Substituted aminothiazoles as DGKZETA inhibitors for immune activation

Abstract

The present invention provides an aminothiazole compound of general formula (I), 1 , R 2 , R 3 and R 4 is as defined herein), processes for preparing said compounds, intermediate compounds useful in preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for the manufacture of pharmaceutical compositions, as sole agents or in combination with other active ingredients, for the treatment and / or prevention of diseases, particularly diacylglycerol kinase zeta (DGKζ) dysregulation. [Formula 1] TIFF2023522250000602.tif31162

Description

[Technical Field]

[0001] The present invention encompasses substituted aminothiazole compounds of general formula (I) as described and defined herein, processes for preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for the manufacture of pharmaceutical compositions, as sole agents or in combination with other active ingredients, for the treatment or prevention of diseases, particularly diacylglycerol kinase zeta (DGKzeta, DGKζ) dysregulation.

[0002] The compounds of general formula (I) inhibit DGKζ, thereby enhancing T cell-mediated immune responses. This is a new strategy for using the patient's own immune system to overcome the immune evasion strategies utilized by many tumor disorders, each cancer, thereby enhancing anti-tumor immunity. Furthermore, the compounds are particularly useful for treating conditions or disorders such as viral infections that involve dysregulated immune responses, or other disorders associated with abnormal DGKζ signaling.

[0003] The present invention further relates to the use of compounds of general formula (I) for preparing a pharmaceutical composition for enhancing a T cell-mediated immune response.

[0004] The present invention further relates to the use of compounds of general formula (I) for preparing a pharmaceutical composition for the treatment of cancer.

[0005] The present invention further relates to the use of compounds of general formula (I) for preparing a pharmaceutical composition for the treatment or prevention of viral infections, lymphoproliferative disorders, asthma, eye diseases, and type 2 diabetes / insulin resistance. [Background technology]

[0006] background Diacylglycerol kinases (DGKs) represent a family of enzymes that catalyze the phosphorylation of the membrane lipid sn-1,2 diacylglycerol (DAG) to form phosphatidic acid (PA) (T.O. Eichmann and A. Lass, Cell. Mol. Life Sci. 2015, 72, 3931-3952). In T cells, DAG is formed downstream of the T cell receptor (TCR) after activation of the gamma 1 isoform of phospholipase C (PLCγ1) and cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into DAG and an additional second messenger, inositol 1,4,5-triphosphate (IP3) (S. Krishna and X.-P. Zhong, Front. Immunol. 2013, 4, 178). IP3 is important for promoting calcium release from the endoplasmic reticulum, while DAG interacts with proteins important in TCR signaling, such as protein kinase Cθ (EJ Quann et al., Nat. Immunol. 2011, 12(7), 647-654) and the Ras activator protein RasGRP1 (S. Krishna and X.-P. Zhong, Front. Immunol. 2013, 4, 178). Although three isoforms of DGK are known to exist in T cells [DGKα (DGKalpha), DGKδ (DGKdelta), and DGKζ (DGKzeta)], only two, DGKα and DGKζ, are thought to play a key role in promoting DAG metabolism downstream of the TCR (RP Joshi and G.A. Koretzky, Int. J. Mol. Sci. 2013, 14(4), 6649-6673).

[0007] Targeting the activity of DGKζ in T cells by germline deletion or by chemical inhibitors enhances and maintains downstream signaling in T cells, as assessed by prolonged phosphorylation of downstream molecules, such as extracellular signal-related kinase 1 / 2 (ERK1 / 2) and NFκB (X.-P.-Zhong et al., Nat. Immunol. 2003, 4, 882-890; B.A. Olenchock et al., Nat. Immunol. 2006, 7(11), 1174-1181; M.J. Riese et al., J. Biol. Chem. 2011, 286, 5254-5265; E.M. Wesley et al., ImmunoHorizons 2018, 2(4), 107-118).

[0008] Deletion of DGKζ in T cells leads to enhanced production of effector cytokines such as IL2 and IFNγ and enhanced proliferation (X.-P. Zhong et al., Nat. Immunol. 2003, 4, 882-890; BAO Lenchock et al., Nat. Immunol. 2006, 7(11), 1174-1181; EMRiese et al., J. Biol. Chem. 2011, 286, 5254-5264).

[0009] Adoptive transfer of DGKζ-deficient T cells reduced leukemia burden after inoculation with C1498.SIY leukemia cells compared with controls. DGKζ-deficient T cells were also at least partially resistant to PD1-mediated inhibitory signals (W. Jing et al., Cancer Res. 2017, 77(20), 5676-5686). Furthermore, DGKζ-deficient mice exhibited reduced tumor size after orthotopic tumor injection in a pancreatic tumor model compared with controls (E.M. Wesley et al., ImmunoHorizons 2018, 2(4), 107-118). S. Wee et al. inoculated C57BL / 6 mice with various syngeneic tumor cell lines—MC38 colon carcinoma, B16F1 melanoma, and C1498 leukemia—and analyzed survival and tumor growth in DGKζ-deficient mice with or without anti-PD1 treatment. DGKζ- / - mice suppressed the growth of subcutaneously implanted tumor cells in three model systems, and the combination of DGKζ-deficiency and anti-PD1 was additive in tumor control (S. Wee et al., Proceedings of the American Association for Cancer Research Annual Meeting 2019; Cancer Res. 2019, 79(13 Suppl):Abstract nr 936).

[0010] These findings suggest that DGKζ may serve as a useful target for enhancing T cell antitumor activity.

[0011] Furthermore, adoptive transfer of CAR (chimeric antigen receptor)-T cells lacking DGKζ showed increased efficacy in treating murine mesothelioma (M.J. Riese et al., Cancer Res. 2013, 73(12), 3566-3577) and glioblastoma xenograft mouse models in combination with DGKα knockout (I.-Y. Jung et al., Cancer Res. 2018, 78(16), 4692-4703) compared to wild-type CAR T cells.

