -S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, - C(0)NR_2iR₂r, -OCH2CH2OR21, -NR2iS(0)₂NR₂rR2r and -C(CH₃)₂OR₂I ; wherein R21, R21' and R21” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

wherein X is selected from a bond, -[C(R_aRb)]_P-, -[CH₂]pC(0)[CH₂]_q-, -[CH₂]_pC(0)N(R_z)[CH₂]_q-, - [CH₂]_pN(R_z)C(0)[CH₂]_q- and -[CH₂]_pN(R_z)[CH₂]_q-;

n is 0 or 1 ;

Ri is

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH2- or C=0;

R5 and R5' are independently selected from halogen, -R51, -OR51, -NO2, - NR51R51', -NR_5iC(0)R_5r, -NR_5iS(0)₂R₅r, -S(0)₂NR_5iR₅-r, - NR_5iC(0)NR_5i R_5i”, - SR51 , -S(0)R5i, -S(0)2R5i, -CN, haloalkyl, haloalkoxy, -C(0)0Rsi, - C(0)NR_5iR₅r, -OCH₂CH₂OR_5I , -NR_5iS(0)₂NR₅rR_5i and -C(CH₃)₂OR_5I ; wherein R51, Rsr and Rsr are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

R₆ is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7; wherein the alkyl, alkenyl or alkynyl defined in R₆, if substituted, is substituted with one or more substituent/s selected from -OR61, halogen, -CN, haloalkyl, haloalkoxy and -NReiRer; wherein the cycloalkyl, aryl and heterocyclyl defined in R₆, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R61, -OR61, -NO2, -NR6iR6r, - NR_6iC(0)R₆r, -NR6iS(0)2R6r, -S(0)2NR6iR6r, - NR6iC(0)NR6i R6i”, -SR61 , - S(0)R6i, -S(0)2R6i, -CN, haloalkyl, haloalkoxy, -C(0)0R6i, -C(0)NR6iR6r, -

OCH2CH2OR61, -NR6iS(0)₂NR₆rR6r' and -C(CH3)20R6i; preferably selected from halogen, -R₆₁, -OR₆₁, -NR_6iR₆r, -CN, haloalkyl and haloalkoxy; wherein R₆₁, Rer and R_6i” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl;

R₇ is selected from substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl; wherein the alkyl, alkenyl or alkynyl defined in R₇, if substituted, is substituted with one or more substituent/s selected from -OR₇₁, halogen, -CN, haloalkyl, haloalkoxy and -NR71R71'; wherein the cycloalkyl, aryl and heterocyclyl, as defined in R₇, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R71, -OR71, -NO2, -NR71R71’, -

NR_7iC(0)R₇r, -NR7iS(0)2R7 , -S(0)2NR7iR7r, - NR7iC(0)NR7-rR7-r, -SR71 , - S(0)R7i, -S(0)2R7i, -CN, haloalkyl, haloalkoxy, -C(0)0R7i, -C(0)NR_7iR7r, - OCH2CH2OR71, -NR7iS(0)₂NR₇rR7r' and -C(CH3)20R7i; preferably selected from halogen, -R₇₁, -OR₇₁, -NR₇₁R_71', -CN, haloalkyl and haloalkoxy; wherein R₇₁, R_71' and R₇r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

R₃ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; wherein, the alkyl, alkenyl or alkynyl defined in R₃, is substituted with one or more substituent/s selected from -OR₃₁, halogen, -CN, haloalkyl, haloalkoxy and -NR31R31'; wherein the cycloalkyl in R₃, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -

R31, -OR31, -NO2, -NR31R31', -NR_3iC(0)R₃r, -NR3iS(0)2R3r,

S(0)₂NR_3iR3r, - NR_3iC(0)NR₃rR₃r', -SR31 , -S(0)R₃₁, -S(0)₂R₃₁, -CN, haloalkyl, haloalkoxy, -C(0)0R3i, -C(0)NR3iR3r, -OCH2CH2OR31, - NR3iS(0)₂NR₃rR3r' and -C(CH3)20R3i; preferably selected from halogen, -R31, -OR31, -NR31R31', -CN, haloalkyl and haloalkoxy; wherein R₃₁, R_31' and R_31” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl;

R₄ and R_4' are independently selected from halogen, -R₄I , -OR₄I , -NO₂, - NR_4iR₄r, -NR_4iC(0)R₄r, -NR_4iS(0)₂R₄r, -S(0)₂NR_4iR₄r, -NR_4iC(0)NR₄rR₄-r, - SR₄I , -S(0)R₄I , -S(0)₂R₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R_4i, -

C(0)NR_4iR₄r, -0CH₂CH₂0R₄I , -NR_4iS(0)₂NR₄ R_4i” and -C(CH₃)₂0R₄I ; wherein R₄I , R₄r and R₄r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl and substituted or unsubstituted cycloalkyl;

Rg and Rg· are independently selected from halogen, -R₂₁, -OR₂₁, -NO₂, - NR21R21’, -NR_2iC(0)R₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2 , - NR2iC(0)NR2i R2i”, -SR21 , -S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, - C(0)NR_2iR₂r, -OCH2CH2OR21, -NR2iS(0)₂NR₂rR2r' and -C(CH₃)₂OR₂I ; wherein R₂₁, R_21' and R_21” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, halogen, -R-u, -OR-u, -NO2, -NR-uR-u', -NRi4C(0)Ri4’, -NRi4S(0)2Ri4’, - S(0)₂NRi₄Ri4', - NRi₄C(0)NRi4'Ri4”, -SR14 , -S(0)Ri4, -S(0)2Ri4, — CN, haloalkyl, haloalkoxy, -C(0)0Ri4, -C(0)NRi4Ri4·, -OCH2CH2OR14, NRi₄S(0)₂NRi4'Ri4” and -C(CH3)20R-i4; wherein R₁₄, Ru· and R-u- are independently selected from hydrogen, unsubstituted C_1-6 alkyl, unsubstituted C_2-6 alkenyl, unsubstituted C_2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l^b)

wherein Ri, R3, R3', R₄, R₄·, R9, RET, X, Ui, Y2 and n are as defined below in the detailed description, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

wherein

Y2 is -C(Rio”Rio )-! wherein Rio- and R₁₀ - are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R_10” and Rio- form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH2- or C=0;

R₇ is selected from substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl; R₃ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

R₄ and R₄· are independently selected from halogen, -R₄I , -OR₄I , -NO2, -

NR_4iR₄r, -NR_4iC(0)R₄r, -NR_4iS(0)₂R₄r, -S(0)₂NR_4iR₄r, -NR_4iC(0)NR₄rR₄-r, - SR₄I , -S(0)R₄I , -S(0)₂R₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R_4i, - C(0)NR_4iR₄r, -0CH₂CH₂0R₄I , -NR_4iS(0)₂NR₄ R_4i” and -C(CH₃)₂0R₄I ; wherein R₄I , R₄r and R₄r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl and substituted or unsubstituted cycloalkyl;

Rg and Rg· are independently selected from halogen, -R21, -OR21, -NO2, - NR21R21', -NR_2iC(0)R₂r, -NR_2iS(0)₂R2r, -S(0)₂NR_2iR2r, - NR_2iC(0)NR₂rR2r,

-SR21 , -S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, - C(0)NR_2iR₂r, -OCH2CH2OR21, -NR2iS(0)₂NR₂rR2r' and -C(CH₃)₂OR₂I ; wherein R₂₁, R_21' and R_21” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l^b)

n is 0 or 1 ;

wherein m is 0, 1 or 2; r is 0 , 1 or 2;

Y is -CH2- or C=0;

NRi₄S(0)₂NRi4'Ri4” and -C(CH3)20Ri4; wherein R₁₄, Ru· and R-u- are independently selected from hydrogen, unsubstituted C_1-6 alkyl, unsubstituted C_2-6 alkenyl, unsubstituted C_2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l^b’)

(l^b ), wherein Ri, R3, R3', R₄, R₄·, R9, R9', X and n are as defined below in the detailed description, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

(I^b ), wherein

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH2- or C=0;

R5 and Rs· are independently selected from halogen, -R51, -OR51, -NO2, -

NR51R51', -NR_5iC(0)R_5r, -NR_5iS(0)₂R₅r, -S(0)₂NR_5iR₅-r, - NR_5iC(0)NR_5i R_5i”, - SR51 , -S(0)R5i, -S(0)2R5i, -CN, haloalkyl, haloalkoxy, -C(0)0Rsi, - C(0)NR_5iR₅r, -OCH₂CH₂OR₅I , -NR_5iS(0)₂NR₅rR₅r and -C(CH₃)₂OR₅I ; wherein R51, Rsr and R₅r are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl; R6 is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7;

R₄ and R_4' are independently selected from halogen, -R₄I , -OR₄I , -NO2, - NR_4iR₄r, -NR_4iC(0)R₄r, -NR_4iS(0)₂R₄r, -S(0)₂NR_4iR₄r, -NR_4iC(0)NR₄rR₄-r, - SR₄I , -S(0)R₄I , -S(0)₂R₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R_4i, - C(0)NR_4iR₄r, -0CH₂CH₂0R₄I , -NR_4iS(0)₂NR₄ R_4i” and -C(CH₃)₂0R₄I ; wherein R₄₁, R₄r and R_41” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl and substituted or unsubstituted cycloalkyl;

(I^b ), wherein

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH2- or C=0;

R5 and Rs· are independently selected from halogen, -R51, -OR51, -NO2, -

NR51R51', -NR_5iC(0)R_5r, -NR_5iS(0)₂R₅r, -S(0)₂NR_5iR₅-r, - NR_5iC(0)NR_5i R_5i”, - SR51 , -S(0)R5i, -S(0)2R5i, -CN, haloalkyl, haloalkoxy, -C(0)0Rsi, - C(0)NR_5iR₅r, -OCH₂CH₂OR₅I , -NR_5iS(0)₂NR₅rR₅r and -C(CH₃)₂OR₅I ; wherein R51, Rsr and R₅r are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl; R₆ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7; wherein the alkyl, alkenyl or alkynyl defined in R₆, if substituted, is substituted with one or more substituent/s selected from -OR₆₁, halogen, -CN, haloalkyl, haloalkoxy and -NR6iR6r; wherein the cycloalkyl, aryl and heterocyclyl defined in R₆, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R61, -OR61, -NO2, -NR6iR6r, - NR_6iC(0)R₆r, -NR6iS(0)2R6r, -S(0)2NR6iR6r, - NR6iC(0)NR6i R6i”, -SR61 , -

S(0)R6i, -S(0)2R6i, -CN, haloalkyl, haloalkoxy, -C(0)0R6i, -C(0)NR6iR6r, - OCH2CH2OR61, -NR6iS(0)₂NR₆rR6r' and -C(CH3)20R6i; preferably selected from halogen, -R61, -OR61, -NR_6iR₆r, -CN, haloalkyl and haloalkoxy; wherein R₆₁, Rer and R₆r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl;

R₇ is selected from substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl; wherein the alkyl, alkenyl or alkynyl defined in R₇, if substituted, is substituted with one or more substituent/s selected from -OR₇₁, halogen, -CN, haloalkyl, haloalkoxy and -NR71R71'; wherein the cycloalkyl, aryl and heterocyclyl, as defined in R₇, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R71, -OR71, -NO2, -NR71R71’, - NR_7iC(0)R₇r, -NR7iS(0)2R7 , -S(0)2NR7iR7r, - NR7iC(0)NR7-rR7-r, -SR71 , - S(0)R7i, -S(0)2R7i, -CN, haloalkyl, haloalkoxy, -C(0)0R7i, -C(0)NR_7iR7r, - OCH2CH2OR71, -NR7iS(0)₂NR₇rR7r' and -C(CH3)20R7i; preferably selected from halogen, -R₇₁, -OR₇₁, -NR₇₁R_71', -CN, haloalkyl and haloalkoxy; wherein R₇₁, R₇r and R₇r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

R₃ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; wherein, the alkyl, alkenyl or alkynyl defined in R₃, is substituted with one or more substituent/s selected from -OR₃₁, halogen, -CN, haloalkyl, haloalkoxy and -NR31R31'; wherein the cycloalkyl in R₃, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, - R31, -OR31, -NO2, -NR31R31', -NR_3iC(0)R₃r, -NR3iS(0)2R3r,

S(0)₂NR_3iR3r, - NR_3iC(0)NR₃rR₃r, -SR31 , -S(0)R₃₁, -S(0)₂R₃₁, -CN, haloalkyl, haloalkoxy, -C(0)0R3i, -C(0)NR3iR3r, -OCH2CH2OR31, - NR3iS(0)₂NR₃rR3r' and -C(CH3)20R3i; preferably selected from halogen, -R31, -OR31, -NR31R31', -CN, haloalkyl and haloalkoxy; wherein R₃₁, R_31' and R_31” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl;

Rg and Rg· are independently selected from halogen, -R₂₁, -OR₂₁, -NO₂, - NR21R21’, -NR_2iC(0)R₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2 , - NR2iC(0)NR2i R2i”, -SR21 , -S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, - C(0)NR_2iR₂r, -OCH2CH2OR21, -NR2iS(0)₂NR₂rR2r' and -C(CH₃)₂OR_2I ; wherein R₂₁, R_21' and R_21” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, halogen, -R-u, -OR14, -NO2, -NR-uR-u', -NRi4C(0)Ri4’, -NRi4S(0)2Ri4’, - S(0)₂NRi₄Ri4', - NRi₄C(0)NRi4'Ri4”, -SR14 , -S(0)Ri4, -S(0)2Ri4, — CN, haloalkyl, haloalkoxy, -C(0)0Ri4, -C(0)NRi4Ri4·, -OCH2CH2OR14, NRi₄S(0)₂NRi4'Ri4” and -C(CH3)20Ri4; wherein R14, Ru· and Ru·· are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l^c)

(I^c), wherein Ri, R3, R3', R₄, R₄·, R9, RET, X, Ui, Y2 and n are as defined below in the detailed description, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l^c)

wherein

X is selected from a bond, -[C(R_aRb)]_P-, -[CH₂]pC(0)[CH₂]_q-, -[CH₂]pC(0)N(Rz)[CH₂]_q-, - [CH₂]pN(Rz)C(0)[CH₂]_q- and -[CH₂]pN(Rz)[CH₂]_q-;

R_a is selected from hydrogen, halogen, substituted or unsubstituted C alkyl, substituted or unsubstituted C2-₆ alkenyl and substituted or unsubstituted C2-₆ alkynyl;

R_b is selected from hydrogen, halogen, substituted or unsubstituted C1-₆ alkyl, substituted or unsubstituted C2-₆ alkenyl and substituted or unsubstituted C2-₆ alkynyl; alternatively, R_a and R_t>, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl;

R_z is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C2-₆ alkenyl, substituted or unsubstituted C2-₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and -C(0)-Ci-₆ alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5; n is 0 or 1 ;

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH2- or C=0;

Rg and Rg· are independently selected from halogen, -R₂₁, -OR₂₁, -NO₂, - NR21R21’, -NR_2iC(0)R₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2 , - NR2iC(0)NR2i R2i”, -SR21 , -S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, - C(0)NR_2iR₂r, -OCH2CH2OR21, -NR2iS(0)₂NR₂rR2r' and -C(CH₃)₂OR₂I ; wherein R₂₁, R_21' and R_21” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l^c)

wherein

X is selected from a bond, -[C(R_aRb)]_P-, -[CH₂]pC(0)[CH₂]_q-, -[CH₂]_pC(0)N(R_z)[CH₂]_q-, - [CH₂]_pN(R_z)C(0)[CH₂]_q- and -[CH₂]_pN(R_z)[CH₂]_q-; R_a is selected from hydrogen, halogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl;

n is 0 or 1 ;

wherein m is 0, 1 or 2; r is 0 , 1 or 2;

Y is -CH2- or C=0;

Rg and Rg· are independently selected from halogen, -R21, -OR21, -NO2, - NR21R21’, -NR_2iC(0)R₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2 , - NR2iC(0)NR2i R2i”,

-SR21 , -S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, - C(0)NR_2iR₂r, -OCH2CH2OR21, -NR2iS(0)₂NR₂rR2r' and -C(CH₃)₂OR₂I ; wherein R₂₁, R_21' and R_21” are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l^c’)

(I^c ), wherein Ri, R3, R3', R₄, R₄·, R9, R9', X and n are as defined below in the detailed description, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

(l^c' wherein

n is 0 or 1 ;

wherein m is 0, 1 or 2; r is 0 , 1 or 2;

Y is -CH2- or C=0;

R₄ and R_4' are independently selected from halogen, -R₄I , -OR₄I , -NO₂, - NR_4iR₄r, -NR_4iC(0)R₄r, -NR_4iS(0)₂R₄r, -S(0)₂NR_4iR₄r, -NR_4iC(0)NR₄rR₄-r, - SR₄I , -S(0)R₄I , -S(0)₂R₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R_4i, - C(0)NR_4iR₄r, -0CH₂CH₂0R₄I , -NR_4iS(0)₂NR₄ R_4i” and -C(CH₃)₂0R₄I ; wherein R₄I , R₄r and R₄r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl and substituted or unsubstituted cycloalkyl; Rg and Rg· are independently selected from halogen, -R21, -OR21, -NO2, - NR21R21’, -NR_2iC(0)R₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2 , - NR2iC(0)NR2i R2i”, -SR21 , -S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, - C(0)NR_2iR₂r, -OCH2CH2OR21, -NR2iS(0)₂NR₂rR2r' and -C(CH₃)₂OR₂I ; wherein R₂₁, R_21' and R_21” are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

(I^c' wherein X is selected from a bond, -[C(R_aRb)]_P-, -[CH₂]pC(0)[CH₂]_q-, -[CH₂]_pC(0)N(R_z)[CH₂]_q-, - [CH₂]_pN(R_z)C(0)[CH₂]_q- and -[CH₂]_pN(R_z)[CH₂]_q-;

n is 0 or 1 ;

Ri is

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH2- or C=0;

R31, -OR31, -NO2, -NR31R31', -NR_3iC(0)R₃r, -NR3iS(0)2R3r,

R_3' is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; wherein, the alkyl, alkenyl or alkynyl defined in R₃·, if substituted, is substituted with one or more substituent/s selected from -OR₃₂, halogen, -CN, haloalkyl, haloalkoxy and -NR₃₂R_32'; wherein R₃₂ and R₃₂· are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

Rg and Rg· are independently selected from halogen, -R₂₁, -OR₂₁, -NO₂, - NR21R21’, -NR_2iC(0)R₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2 , - NR2iC(0)NR2i R2i”, -SR21 , -S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, - C(0)NR_2iR₂r, -OCH2CH2OR21, -NR2iS(0)₂NR₂rR2r and -C(CH₃)₂OR₂I ; wherein R₂₁, R_21' and R_21” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

the alkyl, alkenyl or alkynyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, - OR_I3, halogen, -CN, haloalkyl, haloalkoxy and -NR_I3R_I3·; wherein R_I3 and R_I3· are independently selected from hydrogen, unsubstituted C_1-6 alkyl, unsubstituted C_2-6 alkenyl, and unsubstituted C_2-6 alkynyl; the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, halogen, -R-u, -OR-u, -NO2, -NR14R14', -NRi4C(0)Ri4’, -NRi4S(0)2Ri4’, -

NRi₄S(0)₂NRi4'Ri4” and -C(CH3)20R-i4; wherein R-u, Ru· and Ru·· are independently selected from hydrogen, unsubstituted C_1-6 alkyl, unsubstituted C_2-6 alkenyl, unsubstituted C_2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

For clarity purposes, all groups and definitions described in the present description and referring to compounds of general Formula (I), also apply to compounds of general Markush Formulae (I’), (l^a), (l^a), (l^b), (l^b), (l^c) and (l^c), (where applicable), and to all intermediate of synthesis, when those groups are present in the mentioned general Markush formulae, since compounds of general Markush Formulae (I’), (l^a), (l^a ), (l^b), (l^b), (l^c) and (l^c), are included within the scope of the larger definition of general Markush Formula (I).

For clarity purposes, the general Markush Formula (I)

is equivalent to

wherein only - CH2- is included into the brackets, and n means the number of times that -CH2- is repeated. The same would apply, when applicable, to general Markush Formulae (G), (l^a), (l^a ), (l^b), (l^b ), (l^c) and (l^c ), and to all intermediates of synthesis.

In addition, and for clarity purposes, it should further be understood that naturally if n is 0, the oxygen atom and/or the phenyl group are still present, when applicable, in general Markush Formulae ( ), (l^a), (l^a), (l^b), (l^b ), (l^c) and (l^c ), and to all intermediates of synthesis.

For clarity purposes, the expression e.g. “the cycle in R_a-R_b“, means the cycle resulting when R_a and R_b form, together with the atom(s) to which they are attached. This cycle can then be substituted or not. This definition is also generally applicable and can be also applied as a definition of any other cycle (preferably cycloalkyls, heterocycls or aryls) formed from two different functional groups like e.g.“the cycle in Ri-Ri“ means the cycle resulting when R, and R,· form a cycle together with the atom(s) to which they are attached. This cycle can then be substituted or not.

In the context of this invention, alkyl is understood as meaning saturated, linear or branched hydrocarbons, which may be unsubstituted or substituted once or several times. It encompasses e.g. -CH3 and -CH2-CH3. In these radicals, Ci-2-alkyl represents C1- or C2-alkyl, Ci-3-alkyl represents C1-, C2- or C3-alkyl, Ci-₄-alkyl represents C1-, C2-, C3- or C4-alkyl, Ci-5-alkyl represents C1-, C2-, C3-, C4-, or 05- alkyl, Ci-6-alkyl represents C1-, C2-, C3-, C4-, C5- or C6-alkyl, Ci-7-alkyl represents C1-, C2-, C3-, C4-, C5-, C6- or C7-alkyl, Ci-s-alkyl represents C1-, C2-, C3-, C4-, C5-,

C6-, C7- or C8-alkyl, Ci-10-alkyl represents C1-, C2-, C3-, C4-, C5-, C6-, C7-, C8-, C9- or C10-alkyl and Ci-is-alkyl represents C1-, C2-, C3-, C4-, C5-, C6-, C7-, C8-, C9-, C10-, C11-, C12-, C13-, C14-, C15-, C16-, C17- or C18-alkyl. The alkyl radicals are preferably methyl, ethyl, propyl, methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1 ,1-dimethylethyl, pentyl, 1 ,1-dimethylpropyl, 1 ,2-dimethylpropyl, 2,2-dimethylpropyl, hexyl, 1-methylpentyl, if substituted also CHF2, CF3 or CH2OH etc. Preferably alkyl is understood in the context of this invention as Ci-salkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, or octyl; preferably is Ci-₆alkyl like methyl, ethyl, propyl, butyl, pentyl, or hexyl; more preferably is Ci-₄alkyl like methyl, ethyl, propyl or butyl. Alkenyl is understood as meaning unsaturated, linear or branched hydrocarbons, which may be unsubstituted or substituted once or several times. It encompasses groups like e.g. -CH=CH-CH₃. The alkenyl radicals are preferably vinyl (ethenyl), allyl (2-propenyl). Preferably in the context of this invention alkenyl is C₂-io-alkenyl or C_2-8- alkenyl like ethylene, propylene, butylene, pentylene, hexylene, heptylene or octylene; or is C_2-6-alkenyl like ethylene, propylene, butylene, pentylene, or hexylene; or is C_2-4-alkenyl, like ethylene, propylene, or butylenes.