[0012] Furthermore, DGKζ-deficient mice exhibited a stronger immune response to lymphocytic choriomeningitis virus infection than wild-type mice (X.-P. Zhong et al., Nat. Immunol. 2003, 4, 882-890).

[0013] DGKζ is also associated with natural killer (NK) cells. Upon stimulation through multiple activating receptors, NK cells from DGKζ-deficient mice exhibit increased cytokine production and degranulation in an ERK-dependent manner. Furthermore, they have improved cytotoxicity against tumor cell lines (E. Yang et al., J. Immunol. 2016, 197(3), 934-41).

[0014] Apart from immune cell regulation, DGKζ also plays a role in cancer, mediating multiple aspects of cancer cell progression, including proliferation, apoptosis, survival, invasion, and tumorigenesis, for example in osteosarcoma, colon cancer, breast cancer, prostate cancer, glioma, and leukemia models (W. Yu et al., Front. Oncol. 2019, 8:655; K. Cai et al., BMC Cancer 2014, 14:208; J. Diao et al., Mol. Neurobiol. 2016;53, 5425-35; H. Li et al., Pharmazie 2019, 74(7):418-422).

[0015] Additionally, DGKζ knockout reduced both airway inflammation and airway hyperresponsiveness in mice and also reduced bronchoconstriction in human airway samples in vitro by blocking T helper 2 (TH2) differentiation (BASingh et al., Sci. Signal. 2019, 12:eaax3332).

[0016] Taken together, the findings from these studies argue that suppressing DGKζ activity in T cells and tumor cells may prove useful in generating more vigorous immune responses against pathogens and tumors, as well as ameliorating Th2-driven (auto)immune diseases (in rebalancing the immune system).

[0017] Furthermore, inhibition of DGKα can reverse the life-threatening Epstein-Barr virus (EBV)-associated immune disease that occurs in patients with X-linked cell-spreading disease-1 (XLP-1) (E. Ruffo et al., Sci. Transl. Med. 2016, 8:(321):321ra7; S. Velnati et al., Eur. J. Med. Chem. 2019, 164, 378-390). Based on the underlying mechanism of action, it can be hypothesized that inhibition of DGKζ would have a similar effect.

[0018] The DGKα-inhibitor II (R59949) was able to suppress retinal neovascularization and protect retinal astrocytes in an oxygen-induced retinopathy model (L. Yang et al., J. Mol. Neurosci. 2015, 56, 78-88). Based on the underlying mechanism of action, it can be hypothesized that inhibition of DGKζ would have a similar effect.

[0019] In DGKζ knockout mice, it was shown that DGKζ deficiency increases protection against insulin resistance (B. Benziane et al., J. Lipid Res. 2017, 58(12), 2324-2333).

[0020] In summary, inhibition of DGKζ activity has therapeutic potential in directly targeting tumors as well as addressing viral infections, lymphoproliferative disorders, asthma, eye diseases, and type 2 diabetes / insulin resistance.

[0021] prior art WO2020 / 006016 and WO2020 / 006018 describe naphthyridinone compounds as T cell activators that inhibit the activity of DGKα and / or DGKζ for the treatment of viral infections and proliferative disorders such as cancer. WO2021 / 041588 describes pyridopyrimidinonyl compounds as T cell activators that inhibit the activity of DGKα and / or DGKζ for the treatment of viral infections and proliferative disorders, such as cancer.

[0022] 2,4,5-trisubstituted triazole derivatives featuring a substituted amino group attached to C-2 of the thiazole core have been disclosed in published patent applications in various technical contexts, but not in the context of DGK inhibition.

[0023] WO2014 / 181287 discloses heterocyclyl compounds as inhibitors of interleukin-17 and tumor necrosis factor alpha.

[0024] WO2014 / 173904 discloses compounds with antibacterial activity.

[0025] WO2009 / 149054 discloses small molecule inhibitors for the treatment or prevention of dengue infection.

[0026] WO2007 / 130075 discloses aminothiazole derivatives as human stearoyl-CoA desaturase inhibitors.

[0027] WO2012 / 064715 discloses compositions and methods relating to heat shock transcription factor activating compounds and their targets.

[0028] WO2005 / 103022 discloses substituted thiazole and pyrimidine derivatives as melanocortin receptor modulators.

[0029] CN106109467 discloses the medical use of aromatic compounds, including thiazoles, in the treatment of pyrazinamide-resistant tuberculosis.

[0030] WO2015 / 199206 discloses compounds derived from six-membered rings as TRPV4 inhibitors.

[0031] WO2015 / 046193 discloses aromatic heterocyclic amine derivatives as TRPV4 inhibitors.

[0032] CN103159695 discloses thiazole compounds that can inhibit human immunodeficiency (HIV) virus replication and are effective against drug-resistant HIV virus strains.

[0033] WO2013 / 056684 discloses thiazole derivatives as dihydroorotate dehydrogenase (DHODH) inhibitors.

[0034] WO2013 / 033037 discloses various chemical types of compounds, especially thiazole derivatives, as anti-prion compounds.

[0035] WO2012 / 075393 discloses compounds of various chemical types, in particular thiazole derivatives, as activators of proteasomal degradation.

[0036] JP2011032254 discloses various chemical types of compounds, particularly thiazole derivatives, as pest control agents.

[0037] WO2009 / 041790 discloses 2,4,5-trisubstituted thiazole derivatives as inhibitors of the sphingosylphosphorylcholine (SPC) receptor for the treatment of inflammatory diseases.

[0038] WO2008 / 090382 discloses thiazole and oxazole derivatives for use in the treatment of prion diseases, cancer and conditions of the central nervous system and in the modulation of stem cells.

[0039] WO2007 / 022415 discloses substituted 2-aminothiazoles for treating neurodegenerative diseases.

[0040] WO2006 / 122011 discloses thiazole compounds and methods of use in the treatment of viral infections, particularly hepatitis C virus infections.

[0041] WO2006 / 078287 discloses derivatives of various five-membered heteroarenes, especially thiazoles, as inhibitors of phosphodiesterase 4B.

[0042] WO2005 / 102318, WO2005 / 102325, WO2005 / 102326, WO2005 / 102346, WO2005 / 102455, WO2005 / 112920, WO2005 / 115304, WO2005 / 115385 all deal with various chemical types of c-Kit inhibitors, including 2-aminothiazole derivatives, and various uses thereof.

[0043] EP1543824 and US2005 / 0137239 disclose thiazole derivatives for combating glycation.

[0044] WO2004 / 014884 discloses thiazole derivatives as neuropeptide Y receptor ligands.

[0045] WO2019 / 133445 discloses aminothiazole derivatives as inhibitors of Vanin-1.

[0046] WO2021 / 043966 discloses substituted five-membered nitrogen-containing heteroaryl compounds as inhibitors of the NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3).

[0047] 2,4,5-trisubstituted triazole derivatives structurally related to, but yet structurally distinct from, the compounds of the present invention have also been disclosed in several scientific publications.

[0048] D. Kikelj and U. Urleb, Science of Synthesis (2002), 11, 627-833, is a general review of the synthesis of thiazoles. Most of the specific compounds disclosed share a thiazole core with the compounds of the present invention, but are structurally distinct from them. Some individual compounds disclosed therein, namely, those disclosed on pages 651, 681-683, and 719, including {4-methyl-2-[methyl(phenyl)amino]-1,3-thiazol-5-yl}(phenyl)methanone, are structurally related to, but distinct from, the compounds of the present invention.

[0049] 2,4,5-trisubstituted triazole derivatives that are structurally related to, but still structurally distinct from, the compounds of the present invention have also been disclosed in several journal articles.

[0050] None of the journal articles listed below, which also disclose several compounds that are somewhat structurally related to, but structurally distinct from, the compounds of the present invention, disclose therapeutic pharmaceutical applications of the compounds disclosed therein.

[0051] S. Titus et al., Tetrahedron Lett. 2014, 55, 5465-5467, disclose a four-component synthesis of 4-hydrazinothiazole derivatives.

[0052] TN Birkinshaw et al., J. Chem. Soc. Perkin Trans. 1, 1988, 2209-2212, disclose spectroscopic and chemical studies on 5-acyl and 5-nitroso-2-(N,N-disubstituted amino)thiazoles.

[0053] RAFunnell et al., J. Chem. Soc. Perkin Trans. 1, 1987, 2311-2315, disclose studies on the formation of isomeric 2-(N,N-disubstituted amino)thiazol-5-yl ketones.

[0054] J.C.Brindley et al., J. Chem. Soc. Perkin Trans. 1, 1987, 1153-1158, disclose the conversion of N'-substituted N-acyl and N-imidoyl thioureas to 2-(N,N-disubstituted amino)thiazol-5-yl ketones.

[0055] GD Meakins et al., J. Chem. Soc. Comm. 1984, 837-838, disclose a chemical reaction which unexpectedly affords 5-benzoyl-4-methyl-2-(N-methyl-N-phenylamino)thiazole.

[0056] K. Akiba et al., Tetrahedron Lett. 1975, 7, 459-462, disclose the synthesis of certain 2-arylaminothiazoles by 1,3-cycloaddition of 4-aryl-3-arylimino-5-imino-1,2-4-thiadiazolidine (also known as Hector's base) and acetylene.

[0057] Finally, three structures somewhat structurally related to, but structurally distinct from, the compounds of the present invention are disclosed in the database Chemical Abstracts Registry (CAS Registry®), all without reference and without technical application, and have CAS Registry numbers 1349635-19-3, 1349215-57-1, and 1348293-02-6.

[0058] However, the prior art does not describe: Certain substituted aminothiazole compounds of general formula (I) of the present invention as described and defined herein, i.e., compounds having a 2-aminothiazole core as described and defined herein and hereinafter referred to as "compounds of general formula (I)" or "compounds of the present invention", having: an optionally substituted benzoyl or 6-membered heteroaroyl group attached to C-5, -NH2 or methyl group attached to C-4, and (i) an optionally substituted phenyl or 5- or 6-membered heteroaryl group, and (ii) an alkyl group laterally substituted with a group -S(=O)2-NH2, or in particular -C(=O)-NH2, where both (i) and (ii) are attached to the nitrogen atom attached to C-2, and said laterally substituted alkyl group is essential for the potent inhibition of DGKζ, as shown in the comparative tests below. or a stereoisomer, tautomer, N-oxide, hydrate, solvate, salt thereof, or mixture thereof; · or their pharmacological activity.

[0059] WO2021 / 028382 provides a single compound name N for various chemical types ([1,2,4]triazolo[1.5-c]quinazolin-5-amine compounds) according to formula (I) and the abstract. 2 -(4-amino-5-benzoyl-1,3-thiazol-2-yl)-N 2 -(3-methylphenyl)alaninamide is disclosed without providing a synthesis protocol and without any biological data for said compound name. [Prior art documents] [Patent documents]