Alkynyl is understood as meaning unsaturated, linear or branched hydrocarbons, which may be unsubstituted or substituted once or several times. It encompasses groups like e.g. -C^C-CHs (1-propinyl). Preferably alkynyl in the context of this invention is C₂-io-alkynyl or C_2-8-alkynyl like ethyne, propyne, butyene, pentyne, hexyne, heptyne, or octyne; or is C_2-6-alkynyl like ethyne, propyne, butyene, pentyne, or hexyne; or is C₂₄-alkynyl like ethyne, propyne, butyene, pentyne, or hexyne. In connection with alkyl (also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl), alkenyl, alkynyl and O-alkyl - unless defined otherwise - the term substituted in the context of this invention is understood as meaning replacement of at least one hydrogen radical on a carbon atom by halogen (F, Cl, Br, I), -NRkRk·, -SRk, -S(0)Rk, -S(0)2Rk, -ORk, - C(0)Rk, -C(0)ORk, -CN, -C(0)NRkRk_\ haloalkyl, haloalkoxy, being Rk represented by Ri3, R31 , R32, R61 or R71 (being Rk· represented by R13', R31 ', R32', Rer or R₇r_; being Rk- represented by R13”, R31”, R32 ', Rer or R71 ); wherein R1 to R₇r and R_z and R_a and Rb are as defined in the description, and wherein when different radicals R1 to R₇r and R_z are present simultaneously in Formula I they may be identical or different.

Most preferably in connection with alkyl (also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl), alkenyl, alkynyl or O-alkyl, substituted is understood in the context of this invention that any alkyl (also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl), alkenyl, alkynyl or O-alkyl which is substituted with one or more of halogen (F, Cl, Br, I), -NRkRk·, -ORk, -CN, -SRk, haloalkyl, haloalkoxy, being Rk represented by R13, R31 , R32, R61 or R₇I , (being Rk· represented by R13', R31 ', R32', Rer or R₇r_; being Rk- represented by R13 ", R31 ", R32 ", Rer· or R₇r)_; wherein R1 to R₇r and R_z are as defined in the description, and wherein when different radicals R1 to R₇r and R_z and R_a and R_b are present simultaneously in Formula I they may be identical or different.

More than one replacement on the same molecule and also on the same carbon atom is possible with the same or different substituents. This includes for example 3 hydrogens being replaced on the same C atom, as in the case of CF₃, or at different places of the same molecule, as in the case of e.g. -CH(OH)-CH=CH-CHCl2.

In the context of this invention haloalkyl is understood as meaning an alkyl being substituted once or several times by a halogen (selected from F, Cl, Br, I). It encompasses e.g. -CH2CI, -CH2F, -CHC , -CHF2, -CCI3, -CF3 and -CH2-CHCI2. Preferably haloalkyl is understood in the context of this invention as halogen- substituted Ci-4-alkyl representing halogen substituted C1-, C2-, C3- or C4-alkyl. The halogen-substituted alkyl radicals are thus preferably methyl, ethyl, propyl, and butyl. Preferred examples include -CH₂CI, -CH₂F, -CHCb, -CHF₂, and -CF₃.

In the context of this invention haloalkoxy is understood as meaning an -O-alkyl being substituted once or several times by a halogen (selected from F, Cl, Br, I). It encompasses e.g. -OCH2CI, -OCH2F, -OCHC , -OCHF2, -OCCI3, -OCF3 and - OCH2-CHCI2. Preferably haloalkoxy is understood in the context of this invention as halogen-substituted -OCi-4-alkyl representing halogen substituted C1-, C2-, C3- or C4-alkoxy. The halogen-substituted alkyl radicals are thus preferably O-methyl, O- ethyl, O-propyl, and O-butyl. Preferred examples include -OCH2CI, -OCH2F, - OCHC , -OCHF2, and -OCF3.

In the context of this invention cycloalkyl is understood as meaning saturated and unsaturated (but not aromatic) cyclic hydrocarbons (without a heteroatom in the ring), which can be unsubstituted or once or several times substituted. Furthermore, C3-4- cycloalkyl represents C3- or C4-cycloalkyl, C3-5-cycloalkyl represents C3-, C4- or C5- cycloalkyl, C3-6-cycloalkyl represents C3-, C4-, C5- or C6-cycloalkyl, C3-7-cycloalkyl represents C3-, C4-, C5-, C6- or C7-cycloalkyl, C3-8-cycloalkyl represents C3-, C4-, C5-, C6-, C7- or C8-cycloalkyl, C4-5-cycloalkyl represents C4- or C5-cycloalkyl, C4-6- cycloalkyl represents C4-, C5- or C6-cycloalkyl, C4-7-cycloalkyl represents C4-, C5-, C6- or C7-cycloalkyl, C5-6-cycloalkyl represents C5- or C6-cycloalkyl and C5-7- cycloalkyl represents C5-, C6- or C7-cycloalkyl. Examples are cyclopropyl, 2- methylcyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cycloheptyl, cyclooctyl, and also adamantyl. Preferably in the context of this invention cycloalkyl is C3-8cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; or is C3-7cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; or is C3-6cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, especially cyclopentyl or cyclohexyl.

Aryl is understood as meaning 5 to 18 membered mono or polycyclic ring systems with at least one aromatic ring but without heteroatoms even in only one of the rings. Examples are phenyl, naphthyl, fluoranthenyl, fluorenyl, tetralinyl or indanyl, 9H- fluorenyl or anthracenyl radicals, which can be unsubstituted or once or several times substituted. Most preferably aryl is understood in the context of this invention as phenyl, naphthyl or anthracenyl, preferably is phenyl.

A heterocyclyl radical or group (also called heterocyclyl hereinafter) is understood as meaning 5 to 18 membered mono or polycyclic heterocyclic ring systems, with at least one saturated or unsaturated ring which contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring. A heterocyclic group can also be substituted once or several times. Subgroups inside the heterocyclyls as understood herein include heteroaryls and non-aromatic heterocyclyls.

the heteroaryl (being equivalent to heteroaromatic radicals or aromatic heterocyclyls) is an aromatic 5 to 18 membered mono or polycyclic heterocyclic ring system of one or more rings of which at least one aromatic ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a 5 to 18 membered mono or polycyclic aromatic heterocyclic ring system of one or two rings of which at least one aromatic ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, pyrimidine, pyrazine, quinoline, isoquinoline, phthalazine, benzothiazole, indole, benzotriazole, carbazole, quinazoline, thiazole, imidazole, pyrazole, oxazole, thiophene and benzimidazole;

the non-aromatic heterocyclyl is a 5 to 18 membered mono or polycyclic heterocyclic ring system of one or more rings of which at least one ring - with this (or these) ring(s) then not being aromatic - contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a 5 to 18 membered mono or polycyclic heterocyclic ring system of one or two rings of which one or both rings - with this one or two rings then not being aromatic - contain/s one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepam, pyrrolidine, piperidine, piperazine, tetrahydropyran, morpholine, indoline, oxopyrrolidine, benzodioxane, especially is benzodioxane, morpholine, tetrahydropyran, piperidine, oxopyrrolidine and pyrrolidine.

Preferably in the context of this invention heterocyclyl is defined as a 5 to 18 membered mono or polycyclic heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring. Preferably it is a 5 to 18 membered mono or polycyclic heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring.

Preferred examples of heterocyclyls include oxazepan, pyrrolidine, imidazole, oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine, , benzofuran, benzimidazole, indazole, benzodiazole, thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, tetrahydroisoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and quinazoline, especially is pyridine, pyrazine, indazole, benzodioxane, thiazole, benzothiazole, morpholine, tetrahydropyrane, pyrazole, imidazole, piperidine, thiophene, indole, benzimidazole, pyrrolo[2,3b]pyridine, benzoxazole, oxopyrrolidine, pyrimidine, oxazepane and pyrrolidine.

In the context of this invention oxopyrrolidine is understood as meaning pyrrolidin-2- one.

An /V-containing heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains a nitrogen and optionally one or more further heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains a nitrogen and optionally one or more further heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepam, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzimidazole, indazole, benzothiazole, benzodiazole, morpholine, indoline, triazole, isoxazole, pyrazole, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, quinolone, isoquinoline, tetrahydrothienopyridine, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, carbazole or thiazole.

In the context of this invention, a cyclic amide is defined as a subgroup of a heterocyclyl (as defined above) formed through the cyclization of a carbon sequence, containing at least the sequence

-N-C(0)-C->

¾ forming part of the cycle. Said cyclic amide may optionally be fused to a ring system. Preferably the cyclic amide is an“indoline-2-one”. A cyclic amide may be substituted or unsubstituted as defined for heterocyclyl above.

In the context of this invention, a cyclic urea is defined as a subgroup of a heterocyclyl (as defined above) formed through the cyclization of a carbon sequence containing at least the sequence

>-N-C(0)-N->

^ forming part of the cycle. Said cyclic urea may optionally be fused to a ring system. Preferably the cyclic urea is“1 H-benzo[d]imidazol-2(3H)-one”. A cyclic urea may be substituted or unsubstituted as defined for heterocyclyl above.

In connection with aromatic heterocyclyls (heteroaryls), non-aromatic heterocyclyls, aryls and cycloalkyls, when a ring system falls within two or more of the above cycle definitions simultaneously, then the ring system is defined first as an aromatic heterocyclyl (heteroaryl) if at least one aromatic ring contains a heteroatom. If no aromatic ring contains a heteroatom, then the ring system is defined as a non- aromatic heterocyclyl if at least one non-aromatic ring contains a heteroatom. If no non-aromatic ring contains a heteroatom, then the ring system is defined as an aryl if it contains at least one aryl cycle. If no aryl is present, then the ring system is defined as a cycloalkyl if at least one non-aromatic cyclic hydrocarbon is present. In the context of this invention alkylaryl is understood as meaning an aryl group (see above) being connected to another atom through a Ci-₆-alkyl (see above) which may be branched or linear and is unsubstituted or substituted once or several times. Preferably alkylaryl is understood as meaning an aryl group (see above) being connected to another atom through 1 to 4 (-CH2-) groups. Most preferably alkylaryl is benzyl (i.e. -Chh-phenyl).

In the context of this invention alkylheterocyclyl is understood as meaning an heterocyclyl group being connected to another atom through a Ci-₆-alkyl (see above) which may be branched or linear and is unsubstituted or substituted once or several times. Preferably alkylheterocyclyl is understood as meaning an heterocyclyl group (see above) being connected to another atom through 1 to 4 (-CH2-) groups. Most preferably alkylheterocyclyl is -Chh-pyridine.

In the context of this invention alkylcycloalkyl is understood as meaning an cycloalkyl group being connected to another atom through a Ci-₆-alkyl (see above) which may be branched or linear and is unsubstituted or substituted once or several times. Preferably alkylcycloalkyl is understood as meaning a cycloalkyl group (see above) being connected to another atom through 1 to 4 (-CH2-) groups. Most preferably alkylcycloalkyl is -Chh-cyclopropyl.

An heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepan, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, quinolone, isoquinoline, tetrahydrothienopyridine, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, benzodioxolane, benzodioxane, carbazole, oxaspirodecan or thiazole; In general, such a heterocyclyl may contain between 3 and 32 atoms in the rings (preferably 4 to 20 atoms in the rings, or most preferably 5 to 18 atoms in the rings). Thus, a heterocyclyl may contain between 3 and 12 atoms in the ring (preferably 4 to 10 atoms in the ring, or 5 to 8 atoms in the ring, or 5 to 6 atoms in the ring) in case of a heterocyclyl of one saturated or unsaturated ring. Such a heterocyclyl may also contain between 5 and 22 atoms in both rings together (preferably 6 to 16 atoms in both rings together, or 7 to 12 atoms in both rings together or 8 to 10 atoms in both rings together) in case of a heterocyclyl of two saturated or unsaturated rings. Such a heterocyclyl may also contain between 7 and 32 atoms in the 3 rings together (preferably 10 to 22 atoms in the three rings together, or 12 to 20 atoms in the three rings together or 10 to 18 atoms in the three rings together) in case of a heterocyclyl of three saturated or unsaturated rings.

Preferably, the aryl is a monocyclic aryl. More preferably the aryl is a 5, 6 or 7 membered monocyclic aryl. Even more preferably the aryl is a 5 or 6 membered monocyclic aryl.

Preferably, the heteroaryl is a monocyclic heteroaryl. More preferably the heteroaryl is a 5, 6 or 7 membered monocyclic heteroaryl. Even more preferably the heteroaryl is a 5 or 6 membered monocyclic heteroaryl.

Preferably, the non-aromatic heterocyclyl is a monocyclic non-aromatic heterocyclyl. More preferably the non-aromatic heterocyclyl is a 4, 5, 6 or 7 membered monocyclic non-aromatic heterocyclyl. Even more preferably the non-aromatic heterocyclyl is a 5 or 6 membered monocyclic non-aromatic heterocyclyl.

Preferably, the cycloalkyl is a monocyclic cycloalkyl. More preferably the cycloalkyl is a 3, 4, 5, 6, 7 or 8 membered monocyclic cycloalkyl. Even more preferably the cycloalkyl is a 3, 4, 5 or 6 membered monocyclic cycloalkyl.

In connection with aryl (including alkyl-aryl), cycloalkyl (including alkyl-cycloalkyl), or heterocyclyl (including alkyl-heterocyclyl), substituted is understood - unless defined otherwise - as meaning substitution of the ring-system of the aryl or alkyl-aryl, cycloalkyl or alkyl-cycloalkyl; heterocyclyl or alkyl-heterocyclyl with one or more of halogen (F, Cl, Br, I), -R_k ,-OR_k, -CN, -N0₂ , -NR_kR_k·, -C(0)OR_k, NR_kC(0)R_k· , - C(0)NR_kR_k' , -NR_kS(0)₂R_k' , =0, -OCH₂CH₂OH, -NR_kC(0)NR_k'Rk", -S(0)₂NR_kR_k', - NRkS(0)₂NRk Rk”, haloalkyl, haloalkoxy, -SRk, -S(0)Rk, -S(0)₂Rk or C(CH3)ORk, or substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, with R_k, R_k and R_k- independently being either H or a saturated or unsaturated, linear or branched, substituted or unsubstituted Ci-₆-alkyl; a saturated or unsaturated, linear or branched, substituted or unsubstituted Ci-₆-alkyl; a saturated or unsaturated, linear or branched, substituted or unsubstituted -O-Ci-₆-alkyl (alkoxy); a saturated or unsaturated, linear or branched, substituted or unsubstituted -S-Ci-₆-alkyl; a saturated or unsaturated, linear or branched, substituted or unsubstituted -C(0)-Ci-₆-alkyl-group; a saturated or unsaturated, linear or branched, substituted or unsubstituted -C(0)-0-Ci-₆-alkyl-group; a substituted or unsubstituted aryl or alkyl-aryl; a substituted or unsubstituted cycloalkyl or alkyl-cycloalkyl; a substituted or unsubstituted heterocyclyl or alkyl- heterocyclyl, being R_k one of RM, R21, R31, R61 or R_7i, (being Rk· one of RI₄\ R21', R31’, Rer or R₇r_, being R_k- one of R-u-_, R₂r_, R_{31 ",} R_{61 " O}r R₇r_; wherein R to Rer and R_z and R_a and R_b are as defined in the description, and wherein when different radicals R to R₇r and R_z and R_a and R_b are present simultaneously in Formula I they may be identical or different.

Most preferably in connection with aryl (including alkyl-aryl), cycloalkyl (including alkyl-cycloalkyl), or heterocyclyl (including alkyl-heterocyclyl), substituted is understood in the context of this invention that any aryl, cycloalkyl and heterocyclyl which is substituted is substituted (also in an alyklaryl, alkylcycloalkyl or alkylheterocyclyl) with one or more of halogen (F, Cl, Br, I), -R_k ,-OR_k, -CN , -N0₂ , - NRkRk” , NRkC(0)R_k', -NR_kS(0)₂R_k' , -S(0)₂NR_kR_k', -NR_kC(0)NR_k Rk", haloalkyl, haloalkoxy, -SR_k , -S(0)R_k or S(0)₂R_k, or substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, being R_k one of RM_, R₂I_, R_31, R₆₁ or R_7i, (being R_k· one of RI₄·_, R₂r_, R_31', Rer or R₇r_; being R_k- one of Ri _, R₂r_, R_31”, Rer or R₇r_; wherein R₁ to R₇r and R_z and R_a and R_b are as defined in the description, and wherein when different radicals R₁ to R₇r and R_z and R_a and R_b are present simultaneously in Formula I they may be identical or different.

In connection with cycloalkyl (including alkyl-cycloalkyl), or heterocyclyl (including alkylheterocyclyl) namely non-aromatic heterocyclyl (including non-aromatic alkyl- heterocyclyl), substituted is also understood - unless defined otherwise - as meaning substitution of the ring-system of the cycloalkyl or alkyl-cycloalkyl; non-aromatic heterocyclyl or non aromatic alkyl-heterocyclyl

(leading to a spiro structure) and/or with =0.

Moreover, in connection with cycloalkyl (including alkyl-cycloalkyl), or heterocyclyl (including alkylheterocyclyl) namely non-aromatic heterocyclyl (including non- aromatic alkyl-heterocyclyl), substituted is also understood - unless defined otherwise - as meaning substitution of the ring-system of the cycloalkyl or alkyl-cycloalkyl; non- aromatic heterocyclyl or non aromatic alkyl-heterocyclyl is spirosubstituted or substituted with =0.

Moreover, in connection with cycloalkyl (including alkyl-cycloalkyl), or heterocyclyl (including alkylheterocyclyl) namely non-aromatic heterocyclyl (including non- aromatic alkyl-heterocyclyl), substituted is also understood - unless defined otherwise - as meaning substitution of the ring-system of the cycloalkyl or alkyl-cycloalkyl; non- aromatic heterocyclyl or non aromatic alkyl-heterocyclyl with =0.

For clarity purposes, reference is also made to the following statements in the definitions of substitutions on alkyl etc. or aryl etc. that“when different radicals Ri to R₇₁ - and R_z and R_a and R_b are present simultaneously in Formula I they may be identical or different”. This statement is reflected in, e.g., the definition of X= - [C(R_aRb)]_P- in general Formula (I):

wherein R_a, R_b and p are as defined in the description.

X can also be expressed as:

wherein R_a, R_b and p are as defined in the description. In addition, R_a· and R_b· are added. As said above, this statement is thus reflected in that R_a· and R_b· are or could be different from R_a and R_b or not.

The same would be applicable mutatis mutandis for general Formulas like general Formula (I) as well as the other general Formulas (I ) to (l^c) above and to all intermediates of synthesis.

A ring system is a system consisting of at least one ring of connected atoms but including also systems in which two or more rings of connected atoms are joined with “joined” meaning that the respective rings are sharing one (like a spiro structure), two or more atoms being a member or members of both joined rings.

The term“leaving group” means a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage. Leaving groups can be anions or neutral molecules. Common anionic leaving groups are halides such as CI-, Br-, and I-, and sulfonate esters, such as tosylate (TsO-) or mesylate.

The term“salt” is to be understood as meaning any form of the active compound used according to the invention in which it assumes an ionic form or is charged and is coupled with a counter-ion (a cation or anion) or is in solution. By this are also to be understood complexes of the active compound with other molecules and ions, in particular complexes via ionic interactions. The term“physiologically acceptable salt” means in the context of this invention any salt that is physiologically tolerated (most of the time meaning not being toxic- especially not caused by the counter-ion) if used appropriately for a treatment especially if used on or applied to humans and/or mammals.

These physiologically acceptable salts can be formed with cations or bases and in the context of this invention is understood as meaning salts of at least one of the compounds used according to the invention - usually a (deprotonated) acid - as an anion with at least one, preferably inorganic, cation which is physiologically tolerated - especially if used on humans and/or mammals. The salts of the alkali metals and alkaline earth metals are particularly preferred, and also those with NH₄, but in particular (mono)- or (di)sodium, (mono)- or (di)potassium, magnesium or calcium salts.

Physiologically acceptable salts can also be formed with anions or acids and in the context of this invention is understood as meaning salts of at least one of the compounds used according to the invention as the cation with at least one anion which are physiologically tolerated - especially if used on humans and/or mammals. By this is understood in particular, in the context of this invention, the salt formed with a physiologically tolerated acid, that is to say salts of the particular active compound with inorganic or organic acids which are physiologically tolerated - especially if used on humans and/or mammals. Examples of physiologically tolerated salts of particular acids are salts of: hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, formic acid, acetic acid, oxalic acid, succinic acid, malic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid or citric acid.

The compounds of the invention may be present in crystalline form or in the form of free compounds like a free base or acid.

Any compound that is a solvate of a compound according to the invention like a compound according to general formula I defined above is understood to be also covered by the scope of the invention. Methods of solvation are generally known within the art. Suitable solvates are pharmaceutically acceptable solvates. The term “solvate” according to this invention is to be understood as meaning any form of the active compound according to the invention in which this compound has attached to it via non-covalent binding another molecule (most likely a polar solvent). Especially preferred examples include hydrates and alcoholates, like methanolates or ethanolates.

Any compound that is a prodrug of a compound according to the invention like a compound according to general formula I defined above is understood to be also covered by the scope of the invention. The term“prodrug” is used in its broadest sense and encompasses those derivatives that are converted in vivo to the compounds of the invention. Such derivatives would readily occur to those skilled in the art, and include, depending on the functional groups present in the molecule and without limitation, the following derivatives of the present compounds: esters, amino acid esters, phosphate esters, metal salts sulfonate esters, carbamates, and amides. Examples of well known methods of producing a prodrug of a given acting compound are known to those skilled in the art and can be found e.g. in Krogsgaard-Larsen et al. “Textbook of Drug design and Discovery” Taylor & Francis (April 2002).