[0060] [Patent Document 1] International Publication No. 2020 / 006016 [Patent Document 2] International Publication No. 2020 / 006018 [Patent Document 3] International Publication No. 2021 / 041588 [Patent Document 4] International Publication No. 2014 / 181287 [Patent Document 5] International Publication No. 2014 / 173904 [Patent Document 6] International Publication No. 2009 / 149054 [Patent Document 7] International Publication No. 2007 / 130075 [Patent Document 8] International Publication No. 2012 / 064715 [Patent Document 9] International Publication No. 2005 / 103022 [Patent Document 10] Chinese Patent No. 106109467 [Patent Document 11] International Publication No. 2015 / 199206 [Patent Document 12] International Publication No. 2015 / 046193 [Patent Document 13] Chinese Patent No. 103159695 [Patent Document 14] International Publication No. 2013 / 056684 [Patent Document 15] International Publication No. 2013 / 033037 [Patent Document 16] International Publication No. 2012 / 075393 [Patent Document 17] Japanese Patent Application Laid-Open No. 2011032254 [Patent Document 18] International Publication No. 2009 / 041790 [Patent Document 19] International Publication No. 2008 / 090382 [Patent Document 20] International Publication No. 2007 / 022415 [Patent Document 21] International Publication No. 2006 / 122011 [Patent Document 22] International Publication No. 2006 / 078287 [Patent Document 23] International Publication No. 2005 / 102318 [Patent Document 24] International Publication No. 2005 / 102325 [Patent Document 25] International Publication No. 2005 / 102326 [Patent Document 26] International Publication No. 2005 / 102346 [Patent Document 27] International Publication No. 2005 / 102455 [Patent Document 28] International Publication No. 2005 / 112920 [Patent Document 29] International Publication No. 2005 / 115304 [Patent Document 30] International Publication No. 2005 / 115385 [Patent Document 31] European Patent Application Publication No. 1543824 [Patent Document 32] US Patent Application Publication No. 2005 / 0137239 [Patent Document 33] International Publication No. 2004 / 014884 [Patent Document 34] International Publication No. 2019 / 133445 [Patent Document 35] International Publication No. 2021 / 043966 [Non-patent literature]

[0061] [Non-Patent Document 1] Science of Synthesis(2002), 11, 627-833 [Non-patent document 2] Tetrahedron Lett.2014, 55, 5465-5467 [Non-patent document 3] J.Chem.Soc.Perkin Trans.1, 1988, 2209-2212 [Non-patent document 4] J.Chem.Soc.Perkin Trans.1, 1987, 2311~2315 [Non-patent document 5] J.Chem.Soc.Perkin Trans.1, 1987, 1153~1158 [Non-patent document 6] J.Chem.Soc.Comm.1984, 837-838 [Non-Patent Document 7] Tetrahedron Lett.1975, 7, 459-462 [Non-patent document 8] CAS Registry Number 1349635-19-3 [Non-Patent Document 9] CAS Registry Number 1349215-57-1 [Non-Patent Document 10] CAS Registry Number 1348293-02-6 Summary of the Invention [Problem to be solved by the invention]

[0062] It is desirable to provide new compounds with prophylactic and therapeutic properties.

[0063] Therefore, the object of the present invention is to provide compounds and pharmaceutical compositions containing these compounds for use in the prophylactic and therapeutic treatment of DGKζ dysregulation in a T cell immunostimulatory or immunomodulatory manner. DGKζ dysregulation includes conditions involving dysregulation of the immune response, particularly the immunosuppressive tumor microenvironment in cancer, autoimmune diseases, viral infections, and other disorders associated with abnormal DGKζ signaling. The compounds can be used as a single agent or in combination with other active ingredients.

[0064] It has now been found that the compounds of the invention have surprising and advantageous properties, which form the basis of the present invention.

[0065] In particular, it has been surprisingly found that the compounds of the present invention effectively inhibit DGKζ protein, thereby enhancing T cell-mediated immunity. Thus, the present invention provides novel structures for treating diseases in mammals, including humans, particularly cancer, and can therefore be used to treat or prevent hyperproliferative disorders such as cancer. [Means for solving the problem]