Any compound that is a N-oxide of a compound according to the invention like a compound according to general formula I defined above is understood to be also covered by the scope of the invention.

Unless otherwise stated, the compounds of the invention are also meant to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by ¹³C- or ¹⁴C-enriched carbon or of a nitrogen by ¹⁵N-enriched nitrogen are within the scope of this invention. This would especially also apply to the provisos described above so that any mentioning of hydrogen or any Ή” in a formula would also cover deuterium or tritium.

The compounds of formula (I) as well as their salts or solvates of the compounds are preferably in pharmaceutically acceptable or substantially pure form. By pharmaceutically acceptable form is meant, inter alia, having a pharmaceutically acceptable level of purity excluding normal pharmaceutical additives such as diluents and carriers, and including no material considered toxic at normal dosage levels. Purity levels for the drug substance are preferably above 50%, more preferably above 70%, most preferably above 90%. In a preferred embodiment it is above 95% of the compound of formula (I), or of its salts. This applies also to its solvates or prodrugs.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein

R_a is selected from hydrogen, halogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl;

R_z is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and -C(0)-Ci-₆ alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein X is selected from a bond, -[C(R_aRb)]_P-, -[CH₂]pC(0)[CH₂]_q-, -[CH₂]_pC(0)N(R_z)[CH₂]_q-, - [CH₂]_pN(R_z)C(0)[CH₂]_q- and -[CH₂]_pN(R_z)[CH₂]_q-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein X is selected from a bond, -[C(R_aR_b)]_P-, -[CH₂]_pC(0)[CH₂]_q- and

[CH₂]_pN(R_z)C(0)[CH₂]_q-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_a is selected from hydrogen, halogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein R_a is selected from hydrogen, halogen and substituted or unsubstituted C_1-6 alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_b is selected from hydrogen, halogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_b is selected from hydrogen, halogen and substituted or unsubstituted C_1-6 alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_a and R_b, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_z is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and -C(0)-Ci-₆ alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_z is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and -C(0)-Ci-₆ alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein R_z is selected from hydrogen and substituted or unsubstituted Ci-₆ alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein p is 0, 1 , 2, 3, 4 or 5; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein q is 0, 1 , 2, 3, 4 or 5; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein n is 0 or 1 ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein m is 0, 1 or 2; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein r is 0, 1 or 2; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

Y is -CH₂- or C=0; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

Yi is -C(RioRio')-; wherein R₁₀ and Rio· are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R₁₀ and R-io form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

Y2 is -C(Rio”Rio )-; wherein Rio- and R-io- are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R_10” and Rio- form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein Yi is -C(R-io io')-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

Y₂ is -C(Rio”Rio )-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R2 is selected from substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₃ is selected from substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₃ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R3 is substituted or unsubstituted C1-6 alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R3' is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein R3' is selected from hydrogen and substituted or unsubstituted C1-6 alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₄ and R_4' are independently selected from halogen, -R₄I , -OR₄I , -NO2, -NR_4iR₄r, - NR_4iC(0)R₄r, -NR_4iS(0)₂R₄r, -S(0)₂NR_4iR₄r, -NR_4iC(0)NR₄-rR₄-r, -SR₄I , -S(0)R_4i, - S(0)₂R₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R_4i, -C(0)NR_4iR₄r, -OCFhCFhOR^, -

NR_4iS(0)2NR_{4i '}R_4i” and -C(CH₃)₂0R_4I ; wherein R₄I , R₄r and R₄r are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl and substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₄ and R_4' are independently selected from halogen, -R_4I , -OR_4I , -NO2, -NR_4iR₄r, - NR_4iC(0)R₄r, -NR_4iS(0)₂R₄r, -S(0)₂NR_4iR₄r, -NR_4iC(0)NR₄-rR₄-r, -SR_4I , -S(0)R_4i, - S(0)₂R_4I , -CN, haloalkyl, haloalkoxy, -C(0)0R_4i, -C(0)NR_4iR₄r, -0CH₂CH₂0R_4I , - NR_4iS(0)₂NR_{4i '}R_4i” and -C(CH₃)₂0R_4I ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein

R₄ and R_4' are both -R_4I ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₄ and R_4' are both hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R5 and R5' are independently selected from halogen, -R51, -OR51, -NO2, -NR51R51', - NR_5iC(0)R₅r, -NR_5iS(0)₂R₅r, -S(0)₂NR_5iR₅r, - NR_5iC(0)NR₅rR₅r, -SR₅I , -S(0)R_5i, -S(0)₂R5i, -CN, haloalkyl, haloalkoxy, -C(0)0Rsi, -C(0)NR_5iR5r, -OCH₂CH₂OR5i, - NR_5iS(0)₂NR₅rR₅r and -C(CH3)₂OR5i; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₅ and R_5' are independently selected from -R₅₁ and -OR₅₁,; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R5 is selected from -R51 and -OR51; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₅ is selected from hydrogen and -OH; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein

R5' is -R51; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

Re· is hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₆ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R_?; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₆ is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R_?; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₆ is selected from hydrogen and substituted or unsubstituted Ci-₆ alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R7 is selected from substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₇ is selected from substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

Rg and Rg· are independently selected from halogen, -R21, -OR21, -NO2, -NR21R21', - NR_2iC(0)R₂r, -NR_2iS(0)₂R₂r, -S(0)₂NR_2iR2r, - NR_2iC(0)NR₂rR2r, -SR21 , -S(0)R₂₁, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, -C(0)NR2iR2r, -OCH2CH2OR21, - NR_2iS(0)₂NR₂rR2i” and -C(CH3)20R2i; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

Rg and Rg· are independently selected from -R21 ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

Rg and Rg· are both hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₁₀ and R_10’ are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₁₀ and Rio· are independently selected from hydrogen and substituted or unsubstituted Ci-6 alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₁₀ and Re form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_10” and R_10” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_10” and R_10” are independently selected from hydrogen and substituted or unsubstituted Ci-6 alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_10” and R-io- form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₁₃ and Ri_3' are independently selected from hydrogen, unsubstituted Ci-6 alkyl, unsubstituted C_2-6 alkenyl and unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R13 and Ri3' are independently selected from hydrogen and unsubstituted Ci-₆ alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_M, Ri4’ and R-u- are independently selected from hydrogen, unsubstituted Ci-₆ alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_M, R_M’ and R-u- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₂₁, R_21' and R_21” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₂₁, R_21' and R_21” are independently selected from hydrogen and substituted or unsubstituted C_1-6 alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein R₃₁, R_31' and R_{31 "} are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₃₁, R_31' and R_{31 "} are independently selected from hydrogen and substituted or unsubstituted C_1-6 alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein R₃₂ and R_32' are independently selected from hydrogen, substituted or unsubstituted

C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein

R₃₂ and R_32' are independently selected from hydrogen and substituted or unsubstituted C_1-6 alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₄₁, R_41' and R_41” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl and substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₄₁, R_41' and R_41” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl and substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein

R₅₁, R_51' and R_{51 "} are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₅₁, R_51' and R_{51 "} are independently selected from hydrogen and substituted or unsubstituted C_1-6 alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₆₁, R_61' and Rev are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_6i, R61' and Rev are independently selected from hydrogen and substituted or unsubstituted Ci-₆ alkyll; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein R71 , R71’ and R₇r are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein R71 , R71’ and R₇r are independently selected from hydrogen and substituted or unsubstituted C1-6 alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₂ is selected from substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, wherein the aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R21, -OR21, -NO2, -NR21R21', -NR2iC(0)R2r, - NR_2iS(0)₂R2r, -S(0)₂NR_2iR2r, - NR_2iC(0)NR₂rR2r, -SR21 , -S(0)R₂₁, -S(0)₂R₂₁, - CN, haloalkyl, haloalkoxy, -C(0)0R2i, -C(0)NR2iR2r, -OCH2CH2OR21, NR_2iS(0)₂NR₂rR2i” and -C(CH3)20R2i; wherein R21, R21' and R21” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₃ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; wherein, the alkyl, alkenyl or alkynyl defined in R₃, is substituted with one or more substituent/s selected from -OR₃1 , halogen, -CN, haloalkyl, haloalkoxy and -NR₃1 R₃1'; wherein the cycloalkyl in R₃, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R31 , -OR31 , -NO2, -NR31 R31', - NR_3iC(0)R₃r, -NR_3iS(0)₂R3r, -S(0)₂NR_3i R3r, - N R_3iC(0)NR₃rR3r, -SR31 , -S(0)R₃1 , -S(0)2R3i , -CN, haloalkyl, haloalkoxy, -C(0)0R3i , -C(0)NR3i R3r, -OCH2CH2OR31 , - NR3iS(0)₂NR₃rR3r' and -C(CH3)20R3i; preferably selected from halogen, -R31 , -OR31 , -NR₃1 R₃1', -CN, haloalkyl and haloalkoxy; wherein R₃1 , R₃1' and R₃1” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein R₃ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; wherein, the alkyl, alkenyl or alkynyl defined in R₃, is substituted with one or more substituent/s selected from -OR₃1 , halogen, -CN, haloalkyl, haloalkoxy and -NR31 R31'; wherein the cycloalkyl in R₃, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, - R31 , -OR31 , -NO2, -NR31 R31', -NR_3iC(0)R₃r, -NR3iS(0)2R3r, S(0)₂NR3iR₃r, - NR_3iC(0)NR₃rR₃r, -SR31 , -S(0)R₃₁, -S(0)₂R₃₁, -CN, haloalkyl, haloalkoxy, -C(0)0R3i, -C(0)NR3iR3r, -OCH2CH2OR31, - NR3iS(0)₂NR₃rR3r' and -C(CH3)20R3i; preferably selected from halogen, -R31, -OR31, -NR31R31', -CN, haloalkyl and haloalkoxy; wherein R₃₁, R_31' and R_31” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein R₃ is substituted or unsubstituted C_1-6 alkyl; wherein, the alkyl, alkenyl or alkynyl defined in R₃, is substituted with one or more substituent/s selected from -OR₃₁, halogen, -CN, haloalkyl, haloalkoxy and -NR31R31'; wherein the cycloalkyl in R₃, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, - R31, -OR31, -NO2, -NR31R31', -NR_3iC(0)R₃r, -NR3iS(0)2R3r,

S(0)₂NR_3iR3r, - NR_3iC(0)NR₃rR₃r', -SR31 , -S(0)R₃₁, -S(0)₂R₃₁, -CN, haloalkyl, haloalkoxy, -C(0)0R3i, -C(0)NR3iR3r, -OCH2CH2OR31, - NR3iS(0)₂NR₃rR3r' and -C(CH3)20R3i; preferably selected from halogen,

-R31, -OR31, -NR31R31', -CN, haloalkyl and haloalkoxy; wherein R₃₁, R_31' and R_31” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_3' is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl; wherein, the alkyl, alkenyl or alkynyl defined in R_3', if substituted, is substituted with one or more substituent/s selected from -OR32, halogen, -CN, haloalkyl, haloalkoxy and -N R32R32'; wherein R32 and R32' are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein R_3' is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl; wherein, the alkyl, alkenyl or alkynyl defined in R3', if substituted, is substituted with one or more substituent/s selected from -OR32, halogen, -CN, haloalkyl, haloalkoxy and -N R32R32'; wherein R32 and R32' are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₆ is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R_?; wherein the alkyl, alkenyl or alkynyl defined in R₆, if substituted, is substituted with one or more substituent/s selected from -OR61, halogen, -CN, haloalkyl, haloalkoxy and -NR6iR6r; wherein the cycloalkyl, aryl and heterocyclyl defined in R₆, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R61, -OR61, -NO2, -NR6iR6r, - NR_6iC(0)R₆r, -NR6iS(0)2R6r, -S(0)2NR6iR6r, - NR6iC(0)NR6i R6i”, -SR61 , - S(0)R6i, -S(0)2R6i, -CN, haloalkyl, haloalkoxy, -C(0)0R6i, -C(0)NR6iR6r, - OCH2CH2OR61, -NR6iS(0)₂NR₆rR6r' and -C(CH3)20R6i; preferably selected from halogen, -R61, -OR61, -NR_6iR₆r, -CN, haloalkyl and haloalkoxy; wherein R61, Rer and Rev are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₆ is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R_?; wherein the alkyl, alkenyl or alkynyl defined in R₆, if substituted, is substituted with one or more substituent/s selected from -OR_6i, halogen, -CN, haloalkyl, haloalkoxy and -NR6iR6r; wherein the cycloalkyl, aryl and heterocyclyl defined in R₆, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R6i, -OR6i, -NO2, -NR6i R6r, -

NR_6iC(0)R₆r, -NR6iS(0)2R6r, -S(0)2NR6iR6r, - NR6iC(0)NR6i R6i”, -SR61 , - S(0)R6i, -S(0)2R6i, -CN, haloalkyl, haloalkoxy, -C(0)0R6i, -C(0)NR6iR6r, - OCH2CH2OR61, -NR6iS(0)₂NR₆rR6r' and -C(CH3)20R6i; preferably selected from halogen, -R61, -OR61, -NR_6iR₆r, -CN, haloalkyl and haloalkoxy; wherein R₆₁, R6r and R6r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R6 is selected from hydrogen and substituted or unsubstituted Ci-6 alkyl; wherein the alkyl, alkenyl or alkynyl defined in R6, if substituted, is substituted with one or more substituent/s selected from -OR₆₁, halogen, -CN, haloalkyl, haloalkoxy and -NR6iR6r; wherein R₆₁ and R6r are independently selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₇ is selected from substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkyl heterocyclyl; wherein the alkyl, alkenyl or alkynyl defined in R₇, if substituted, is substituted with one or more substituent/s selected from -OR₇₁, halogen, -CN, haloalkyl, haloalkoxy and -NR71R71'; wherein the cycloalkyl, aryl and heterocyclyl, as defined in R₇, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R71, -OR71, -NO2, -NR_7i R₇r, - NR_7iC(0)R₇r, -NR7iS(0)2R7 , -S(0)2NR7iR7r, - NR7iC(0)NR7-rR7-r, -SR71 , - S(0)R7i, -S(0)2R7i, -CN, haloalkyl, haloalkoxy, -C(0)0R7i, -C(0)NR_7iR7r, - OCH2CH2OR71, -NR7iS(0)₂NR₇rR7r and -C(CH3)20R7i; preferably selected from halogen, -R71, -OR71, -NR71R71', -CN, haloalkyl and haloalkoxy; wherein R₇₁, R₇r and R₇r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₇ is selected from substituted or unsubstituted C_1-6 alkyl, substituted or substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkyl heterocyclyl; wherein the alkyl, alkenyl or alkynyl defined in R₇, if substituted, is substituted with one or more substituent/s selected from -O R71 , halogen, -CN, haloalkyl, haloalkoxy and -N R71 R71 '; wherein the cycloalkyl, aryl and heterocyclyl, as defined in R₇, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R71, -OR71, -NO2, -NR71 R71’, -

NR_7iC(0)R₇r, -NR7iS(0)2R7 , -S(0)2NR7iR7r, - NR7iC(0)NR7-rR7-r, -SR71 , - S(0)R7i, -S(0)2R7i, -CN, haloalkyl, haloalkoxy, -C(0)0R7i, -C(0)NR_7iR7r, - OCH2CH2OR71, -NR7iS(0)₂NR₇rR7r' and -C(CH3)20R7i; preferably selected from halogen, -R₇₁, -OR₇₁, -NR₇₁R_71', -CN, haloalkyl and haloalkoxy; wherein R71 , R₇r and R₇r are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein the alkyl, alkenyl or alkynyl, also in alkylaryl, alkyl heterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, - OR13, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13'; wherein R₁₃ and R_13' are independently selected from hydrogen, unsubstituted C_1-6 alkyl, unsubstituted C_2-6 alkenyl and unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, halogen, -R-u, -OR-u, -NO2, -NR-uR-u', -NRi4C(0)Ri4’, -NRi4S(0)2Ri4’, -

NRi₄S(0)₂NRi4'Ri4” and -C(CH3)20R-i4; wherein R₁₄, Ru· and Ru·· are independently selected from hydrogen, unsubstituted C_1-6 alkyl, unsubstituted C_2-6 alkenyl, unsubstituted C_2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein the aryl or heterocyclyl in R₂, if substituted, is substituted with one or more substituent/s selected from halogen, -R21, -OR21, -NO2, -NR21R21', -

NR_2iC(0)R₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2r, - NR2iC(0)NR2i R2i”, -SR21 , - S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, -C(0)NR2iR2r, - OCH2CH2OR21, -NR2iS(0)₂NR₂rR2r' and -C(CH₃)₂OR₂I ; wherein R₂₁, R_21' and R_21” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein the alkyl, alkenyl or alkynyl defined in R₃, is substituted with one or more substituent/s selected from -OR₃₁, halogen, -CN, haloalkyl, haloalkoxy and -NR31R31'; wherein the cycloalkyl in R₃, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -

R31, -OR31, -NO2, -NR31R31', -NR_3iC(0)R₃r, -NR3iS(0)2R3r,

S(0)₂NR_3iR3r, - NR_3iC(0)NR₃rR₃r', -SR31 , -S(0)R₃₁, -S(0)₂R₃₁, -CN, haloalkyl, haloalkoxy, -C(0)0R3i, -C(0)NR3iR3r, -OCH2CH2OR31, - NR3iS(0)₂NR₃rR3r and -C(CH3)20R3i; preferably selected from halogen, -R31, -OR31, -NR31R31', -CN, haloalkyl and haloalkoxy; wherein R₃₁, R_31' and R_31” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein the alkyl, alkenyl or alkynyl defined in R3', if substituted, is substituted with one or more substituent/s selected from -OR₃₂, halogen, -CN, haloalkyl, haloalkoxy and -NR32R32'; wherein R₃₂ and R_32' are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein the alkyl, alkenyl or alkynyl defined in R₆, if substituted, is substituted with one or more substituent/s selected from -OR61, halogen, -CN, haloalkyl, haloalkoxy and - NR_6iR_6i'! the cycloalkyl, aryl and heterocyclyl defined in R₆, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R_6I , -ORei, -NO2, -NReiRer, -NR_6iC(0)R6r, -NR_6iS(0)2R6r, - S(0)₂NR_6iR6r, - NR_6iC(0)NR₆rR_6i”, -SR61 , -S(0)R6i, -S(0)2R6i, — CN, haloalkyl, haloalkoxy, -C(0)0R6i, -C(0)NR6iR6r, -OCH₂CH₂OR6i, -NR6iS(0)₂NR6rR6i” and - C(CH3)₂OR6i; preferably selected from halogen, -R61, -OR61, -NR6iR6r, -CN, haloalkyl and haloalkoxy; wherein R61, Rer and R₆r are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein the alkyl, alkenyl or alkynyl defined in R₇, if substituted, is substituted with one or more substituent/s selected from -OR₇₁, halogen, -CN, haloalkyl, haloalkoxy and - NR71R71I the cycloalkyl, aryl and heterocyclyl, as defined in R₇, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R71, -OR71, -NO2, -NR71R71’, -NR_7iC(0)R_{7i '}, - NR_7iS(0)₂R₇r, -S(0)₂NR_7iR₇r, - NR7iC(0)NR₇rR₇r, -SR71 , -S(0)R₇₁, -S(0)₂R₇₁, -

CN, haloalkyl, haloalkoxy, -C(0)0R_7i, -C(0)NR_7iR7r, -OCH₂CH₂OR_7i,

NR_7iS(0)₂NR₇rR7i” and -C(CH3)₂OR_7i; preferably selected from halogen, -R71, -OR71, -NR₇₁R_{71 '}, -CN, haloalkyl and haloalkoxy; wherein R₇₁, R₇r and R₇r are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein the alkyl, alkenyl or alkynyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, -OR13, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13'; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound wherein the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, halogen, -R-u, -OR-u, - NO2, -NR14R14', -NRi₄C(0)Ri4·, -NRi4S(0)2Ri4’, -S(0)₂NRi₄Ri4', - NRi₄C(0)NRi4'Ri4”, - SR14 , -S(0)Ri4, -S(0)2Ri4, -CN, haloalkyl, haloalkoxy, -C(0)0Ri4, -C(0)NRi4Ri4·, - OCH2CH2OR14, -NRi₄S(0)₂NRi4'Ri4” and -C(CH3)20Ri4; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the compound according to the according to the invention of general Formula (I) is a compound wherein the aryl or heterocyclyl in R₂, if substituted, is substituted with one or more

NR2iS(0)₂NR2i'R_2i” and -C(CH3)20R_2I ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the compound according to the according to the invention of general Formula (I) is a compound wherein the alkyl, alkenyl or alkynyl defined in R₃, is substituted with one or more substituent/s selected from -O R31 , halogen, -CN, haloalkyl, haloalkoxy and -N R31 R31 '; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the compound according to the according to the invention of general Formula (I) is a compound wherein the cycloalkyl in R3, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R31, -OR31, -N0₂, -NR31R31', - NR_3iC(0)R₃r, -NR_3iS(0)₂R₃r, -S(0)₂NR_3iR₃r, - NR_3iC(0)NR₃rR3r, -SR31 , -S(0)R₃₁, -S(0)₂R3i, -CN, haloalkyl, haloalkoxy, -C(0)OR3i, -C(0)NR3iR3r, -OCH2CH2OR31, - NR3iS(0)₂NR₃rR3r and -C(CH3)20R3i; preferably selected from halogen, -R31, -OR31, -NR₃₁R_{31 '}, -CN, haloalkyl and haloalkoxy; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the compound according to the according to the invention of general Formula (I) is a compound wherein the alkyl, alkenyl or alkynyl defined in R_3', if substituted, is substituted with one or more substituent/s selected from -OR₃₂, halogen, -CN, haloalkyl, haloalkoxy and -

NR32R32I optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the compound according to the according to the invention of general Formula (I) is a compound wherein the alkyl, alkenyl or alkynyl defined in R₆, if substituted, is substituted with one or more substituent/s selected from -OR₆₁, halogen, -CN, haloalkyl, haloalkoxy and -NR6iR6r; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the compound according to the according to the invention of general Formula (I) is a compound wherein the cycloalkyl, aryl and heterocyclyl defined in R₆, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R61, -OR61, -NO2, -NR6i R6r, -