[0066] Description of the Invention According to a first aspect, the present invention provides a compound of general formula (I): [ka] [During the ceremony: R 1 is a halogen atom or hydroxy, cyano, nitro, C1-C6-alkyl, (phenyl)-(C1-C3-alkyl)-, C1-C6-haloalkyl, C1-C6-alkoxy, (phenyl)-(C1-C3-alkoxy)-, C1-C6-haloalkoxy, -N(R) 5 (R 6 phenyl or 6-membered heteroaryl group, optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of wherein the phenyl group in the (phenyl)-(C1-C3-alkyl)- and (phenyl)-(C1-C3-alkoxy) groups is optionally substituted once or twice by a halogen atom or by a substituent independently selected from the group consisting of cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy, or two substituents attached to adjacent carbon atoms of said phenyl or 6-membered heteroaryl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -(CH2)2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O-, -O-CF2-O-, -O-CH2-CF2-O-, and -O-CF2-CF2-O-; or R 1 represents a 5-membered heteroaryl group optionally substituted one or two times with a halogen atom or with substituents independently selected from the group consisting of cyano, C1-C3-alkyl, and C1-C3-alkoxy; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3represents a group selected from methyl and -NH; R 4 is a halogen atom or cyano, nitro, C1-C6-alkyl, (phenyl)-(C1-C3-alkyl)-, (5- or 6-membered heteroaryl)-(C1-C3-alkyl)-, (C3-C7-cycloalkyl)-(C1-C3-alkyl)-, ((R 9 )O)-(C1-C6-alkyl)-, C1-C6-haloalkyl, C3-C7-cycloalkyl, -OR 9 , -N(R 10 )(R 11 ), ((R 10 )(R 11 )N)-(C1-C3-alkyl)-, -C(=O)-N(R 12 )(R 13 ), -S(=O) n -R 14 , -C(=O)R 14 , -C(=O)-OR 17 and a 5- or 6-membered heteroaryl group, which may itself be substituted with 1 or 2 substituents selected from halogen atoms and methyl groups; or two substituents attached to adjacent carbon atoms of said phenyl group or 6-membered heteroaryl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -(CH2)2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O-, -O-CF2-O-, -O-CH2-CF2-O-, and -O-CF2-CF2-O-; R 5 and R 6 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl and (phenyl)-(C-C-alkyl)-, or R 5 and R 6together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one, two or three times with halogen atoms or with substituents independently selected from the group consisting of oxo, hydroxy, C1-C4-alkyl, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl and C1-C4-alkoxy; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a group selected from -C(=O)-NH2 and -S(=O)2-NH2; R 9 is a hydrogen atom or C1-C6-alkyl, (5- or 6-membered heteroaryl)-(C1-C3-alkyl)-, (phenyl)-(C1-C3-alkyl)-, C1-C6-haloalkyl, C2-C4-hydroxyalkyl, (C1-C3-alkoxy)-C2-C3-alkyl-, ((C1-C3-alkyl)-C(=O)-O)-C2-C3-alkyl-, -C(R 18 )(R 19 )-C(=O)-OR 17 , -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ), -C(=O)-N(R 20 )(R 21 ), phenyl and 5- or 6-membered heteroaryl groups, wherein the phenyl group in the (phenyl)-(C1-C3-alkyl) group and the phenyl group itself, and the 5- or 6-membered heteroaryl group in the (5- or 6-membered heteroaryl)-(C1-C3-alkyl) group, and the 5- or 6-membered heteroaryl group itself, are optionally substituted one or two times with each substituent independently selected from halogen atoms or groups selected from cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy; R 10 and R 11is independently in each occurrence a hydrogen atom or C1-C4-alkyl, C1-C4-haloalkyl, C2-C4-hydroxyalkyl, (C1-C3-alkoxy)-C2-C3-alkyl-, ((R 22 )(R 23 )N)—C2-C3-alkyl, (C3-C7-cycloalkyl)-(C1-C3-alkyl)-, (C1-C4-alkyl)-C(═O)—, C3-C7-cycloalkyl, (C3-C7-cycloalkyl)-C(═O)—, (phenyl)-(C1-C3-alkyl)-, (phenyl)-(C1-C3-alkyl)-C(═O)—, (phenyl)-(C1-C3-alkyl)-OC(═O)—, phenyl and a 5- or 6-membered heteroaryl group, wherein C3-C7-cycloalkyl, and C3-C7-cycloalkyl in the (C3-C7-cycloalkyl)-(C1-C3-alkyl)- and (C3-C7-cycloalkyl)-C(=O)- groups, are optionally substituted one or two times by fluorine atoms or by substituents independently selected from the group selected from cyano, C1-C2-alkyl and C1-C2-haloalkyl, and the phenyl and the 5- or 6-membered heteroaryl groups, and the phenyl groups in the (phenyl)-(C1-C3-alkyl)-, (phenyl)-(C1-C3-alkyl)-C(=O)- and (phenyl)-(C1-C3-alkyl)-OC(=O)- groups, are optionally substituted one or two times by a halogen atom or a substituent independently selected from the group consisting of cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy, or R 10 and R 11together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group or a bicyclic nitrogen-containing 5- to 11-membered heterocycloalkyl group, which are optionally substituted with a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, -N(R 22 )(R 23 ), and monocyclic 4- to 7-membered heterocycloalkyl groups; R 12 and R 13 represents, independently at each occurrence, a hydrogen atom or C-C-alkyl, C-C-haloalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-C-alkyl-, (C-C-haloalkoxy)-C-C-alkyl-, (phenoxy)-C-C-alkyl-, C-C-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one, two or three times by halogen atoms or by substituents independently selected from the group selected from cyano, oxo, hydroxy, C1-C4-alkyl, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl and C1-C4-alkoxy, and the phenyl group in the (phenoxy)-C2-C3-alkyl- group and the (phenyl)-(C1-C3-alkyl)- group is optionally substituted once or twice by a halogen atom or a substituent independently selected from the group consisting of cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy, or R 12 and R 13together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one, two or three times with halogen atoms or with substituents independently selected from the group consisting of cyano, oxo, hydroxy, C1-C4-alkyl, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl and C1-C4-alkoxy; R 14 represents a group selected from C1-C4-alkyl, C1-C4-haloalkyl and phenyl, wherein the phenyl group is optionally substituted one or two times with each substituent independently selected from a halogen atom or a group selected from cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino, and trifluoromethoxy; R 17 represents a C1-C4-alkyl group; R 18 and R 19 represents, independently in each occurrence, a hydrogen atom or a C1-C4-alkyl group; R 20 is a hydrogen atom or a C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C5-C 11 -represents a group selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 5- to 11-membered heterocycloalkyl, phenyl, naphthyl, and 5- to 10-membered heteroaryl; wherein the C1-C6-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, bicyclic C5-C 11-optionally substituted one, two or three times with substituents independently selected from groups selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 5- to 11-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted one or two times with halogen atoms or substituents independently selected from groups selected from cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino, and trifluoromethoxy; and C3-C7-cycloalkyl, bicyclic C5-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl and bicyclic 5- to 11-membered heterocycloalkyl are optionally substituted 1, 2 or 3 times by halogen atoms or by substituents independently selected from cyano, oxo, hydroxy, C-C-alkyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl and C-C-alkoxy; and the phenyl, naphthyl and 5-10 membered heteroaryl groups are each independently selected from the group consisting of a halogen atom or cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and optionally substituted one, two or three times with each substituent independently selected from the group R 21 represents a hydrogen atom or a C1-C4-alkyl group, or R 20 and R 21may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (phenyl)-(C-C-alkyl)-, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of: R 22 and R 23 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 24 and R 25 represents, independently at each occurrence, a hydrogen atom or a C1-C4-alkyl group, and n represents an integer of 0, 1, or 2. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof. DETAILED DESCRIPTION OF THE INVENTION

[0067] definition The term "substituted" means that one or more hydrogen atoms on the specified atom or group are replaced with a selection from the specified group, provided that the replacement does not exceed the normal valence of the specified atom under the existing circumstances. Combinations of substituents and / or variables are permissible.

[0068] The term "optionally substituted" means that the number of substituents can be equal to or different from zero. Unless otherwise specified, an optionally substituted group can be substituted with as many optional substituents as possible by replacing the hydrogen atom on any available carbon or nitrogen atom with a non-hydrogen substituent. Generally, if present, the number of optional substituents can be 1, 2, 3 or 4, particularly 1, 2 or 3.

[0069] When radicals in the compounds of the present invention are substituted, said radicals can be mono- or polysubstituted by substituents unless otherwise specified.Within the scope of the present invention, the meanings of all repeating radicals are independent of each other.The radicals in the compounds of the present invention can be substituted with 1, 2 or 3 identical or different substituents, particularly with 1 substituent.

[0070] As used herein, an oxo substituent represents an oxygen atom that is attached to a carbon or sulfur atom via a double bond.

[0071] When a composite substituent is composed of two or more moieties, such as (C-C-alkoxy)-(C-C-alkyl), a given moiety can be attached to any suitable position on the composite substituent, e.g., a C-C-alkoxy moiety can be attached to any suitable carbon atom on the C-C-alkyl portion of the (C-C-alkoxy)-(C-C-alkyl) group. The initial or final hyphen on such a composite substituent indicates the point of attachment of the composite substituent to the rest of the molecule. For example, when a ring containing carbon atoms and, optionally, one or more heteroatoms, such as nitrogen, oxygen, or sulfur atoms, is substituted with a substituent, the substituent can be attached at any suitable position on the ring and be attached to any suitable carbon atom and / or heteroatom.

[0072] The term "comprising" as used herein includes "consisting of."

[0073] In the text, when any item is referred to as "mentioned in this specification", it means that it can be mentioned anywhere in the text.

[0074] The terms mentioned herein have the following meanings: The term "halogen atom" means a fluorine, chlorine, bromine or iodine atom, in particular a fluorine, chlorine or bromine atom.

[0075] The term "C1-C6-alkyl" means a straight-chain or branched, saturated, monovalent hydrocarbon radical having 1, 2, 3, 4, 5 or 6 carbon atoms, such as a methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neo-pentyl, 1,1-dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2,3-dimethylbutyl, 1,2-dimethylbutyl or 1,3-dimethylbutyl group, or an isomer thereof. In particular, the group has 1, 2, 3 or 4 carbon atoms ("C1-C4-alkyl"), such as a methyl, ethyl, propyl, isopropyl, butyl, sec-butyl isobutyl or tert-butyl group, more particularly 1, 2 or 3 carbon atoms ("C1-C3-alkyl"), such as a methyl, ethyl, n-propyl or isopropyl group, more particularly 1 or 2 carbon atoms ("C1-C2-alkyl"), such as a methyl or ethyl group.

[0076] The term "C1-C4-hydroxyalkyl" means a linear or branched, saturated, monovalent hydrocarbon radical, wherein the term "C1-C4-alkyl" is defined above, in which one or two hydrogen atoms have been replaced by a hydroxy group, such as a hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1,2-dihydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-hydroxypropyl, 1-hydroxypropan-2-yl, 2-hydroxypropan-2-yl, 2,3-dihydroxypropyl, 1,3-dihydroxypropan-2-yl, 3-hydroxy-2-methyl-propyl, 2-hydroxy-2-methyl-propyl, 1-hydroxy-2-methyl-propyl, 1-hydroxybutyl, 2-hydroxybutyl, 3-hydroxybutyl, 4-hydroxybutyl group, or an isomer thereof.

[0077] The term "C1-C6-haloalkyl" means a linear or branched, saturated, monovalent hydrocarbon group, wherein the term "C1-C6-alkyl" is as defined above, and one or more hydrogen atoms are replaced with identical or different halogen atoms. In particular, the halogen atoms are fluorine atoms. The C1-C6-haloalkyl group is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3,3,3-trifluoropropyl, or 1,3-difluoropropan-2-yl.

[0078] The term "C1-C6-alkoxy" means a straight-chain or branched, saturated, monovalent radical of the formula (C1-C6-alkyl)-O-, where the term "C1-C6-alkyl" is as defined above, for example a methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, tert-butoxy, pentyloxy, isopentyloxy or n-hexyloxy radical, or an isomer thereof.

[0079] The term "C1-C6-haloalkoxy" refers to a linear or branched, saturated, monovalent C1-C6-alkoxy group as defined above, in which one or more hydrogen atoms are replaced by identical or different halogen atoms. In particular, the halogen atoms are fluorine atoms. The C1-C6-haloalkoxy group is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy or pentafluoroethoxy.

[0080] The term "C3-C4-alkenyl" refers to a linear or branched, monovalent hydrocarbon group containing one or two double bonds and having three or four carbon atoms. The alkenyl group is, for example, a prop-2-en-1-yl (or "allyl"), prop-1-en-1-yl, but-3-enyl, but-2-enyl or but-1-enyl group.

[0081] The term "C3-C4-alkynyl" refers to a linear or branched monovalent hydrocarbon radical containing one triple bond and containing 3 or 4 carbon atoms. The C3-C4-alkynyl radical is, for example, a prop-1-ynyl, prop-2-ynyl (or "propargyl"), but-1-ynyl, but-2-ynyl or but-3-ynyl radical.

[0082] The term "C3-C7-cycloalkyl" denotes a saturated, monovalent, monocyclic hydrocarbon ring containing 3, 4, 5, 6 or 7 carbon ring atoms ("C3-C7-cycloalkyl"). The C3-C7-cycloalkyl group is, for example, a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl group.

[0083] The term “bicyclic C6-C 11 -cycloalkyl" means a spirocycloalkyl, as defined below, a fused C-C 10 -cycloalkyl or bridged C7-C 10 means a cycloalkyl group: The term "spirocycloalkyl" refers to a bicyclic, saturated, monovalent C-C alkyl group in which the two rings share one common ring carbon atom. 11 means a hydrocarbon group, said bicyclic hydrocarbon group containing 5, 6, 7, 8, 9, 10 or 11 carbon atoms, and said spirocycloalkyl group can be attached to the rest of the molecule through any one of the carbon atoms except the spiro carbon atom, for example, spiro[2.6]nonyl, spiro[3.3]heptyl, spiro[3.4]octyl, spiro[3.5]nonyl, spiro[3.6]decyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[4.6]undecyl or spiro[5.5]undecyl. The term “Fused C6-C 10 "-Cycloalkyl" means a bicyclic, saturated, monovalent hydrocarbon group in which the two rings share two adjacent ring atoms, for example, bicyclo[4.2.0]octyl, octahydropentalenyl, or decalinyl. The term “Bridged C7-C 10 "-Cycloalkyl" means a bicyclic, saturated, monovalent hydrocarbon group in which the two rings share two common non-adjacent ring atoms, for example, bicyclo[2.2.1]heptyl (also known as norbornyl).