NR_6iC(0)R₆r, -NR6iS(0)2R6r, -S(0)2NR6iR6r, - NR6iC(0)NR6i R6i”, -SR61 , - S(0)R6i, -S(0)2R6i, -CN, haloalkyl, haloalkoxy, -C(0)0R6i, -C(0)NR6iR6r, - OCH2CH2OR61, -NR6iS(0)₂NR₆rR6r and -C(CH3)20R6i; preferably selected from halogen, -R61, -OR61, -NR_6iR₆r, -CN, haloalkyl and haloalkoxy; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the compound according to the according to the invention of general Formula (I) is a compound wherein the alkyl, alkenyl or alkynyl defined in R₇, if substituted, is substituted with one or more substituent/s selected from -OR71, halogen, -CN, haloalkyl, haloalkoxy and -NR71R71'; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the compound according to the according to the invention of general Formula (I) is a compound wherein the cycloalkyl, aryl and heterocyclyl, as defined in R₇, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R71, -OR71, -NO2, -NR71 R71', - NR_7iC(0)R₇r, -NR_7iS(0)₂R₇r, -S(0)₂NR_7iR₇r, - NR_7iC(0)NR₇-rR₇-r, -SR_7I , - S(0)R_7I , -S(0)₂R₇₁, -CN, haloalkyl, haloalkoxy, -C(0)0R_7i, -C(0)NR_7iR₇r, - 0CH₂CH₂0R_7I , -NR_7IS(0)₂NR_7I R_7I” and -C(CH₃)₂0R_7I ; preferably selected from halogen, -R_7I , -OR_7I , -NR_7iR₇r, -CN, haloalkyl and haloalkoxy; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the compound according to the according to the invention of general Formula (I) is a compound wherein

X is a bond, -[C(R_aRb)]_P-, -[C(R_aRb)]pC(0)[C(R_cRd)]_q-, -[C(R_aRb)]_PC(0)N(R_z)[C(R_cRd)]_q- , [C(R_aRb)]pN(R_z)C(0)[C(RcRd)]_q- or -[C(R_aR_b)]_PN(R_z)[C(R_cRd)]_q-;

R_z is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C2-₆ alkenyl, substituted or unsubstituted C2-₆ alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and -C(0)-Ci-₆ alkyl;

R_a is selected from hydrogen, halogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-₆ alkenyl and substituted or unsubstituted C2-₆ alkynyl;

R_b is selected from hydrogen, halogen, substituted or unsubstituted C1-₆ alkyl, substituted or unsubstituted C2-₆ alkenyl and substituted or unsubstituted C2-₆ alkynyl; alternatively, R_a and R_b, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl; R_c is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-₆ alkenyl and substituted or unsubstituted C2-₆ alkynyl;

R_d is selected from hydrogen, substituted or unsubstituted C1-₆ alkyl, substituted or unsubstituted C2-₆ alkenyl and substituted or unsubstituted C2-₆ alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

X is a bond, -[C(R_aRb)]_P-, -[C(RaRb)]_PC(0)[C(R_cRd)]_q-, -[C(R_aRb)]_PC(0)N(R_z)[C(R_cRd)]_q- , [C(R_aRb)]_PN(R_z)C(0)[C(RcRd)]_q- or -[C(R_aR_b)]_PN(R_z)[C(R_cRd)]_q-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_z is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and -C(0)-Ci-₆ alkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the compound according to the according to the invention of general Formula (I) is a compound wherein

R_a is selected from hydrogen, halogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

Rb is selected from hydrogen, halogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_c is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the compound according to the according to the invention of general Formula (I) is a compound wherein R_d is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein

X is selected from a bond, -[C(R_aRb)]_P-, -[CH₂]pC(0)[CH₂]_q-, -[CH₂]pC(0)N(Rz)[CH₂]_q-, - [CH2]pN(R_z)C(0)[CH2]_q- and -[CH2] N(R_z)[CH2]_q-; preferably X is selected from a bond,

-[C(RaRb)]_P-, -[CH₂]pC(0)[CH₂]_q- and -[CH₂]pN(Rz)C(0)[CH₂]_q; more preferably selected from a bond, -CH₂-, -CH₂CH₂-, -C(O)-, -NHC(0)CH₂-, -NHC(0)CH₂CH₂- and -N(CH₃)C(0)CH₂-; and/or

R_a is selected from hydrogen, halogen, substituted or unsubstituted

alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; preferably R_a is hydrogen; and/or

R_b is selected from hydrogen, halogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; preferably R_b is hydrogen; and/or

R_a and R_b, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl; and/or R_z is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and -C(0)-Ci-₆ alkyl; preferably R_z is selected from hydrogen and substituted or unsubstituted Ci-₆ alkyl; more preferably R_z is selected from hydrogen, substituted or unsubstituted methyl; and/or

and/or

p is 0, 1 , 2, 3, 4 or 5; preferably p is 0, 1 or 2; and/or

q is 0, 1 , 2, 3, 4 or 5; preferably q is 0, 1 or 2; and/or

Yi is -C(RioRio')-; preferably Yi is -CH2-; and/or

Y2 is -C(RioRio')-; preferably Y2 is -CH2-; and/or

n is 0 or 1 ;

and/or

m is 0, 1 or 2; preferably m is 1 ;

and/or

r is 0, 1 or 2; preferably r is 1 ;

and/or Y is -CH2- or C=0; preferably Y is -CH2-; and/or

R₂ is selected from substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; preferably R₂ is selected from substituted or unsubstituted aryl and substituted or unsubstituted aromatic heterocyclyl, more preferably R₂ is a substituted or unsubstituted group selected from phenyl and thiophen; and/or

R₃ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; preferably R₃ is substituted or unsubstituted C_1-6 alkyl; more preferably R₃ is substituted or unsubstituted methyl; and/or

R_3' is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl; preferably R_3' is hydrogen; and/or

R₄ and R_4' are independently selected from halogen, -R₄I , -OR₄I , -NO2, -NR_4iR₄r, - NR_4iC(0)R₄r, -NR_4iS(0)₂R₄r, -S(0)₂NR_4iR₄r, -NR_4iC(0)NR₄-rR₄-r, -SR₄I , -S(0)R_4i, - S(0)₂R₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R_4i, -C(0)NR_4iR₄r, -0CH₂CH₂0R₄I , - NR_4iS(0)₂NR_{4i '}R_4i” and -C(CH₃)₂0R₄I ; preferably R₄ and R₄· are both -R₄I , more preferably R₄ and R₄· are both hydrogen; and/or

R5 and R5' are independently selected from halogen, -R51, -OR51, -NO2, -NR51R51', - NR_5iC(0)R₅r, -NR_5iS(0)₂R₅r, -S(0)₂NR_5iR₅r, - NR_5iC(0)NR₅rR_5i ·, -SR₅I , -S(0)R_5i, -S(0)2R5i, -CN, haloalkyl, haloalkoxy, -C(0)0Rsi, -C(0)NR_5iR5r, -OCH2CH2OR51, - NR_5iS(0)₂NR₅rR₅r and -C(CH3)20R5i; preferably R5 and Rs· are both hydrogen or R₅ is -OH while Rs· is hydrogen; and/or

R₆ is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R₇; preferably R₆ is selected from hydrogen and substituted or unsubstituted C1-6 alkyl; more preferably R₆ is selected from hydrogen and substituted or unsubstituted methyl; and/or

R7 is selected from substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl;

and/or

Rg and Rg· are independently selected from halogen, -R21, -OR21, -NO2, -NR21R21', - NR_2iC(0)R₂r, -NR_2iS(0)₂R₂r, -S(0)₂NR_2iR2r, - NR_2iC(0)NR₂rR2r, -SR21 , -S(0)R₂₁, -S(0)₂R₂I , -CN, haloalkyl, haloalkoxy, -C(0)0R_2i, -C(0)NR_2iR₂r, -OCH2CH2OR21, -

NR2iS(0)₂NR₂rR2r' and -C(CH3)20R2i preferably Rg and Rg· are both -R21; more preferably Rg and Rg· are both hydrogen; and/or

R₁₀ and Rio· are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted

C_2-6 alkynyl; preferably R₁₀ and Rio are both hydrogen; and/or Rio and R-io form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl; and/or

Rio” and Rio” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; preferably Rio- and Rio- are both hydrogen; and/or

R_10” and Rio form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl; and/or

R₁₃ and Ri_3' are independently selected from hydrogen, unsubstituted C_1-6 alkyl, unsubstituted C_2-6 alkenyl and unsubstituted C_2-6 alkynyl; and/or

R₁₄, Ri_4’ and R-u- are independently selected from hydrogen, unsubstituted C_1-6 alkyl, unsubstituted C_2-6 alkenyl, unsubstituted C_2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; and/or

R₂₁, R_21' and R_21” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; and/or

R₃₁, R_31' and R_{31 "} are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; and/or R₃₂ and R_32' are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl; and/or R₄₁, R_41’ and R_41” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl and substituted or unsubstituted cycloalkyl; preferably R₄₁ is hydrogen; and/or R₅₁, R_51' and Rsr are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; preferably R₅₁ is hydrogen; and/or

R₆₁, R_61' and R₆r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; and/or

R₇₁, R_71’ and R_71” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the compound according to the invention of general Formula (I) is a compound wherein X is selected from a bond, -[C(R_aRb)]_P-, -[CH₂]pC(0)[CH₂]_q-, -[CH₂]_pC(0)N(R_z)[CH₂]_q-, - [CH₂]_pN(R_z)C(0)[CH₂]_q- and -[CH₂]_pN(R_z)[CH₂]_q-;

and/or

p is 0, 1 , 2, 3, 4 or 5;

and/or

q is 0, 1 , 2, 3, 4 or 5;

and/or

n is 0 or 1 ;

and/or

Yi is -C(RioRio')-;

and/or

Y₂ is -C(Rio”Rio )-;

and/or

and/or

m is 0, 1 or 2;

and/or r is 0, 1 or 2; and/or

Y is -CH2- or C=0; and/or R_a is selected from hydrogen, halogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; wherein the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;

and/or R_b is selected from hydrogen, halogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; wherein the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;

and/or

R_a and R_t>, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl; wherein the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;

and/or

R_z is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and -C(0)-Ci-₆ alkyl; wherein the alkyl is C1-6 alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2- methylpropyl; and/or the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; more preferably the C1-6 alkyl is methyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or

R₂ is selected from substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein the aryl is selected from phenyl, naphthyl, or anthracene; preferably is naphthyl and phenyl; preferably the aryl is phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepan, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole, indoline-2-one and quinazoline; preferably the heterocyclyl is thiophen; and/or

R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; wherein

the alkyl is C1-6 alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2- methylpropyl; and/or the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; preferably the C1-6 alkyl is methyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C_3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C_3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C_3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;

and/or

R_3' is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; wherein the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;

and/or R₄ and R_4' are independently selected from halogen, -R₄I , -OR₄I , -N0₂, -NR_4iR₄r, - NR_4iC(0)R₄r, -NR_4iS(0)₂R₄r, -S(0)₂NR_4iR₄r, -NR_4iC(0)NR₄-rR₄-r, -SR₄I , -S(0)R_4i, - S(0)₂R₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R_4i, -C(0)NR_4iR₄r, -OCH₂CH₂OR₄I , - NR_4iS(0)₂NR_{4i '}R_4i” and -C(CH3)₂OR₄I ; wherein

the alkyl is Ci-₆ alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2- methylpropyl;

and/or

R5 and R5' are independently selected from halogen, -R51, -OR51, -NO2, -NR51R51', - NR_5iC(0)R₅r, -NR_5iS(0)₂R₅r, -S(0)₂NR_5iR₅r, - NR_5iC(0)NR₅rR_5i ·, -SR₅I , -S(0)R_5i, -S(0)₂R5i, -CN, haloalkyl, haloalkoxy, -C(0)0Rsi, -C(0)NR_5iR5r, -OCH₂CH₂OR5i, - NR_5iS(0)₂NR₅rR₅r' and -C(CH₃)₂OR_5i; wherein

the alkyl is C1-6 alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2- methylpropyl;

and/or

R₆ is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R_?;

wherein the alkyl is Ci-₆ alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2- methylpropyl; and/or the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; preferably the Ci-₆ alkyl is methyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C_3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C_3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C_3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or the aryl is selected from phenyl, naphthyl, or anthracene; preferably is naphthyl and phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepan, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole, indoline-2-one and quinazoline; and/or

Wherein the alkyl is C1-6 alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2- methylpropyl; and/or the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or the aryl is selected from phenyl, naphthyl, or anthracene; preferably is naphthyl and phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepan, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole, indoline-2-one and quinazoline;

and/or Rg and Rg· are independently selected from halogen, -R21, -OR21, -NO2, -NR21R21', - NR_2iC(0)R₂r, -NR_2iS(0)₂R₂r, -S(0)₂NR_2iR2r, - NR_2iC(0)NR₂rR2r, -SR21 , -S(0)R₂₁, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, -C(0)NR2iR2r, -OCH2CH2OR21, - NR_2iS(0)₂NR₂rR2i” and -C(CH3)20R2i wherein the alkyl is C_1-6 alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2- methylpropyl; and/or

R₁₀ and Rio· are independently selected from hydrogen, substituted or unsubstituted

C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; wherein

the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;

and/or R₁₀ and R-io' form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl; wherein the cycloalkyl is C_3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C_3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C_3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or R_10” and R-io- are independently selected from hydrogen, substituted or unsubstituted

the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or

R_10” and R-io- form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl; wherein

the cycloalkyl is C_3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C_3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C_3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or R₁₃ and R_13' are independently selected from hydrogen, unsubstituted C_1-6 alkyl, unsubstituted C_2-6 alkenyl and unsubstituted C_2-6 alkynyl;

wherein the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or

R₁₄, R_I4· and R-u- are independently selected from hydrogen, unsubstituted C_1-6 alkyl, unsubstituted C_2-6 alkenyl, unsubstituted C_2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; wherein

the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or the aryl is selected from phenyl, naphthyl, or anthracene; preferably is naphthyl and phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepan, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole, indoline-2-one and quinazoline; and/or

R₂₁, R_21' and R_21” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; wherein

the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the C_1-6 alkyl is methyl, ethyl or propyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;

and/or R₃₁, R_31' and R_{31 "} are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; wherein the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;

and/or

R₃₂ and R_32' are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted

C2-6 alkynyl; wherein the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;

and/or

R₄₁, R_41’ and R_41” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl and substituted or unsubstituted cycloalkyl; wherein

the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the C_1-6 alkyl is methyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C_3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C_3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C_3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;

and/or R₅₁, R_51' and R_{51 "} are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; wherein

and/or

R₆₁, R_61' and R₆r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; wherein the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the C_1-6 alkyl is methyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or

R₇₁, R_71’ and R_71” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

wherein the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R_a as defined in any of the embodiments of the present invention, the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R_b as defined in any of the embodiments of the present invention, the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R_a-R_b as defined in any of the embodiments of the present invention, the cycloalkyl is C_3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C_3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C_3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R_z as defined in any of the embodiments of the present invention, the alkyl is C_1-6 alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2- methylpropyl; and/or the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; more preferably the C_1-6 alkyl is methyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C_3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C_3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C_3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in F¾ as defined in any of the embodiments of the present invention, the aryl is selected from phenyl, naphthyl, or anthracene; preferably is naphthyl and phenyl; preferably the aryl is phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepan, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole, indoline-2-one and quinazoline; preferably the heterocyclyl is thiophen;

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in Rs as defined in any of the embodiments of the present invention, the alkyl is Ci-₆ alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2- methylpropyl; and/or the C alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; preferably the Ci-₆ alkyl is methyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C_3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C_3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C_3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in F^ as defined in any of the embodiments of the present invention, the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R₄ and R₄· as defined in any of the embodiments of the present invention, the alkyl is Ci-₆ alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2- methylpropyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R₅ and R₅· as defined in any of the embodiments of the present invention, the alkyl is Ci-₆ alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2- methylpropyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in F¾ as defined in any of the embodiments of the present invention, the alkyl is Ci-₆ alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2- methylpropyl; and/or the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; preferably the Ci-₆ alkyl is methyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C_3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C_3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C_3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or the aryl is selected from phenyl, naphthyl, or anthracene; preferably is naphthyl and phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepan, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole, indoline-2-one and quinazoline; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R₇ as defined in any of the embodiments of the present invention, the alkyl is Ci-₆ alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2- methylpropyl; and/or the C alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or the aryl is selected from phenyl, naphthyl, or anthracene; preferably is naphthyl and phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepan, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole, indoline-2-one and quinazoline; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in Rg and Rg· as defined in any of the embodiments of the present invention, the alkyl is Ci-₆ alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2- methylpropyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in Rio and Rio· as defined in any of the embodiments of the present invention, the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in Rio and Rio· as defined in any of the embodiments of the present invention, the cycloalkyl is C_3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C_3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C_3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in Rio- and R_10” as defined in any of the embodiments of the present invention, the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in Rio- and R_10” as defined in any of the embodiments of the present invention, the cycloalkyl is C_3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C_3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C_3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R₁₃ and R_13' as defined in any of the embodiments of the present invention, the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R-u, R-u· and R-u- as defined in any of the embodiments of the present invention, the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C_3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C_3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or the aryl is selected from phenyl, naphthyl, or anthracene; preferably is naphthyl and phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepan, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyrane, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole, indoline-2-one and quinazoline;

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R21, R₂r and R21” as defined in any of the embodiments of the present invention, the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the C_1-6 alkyl is methyl, ethyl or propyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R₃₁, R_31' and R_31” as defined in any of the embodiments of the present invention,

the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R32 and R32' as defined in any of the embodiments of the present invention,

the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R₄₁, R₄r and R_41” as defined in any of the embodiments of the present invention,

the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the C_1-6 alkyl is methyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C_3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C_3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C_3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R₅₁, Rsr and R₅r as defined in any of the embodiments of the present invention, the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C_2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in [¾i, R₆r and Rev as defined in any of the embodiments of the present invention,

the C_1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the C_1-6 alkyl is methyl; and/or the C_2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein in R71 , R71 ' and R₇r as defined in any of the embodiments of the present invention,

the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein p is 0, 1 , 2, 3, 4 or 5; preferably p is 0, 1 or 2; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein q is 0, 1 , 2, 3, 4 or 5; preferably q is 0, 1 or 2; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein n is 0 or 1 ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein m is 0, 1 or 2; preferably m is 1 ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein r is 0, 1 or 2; preferably r is 1 ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

X is selected from a bond, -[C(R_aRb)]_P-, -[CH₂]pC(0)[CH₂]_q-, -[CH₂]_pC(0)N(R_z)[CH₂]_q-, - [CH₂]_pN(R_z)C(0)[CH₂]_q- and -[CH₂]_pN(R_z)[CH₂]_q-; preferably X is selected from a bond, -[C(R_aR_b)]p-, -[CH₂]_pC(0)[CH₂]_q- and -[CH₂]_pN(R_z)C(0)[CH₂]_q; more preferably selected from a bond, -CH₂-, -CH₂CH₂-, -C(O)-, -NHC(0)CH₂-, -NHC(0)CH₂CH₂- and -N(CH₃)C(0)CH₂-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein

R_a is selected from hydrogen, halogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; preferably R_a is hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_b is selected from hydrogen, halogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; preferably R_b is hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

Y is -CH2- or C=0; preferably Y is -CH2-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

Yi is -C(RioRio')-; preferably Y1 is -CH2-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

Y2 is -C(RioRio')-; preferably Y2 is -CH2-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein

R_z is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and -C(0)-Ci-₆ alkyl; preferably R_z is selected from hydrogen and substituted or unsubstituted C_1-6 alkyl; more preferably R_z is selected from hydrogen, substituted or unsubstituted methyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₂ is selected from substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; preferably R₂ is selected from substituted or unsubstituted aryl and substituted or unsubstituted aromatic heterocyclyl, more preferably R₂ is a substituted or unsubstituted group selected from phenyl and thiophen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein R₃ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; preferably R₃ is substituted or unsubstituted C_1-6 alkyl; more preferably R₃ is substituted or unsubstituted methyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R_3' is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; preferably R_3' is hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

NR_4iS(0)₂NR_{4i '}R_4i” and -C(CH₃)₂0R₄I ; preferably R₄ and R₄· are both -R₄I , more preferably R₄ and R₄· are both hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R5 and R5' are independently selected from halogen, -R51, -OR51, -NO2, -NR51R51', - NR_5iC(0)R₅r, -NR_5iS(0)₂R₅r, -S(0)₂NR_5iR₅r, - NR_5iC(0)NR₅rR_5i ·, -SR_5I , -S(0)R_5i, -S(0)₂R5i, -CN, haloalkyl, haloalkoxy, -C(0)0Rsi, -C(0)NR_5iR5r, -OCH₂CH₂OR5i, - NR_5iS(0)₂NR₅rR₅r and -C(CH3)₂OR5i; preferably R5 and Rs· are both hydrogen or R₅ is -OH while Rs· is hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₆ is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R₇; preferably R₆ is selected from hydrogen and substituted or unsubstituted C1-6 alkyl; more preferably R₆ is selected from hydrogen and substituted or unsubstituted methyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein

R₇ is selected from substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

Rg and Rg· are independently selected from halogen, -R21, -OR21, -NO2, -NR21R21', - NR_2iC(0)R₂r, -NR_2iS(0)₂R₂r, -S(0)₂NR_2iR2r, - NR_2iC(0)NR₂rR2r, -SR21 , -S(0)R₂₁, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, -C(0)NR2iR2r, -OCH2CH2OR21, - NR2iS(0)₂NR₂rR2r and -C(CH3)20R2i preferably Rg and Rg· are both -R21; more preferably Rg and Rg· are both hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R10 and Rio· are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; preferably R10 and Rio are both hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

Rio” and Rio- are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; preferably Rio- and Rio- are both hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R13 and Ri3' are independently selected from hydrogen, unsubstituted Ci-₆ alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R14, Ri4’ and R-u- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein R₂₁, R_21' and R_21” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₃₁, R_31' and R_{31 "} are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₃₂ and R_32' are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein

R₄₁, R_41’ and R_41” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl and substituted or unsubstituted cycloalkyl; preferably R₄₁ is hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R₅₁, R_51' and R_{51 "} are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl; preferably R₅₁ is hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

R71 , R71’ and R71” are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In another preferred embodiment of the invention according to general Formula (I) the compound is a compound, wherein p is 0, 1 or 2; and/or q is 0, 1 or 2; and/or n is 0 or 1 ; and/or m is 1 ; and/or r is 1 ; and/or

X is selected from a bond, -CH₂-, -CH₂CH₂-, -C(O)-, -NHC(0)CH₂-, -NHC(0)CH₂CH₂- and -N(CH₃)C(0)CH₂-; and/or Y is -CH₂-; and/or Yi is -CH₂-; and/or Y₂ is -CH₂-; and/or

R_a is hydrogen; and/or

Rb is hydrogen; and/or R₂ is a substituted or unsubstituted group selected from phenyl and thiophen; and/or

R₃ is substituted or unsubstituted methyl; and/or

R_3' is hydrogen; and/or

R₄ and R_4' are both hydrogen; and/or

R₅ and R_5' are both hydrogen or R₅ is -OH while R₅· is hydrogen; and/or

R₆ is selected from hydrogen and substituted or unsubstituted methyl; and/or

Rg and Rg· are both hydrogen; and/or

Rio and Rio are both hydrogen; and/or

Rio” and Rio- are both hydrogen; and/or R₄₁ is hydrogen; and/or

R₅₁ is hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a preferred embodiment p is 0, 1 or 2. In a preferred embodiment q is 0, 1 or 2.