[0084] The term “bicyclic C5-C 11 -cycloalkyl" means a spirocycloalkyl, as defined below, a fused C-C 10 -cycloalkyl or bridged C5-C 10 means a cycloalkyl group: The term "spirocycloalkyl" refers to a bicyclic, saturated, monovalent C-C alkyl group in which the two rings share one common ring carbon atom. 11means a hydrocarbon group, said bicyclic hydrocarbon group containing 5, 6, 7, 8, 9, 10 or 11 carbon atoms, and said spirocycloalkyl group can be attached to the rest of the molecule through any one of the carbon atoms except the spiro carbon atom, for example, spiro[2.6]nonyl, spiro[3.3]heptyl, spiro[3.4]octyl, spiro[3.5]nonyl, spiro[3.6]decyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[4.6]undecyl or spiro[5.5]undecyl. The term “Fused C5-C 10 "-Cycloalkyl" means a bicyclic, saturated, monovalent hydrocarbon group, where the two rings share two adjacent ring atoms, e.g., bicyclo[4.2.0]octyl, octahydropentalenyl, or decalinyl. The term “Bridged C5-C 10 "-Cycloalkyl" means a bicyclic, saturated, monovalent hydrocarbon group in which the two rings share two common non-adjacent ring atoms, for example, bicyclo[1.1.1]pentyl or bicyclo[2.2.1]heptyl (also known as norbornyl).

[0085] The term "monocyclic 4- to 7-membered heterocycloalkyl" means a monocyclic, saturated, heterocyclic ring having a total of 4, 5, 6, or 7 ring atoms, which contains one or two identical or different ring heteroatoms from the series N, O, and S.

[0086] The monocyclic heterocycloalkyl group can be, but is not limited to, a four-membered ring such as, for example, azetidinyl, oxetanyl, or thietanyl; or a five-membered ring such as, for example, tetrahydrofuranyl, 1,3-dioxolanyl, thiolanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, 1,1-dioxidethiolanyl, 1,2-oxazolidinyl, 1,3-oxazolidinyl, or 1,3-thiazolidinyl; or a six-membered ring such as, for example, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, 1,3-dioxanyl, 1,4-dioxanyl, or 1,2-oxazinanyl, or a seven-membered ring such as, for example, azepanyl, 1,4-diazepanyl, or 1,4-oxazepanyl.

[0087] The term "monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group" means a monocyclic, saturated heterocycle having a total of 4, 5, 6, or 7 ring atoms, which contains one ring nitrogen atom and, optionally, one additional ring heteroatom from the series N, O, and S.

[0088] The monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group can be, but is not limited to, a 4-membered ring such as azetidinyl; or a 5-membered ring such as pyrrolidinyl, imidazolidinyl, pyrazolidinyl, 1,2-oxazolidinyl, 1,3-oxazolidinyl, or 1,3-thiazolidinyl; or a 6-membered ring such as piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, or 1,2-oxazinyl, or a 7-membered ring such as azepanyl, 1,4-diazepanyl, or 1,4-oxazepanyl.

[0089] The term "optionally benzo-fused monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group" means a monocyclic, saturated heterocycle having a total of 4, 5, 6, or 7 ring atoms, containing one ring nitrogen atom and optionally one further ring heteroatom from the series N, O, and S, and in which two adjacent ring carbon atoms are optionally shared with a benzene ring to which it is optionally fused; such a group is one of the aforementioned monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl groups, such as pyrrolidinyl, piperidinyl, or a benzo-fused group, for example, 3,4-dihydroquinolin-1(2H)-yl, 3,4-dihydroisoquinolin-2(1H)-yl, 1,3-dihydro-2H-isoindol-2-yl, or 2,3-dihydro-1H-indol-1-yl.