In a preferred embodiment n is 0 or 1. In a preferred embodiment m is 1.

In a preferred embodiment r is 1. In a preferred embodiment m and r are both 1.

In a preferred embodiment

X is selected from a bond, -CH₂-, -CH₂CH₂-, -C(O)-, -NHC(0)CH₂-, -NHC(0)CH₂CH₂- and -N(CH₃)C(0)CH₂-. In a preferred embodiment

R_a is hydrogen.

In a preferred embodiment

Rb is hydrogen.

In a preferred embodiment R_a and R_b are both hydrogen.

In a preferred embodiment

In a preferred embodiment

selected from

-Ri, -CH₂RI , -CH₂CH₂RI , -C(0)RI , -NHC(0)CH₂RI , -NHC(0)CH₂CH₂RI and - N(CH₃)C(0)CH₂RI .

In a preferred embodiment Y is -CH2-.

In a preferred embodiment Yi is -CH2-.

In a preferred embodiment Y₂ is -CH2-.

In a preferred embodiment Yi and Y2 are both -CH2-.

In a preferred embodiment

R₂ is selected from substituted or unsubstituted aryl and substituted or unsubstituted aromatic heterocyclyl, more preferably R₂ is a substituted or unsubstituted group selected from phenyl and thiophen.

In a preferred embodiment

R₃ is substituted or unsubstituted C_1-6 alkyl; more preferably R₃ is substituted or unsubstituted methyl. In a preferred embodiment

R_3' is hydrogen.

In a preferred embodiment

R₃ is substituted or unsubstituted C_1-6 alkyl; more preferably R₃ is substituted or unsubstituted methyl while R_3' is hydrogen. In a preferred embodiment

R₄ is hydrogen.

In a preferred embodiment

R_4' is hydrogen.

In a preferred embodiment

R₄ and R_4' are both hydrogen.

In a preferred embodiment

R₅ is hydrogen or -OH.

In a preferred embodiment

Re· is hydrogen.

In a preferred embodiment

R₅ is hydrogen or -OH, while R₅· is hydrogen.

In a preferred embodiment

Rs is -OH, while Rs· is hydrogen.

In a preferred embodiment

Rs and Rs· are both hydrogen.

In a preferred embodiment

R₆ is selected from hydrogen and substituted or unsubstituted methyl. In a preferred embodiment

Rg and Rg· are both hydrogen.

In a preferred embodiment R₁₀ and Rio are both hydrogen.

In a preferred embodiment R_10” and R₁₀ - are both hydrogen.

In a preferred embodiment R10, Rio·, R10” and Rio- are all hydrogen.

In a preferred embodiment R₄₁ is hydrogen.

In a preferred embodiment R₅₁ is hydrogen. In a preferred embodiment the halogen is fluorine, chlorine, iodine or bromine.

In a preferred embodiment the halogen is fluorine.

In a preferred embodiment the haloalkyl is -CF₃.

In a preferred embodiment the haloalkoxy is -OCF₃.

In a preferred further embodiment, the compounds of the general Formula (I) are selected from

In a very preferred embodiment, the compounds are selected which act as dual ligands of the a2d subunit, particularly the a2d-1 subunit, of the voltage-gated calcium channel and the m-opioid receptor and especially compounds which have a binding expressed as K, responding to the following scales:

Ki(p) is preferably < 1000 nM, more preferably < 500 nM, even more preferably < 100 nM.

Kί(a2d1 ) is preferably < 10000 nM, more preferably < 5000 nM, even more preferably < 500 nM.

In the following the phrase “compound of the invention” is used. This is to be understood as any compound according to the invention as described above according to general Formula (I), (I’), (l^a), (l^a’), (l^b), (l^b’), (l^c), (l^c’) and (IZ). The compounds of the invention represented by the above described Formula (I) may include enantiomers depending on the presence of chiral centres or isomers depending on the presence of multiple bonds (e.g. Z, E). The single isomers, enantiomers or diastereoisomers and mixtures thereof fall within the scope of the present invention.

For the sake of clarity the expression“a compound according to Formula (I), wherein e.g. Ri, R₂, R3, R3', R₄, R_4', X, Ui, Y2 and n are as defined below in the detailed description” would (just like the expression“a compound of Formula (I) as defined in any one of claims e.g. 1 to 8” found in the claims) refer to“a compound according to Formula (I)”, wherein the definitions of the respective substituents R1 etc. (also from the cited claims) are applied. In addition, this would also mean, though (especially in regards to the claims) that also one or more disclaimers defined in the description (or used in any of the cited claims like e.g. claim 1 ) would be applicable to define the respective compound. Thus, a disclaimer found in e.g. claim 1 would be also used to define the compound“of Formula (I) as defined in any one of the corresponding related claims e.g. 1 to 8”.

In general the processes are described below in the experimental part. The starting materials are commercially available or can be prepared by conventional methods.

A preferred embodiment of the invention is a process for the production of a compound according to Formula (I), wherein, if not defined otherwise, R₁, R₂, R₃, R_3', R₄, R_4', X, Ui, Y2 and n have the meanings defined in the description. LG represents a leaving group (such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate).

In a particular embodiment there is a process for the production of a compound according to Formula (I),

wherein X represents a bond, and wherein Ri, R₂, R3, R3', R₄, R₄·, Ui, Y2 and n have the meanings as defined in the description, said process comprises treating a compound of formula (I la),

wherein Q represents chloro, bromo, iodo or triflate, with a suitable /V-containing cyclic reagent of formula (ill-1 )

R H

MI-1 under Buchwald-Hartwig or Ullmann arylation conditions.

In a particular embodiment there is a process for the production of a compound according to Formula (I), wherein -X- represents -[C(R_aR_b)]_P-, and wherein R_a, R_t>, R₁, R2, R3, R3', R₄, R_4', YI , Y2 and n and p have the meanings as defined in the description, said process comprises treating a compound of formula (lib’)

wherein r represents 0 to 4, with a /V-containing cyclic reagent of formula (ill-1 )

R-i-H

MI-1 under standard reductive amination conditions.

In a particular embodiment there is a process for the production of a compound according to Formula (I), wherein -X- represents -[C(R_aR_b)]_P-, and wherein R_a, R_b, R₁, R2, R3, R3', R₄, R_4', YI , Y2 and n and p have the meanings as defined in the description, said process comprises treating a compound of formula (I la),

wherein Q represents chloro, bromo, iodo or triflate, with an organometallic reagent of formula (ill-2’)

p

1 2 wherein M represents a suitable organometallic group, preferably a boron or zinc reagent, and p has the meaning as defined in the description. In a particular embodiment there is a process for the production of a compound according to Formula (I), wherein -X- represents -[CR_aR_b]_PC(0)[CH₂]q- and q is 0, wherein R_a and Rb are hydrogen and wherein Ri, R₂, R3, R3', R₄, R₄·, Yi, Y2, n, p and q have the meanings as defined in the description, said process comprises treating a compound of formula (lie’)

with a /V-containing cyclic reagent of formula (ill-1 )

R H

MI-1 under conventional amidation conditions.

In a particular embodiment there is a process for the production of a compound according to Formula (I), wherein -X- represents -[CR_aR_b]_PN(R_z)C(0)[CH₂]q-, wherein R_a and R_b are hydrogen and wherein R₁, R₂, R3, R3', R₄, R₄·, Y₁, Y₂ , n, p and q have the meanings as defined in the description, said process comprises treating a compound of formula (VI’)

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, p, q and Rz have the meanings as defined in the description, with a /V-containing cyclic reagent of formula (ill-1 )

R-i-H

MI-1 under conventional alkylation conditions.

In a particular embodiment there is a process for the production of a compound according to Formula (I), wherein -X- represents -[CR_aR_b]pN(R_z)C(0)[CH₂]q-, wherein R_a and Rb are hydrogen and wherein Ri, R₂, R3, R3', R₄, R₄·, Y1, Y2, n, p and q have the meanings as defined in the description, said process comprises treating an amino compound of formula (lid’)

wherein p and Rz have the meanings as defined in the description, with an acyl reagent of formula (ill-3),

under amidation conditions, wherein Z represents OH or halogen and q has the meaning as defined in the description. In a particular embodiment there is a process for the production of a compound according to Formula (I), wherein -X- represents -[CR_aR_b]pN(R_z)C(0)[CH₂]q-, p is 0, wherein R_a and Rb are hydrogen and wherein Ri, R₂, R3, R3', R₄, R₄·, Y1, Y2 , n, p and q have the meanings as defined in the description, said process comprises reacting a compound of formula (lla)

wherein Q represents chloro, bromo, iodo or triflate, with a carboxamido compound of formula (ill-5)

under Ullmann arylation conditions, wherein q and Rz have the meanings as defined in the description.

In a particular embodiment there is a process for the production of a compound according to Formula (I), wherein n is 0, and wherein Ri, R₂, R₃, R_3', R₄, R₄·, X, Y1 and Y₂ have the meanings as defined in the description, said process comprises reacting a compound of formula (Vila) wherein G is OH,

Vila with an alkylating agent of formula (VIII)

wherein Z represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate.

In a particular embodiment there is a process for the production of a compound according to Formula (I), wherein n is 0, and wherein R1, R₂, R₃, R_3', R₄, R₄·, X, Y1 and Y2 have the meanings as defined in the description, said process comprises reacting a compound of formula (Vila) wherein G is OH,

Vila with an alcohol of formula (VIII) wherein Z represents OH,

in the presence of a suitable azo compound.

In a particular embodiment there is a process for the production of a compound according to Formula (I), wherein n is 0, and wherein R1, R₂, R₃, R_3', R₄, R₄·, X, Y1 and Y₂ have the meanings as defined in the description, said process comprises reacting a compound of formula (Vila) wherein G is halogen,

Vila with an alcohol of formula (VIII) wherein Z represents OH,

in the presence of a strong base .

In a particular embodiment there is a process for the production of a compound according to Formula (I), wherein n is 1 , and wherein Ri, R₂, R3, R3', R₄, R₄·, X, Y1 and Y2 have the meanings as defined in the description, said process comprises reacting a compound of formula (VI lb)

with an agent of formula (VIII),

wherein either Z represents OH and G represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, or alternatively Z represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate and G represents OH. In a particular embodiment there is a process for the production of a compound according to Formula (I),

a) wherein X represents a bond, and wherein Ri, R₂, R3, R3', R₄, R₄·, Ui, Y2 and n have the meanings as defined in the description, said process comprises treating a compound of formula (I la),

R H

MI-1 under Buchwald-Hartwig or Ullmann arylation conditions;

or b) wherein -X- represents -[C(R_aRb)]_P-, and wherein R_a, Rb, R1, R2, R3, R3', R₄, R₄·, Y1 , Y₂ and n and p have the meanings as defined in the description, said process comprises treating a compound of formula (lib’)

R-i-H

MI-1 under standard reductive amination conditions;

or

c) wherein -X- represents -[C(R_aRb)]_P-, and wherein R_a, Rt_>, Ri, R2, R3, R3', R₄, R₄·, Yi, Y2 and n and p have the meanings as defined in the description, said process comprises treating a compound of formula (I la),

I-2' wherein M represents a suitable organometallic group, preferably a boron or zinc reagent, and p has the meaning as defined in the description;

or d) wherein -X- represents -[CR_aR_b]_PC(0)[CH₂]q- and q is 0, wherein R_a and R_b are hydrogen and wherein Ri, R₂, R3, R3', R₄, R₄·, Yi, Y2, n, p and q have the meanings as defined in the description, said process comprises treating a compound of formula (lie’)

with a /V-containing cyclic reagent of formula (ill-1 )

R H

MI-1 under conventional amidation conditions;

or e) wherein -X- represents -[CR_aRb]_PN(R_z)C(0)[CH2]q-, wherein R_a and Rb are hydrogen and wherein R1, R₂, R3, R3', R₄, R₄·, Y1, Y2 , n, p and q have the meanings as defined in the description, said process comprises treating a compound of formula (VI’)

R-i-H

MI-1 under conventional alkylation conditions;

or

f) wherein -X- represents -[CR_aR_b]pN(R_z)C(0)[CH₂]q-, wherein R_a and R_b are hydrogen and wherein Ri, R₂, R3, R3', R₄, R₄·, Yi, Y2, n, p and q have the meanings as defined in the description, said process comprises treating an amino compound of formula (Hd’)

under amidation conditions, wherein Z represents OH or halogen and q has the meaning as defined in the description;

or g) wherein -X- represents -[CR_aRb]pN(R_z)C(0)[CH2]q-, p is 0, wherein R_a and Rb are hydrogen and wherein Ri, R₂, R3, R3', R₄, R₄·, Y1, Y2 , n, p and q have the meanings as defined in the description, said process comprises reacting a compound of formula (I la)

under Ullmann arylation conditions, wherein q and Rz have the meanings as defined in the description; or

h) wherein n is 0, and wherein Ri, R₂, R₃, R_3', R₄, R₄·, X, Y1 and Y₂ have the meanings as defined in the description, said process comprises reacting a compound of formula (Vila) wherein G is OH,

Vila with an alkylating agent of formula (VIII)

wherein Z represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate;

or

i) wherein n is 0, and wherein R₁, R₂, R₃, R_3', R₄, R₄·, X, Y1 and Y₂ have the meanings as defined in the description, said process comprises reacting a compound of formula (Vila) wherein G is OH,

Vila with an alcohol of formula (VIII) wherein Z represents OH,

in the presence of a suitable azo compound;

or

j) wherein n is 0, and wherein R1, R₂, R3, R3', R₄, R₄·, X, Y1 and Y₂ have the meanings as defined in the description, said process comprises reacting a compound of formula (Vila) wherein G is halogen,

Vila with an alcohol of formula (VIII) wherein Z represents OH,

in the presence of a strong base;

or

k) wherein n is 1 , and wherein R1, R₂, R3, R3', R₄, R₄·, X, Y1 and Y₂ have the meanings as defined in the description, said process comprises reacting a compound of formula (VI lb)

with an agent of formula (VIII),

wherein either Z represents OH and G represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, or alternatively Z represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate and G represents OH.

In a particular embodiment there is a process for the production of a compound according to Formula (I), by the reduction reaction of a carbonyl derivative with a suitable reductive reagent, preferably sodium borohydride, in an organic solvent, preferably MeOH, to afford a hydroxyl compound.

In a particular embodiment there is a process for the production of a compound according to Formula (I), by deprotection reaction of a compound of formula I that contains an amine protecting group such as a carbamate, preferably tert-butoxy carbonyl, by any suitable method, such as treatment with an acid, preferably HCI or trifluoroacetic acid in an appropriate solvent such as 1 ,4-dioxane, DCM, ethyl acetate or a mixture of an organic solvent and water.

In a particular embodiment there is a process for the production of a compound according to Formula (I), by reductive amination reaction of a compound of formula I that contains an amino group with an aldehyde, preferably carried out with a reductive reagent, preferably sodium triacetoxyborohydride, in an organic solvent, preferably DCE, in the presence of an organic base, preferably DIPEA or TEA. Alternatively, the reaction can be carried out in the presence of an acid, preferably acetic acid.

In a particular embodiment there is a process for the production of a compound according to Formula (I), by reaction of a compound of formula I that contains an amino group with an alkylating reagent, in the presence of a base, preferably DIPEA or K₂CO₃, in an organic solvent, preferably acetonitrile, at suitable temperature, such as in the range of 0-120 °C.

In a particular embodiment there is a process for the production of a compound according to Formula (I), by reaction of a compound of formula I that contains an amino group with a vinyl derivative, in an organic solvent, preferably 2- methoxyethanol, at suitable temperature, such as in the range of 20-140 °C.

A particular embodiment of the invention refers to the use of a compound of Formula

(II),

wherein Z represents OH or halogen, R₂, R3, R3', R₄, R₄·, Y-i, Y2 and n have the meanings as defined in the description, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (I la),

wherein Q represents chloro, bromo, iodo or triflate, R₂, R3, R3', R₄, R₄·, Ui, Y2 and n have the meanings as defined in the description, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (lla-LG),

lla-LG

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, Q represents chloro, bromo, iodo or triflate, R₂, R₄, R₄·, Yi, Y₂ and n have the meanings as defined in the description, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (lib),

wherein R₂, R₃, R_3', R₄, R₄·, Yi, Y₂, n and r have the meanings as defined in the description, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (lib’),

wherein R_a, Rb, R₂, R3, R3’, R₄, R₄·, Yi, Y₂, n and r have the meanings as defined in the description, for the preparation of compounds of Formula (I).

(llb-LG),

llb-LG

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, R₂, R₄, R₄·, Yi, Y₂, n and r have the meanings as defined in the description, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (llb’-LG),

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, R_a, Rt_>, R2, R₄, R₄·, Yi, Y₂, n and r have the meanings as defined in the description, for the preparation of compounds of Formula (I). A particular embodiment of the invention refers to the use of a compound of Formula (lie),

wherein R₂, R3, R3', R₄, R₄·, Yi, Y₂, n and p have the meanings as defined in the description, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (lie’),

wherein R_a, Rb, R₂, R3, R3', R₄, R₄·, Yi, Y₂, n and p have the meanings as defined in the description, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (llc-LG),

llc-LG

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, R₂, R₄, R₄·, Yi, Y₂, n and p have the meanings as defined in the description, for the preparation of compounds of Formula (I). A particular embodiment of the invention refers to the use of a compound of Formula (llc’-LG),

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, R_a, R_t>, R2, R₄, R₄·, Y1, Y₂, n and p have the meanings as defined in the description, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (lid),

wherein R₂, R3, R3', R₄, R₄·, Yi, Y2, n, p and R_z have the meanings as defined in the description, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (lid’),

wherein R_a, Rt_>, R2, R3, R3', R₄, R₄·, Yi, Y2, n, p and R_z have the meanings as defined in the description, for the preparation of compounds of Formula (I). A particular embodiment of the invention refers to the use of a compound of Formula (Ild’-LG),

lld-LG

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, R_a, Rt_>, R2, R₄, R₄·, Yi, Y2, n, p and R_z have the meanings as defined in the description, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (Ild’-LG),

(ill-1 ),

R H

MI-1

wherein R1 has the meaning as defined in the description, for the preparation of compounds of Formula (I). A particular embodiment of the invention refers to the use of a compound of Formula (ill-2),

wherein p and Ri have the meaning as defined in the description, and M represents a suitable organometallic group, preferably a boron or zinc reagent, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (lll’-2),

wherein p and R_a, R_t>, Ri have the meaning as defined in the description, and M represents a suitable organometallic group, preferably a boron or zinc reagent, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (HI-3),

z ,^R'

MI-3

wherein q and Ri have the meaning as defined in the description, and Z represents OH or halogen, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (HI-4),

MI-4

wherein q has the meaning as defined in the description, Z represents OH or halogen, and LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (MI-5),

wherein q, R_z and Ri have the meaning as defined in the description, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (IVa),

IVa

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, Ri, R₂, R₄, R₄·, Yi, Y₂ and n have the meanings as defined in the description, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (IVb),

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, Ri, R₂, R₄, R₄·, Yi, Y_2, p and n have the meanings as defined in the description, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (IVb’),

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, R_a, Rt_>, Ri, R₂, R₄, R₄·, Yi, Y_2, p and n have the meanings as defined in the description, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (IVc),

A particular embodiment of the invention refers to the use of a compound of Formula (IVc·),

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, R_a, Rt_>, Ri, R2, R₄, R₄·, Yi, Y2, p and n have the meanings as defined in the description, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (IVd),

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, R_z, R1, R2, R₄, R₄·, Yi, Y2, p and n have the meanings as defined in the description, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (IVd’),

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, R_a, Rt_>, R_z, R1, R2, R₄, R₄·, Yi, Y2, p and n have the meanings as defined in the description, for the preparation of compounds of Formula

(I). A particular embodiment of the invention refers to the use of a compound of Formula (IVe),

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, Ri, R₂, R₄, R₄·, Yi and Y₂ have the meanings as defined in the description, for the preparation of compounds of Formula (I).

(ivf),

A particular embodiment of the invention refers to the use of a compound of Formula (V),

HNR3R3'

V

wherein R3 and R3' have the meaning as defined in the description, for the preparation of compounds of Formula (I). A particular embodiment of the invention refers to the use of a compound of Formula (VI),

wherein R₂, R3, R3', R₄, R₄·, Yi, Y2, n, p, q and R_z have the meanings as defined in the description, and LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, for the preparation of compounds of Formula

(I).

A particular embodiment of the invention refers to the use of a compound of Formula (VI’),

wherein R_a, Rb, R2, R3, R3', R₄, R₄·, Yi, Y2, n, p, q and R_z have the meanings as defined in the description, and LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (VII),

VII

wherein n, Ri, R₄, R₄· and X have the meanings as defined in the description, and G is OH or halogen, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (Vila),

Vila

wherein Ri, R₄, R₄· and X have the meanings as defined in the description, and G is OH or halogen, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (VI lb),

wherein Ri, R₄, R₄· and X have the meanings as defined in the description, and G is OH or a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (VIII),

wherein R₂, R₃, R_3', Y1 and Y2 have the meaning as defined in the description, and Z represents OH or halogen, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (VIII-LG),

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, R2, Y1, and Y2 have the meaning as defined in the description, and Z represents OH or halogen, for the preparation of compounds of Formula (I).