[0090] The term "bicyclic 6-11 membered heterocycloalkyl" means a 6-11 membered heterospirocycloalkyl, a 6-10 membered fused heterocycloalkyl, or a 7-10 membered bridged heterocycloalkyl group as defined below: The term "6- to 11-membered heterospirocycloalkyl" means a bicyclic, saturated, heterocyclic ring having a total of 6, 7, 8, 9, 10, or 11 ring atoms, where the two rings share one common ring carbon atom, and "heterospirocycloalkyl" contains one or two identical or different ring heteroatoms from the series: N, O, S; said heterospirocycloalkyl group can be attached to the rest of the molecule through any one of the carbon atoms excluding the spiro carbon atom or, if present, the nitrogen atom. Examples of the heterospirocycloalkyl group include azaspiro[2.3]hexyl, azaspiro[3.3]heptyl, oxazaspiro[3.3]heptyl, thiazaspiro[3.3]heptyl, oxaspiro[3.3]heptyl, oxaspiro[5.3]nonyl, oxazaspiro[4.3]octyl, azaspiro[4,5]decyl, oxazaspiro[5.5]undecyl, diazaspiro[ 3.3]heptyl, thiazaspiro[3.3]heptyl, thiazaspiro[4.3]octyl, azaspiro[5.5]undecyl, or one of the further homologous skeletons such as spiro[3.4]-, spiro[4.4]-, spiro[2.4]-, spiro[2.5]-, spiro[2.6]-, spiro[3.5]-, spiro[3.6]-, spiro[4.5]- and spiro[4.6]-. The term "6- to 10-membered fused heterocycloalkyl" means a bicyclic, saturated heterocycle having a total of 6, 7, 8, 9, or 10 ring atoms, where the two rings share two adjacent ring atoms, and the "fused heterocycloalkyl" contains one or two identical or different ring heteroatoms from the series: N, O, S; said fused heterocycloalkyl group can be attached to the rest of the molecule through any one of the carbon atoms or, if present, the nitrogen atom. Said fused heterocycloalkyl group is for example azabicyclo[3.3.0]octyl, azabicyclo[4.3.0]nonyl, diazabicyclo[4.3.0]nonyl, oxazabicyclo[4.3.0]nonyl, thiazabicyclo[4.3.0]nonyl or azabicyclo[4.4.0]decyl. The term "7-10 membered bridged heterocycloalkyl" means a bicyclic, saturated heterocycle having a total of 7, 8, 9, or 10 ring atoms, where the two rings share two common ring atoms that are not adjacent, and "bridged heterocycloalkyl" contains one or two identical or different ring heteroatoms from the series: N, O, S; said bridged heterocycloalkyl group can be attached to the rest of the molecule through any one of the carbon atoms, excluding the spiro carbon atom, or, if present, the nitrogen atom. Examples of the bridged heterocycloalkyl group include azabicyclo[2.2.1]heptyl, oxazabicyclo[2.2.1]heptyl, thiazabicyclo[2.2.1]heptyl, diazabicyclo[2.2.1]heptyl, azabicyclo[2.2.2]octyl, diazabicyclo[2.2.2]octyl, oxazabicyclo[2.2.2]octyl, thiazabicyclo[2.2.2]octyl, azabicyclo[3.2.1]octyl, diazabicyclo[3.2.1]octyl, oxazabicyclo[3.2.1]octyl, thiazabicyclo[3.2.1] octyl, azabicyclo[3.3.1]nonyl, diazabicyclo[3.3.1]nonyl, oxazabicyclo[3.3.1]nonyl, thiazabicyclo[3.3.1]nonyl, azabicyclo[4.2.1]nonyl, diazabicyclo[4.2.1]nonyl, oxazabicyclo[4.2.1]nonyl, thiazabicyclo[4.2.1]nonyl, azabicyclo[3.3.2]decyl, diazabicyclo[3.3.2]decyl, oxazabicyclo[3.3.2]decyl, thiazabicyclo[3.3.2]decyl or azabicyclo[4.2.2]decyl.

[0091] The term "bicyclic nitrogen-containing 6-11-membered heterocycloalkyl" means a 6-11-membered heterospirocycloalkyl, a 6-10-membered fused heterocycloalkyl, or a 7-10-membered bridged heterocycloalkyl group as defined above, but containing one ring nitrogen atom and, optionally, one or two additional ring heteroatoms from the N, O, and S series; said bicyclic nitrogen-containing 6-11-membered heterocycloalkyl group can be attached to the remainder of the molecule via the nitrogen atom or any one of the carbon atoms excluding the spiro carbon atom.

[0092] The term "bicyclic 5-11 membered heterocycloalkyl" means a 5-11 membered heterospirocycloalkyl, a 5-11 membered fused heterocycloalkyl, or a 5-11 membered bridged heterocycloalkyl group as defined below: The term "5- to 11-membered heterospirocycloalkyl" means a bicyclic, saturated heterocycle having a total of 5, 6, 7, 8, 9, 10, or 11 ring atoms, where the two rings share one common ring carbon atom, and "heterospirocycloalkyl" contains one or two identical or different ring heteroatoms from the series: N, O, S; said heterospirocycloalkyl group can be attached to the remainder of the molecule through any one of the carbon atoms excluding the spiro carbon atom or through the nitrogen atom, if present. Examples of the heterospirocycloalkyl group include azaspiro[2.2]pentyl, azaspiro[2.3]hexyl, azaspiro[3.3]heptyl, oxazaspiro[3.3]heptyl, thiazaspiro[3.3]heptyl, oxaspiro[3.3]heptyl, oxazaspiro[5.3]nonyl, oxazaspiro[4.3]octyl, azaspiro[4.5]decyl, and oxazaspiro[5.5]undecyl. , diazaspiro[3.3]heptyl, thiazaspiro[3.3]heptyl, thiazaspiro[4.3]octyl, azaspiro[5.5]undecyl, or one of the further homologous skeletons such as spiro[3.4]-, spiro[4.4]-, spiro[2.4]-, spiro[2.5]-, spiro[2.6]-, spiro[3.5]-, spiro[3.6]-, spiro[4.5]- and spiro[4.6]-. The term "5- to 11-membered fused heterocycloalkyl" means a bicyclic, saturated heterocycle having a total of 5, 6, 7, 8, 9, or 10 ring atoms, where two rings share two adjacent ring atoms, and "fused heterocycloalkyl" contains one or two identical or different ring heteroatoms from the series: N, O, S; said fused heterocycloalkyl group can be attached to the remainder of the molecule through any one of the carbon atoms or, if present, the nitrogen atom. The fused heterocycloalkyl group may be, for example, azabicyclo[3.1.0]hexyl, azabicyclo[3.3.0]octyl, azabicyclo[4.3.0]nonyl, diazabicyclo[4.3.0]nonyl, oxazabicyclo[4.3.0]nonyl, thiazabicyclo[4.3.0]nonyl or azabicyclo[4.4.0]decyl. The term "5- to 11-membered bridged heterocycloalkyl" means a bicyclic, saturated heterocycle having a total of 5, 6, 7, 8, 9, or 10 ring atoms, where the two rings share two common ring atoms that are not adjacent, and the "bridged heterocycloalkyl" contains one or two identical or different ring heteroatoms from the series: N, O, S; said bridged heterocycloalkyl group can be attached to the remainder of the molecule through any one of the carbon atoms, excluding the spiro carbon atom, or through the nitrogen atom, if present. Examples of the