(IX).

wherein n, R₄, R₄· have the meanings as defined in the description, and Z represents OH or halogen and G is OH or halogen, for the preparation of compounds of Formula

(I). A particular embodiment of the invention refers to the use of a compound of Formula

(X).

wherein R₃, R_3', R₄, R₄·, n, Y₁ and Y₂ have the meaning as defined in the description, and r represents 0 to 4, for the preparation of compounds of Formula (I).

(X’),

wherein R_a, Rt_>, R3, R3', R₄, R₄·, n, Y1 and Y2 have the meaning as defined in the description, and r represents 0 to 4, for the preparation of compounds of Formula (I).

A particular embodiment of the invention refers to the use of a compound of Formula (X-LG),

X-LG

A particular embodiment of the invention refers to the use of a compound of Formula (X’-LG),

(XI),

XI

A particular embodiment of the invention refers to the use of a compound of Formula (XI-LG),

XI-LG

A particular embodiment of the invention refers to the use of a compound of Formula (XI’-LG),

(XI’-LG),

XI'-LG

A particular embodiment of the invention refers to the use of a compound of Formula II, I la, lla-LG, lib, lib’, llb-LG, llb’-LG, lie, lie’, llc-LG, llc’-LG, lid, lid’, lld-LG, Ild’-LG, ill-1 , ill-2, MI -2, ill-3, III-4, III-5, IVa, IVb, IVb’, IVc, IVc’, IVd, IVd’, IVe, IVf, V, VI, VI’, VII, Vila, VI lb, VIII, VIII-LG, IX, X, X’, X-LG, X’-LG, XI, XI-LG, XI’ or XI’-LG

XI'-LG

wherein R_a, Rt_>, R1, R2, R3, R3', R₄, R₄·, Ui, Y2 , n, p, q, r and R_z have the meanings as defined in the description, Q represents chloro, bromo, iodo or triflate, LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, have the meanings as defined in the description, M represents a suitable organometallic group, Z represents OH or halogen, and G is OH, halogen or a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, for the preparation of compounds of Formula (I).

The obtained reaction products may, if desired, be purified by conventional methods, such as crystallisation and chromatography. Where the above described processes for the preparation of compounds of the invention give rise to mixtures of stereoisomers, these isomers may be separated by conventional techniques such as preparative chromatography. If there are chiral centers the compounds may be prepared in racemic form, or individual enantiomers may be prepared either by enantiospecific synthesis or by resolution.

One preferred pharmaceutically acceptable form of a compound of the invention is the crystalline form, including such form in pharmaceutical composition. In the case of salts and also solvates of the compounds of the invention the additional ionic and solvent moieties must also be non-toxic. The compounds of the invention may present different polymorphic forms, it is intended that the invention encompasses all such forms.

Another aspect of the invention refers to a pharmaceutical composition which comprises a compound according to the invention as described above according to general formula I or a pharmaceutically acceptable salt or steroisomer thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle. The present invention thus provides pharmaceutical compositions comprising a compound of this invention, or a pharmaceutically acceptable salt or stereoisomers thereof together with a pharmaceutically acceptable carrier, adjuvant, or vehicle, for administration to a patient.

Examples of pharmaceutical compositions include any solid (tablets, pills, capsules, granules etc.) or liquid (solutions, suspensions or emulsions) composition for oral, topical or parenteral administration. In a preferred embodiment the pharmaceutical compositions are in oral form, either solid or liquid. Suitable dose forms for oral administration may be tablets, capsules, syrops or solutions and may contain conventional excipients known in the art such as binding agents, for example syrup, acacia, gelatin, sorbitol, tragacanth, or polyvinylpyrrolidone; fillers, for example lactose, sugar, maize starch, calcium phosphate, sorbitol or glycine; tabletting lubricants, for example magnesium stearate; disintegrants, for example starch, polyvinylpyrrolidone, sodium starch glycollate or microcrystalline cellulose; or pharmaceutically acceptable wetting agents such as sodium lauryl sulfate.

The solid oral compositions may be prepared by conventional methods of blending, filling or tabletting. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are conventional in the art. The tablets may for example be prepared by wet or dry granulation and optionally coated according to methods well known in normal pharmaceutical practice, in particular with an enteric coating. The pharmaceutical compositions may also be adapted for parenteral administration, such as sterile solutions, suspensions or lyophilized products in the apropriate unit dosage form. Adequate excipients can be used, such as bulking agents, buffering agents or surfactants.

The mentioned formulations will be prepared using standard methods such as those described or referred to in the Spanish and US Pharmacopoeias and similar reference texts.

Administration of the compounds or compositions of the present invention may be by any suitable method, such as intravenous infusion, oral preparations, and intraperitoneal and intravenous administration. Oral administration is preferred because of the convenience for the patient and the chronic character of the diseases to be treated.

Generally an effective administered amount of a compound of the invention will depend on the relative efficacy of the compound chosen, the severity of the disorder being treated and the weight of the sufferer. However, active compounds will typically be administered once or more times a day for example 1 , 2, 3 or 4 times daily, with typical total daily doses in the range of from 0.1 to 1000 mg/kg/day.

The compounds and compositions of this invention may be used with other drugs to provide a combination therapy. The other drugs may form part of the same composition, or be provided as a separate composition for administration at the same time or at different time.

Another aspect of the invention refers to the use of a compound of the invention or a pharmaceutically acceptable salt or isomer thereof in the manufacture of a medicament.

Another aspect of the invention refers to a compound of the invention according as described above according to general formula I, or a pharmaceutically acceptable salt or isomer thereof, for use as a medicament for the treatment of pain. Preferably the pain is medium to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia. This may include mechanical allodynia or thermal hyperalgesia.

Another aspect of the invention refers to the use of a compound of the invention in the manufacture of a medicament for the treatment or prophylaxis of pain. In a preferred embodiment the pain is selected from medium to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia, also preferably including mechanical allodynia or thermal hyperalgesia. Another aspect of this invention relates to a method of treating or preventing pain which method comprises administering to a patient in need of such a treatment a therapeutically effective amount of a compound as above defined or a pharmaceutical composition thereof. Among the pain syndromes that can be treated are medium to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia, whereas this could also include mechanical allodynia or thermal hyperalgesia.

The present invention is illustrated below with the aid of examples. These illustrations are given solely by way of example and do not limit the general spirit of the present invention.

General Experimental Part

SYNTHESIS DESCRIPTION

Two different general methods have been developed for obtaining the compounds of the invention, as described below in methods A and B, and further detailed in Schemes 1 to 8.

METHOD A

A one-step process is described for the preparation of compounds of general formula (I) starting from a compound of formula (II), as shown in the following scheme:

Method A

wherein R1, R₂, R3, R3', R₄, R₄·, X, Ui, Y2 and n have the meanings as defined in claim 1 , LG represents a leaving group, and Zrepresents a suitable functional group to perform such transformation, and R-i-W represents a compound of formula ill-1 , III-2, III-3 or NI-5, as it is detailed below in Schemes 1 to 4.

In addition, the amino group NR₃R_3' present in a compound of formula (I) can be incorporated later in the synthesis by reaction of a compound of formula (IV) wherein LG represents a leaving group (such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate) with an amine of formula (V) to render a compound of formula (I) as shown in the scheme above. The alkylation reaction is carried out in a suitable solvent, such as ethanol, dimethylformamide, dimethylsulfoxide or acetonitrile, preferably ethanol; using an excess of amine (V) or optionally in the presence of a base such as K₂CO₃, /V,/V-diisopropylethylamine or triethylamine; at a suitable temperature comprised between room temperature and the reflux temperature, preferably heating, or alternatively, the reactions can be carried out under microwave heating. Additionally, an activating agent such as sodium iodide or potassium iodide can be used. Such transformation can also be performed starting from a compound of formula (ll-LG) to prepare a compound of formula (II).

Scheme 1

The general synthetic route according to method A for preparing compounds of formula (I) wherein X represents a bond, resulting in compounds of formula (la) starting from a compound of formula (I la) is represented in Scheme 1 :

HNR3R3.

V wherein R1, R₂, R3, R3', R₄, R₄·, Y-i, Y2 and n have the meanings as defined in claim 1 , Q represents chloro, bromo, iodo or triflate and LG represents a leaving group (such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate).

The preparation of a compound of formula (la) from a compound of formula (Ila) is carried out by treating a compound of formula (Ila) with a suitable /V-containing cyclic reagent of formula (ill-1 ) under Buchwald-Hartwig conditions, using a Pd catalyst such as tris(dibenzylideneacetone)dipalladium(0) or palladium acetate, and a suitable ligand, preferably a phosphine ligand such as BINAP or XPhos, using a suitable base such as sodium tert- butoxide or cesium carbonate, in a suitable solvent such as toluene or 1 ,4-dioxane, at a suitable temperature, preferably heating. Alternatively, the reaction can be carried out under Ullmann arylation conditions, using a Cu catalyst such as copper iodide and a suitable ligand, preferably an amino ligand such as /V.A^-dimethylethane-l ,2-diamine, in the presence of a suitable base such as potassium phosphate or potassium carbonate, in a suitable solvent such as 1 ,4- dioxane or dimethylformamide, at a suitable temperature, preferably heating.

Alternatively, the amino group NR3R3' present in a compound of formula (la) or (I la) can be incorporated later in the synthesis by reaction of a precursor compound of formula (IVa) or (lla-LG), respectively, with an amine of formula (V) following the conditions described above in Method A.

Scheme 2 The general synthetic route according to method A for preparing compounds of formula (I) wherein -X- represents -[Chhjp-, resulting in compounds of formula (lb), starting from a compound of formula (I la) or (lib), is represented in Scheme 2:

lla A=NR₃R₃. _

lla-LG A=LG ^v wherein Ri, R₂, R3, R3', R₄, R₄·, Y1, Y2, n and p have the meanings as defined in claim 1 , LG represents a leaving group (such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate), Q represents chloro, bromo, iodo or triflate, M represents a suitable organometallic group (preferably a boron or zinc reagent) and r represents 0 to 4. The preparation of a compound of formula (lb) from an aldehyde compound of formula (lib) can be carried out by treating a compound of formula (lib) with a N- containing cyclic reagent of formula (111-1 ) under standard reductive amination conditions. The reaction is carried out in the presence of a reductive reagent, such as sodium triacetoxyborohydride, sodium borohydride or sodium cyanoborohydride, in a suitable solvent, preferably tetrahydrofuran, dichloroethane or methanol, optionally in the presence of an acid (preferably acetic acid) or a base (preferably N,N- diisopropylethylamine).

Alternatively, a compound of formula (lb) can be prepared by reacting a compound of formula (lla) with an organometallic reagent of formula (ill-2), preferably a boron or zinc reagent. The coupling reaction is carried out under conventional coupling procedures described in the literature, using a suitable catalyst (preferably a Pd catalyst) and a suitable ligand (preferably a phosphine ligand), such as for example tetrakis(triphenylphosphine)palladium(0), or palladium acetate and XPhos, in the presence of a suitable base such as potassium carbonate or cesium carbonate, in a suitable solvent such as tetrahydrofuran, 1 ,2-dimethoxyethane or 1 ,4-dioxane, or mixtures thereof with water.

In addition, the amino group NR3R3' present in a compound of formula (lb), (lla) or (lib) can be incorporated later in the synthesis by reaction of a precursor compound of formula (I Vb), (lla-LG) or (llb-LG), respectively, with an amine of formula (V), following the conditions described above in Method A.

This process can easily be adapted wherein -X- represents -[CR_aR_b]_P-, by choosing the corresponding reagents

Scheme 3

The general synthetic route according to method A for preparing compounds of formula (I) wherein -X- represents -[CH₂]_PC(0)[CH₂]_q- and q is 0, resulting in compounds of formula (lc), starting from a compound of formula (lie) is represented in Scheme 3:

wherein Ri, R₂, R3, R3', R₄, R₄·, Yi, Y2, n and p have the meanings as defined in claim 1 and LG represents a leaving group (such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate).

The preparation of a compound of formula (lc) from an acid compound of formula (lie) and a /V-containing cyclic reagent of formula (ill-1 ) can be carried out under conventional amidation conditions. As a way of example, the reaction is carried out using a suitable coupling reagent such as /V-(3-dimethylaminopropyl)-/V'- ethylcarbodiimide (EDO), dicyclohexylcarbodiimide (DCC), /V-[(dimethylamino)-1 /-/- 1 ,2,3-triazolo-[4,5-b]pyridin-1-ylmethylene]-/V-methylmethanaminium

hexafluorophosphate N- oxide (HATU) or /V,/V,/V',/V'-tetramethyl-0-( //-/-benzotriazol-1- yl)uronium hexafluorophosphate (HBTU), optionally in the presence of 1- hydroxybenzotriazole, optionally in the presence of an organic base such as N- methylmorpholine or /V,/V-diisopropylethylamine, in a suitable solvent such as dichloromethane or dimethylformamide, and at a suitable temperature, preferably at room temperature. Alternatively, the amidation can be performed in two steps by first converting an acid of formula (lie) into its corresponding acyl halide following standard conditions described in the literature, and then reacting it with a compound of formula (ill-1 ) in a suitable solvent, such as dichloromethane, tetrahydrofuran, ethyl acetate or ethyl acetate-water mixtures; in the presence of an organic base such as triethylamine or /V,/V-diisopropylethylamine or an inorganic base such as K₂CO₃; and at a suitable temperature, preferably comprised between 0 °C and room temperature. Additionally, an activating agent such as 4-dimethylaminopyridine can be used.

In addition, the amino group NR₃R_3' present in a compound of formula (lc) or (lie) can be incorporated later in the synthesis by reaction of a precursor compound of formula (IVc) or (llc-LG), respectively, with an amine of formula (V) following the conditions described above in Method A.

This process can easily be adapted wherein -X- represents -[CR_aR_b]pC(0)[CH2]_q- or - [CR_aRb]pC(0)[CR_cRd]q-, by choosing the corresponding reagents.

Scheme 4

The general synthetic route according to method A for preparing compounds of formula (I) wherein -X- represents -[CH2]pN(R_z)C(0)[CH2]_q-, resulting in compounds of formula (Id), starting from a compound of formula (lid) or (I la), is represented in Scheme 4:

lla-LG A=LG ^v

Id A=NR₃R₃.

IVd A=LG ^ ^V wherein Ri, R₂, R3, R3', R₄, R₄·, R_z, Yi, Y2, n, p and q have the meanings as defined in claim 1 , LG represents a leaving group (such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate) and Z represents OH or halogen (preferably bromo or chloro).

The reaction between an amino compound of formula (lid) with an acyl reagent of formula (III-3) to render a compound of formula (Id) can be carried out under the amidation conditions described above in Scheme 3 for the preparation of compounds of formula (lc). Alternatively, the compounds of formula (Id) can be prepared in 2 steps by treating a compound of formula (lid) with an acylating agent of formula (111-4) under the same amidation conditions to obtain a compound of formula (VI), followed by reaction with a /V-containing cyclic reagent of formula (III-1 ), under conventional alkylation conditions such as those described in Method A for the reaction of a compound of formula (IV) with an amine of formula (V).

Finally, a compound of formula (Id) wherein p is 0 can be alternatively prepared by reacting a compound of formula (lla) with a carboxamido compound of formula (NI-5). The reaction can be carried out under Ullmann arylation conditions, using a Cu catalyst such as copper iodide and a suitable ligand, preferably an amino ligand such as /V.A^-dimethylethane-l ,2-diamine, in the presence of a suitable base such as potassium phosphate, in a suitable solvent such as 1 ,4-dioxane or dimethylformamide, at a suitable temperature, preferably heating. Alternatively, the coupling reaction can be performed under Buchwald-Hartwig conditions, using a suitable Pd catalyst and a suitable ligand (preferably a phosphine ligand).

In addition, the amino group NR₃R_3' present in a compound of formula (Id), (lla) or (lid) can be incorporated later in the synthesis by reaction of a precursor compound of formula (I Vd), (lla-LG) or (lld-LG), respectively, with an amine of formula (V) following the conditions described above in Method A. This process can easily be adapted wherein -X- represents [CR_aR_b]pN(R_z)C(0)[CH2]q-, by choosing the corresponding reagents.

METHOD B An alternative one-step process is described for the preparation of compounds of general formula (I) starting from a compound of formula (VII), as shown in the following scheme:

Method B

wherein Ri, R₂, R3, R3', R₄, R₄·, X, Ui, Y2 and n have the meanings as defined in claim 1 , Z represents OH or a leaving group, and G represents OH, halogen or a leaving group depending on the meaning of n. Specific reaction conditions are detailed below in Schemes 5 and 6. As it has been mentioned before, alternatively the amino group NR3R3' present in a compound of formula (I) can be incorporated later in the synthesis by reaction of a precursor compound of formula (IV) with an amine of formula (V) following the conditions described above in Method A.

Scheme 5

The general synthetic route according to method B for preparing compounds of formula (I) wherein n is 0, resulting in compounds of formula (le), is represented in Scheme 5:

wherein Ri, R₂, R3, R3', R₄, R₄·, X, Y1 and Y₂ have the meanings as defined in claim 1 , n is 0, Z represents OH or a leaving group, and G represents OH or halogen.

Depending on the meaning of G and Z different reaction conditions will apply: a) When G is OH and Z represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, the alkylation reaction between a phenol of formula (Vila) and an alkylating agent of formula (VIII) is carried out in a suitable solvent, such as dimethylformamide, dimethylacetamide, dimethylsulfoxide, acetonitrile, dichloromethane or 1 ,4-dioxane; in the presence of a base such as K₂C0₃, Cs₂C0₃, sodium hydride or potassium tert- butoxide; at a suitable temperature comprised between room temperature and the reflux temperature, or alternatively, the reactions can be carried out in a microwave reactor. Additionally, an activating agent such as sodium iodide can be used. b) When G is OH and Z represents OH, the reaction is carried out under conventional Mitsunobu conditions by treating a phenol of formula (Vila) with an alcohol of formula (VIII) in the presence of an azo compound such as 1 ,1 '- (azodicarbonyl)dipiperidine (ADDP), diisopropylazodicarboxylate (DIAD) or diethyl azodicarboxylate (DEAD) and a phosphine such as tributylphosphine or triphenylphoshine. The Mitsunobu reaction is carried out in a suitable solvent, such as toluene or tetrahydrofuran; at a suitable temperature comprised between room temperature and the reflux temperature. c) When G is halogen and Z represents OH, the reaction is carried out under conventional aromatic nucleophilic substitution conditions by treating an alcohol of formula (VIII) with a compound of formula (Vila) wherein G represents halogen (preferably fluoro), in the presence of a strong base such as sodium hydride or potassium tert- butoxide. The reaction is carried out in a suitable solvent, such as a polar aprotic solvent, preferably dimethylformamide, dimethylacetamide or dimethylsulfoxide; at a suitable temperature comprised between room temperature and the reflux temperature, preferably heating, or alternatively, the reactions can be carried out in a microwave reactor. Alternatively, when G is bromo or iodo, the compound of formula (VIII) can be introduced under cross-coupling conditions, using a Pd or Cu catalyst and a suitable ligand.

Scheme 6 The general synthetic route according to method B for preparing compounds of formula (I) wherein n is 1 , resulting in compounds of formula (If), is represented in Scheme 6:

IVf A=LG V HNR R. wherein Ri, R₂, R3, R3', R₄, R₄·, X, Y1 and Y₂ have the meanings as defined in claim 1 , n is i , and either Z represents OH and G represents a leaving group or alternatively Z represents a leaving group and G represents OH.

The reaction is carried out under standard alkylation reaction conditions such as those described in Scheme 5 above.

Scheme 7

The preparation of key compounds of formula (II) and (VII) from a common precursor of formula (IX) is summarized in Scheme 7 below:

wherein Ri, R₂, R3, R3', R₄, R₄·, X, Ui, Y2 and n have the meanings as defined in claim 1 , and G and Z have the meanings as defined above in Schemes 1 to 6, and R-i-W represents a compound of formula ill-1 , ill-2, ill-3 or ill-5 as defined above in Schemes 1 to 6.

The preparation of a compound of formula (VII) from a compound of formula (IX) and a compound of formula (III) can be carried out under the reaction conditions described above in general Method A and further detailed in Schemes 1 to 4. The preparation of a compound of formula (II) or (ll-LG) from a compound of formula (IX) and a compound of formula (VIII) can be carried out under the reaction conditions described above in general Method B and further detailed in Schemes 5 and 6.

Scheme 8 In addition, a compound of formula (lib) can be prepared from a compound of formula (I la) following several methods described in the literature. As a way of example, two routes of synthesis are described in Scheme 8 below:

I A=NR₃R₃.

l-LG A=LG ^{J V}

wherein R₂, R3, R3', R₄, R₄·, R_a, Rb, Ui, Y2 and n have the meanings as defined in claim 1 , Q represents chloro, bromo, iodo or triflate and and r represents 0 to 4.

Following Route A, a compound of formula (lla) is converted into a nitrile compound of formula (X) (under standard conditions described in the literature depending on the nature of r), followed by reduction with a suitable hydride source such as diisobutylaluminum hydride, to render a compound of formula lib.

Alternatively and following Route B, a compound of formula (lla) is converted into an alkenyl compound of formula (XI) via a cross-coupling reaction using conventional reaction conditions, preferably a Suzuki coupling, followed by oxidative cleavage by treatment with a reagent such as osmium tetroxide followed by treatment with an oxidant such as sodium periodate, optionally in the presence of an additive such as pyrimidine or 2,6-lutidine, to render a compound of formula lib.

By choosing the corresponding reagents, this process can easily be adapted to prepare compounds of formula lib’ or llb’-LG, that can be used according to Scheme 2 for the preparation of compounds of formula lb or IVb wherein -X- represents - [CRaRb]p^_, The compounds of formula (III), (111-1 ), (ill-2), (III-3), (ill-4), (III-5), (V), (VIII) and (IX) used in the methods and schemes disclosed above are commercially available or can be synthesized following common procedures described in the literature.

Moreover, certain compounds of the present invention can also be obtained starting from other compounds of formula (I) by appropriate conversion reactions of functional groups, in one or several steps, using well-known reactions in organic chemistry under standard experimental conditions.

In some of the processes described above it may be necessary to protect the reactive or labile groups present with suitable protecting groups, such as for example Boc (tert- butoxycarbonyl), Teoc (2-(trimethylsilyl)ethoxycarbonyl) or benzyl for the protection of amino groups, and common silyl protecting groups for the protection of the hydroxyl group. The procedures for the introduction and removal of these protecting groups are well known in the art and can be found thoroughly described in the literature. In addition, a compound of formula (I) can be obtained in enantiopure form by resolution of a racemic compound of formula (I) either by chiral preparative HPLC or by crystallization of a diastereomeric salt or co-crystal. Alternatively, the resolution step can be carried out at a previous stage, using any suitable intermediate.

Examples

The following abbreviations are used in the examples:

ACN: acetonitrile

ADDP: 1 ,T-(azodicarbonyl)dipiperidine

aq.: aqueous

BINAP: 2,2'-bis(diphenylphosphino)-1 ,T-binaphthyl

Boc: tert- butoxycarbonyl

CH: cyclohexane cone.: concentrated

DCE: dichloroethane

DCM: dichloromethane

Deprot.: deprotection

DIAD: diisopropyl azodicarboxylate

DIBAL-H: diisobutylaluminum hydride

DIPEA: /V,/V-diisopropylethylamine

DMF: /V,/V-dimethylformamide

DMSO: dimethylsulfoxide

EtOAc: ethyl acetate

EtOH: ethanol

EX: example

h: hour/s

HATU: 0-(7-azabenzotriazol-1 -yl)-/V,/\/,/\/^,,/\/^,-tetrarnethyluroniurn hexafluorophosphate

HPLC: high performance liquid chromatography

I NT: intermediate

MeOH: methanol

MS: mass spectrometry

Min: minutes

Pd2(dba)3: tris(dibenzylideneacetone)dipalladium(0)

Quant: quantitative

Ret.: retention

r.t: room temperature

Sat: saturated

Sol.: solution

Teoc: 2-(trimethylsilyl)ethoxycarbonyl TEA: triethylamine

TFA: trifluoroacetic acid

THF: tetrahydrofuran

TMSI: trimethylsilyl iodide (or also named iodotrimethylsilane)

wt: weight

The following methods were used to determine the HPLC-MS spectra:

Method A

Column: Kinetex EVO 50 x 4.6 mm, 2.6 urn

Temperature: 40 °C

Flow: 2.0 mL/min

Gradient: NH₄HCO₃ pH 8 : ACN (95:5)— 0.5min— (95:5)— 6.5min— (0:100)— 1 min— (0:100)

Sample dissolved approx. 1 mg/ml_ in NH₄HCO₃ PH 8/ ACN Method B

Column: Kinetex EVO 50 x 4.6 mm, 2.6 urn

Temperature: 40 °C

Flow: 1.5 mL/min

Gradient: NH₄HCO₃ pH 8 : ACN (95:5)— 0.5min— (95:5)— 6.5min— (0:100)— 2min— (0:100)

Sample dissolved approx. 1 mg/mL in NH₄HCO₃ PH 8/ ACN Method C

Column: Gemini C18 30 x 4,6 mm, 3um

Temperature: 40 °C

Flow: 1.5 mL/min

Gradient H₂O-0.1 %HCOOH / ACN (95:5)— 0.5min— (95:5)— 8.5min - (0:100)—

1 min— (0:100)

Sample dissolved approx. 1 mg/mL in ACN Method D

Column: Gemini-NX 30 x 4.6 mm, 3 urn

Temperature: 40 °C

Flow: 2.0 mL/min

Sample dissolved approx. 1 mg/ml_ in NH₄HCO₃ PH 8/ ACN

Synthesis of Intermediates

Intermediate 1 : (R)-2-(Trimethylsilyl)ethyl (3-(2-bromophenoxy)-3-(thiophen-2- yl)propyl)(methyl)carbamate

Step 1. (R)-3-(Methylamino)-1-(thiophen-2-yl)propan-1-ol: A solution of (R)-3-chloro- 1-(thiophen-2-yl)propan-1-ol (2.89 g, 16.2 mmol) and methylamine (40 wt% in EtOH, 14 ml_, 162 mmol) in EtOH (74 ml.) was heated in a sealed flask at 90 °C overnight. The solvent was evaporated, the residue was dissolved in DCM and it was washed with 1 N NaOH, dried over MgS0₄, filtered and concentrated to dryness. The crude product (1.7 g) was slurried in methylcyclohexane:toluene (3:1 , 6 vol, 10.2 ml.) and heated at 60 °C for 1 h. Then, it was allowed to cool down and it was stirred at r.t. for 1 h. The solids were filtered, washed with methylcyclohexane and dried under vacuum to provide the title compound (1.13 g, 41% yield).

Step 2. (R)-3-(2-Bromophenoxy)-/V-methyl-3-(thiophen-2-yl)propan-1 -amine: To a solution of the product obtained in Step 1 (1.13 g, 6.6 mmol) and 1-bromo-2- fluorobenzene (2.87 ml_, 26.4 mmol) in DMSO (2 ml_), under a N2 atmosphere, potassium tert- butoxide (0.74 g, 6.6 mmol) was added and the reaction mixture was heated at 60 °C for 8 h. It was then cooled to r.t., water was added and the aqueous phase was extracted twice with EtOAc. The combined organic phases were dried over MgS0₄, filtered and evaporated to dryness. The crude product was purified by flash chromatography, silica gel, gradient DCM to MeOH:DCM (1 :4), to give the title compound (1.67 g, 78% yield). Step 3. Title compound: To a solution of the product obtained in Step 2 (1.67 g, 5.1 mmol) in DCM (5 ml_), under a N₂ atmosphere, DIPEA (0.89 ml_, 5.1 mmol) and a solution of 4-nitrophenyl (2-(trimethylsilyl)ethyl) carbonate (1.45 g, 5.1 mmol) in DCM (7 ml.) were added and the mixture was stirred at r.t. overnight. NaHCC>3 sat. solution was added and it was extracted twice with DCM. The combined organic phases were washed with 2 N NaOH solution, dried over MgS0₄, filtered and concentrated to dryness. The residue was purified by flash chromatography, silica gel, gradient CH to EtOAc, to give the title compound (2.17 g, 91% yield).

This method was used for the preparation of Intermediates 2-3 using suitable starting materials:

Intermediate 4: 2-(3-Chloro-1-(thiophen-2-yl)propoxy)benzaldehyde

Step 1. 2-(3-Chloro-1-(thiophen-2-yl)propoxy)benzonitrile: To a solution of 3-chloro-1- (thiophen-2-yl)propan-1-ol (10 g, 52 mmol), triphenylphosphine (15 g, 57.2 mmol) and 2-hydroxybenzonitrile (6.8 g, 57.2 mmol) in dry THF (252 ml_), cooled at 0 °C, DIAD (1 1.5 ml_, 58.3 mmol) was added dropwise and the mixture was stirred at r.t. overnight. The solvent was concentrated under vacuum and the residue was purified by flash chromatography, silica gel, gradient CH to EtOAc to give the title compound (13.9 g, 96% yield).

Step 2. Title compound: To a solution of the product obtained in Step 1 (4 g, 14.4 mol) in toluene (40 ml_), cooled at 0 °C, DIBAL-H (25 wt% solution in toluene, 13.5 mL, 20.2 mmol) was added dropwise and the reaction mixture was stirred at 0-5 °C for 4 h. Then, 10% HCI aq. solution was slowly added to quench the reaction and the mixture was stirred at r.t. for 10 min. It was extracted with EtOAc and the combined organic phases were washed with water and brine, dried over Na2S0₄ and concentrated to dryness. The residue was purified by flash chromatography, silica gel, gradient CH to EtOAc, to give the title compound (4 g, 38% yield).

This method was used for the preparation of Intermediate 5 using suitable starting materials:

(1 ) 1 M DIBAL-H in DCM was used in Step 2 Intermediate 6: Lithium 2-(3-chloro-1-(thiophen-2-yl)propoxy)benzoate

Step 1. Methyl 2-(3-chloro-1-(thiophen-2-yl)propoxy)benzoate: To a solution of 3- chloro-1-(thiophen-2-yl)propan-1-ol (2 g, 11.3 mmol), tributylphosphine (3.4 mL, 13.6 mmol) and methyl 2-hydroxybenzoate (1.45 mL, 11.3 mmol) in dry THF (20 mL), ADDP (3.4 g, 13.6 mmol) was added and the mixture was stirred at r.t. overnight. The reaction crude was filtered through a pad of Celite that was washed with THF, and the filtrate was concentrated under vacuum. The crude product was purified by flash chromatography, silica gel, gradient CH to EtOAc, to give the title compound (1.27 g, 36% yield).

Step 2. Title compound: A solution of the compound obtained in Step 1 (1.05 g, 3.4 mmol) in a mixture of THF (17 mL) and 1 N LiOH solution (17 mL, 17 mmol) was heated at 50 °C overnight. The solvent was evaporated, toluene was added and it was again concentrated to dryness to remove residual water, rendering the title compound (1.76 g, overweight, quantitative yield) as a crude product that was used in the next step without further purification.

Intermediate 7: tert- Butyl (3-(2-bromophenoxy)-3-(thiophen-2- yl)propyl)(methyl)carbamate

Step 1. 2-(1-(2-Bromophenoxy)-3-chloropropyl)thiophene: To a solution of 3-chloro-1- (thiophen-2-yl)propan-1-ol (2 g, 11.3 mmol), triphenylphosphine (3.5 g, 13.6 mmol) and 2-bromophenol (1.96 g, 11.3 mmol) in dry THF (40 mL), cooled at 0 °C under a N2 atmosphere, DIAD (2.64 ml_, 13.6 mmol) was added dropwise and the mixture was stirred at r.t. overnight. The solvent was concentrated to dryness and the residue was slurried in hexane. The suspension was filtered, the collected solids were washed with hexane and discarded, and the filtrate was concentrated under vacuum to afford the title compound that was used without further purification (3.85 g, quant yield).

Step 2. 3-(2-Bromophenoxy)-/V-methyl-3-(thiophen-2-yl)propan-1 -amine: In a sealed tube, a mixture of the product obtained in Step 1 (3.75 g, 1 1.3 mmol) and methylamine (33 wt% in EtOH, 30 ml_, 226 mmol) was heated at 100 °C overnight. Then, it was concentrated to dryness and the crude product was used in the next step without further purification (3.72 g, quant yield).

Step 3. Title compound: To a solution of the product obtained in Step 2 (3.7 g, 11.3 mmol) in tert- butanol (10 ml_), 2 N NaOH solution (10 ml.) and di-fe/f-butyl dicarbonate (2.5 g, 1 1.3 mmol) were added and the reaction mixture was stirred at r.t. overnight. Brine and DCM were added, the phases were separated and the aqueous layer was extracted with DCM. The combined organic phases were washed with brine, dried over MgS0₄, filtered and concentrated to dryness. The residue was purified by flash chromatography, silica gel, gradient CH to EtOAc to give the title compound (1.34 g, 28% yield for the 3 steps).

Intermediate 8: tert- Butyl (3-(2-bromophenoxy)-3-phenylpropyl)(methyl)carbamate:

In a sealed tube, a mixture of tert- butyl (3-chloro-3-phenylpropyl)(methyl)carbamate (4 g, 14.1 mmol), K₂CO₃ (5.84 g, 42.3 mmol), Kl (234 mg, 1.41 mmol) and 2- bromophenol (2.4 g, 14.1 mmol) in ACN (92 ml.) was heated at 60 °C overnight. After cooling down to r.t, water was added and it was extracted with EtOAc. The combined organic phases were dried over MgS0₄, filtered and concentrated to dryness. The residue was purified by flash chromatography, silica gel, gradient CH to EtOAc, to give the title compound (2.36 g, 40% yield). This method was used for the preparation of Intermediate 9 using suitable starting materials:

Intermediate 10: 2-(3-((fe/f-Butoxycarbonyl)(methyl)amino)-1-phenylpropoxy)benzoic acid

Step 1. Methyl 2-(3-((fe/f-butoxycarbonyl)(methyl)amino)-1-phenylpropoxy)benzoate: Following the experimental procedure described in Intermediate 8, but using methyl 2-hydroxybenzoate instead of 2-bromophenol as starting material, the title compound was obtained (1.48 g, 63% yield).

Step 2. Title compound: To a solution of the compound obtained in Step 1 (1.48 g, 3.7 mmol) in a mixture of THF (7.5 ml.) and water (7.5 ml_), lithium hydroxide monohydrate (1.2 g, 30 mmol) was added and the reaction mixture was heated at 50 °C overnight. The solvent was concentrated, pH was adjusted to 3 with 6 N HCI and it was extracted with EtOAc. The combined organic phases were dried over MgS0₄, filtered and concentrated to dryness to afford the title compound (1.1 g, 78% yield).

Intermediate 1 1 : tert- Butyl (3-((2-bromobenzyl)oxy)-3- phenylpropyl)(methyl)carbamate

To a solution of tert- butyl (3-hydroxy-3-phenylpropyl)(methyl)carbamate (2 g, 7.5 mmol) and tetrabutylammonium iodide (2.8 g, 7.5 mmol) in DMF (10 ml_), cooled at 0 °C under a N₂ atmosphere, NaH (60 wt% dispersion in mineral oil, 603 mg, 15 mmol) was added portionwise and the mixture was stirred at 0 °C for 30 min. Then a solution of 1-bromo-2-(bromomethyl)benzene (1.8 g, 7.5 mmol) in DMF (4 ml.) was added and the reaction mixture was stirred at r.t. overnight. Water and EtOAc were added, the phases were separated and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with water and brine, dried over MgS0_4, filtered and concentrated to dryness. The crude product was purified by flash chromatography, silica gel, gradient CH to EtOAc to give the title compound (2.34 g, 71% yield).

Intermediate 12. tert- Butyl (3-(2-aminophenoxy)-3-phenylpropyl)(methyl)carbamate

Step 1. tert- Butyl methyl(3-(2-nitrophenoxy)-3-phenylpropyl)carbamate: Following the experimental procedure described in Step 1 of Intermediate 7, using tert- butyl (3- hydroxy-3-phenylpropyl)(methyl)carbamate and 2-nitrophenol as starting materials, the title compound was obtained (1.55 g, 63% yield).

Step 2. Title compound: To a solution of the compound obtained in Step 1 (1.55 g, 4 mmol) in a mixture of EtOH-water 4:1 (33 ml_), iron (2.2 g, 40 mmol) and ammonium chloride (107 mg, 2 mmol) were added and the mixture was heated to reflux for 4 h. It was allowed to cool down to r.t. and the suspension was filtered through a pad of Celite, that was washed with EtOH. The filtrate was concentrated to dryness to render the title compound that was used without further purification (1.24 g, 87% yield).

Intermediate 13: tert- Butyl methyl(3-(2-(2-oxoethyl)phenoxy)-3- phenylpropyl)carbamate

Step 1. tert- Butyl (3-(2-(2-hydroxyethyl)phenoxy)-3-phenylpropyl)(methyl)carbamate: Following the experimental procedure described for the preparation of Intermediate 8, but using 2-(2-hydroxyethyl)phenol instead of 2-bromophenol, the title compound was obtained (1.51 g, 22% yield).

Step 2. Title compound: To a solution of oxalyl chloride (0.77 ml_, 4.31 mmol) in DCM (1 1 ml_), cooled at -78 °C under a N₂ atmosphere, DMSO (0.61 ml_, 8.62 mmol) was added. The solution was stirred for 5 min at -78 ⁰ C, and then a solution of the compound obtained in Step 1 (1.51 g, 3.92 mmol) in DCM (1 1 ml.) and TEA (1.64 ml_, 1 1.75 mmol) were sequentially added. The reaction mixture was left to warm to r.t. during 1.5 h. Then, 1 N NaOH solution was added and the mixture extracted with DCM. The combined organic phases were washed with brine, dried over MgS0_4, filtered and concentrated to dryness. The crude product was purified by flash chromatography, silica gel, gradient CH to EtOAc, to give the title compound (628 mg, 42% yield).

Intermediate 14: 2-(Trimethylsilyl)ethyl (3-((2-bromobenzyl)oxy)-3-(thiophen-2- yl)propyl)(methyl)carbamate

Step 1. /V-Benzyl-3-((2-bromobenzyl)oxy)-/V-methyl-3-(thiophen-2-yl)propan-1 -amine: To a solution of 3-(benzyl(methyl)amino)-1-(thiophen-2-yl)propan-1-ol (0.45 g, 1.7 mmol) and tetrabutylammonium iodide (0.63 g, 1.7 mmol) in DMF (2.2 ml_), cooled at 0 °C, NaH (60% dispersion in mineral oil, 0.14 g, 3.4 mmol) was added portionwise under a N₂ atmosphere. The reaction was stirred at 0 °C for 30 min and then a solution of 1-bromo-2-(bromomethyl)benzene (0.43 g, 1.7 mmol) in DMF (0.9 ml.) was added. The reaction mixture was stirred at r.t. overnight. Water and EtOAc were added, the phases were separated and the aqueous phase was extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over MgS0₄, filtered and concentrated to dryness. The crude product was purified by flash chromatography, silica gel, gradient CH to EtOAc to give the title compound (0.335 g, 45% yield).

Step 2. Title compound: To a mixture of 2-(trimethylsilyl)ethanol (276 mg, 2.33 mmol) and K3PO4 (700 mg, 3 mmol) in toluene (2 ml_), cooled at 0 °C, a solution of triphosgene (231 mg, 0.78 mmol) in toluene (1 ml.) was added dropwise and the mixture was stirred at r.t. for 1 h. The reaction mixture was then cooled at 0 °C, a solution of the product obtained in Step 1 (335 mg, 0.78 mmol) in toluene (2 mL) was added and the mixture was stirred at r.t. overnight. NaHCC>3 sat. solution was added, it was extracted with EtOAc and the organic layer was concentrated under vacuum. The residue was purified by flash chromatography, silica gel, gradient hexane to EtOAc to give the title compound (201 mg, 60% yield).

Synthesis of Examples General Deprotection Methods

Method 1. Boc deprotection with TMSI. To a solution of the N- Boc protected compound (1 mmol) in dry ACN (45 mL), TMSI (2 mmol) was added dropwise. After stirring for 15 min at r.t., NaHCC>3 sat. solution and DCM were added and the mixture was stirred for additional 10 minutes. The phases were separated, the organic phase was dried over MgS0₄ and concentrated to dryness, to afford the crude compound, which was purified by flash chromatography, silica gel, gradient DCM to MeOH:DCM (1 :4).

Method 2. Boc deprotection with TFA. A solution of the N- Boc protected compound (1 mmol) in a mixture of DCM (15 ml.) and TFA (10 mmol) was stirred at r.t. until full conversion was achieved. The volatiles were evaporated and the residue was re- dissolved in DCM and washed with 1 M NaOH solution and brine, dried over MgS0₄ and concentrated. The crude compound was purified by flash chromatography, silica gel, gradient DCM to MeOH:DCM (1 :4).

Method 3. Boc deprotection with HCI. To a solution of the N- Boc protected compound (1 mmol) in dioxane (10 ml_), HCI (4 N solution in dioxane, 10 mmol) was added under a N₂ atmosphere. The reaction was stirred at r.t. overnight. The solvent was evaporated and the residue was purified by eluting through an acidic ion exchange resin cartridge (SCX), to give the desired compound, which was further purified by flash chromatography, silica gel, gradient DCM to MeOH:DCM (1 :4).

Method 4. Boc deprotection with ZnBr₂. A solution of the N- Boc protected compound (1 mmol) in DCM (5 ml.) was added to a stirred suspension of ZnBr₂ (5.7 mmol) in DCM (50 ml.) under a N₂ atmosphere. After stirring the mixture at r.t. overnight, water was added and it was stirred for 5 min. The layers were separated and the aqueous phase was extracted with DCM. The combined organic extracts were dried over MgS0₄ and concentrated. The crude compound was purified by flash chromatography, silica gel, gradient DCM to MeOH:DCM (1 :4).

Method 5. Teoc deprotection with CsF. A solution of the N- Teoc protected compound (1 mmol) and cesium fluoride (5 mmol) in DMF (26 ml.) was heated at 90 °C for 1 h. The solvent was concentrated to dryness and the crude product was purified by flash chromatography, silica gel, gradient DCM to MeOH:DCM (1 :4).

Example 1 : (R)-/V-Methyl-3-(2-(2-methyl-3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'- piperidin]-T-yl)phenoxy)-3-(thiophen-2-yl)propan-1 -amine

Step 1. (R)-2-(Trimethylsilyl)ethyl methyl(3-(2-(2-methyl-3,4-dihydro-2/-/- spiro[isoquinoline-1 ,4'-piperidin]-1 '-yl)phenoxy)-3-(thiophen-2-yl)propyl)carbamate: In a sealed tube, a mixture of Intermediate 1 (150 mg, 0.32 mmol), 2-methyl-3,4- dihydro-2/-/-spiro[isoquinoline-1 ,4'-piperidine] dihydrochloride (prepared according to W02016078770, 95 mg, 0.37 mmol), Pd₂(dba)₃ (29 mg, 0.032 mmol), BINAP (39 mg, 0.064 mmol) and sodium tert- butoxide (92 mg, 0.956 mmol) in dry toluene (6 ml.) was heated at 130 °C overnight under an argon atmosphere. The reaction mixture was filtered through a pad of Celite that was washed with EtOAc, and the filtrate was concentrated to dryness. The residue was purified by flash chromatography, silica gel, gradient CH to EtOAc to give the title compound (78 mg, 40% yield).

Step 2. Title compound: Starting from the compound obtained in Step 1 (78 mg, 0.13 mmol) and following General Deprotection Method 5, the title compound was obtained (39 mg, 66% yield).

HPLC retention time (method B): 5.84 min; MS: 462.1 (M+H).

This method was used for the preparation of Examples 2-9 using suitable starting materials:

Example 10: (R)-2-(2-Methyl-3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'-piperidin]-1 '-yl )-N- (2-(3-(methylamino)-1-(thiophen-2-yl)propoxy)phenyl)acetamide

Step 1. 2-(2-Methyl-3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'-piperidin]-1'-yl)acetamide: A mixture of 2-methyl-3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'-piperidine] dihydrochloride (300 mg, 1.19 mmol), 2-bromoacetamide (175 mg, 1.27 mmol), Kl (19 mg, 0.12 mmol) and K₂CO₃ (344 mg, 2.49 mmol) in ACN (12 ml.) was heated at 50 °C for 2 h. The suspension was filtered, the collected solids were washed with ACN and discarded, and the filtrate was concentrated to dryness to afford the title compound (315 mg, 97% yield), which was used without further purification.

Step 2. (R)-2-(Trimethylsilyl)ethyl methyl(3-(2-(2-(2-methyl-3,4-dihydro-2/-/- spiro[isoquinoline-1 ,4'-piperidin]-T-yl)acetamido)phenoxy)-3-(thiophen-2- yl)propyl)carbamate: In a sealed tube, a mixture of Intermediate 1 (205 mg, 0.44 mmol), the product obtained in Step 1 (155 mg, 0.57 mmol), /V.A^-dimethylethane- 1 ,2-diamine (0.015 ml_, 0.131 mmol), copper (I) iodide (25 mg, 0.131 mmol) and potassium phosphate (185 mg, 0.87 mmol) in 1 ,4-dioxane (6.1 ml.) was heated at 120 °C overnight under an argon atmosphere. It was filtered through a pad of Celite that was washed with DCM, and the filtrate was concentrated to dryness. The residue was purified by flash chromatography, silica gel, gradient DCM to MeOH:DCM (1 :4) to give the title compound (140 mg, 48% yield).

Step 3. Title compound: Starting from the compound obtained in Step 2 (140 mg, 0.21 mmol) and following General Deprotection Method 5, the title compound was obtained (94 mg, 85% yield).

HPLC retention time (method B): 5.30 min; MS: 519.1 (M+H). This method was used for the preparation of Examples 1 1-13 using suitable starting materials:

Example 14: /V-Methyl-3-(2-(2-(2-methyl-3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'- piperidin]-1 '-yl)ethyl)phenoxy)-3-(thiophen-2-yl)propan-1 -amine

Step 1. T-(2-(3-Chloro-1-(thiophen-2-yl)propoxy)phenethyl)-2-methyl-3,4-dihydro-2/-/- spiro[isoquinoline-1 ,4'-piperidine]: A solution of Intermediate 5 (100 mg, 0.34 mmol), 2-methyl-3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'-piperidine] (98 mg, 0.34 mmol) and DIPEA (0.07 ml_, 0.41 mmol) in DCE (2 ml.) was stirred for 30 min at r.t. under a N₂ atmosphere. Then, sodium triacetoxyborohydride (144 mg, 0.68 mmol) was added and the reaction mixture was stirred at r.t. overnight. NaHCC>3 sat. solution was added and it was extracted with DCM. The combined organic phases were washed with brine, dried over Na₂S0₄ and concentrated to dryness. The crude product was purified by flash chromatography, silica gel, gradient DCM to MeOH:DCM (1 :4) to give the title compound (47 mg, 28% yield).

Step 2. Title compound: A solution of the compound obtained in Step 1 (47 mg, 0.096 mmol) and dimethylamine (33 wt% solution in EtOH, 0.24 ml_, 1.93 mmol) in EtOH (1 ml.) was heated in a sealed tube at 100 °C overnight. The solvent was evaporated to dryness and the crude product was purified by flash chromatography, silica gel, gradient DCM to MeOH:DCM (1 :4) to give the title compound (30 mg, 64% yield).

HPLC retention time (method B): 5.59 min; MS: 490.1 (M+H).

This method was used for the preparation of Examples 15-16 using suitable starting materials:

Example 17: 3-(2-((3,4-Dihydro-2/-/-spiro[isoquinoline-1 ,4'-piperidin]-1 '- yl)methyl)phenoxy)-/V-methyl-3-phenylpropan-1 -amine

Step 1 . tert- Butyl (3-(2-((3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'-piperidin]-1 '- yl)methyl)phenoxy)-3-phenylpropyl)(methyl)carbamate: Following the experimental procedure described in Step 1 of Example 14, starting from Intermediate 9 (200 mg, 0.541 mmol) and 3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'-piperidine] (109 mg, 0.54 mmol), the title compound was obtained (154 mg, 51 % yield). Step 2. Title compound: Starting from the compound obtained in Step 1 (50 mg, 0.090 mmol) and following General Deprotection Method 3, the title compound was obtained (18 mg, 43% yield).

HPLC retention time (method D): 4.91 min; MS: 456.3 (M+H). This method was used for the preparation of Example 18 using suitable starting materials:

Example 19: (3,4-Dihydro-2/-/-spiro[isoquinoline-1 ,4'-piperidin]-1 '-yl)(2-(3- (methylamino)-1 -phenylpropoxy)phenyl)methanone

Step 1. tert- Butyl (3-(2-(3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'-piperidin]-T- ylcarbonyl)phenoxy)-3-phenylpropyl)(methyl)carbamate: To a solution of Intermediate 10 (300 mg, 0.78 mmol) and 3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'-piperidine] (158 mg, 0.78 mmol) in dry DMF (4 ml_), DIPEA (0.41 ml_, 2.34 mmol) and HATU (296 mg, 0.78 mmol) were added and the reaction mixture was stirred at r.t. overnight. NaHCC>3 sat. solution was added and it was extracted with EtOAc. The combined organic phases were washed with water and brine, dried over MgS0₄ and concentrated to dryness. The crude product was purified by flash chromatography, silica gel, gradient DCM to MeOH:DCM (1 :4) to give the title compound (267 mg, 60% yield).

Step 2. Title compound: Starting from the compound obtained in Step 1 (62 mg, 0.1 1 mmol) and following General Deprotection Method 4, the title compound was obtained (17 mg, 33% yield).

HPLC retention time (method D): 4.66 min; MS: 470.2 (M+H).

Example 20: (2-Methyl-3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'-piperidin]-1 '-yl)(2-(3- (methylamino)-1 -(thiophen-2-yl)propoxy)phenyl)methanone

Step 1 . (2-(3-Chloro-1 -(thiophen-2-yl)propoxy)phenyl)(2-methyl-3,4-dihydro-2/-/- spiro[isoquinoline-1 ,4'-piperidin]-T-yl)methanone: Following the experimental procedure described in Step 1 of Example 19, using Intermediate 6 (150 mg, 0.51 mmol) and 2-methyl-3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'-piperidine] dihydrochloride (146 mg, 0.51 mmol) as starting materials, the title compound was obtained (262 mg, quant yield).

Step 2. Title compound: Following the experimental procedure described in Step 2 of Example 14, starting from the product obtained in Step 1 (250 mg, 0.50 mmol) and methylamine, the title compound was obtained (81 mg, 33 % yield).

HPLC retention time (method A): 4.1 1 min; MS: 490.2 (M+H).

This method was used for the preparation of Example 21 using suitable starting materials:

Example 22: 3-(2-Methyl-3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'-piperidin]-T-yl)-/V-(2- (3-(methylamino)-1-phenylpropoxy)phenyl)propanamide

Step 1. fe/f-Sutyl (3-(2-(3-chloropropanamido)phenoxy)-3- phenylpropyl)(methyl)carbamate: To a solution of Intermediate 12 (400 mg, 1.12 mmol) in ACN (5 ml_), DIPEA (0.49 ml_, 2.8 mmol) and 3-chloropropanoyl chloride (0.129 ml_, 1.35 mmol) were added dropwise under a N₂ atmosphere. The mixture was stirred for 1 h at r.t. and then it was concentrated to dryness. The residue was purified by flash chromatography, silica gel, gradient CH to EtOAc to give the title compound (358 mg, 72% yield).

Step 2. tert- Butyl methyl(3-(2-(3-(2-methyl-3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'- piperidin]-T-yl)propanamido)phenoxy)-3-phenylpropyl)carbamate: A solution of the product obtained in Step 1 (179 mg, 0.40 mmol), 2-methyl-3,4-dihydro-2/-/- spiro[isoquinoline-1 ,4'-piperidine] (52 mg, 0.24 mmol) and DIPEA (0.1 ml.) in EtOH (17 ml.) was heated in a sealed tube at 80 °C for 3 days. The solvent was evaporated and the residue was dissolved in EtOAc. The organic phase was washed with 1 N NaOH solution, dried over MgS0₄ and concentrated to dryness. The crude product was purified by flash chromatography, silica gel, gradient DCM to MeOH:DCM (1 :4) to give the title compound (47 mg, 37% yield).

Step 3. Title compound: Following General Deprotection Method 2, starting from the compound obtained in Step 2 (47 mg, 0.075 mmol), the title compound was obtained (24 mg, 61 % yield).

HPLC retention time (method A): 4.51 min; MS: 527.3 (M+H).

This method was used for the preparation of Example 23 using suitable starting materials:

Example 24: /V-Methyl-3-(2-((2-methyl-3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'- piperidin]-1'-yl)methyl)phenoxy)-3-phenylpropan-1 -amine

Step 1. tert- Butyl methyl(3-(2-((2-methyl-3,4-dihydro-2/-/-spiro[isoquinoline-1 ,4'- piperidin]-1'-yl)methyl)phenoxy)-3-phenylpropyl)carbamate: To a stirred solution of the compound obtained in Step 1 of Example 17 (100 mg, 0.18 mmol) and formaldehyde (37 wt% solution, 0.24 ml_, 3.24 mmol) in MeOH (1.8 ml_), sodium triacetoxyborohydride (105 mg, 0.49 mmol) was added and the reaction was stirred at r.t. overnight. Then, acetic acid (0.02 ml_, 0.36 mmol) was added and the mixture was stirred at the same temperature overnight. The solvent was evaporated and the residue was partitioned between DCM and NaHCC>3 sat. solution. The layers were separated and the aqueous phase was extracted with DCM. The combined organic phases were washed with brine, dried over MgSCU and concentrated to dryness. The crude product was purified by flash chromatography, silica gel, gradient DCM to MeOH:DCM (1 :4) to give the title compound (46 mg, 45% yield).

Step 2. Title compound: Following General Deprotection Method 3, starting from the compound obtained in Step 1 (46 mg, 0.081 mmol), the title compound was obtained (30 mg, 79% yield).

HPLC retention time (method D): 5.16 min; MS: 470.3 (M+H).

This method was used for the preparation of Examples 25-26 using suitable starting materials:

Table of Examples with binding to the u-opioid Receptor and the a₂d-1 Subunit of the voltage-gated calcium channel: BIOLOGICAL ACTIVITY

Pharmacological study

Human a₂d-1 subunit of Ca_v2.2 calcium channel assay

Human 0,26- 1 enriched membranes (2.5 pg) were incubated with 15 nM of radiolabeled [3H]-Gabapentin in assay buffer containing Hepes-KOH 10mM, pH 7.4. NSB (non specific binding) was measured by adding 10 mM pregabalin. The binding of the test compound was measured at five different concentrations. After 60 min incubation at 27 °C, binding reaction was terminated by filtering through Multiscreen GF/C (Millipore) presoaked in 0.5 % polyethyleneimine in Vacuum Manifold Station, followed by 3 washes with ice-cold filtration buffer containing 50 mM Tris-HCI, pH 7.4. Filter plates were dried at 60 °C for 1 hour and 30 mI of scintillation cocktail were added to each well before radioactivity reading. Readings were performed in a Trilux 1450 Microbeta radioactive counter (Perkin Elmer).

Human u-opioid receptor radioligand assay Transfected CHO-K1 cell membranes (20 pg) were incubated with [³H]-DAMGO (1 nM) in assay buffer containing Tris-HCI 50 mM, MgCl2 5 mM at pH 7.4. NBS (non- specific binding) was measured by adding 10 mM Naloxone. The binding of the test compound was measured at five different concentrations. Plates were incubated at 27 °C for 60 min. After the incubation period, the reaction mixture was then transferred to Multiscreen HTS, FC plates (Millipore), filtered and plates were washed 3 times with ice-cold 10 mM Tris-HCI (pH 7.4). Filters were dried and counted at approximately 40% efficiency in a MicroBeta scintillation counter (Perkin-Elmer) using EcoScint liquid scintillation cocktail.

Results:

As this invention is aimed at providing a compound or a chemically related series of compounds which act as dual ligands of the a2d subunit of voltage- gated calcium channels and the m-opioid receptor it is a very preferred embodiment in which the compounds are selected which act as dual ligands of the a₂d subunit of voltage-gated calcium channels and the m-opioid receptor and especially compounds which have a binding expressed as K, responding to the following scales:

Kί(m) is preferably < 1000 nM, more preferably < 500 nM, even more preferably < 100 nM.

K(a₂d-1 ) is preferably < 10000 nM, more preferably < 5000 nM, or even more preferably < 500 nM.

The following scale has been adopted for representing the binding to m-opioid receptor expressed as K:

+ Ki (m) >= 500 nM

++ 100 nM <= K,(m) < 500 nM

+++ Kί(m) < 100 nM The following scale has been adopted for representing the binding to the a2d-1 subunit of voltage-gated calcium channels expressed as K:

+ K(a₂d-1) >= 5000 nM

++ 500 nM <= K(a₂d-1) <5000 nM

+++ Kί(a₂d-1) <500 nM

All compounds prepared in the present application exhibit binding to the a₂d-1 subunit of voltage-gated calcium channels and the m-opioid receptor, in particular the following binding results are shown:

Claims

CLAIMS:

1. Compound of general formula (I),

wherein

X is selected from a bond, -[C(R_aRb)]_P-, -[CH2]_PC(0)[CH2]_q-, -

[CH₂]_PC(0)N(R_z)[CH₂]q-, -[CH₂]_PN(R_z)C(0)[CH₂]q- and -[CH₂]_PN(R_z)[CH₂]_q-; R_a is selected from hydrogen, halogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl;

R_b is selected from hydrogen, halogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R_a and R_b, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl;

R_z is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and -C(0)-Ci-₆ alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5; n is 0 or 1 ;

Yi is -C(RioRio')-; wherein R₁₀ and Rio· are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R₁₀ and Rio· form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

Y2 is -C(Rio”Rio'”)-; wherein Rio- and R-io- are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R_10” and Rio- form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH2- or C=0;

R₅ and R_5' are independently selected from halogen, -R₅₁, -OR₅₁, -NO₂, - NR51R51', -NR_5iC(0)R₅r, -NR5iS(0)2R5r, -S(0)2NR5iR5-r,

NR_5iC(0)NR₅rR₅r', -SR₅₁ , -S(0)Rsi, -S(0)₂R_SI , -CN, haloalkyl, haloalkoxy, - C(0)OR_5I , -C(0)NR_5iR₅r, -OCH₂CH₂OR_5I , -NR_5iS(0)₂NR₅rR_5i and - C(CH₃)₂OR_5I ; wherein R₅₁, Rsr and R₅r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

R₆ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R_?;

R₂ is selected from substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

R3' is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

R₄ and R_4' are independently selected from halogen, -R₄I , -OR₄I , -NO₂, - NR_4iR₄r, -NR_4iC(0)R₄r, -NR_4iS(0)₂R₄r, -S(0)₂NR_4iR₄r, -NR_4iC(0)NR₄rR₄-r, - SR₄I , -S(0)R₄I , -S(0)₂R₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R_4i, - C(0)NR_4iR₄r, -0CH₂CH₂0R₄I , -NR_4iS(0)₂NR₄ R_4i” and -C(CH₃)₂0R₄I ; wherein R₄I , R₄r and R₄r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl and substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

2. Compound according to claim 1 wherein R2 is a substituted or unsubstituted group selected from phenyl and thienyl.

3. Compound according to any one of claims 1 or 2 wherein the compound of Formula (I) is a compound of Formula (G), (l^a), ( ), (l^b), (l^b), (l^c) or (l^c),

(I’

(I^a' 18

319

wherein Rg and Rg· are independently selected from halogen, -R21, -OR21, - NO2, -NR21R21’, -NR_2iC(0)R₂r, -NR2iS(0)2R2r, -S(0)2NR2iR2r,

NR2iC(0)NR₂rR2i”, -SR21 , -S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, - C(0)0R₂I , -C(0)NR_2iR₂r, -OCH2CH2OR21, -NR2iS(0)₂NR₂rR2r' and - C(CH₃)₂OR₂I ; wherein R₂₁, R₂r and R_21” are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

4. Compound according to any one of claims 1 to 3 wherein

wherein

p is 0, 1 , 2, 3, 4 or 5;

q is 0, 1 , 2, 3, 4 or 5;

and Ri and R_z are as defined in the previous claims.

5. Compound according to any one of claims 1 to 4 wherein X is a bond, -C(O)- or a substituted or unsubstituted group selected from -CH2-, -CH2CH2-, - NHC(0)CH₂-, -NHC(0)CH₂CH2- and -N(CH₃)C(0)CH₂-.

6. Compound according to any one of claims 1 to 5 wherein

p is 0, 1 , 2, 3, 4 or 5; preferably p is 0, 1 or 2.

7. Compound according to any one of claims 1 to 5 wherein

q is 0, 1 , 2, 3, 4 or 5; preferably q is 0, 1 or 2.

8. Compound according to any one of claims 1 to 7 wherein the compound is selected from:

9. Process for the preparation of compounds of Formula (I) as defined in any one of claims 1 to 8,

said process comprises:

a) wherein X represents a bond, and wherein Ri, R₂, R3, R3', R₄, R₄·, Ui, Y2 and n have the meanings as defined in the preceding claims , said process comprises treating a compound of formula (I la),

wherein Q represents chloro, bromo, iodo or triflate, with a suitable N- containing cyclic reagent of formula (ill-1 )

R H

MI-1 under Buchwald-Hartwig or Ullmann arylation conditions;

or

b) wherein -X- represents -[C(R_aRb)]_P-, and wherein R_a, Rb, R1, R2, R3, R3', R₄, R_4', Y_I , Y2 and n and p have the meanings as defined in the preceding claims , said process comprises treating a compound of formula (lib’)

R-i-H

HI-1 under standard reductive amination conditions; or

c) wherein -X- represents -[C(R_aRb)]_P-, and wherein R_a, Rb, Ri, R2, R3, R3', R₄, R_4', Y_I , Y2 and n and p have the meanings as defined in the preceding claims , said process comprises treating a compound of formula (I la),

p

1 2 wherein M represents a suitable organometallic group, preferably a boron or zinc reagent, and p has the meaning as defined in the preceding claims;

or d) wherein -X- represents -[CR_aR_b]_PC(0)[CH₂]_q- and q is 0, wherein R_a and R_b are hydrogen and wherein Ri, R2, R3, R3', R₄, R₄·, Y1, Y2, n, p and q have the meanings as defined in the preceding claims , said process comprises treating a compound of formula (lie’)

with a /V-containing cyclic reagent of formula (ill-1 )

R-i-H

MI-1 under conventional amidation conditions;

or

e) wherein -X- represents -[CR_aRb]pN(R_z)C(0)[CH2]q-, wherein R_a and Rb are hydrogen and wherein Ri, R₂, R₃, R_3', R₄, R₄·, Y₁, Y₂ , n, p and q have the meanings as defined in the preceding claims , said process comprises treating a compound of formula (VI’)

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, p, q and Rz have the meanings as defined in the preceding claims , with a /V-containing cyclic reagent of formula (ill-1 )

R-i-H

MI-1 under conventional alkylation conditions; or

f) wherein -X- represents -[CR_aRb]pN(R_z)C(0)[CH2]q-, wherein R_a and Rb are hydrogen and wherein Ri, R₂, R3, R3', R₄, R₄·, Yi, Y2, n, p and q have the meanings as defined in the preceding claims , said process comprises treating an amino compound of formula (lid’)

wherein p and Rz have the meanings as defined in the preceding claims , with an acyl reagent of formula (ill-3),

å '

MI-3 under amidation conditions, wherein Z represents OH or halogen and q has the meaning as defined in the preceding claims ;

or g) wherein -X- represents -[CR_aR_b]_PN(R_z)C(0)[CH₂]_q-, p is 0, wherein R_a and Rb are hydrogen and wherein R1, R₂, R3, R3', R₄, R₄·, Y1, Y2 , n, p and q have the meanings as defined in the preceding claims , said process comprises reacting a compound of formula (I la)

under Ullmann arylation conditions, wherein q and Rz have the meanings as defined in the preceding claims ;

or

h) wherein n is 0, and wherein Ri, R₂, R3, R3', R₄, R₄·, X, Y1 and Y₂ have the meanings as defined in the preceding claims , said process comprises reacting a compound of formula (Vila) wherein G is OH,

Vila with an alkylating agent of formula (VIII)

or

i) wherein n is 0, and wherein R1, R2, R3, R3', R₄, R₄·, X, Y1 and Y2 have the meanings as defined in the preceding claims , said process comprises reacting a compound of formula (Vila) wherein G is OH,

Vila with an alcohol of formula (VIII) wherein Z represents OH,

in the presence of an azo compound;

or

j) wherein n is 0, and wherein R1, R₂, R3, R3', R₄, R₄·, X, Y1 and Y2 have the meanings as defined in the preceding claims , said process comprises reacting a compound of formula (Vila) wherein G is halogen,

Vila with an alcohol of formula (VIII) wherein Z represents OH,

in the presence of a strong base ;

or

k) wherein n is 1 , and wherein Ri, R₂, R₃, R₃·, R₄, R₄·, X, Yi and Y₂ have the meanings as defined in the preceding claims , said process comprises reacting a compound of formula (VI lb)

with an agent of formula (VIII),

10. Use of a compound of Formula II, I la, lla-LG, lib, Mb’, llb-LG, Ilb’-LG, lie, lie’, llc-LG, llc’-LG, lid, lid’, lld-LG, Ild’-LG, 111-1 , III-2, lll’-2, III-3, NI-4, NI-5, IVa, IVb, IVb’, IVc, IVc’, IVd, IVd’, IVe, IVf, V, VI, VI’, VII, Vila, Vllb, VIII, VIII-LG, IX,

X, X’, X-LG, X’-LG, XI, XI-LG, XI’ or XI’-LG

XI'-LG

wherein R_a, Rb, R1, R2, R3, R3', R₄, R₄·, Ui, Y2 , n, p, q, r and R_z have the meanings as defined in the preceding claims , Q represents chloro, bromo, iodo or triflate, LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, have the meanings as defined in the description, M represents a suitable organometallic group, Z represents OH or halogen, and G is OH, halogen or a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, for the preparation of compounds of Formula (I) as defined in any one of claims 1 to 8.

1 1. A pharmaceutical composition which comprises a compound of Formula (I) as defined in any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.

12. A compound of Formula (I) as defined in any one of claims 1 to 8 for use as a medicament.

13. A compound of Formula (I) as defined in any one of claims 1 to 8 for use as a medicament; preferably for use as a medicament for the treatment of pain, especially medium to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia.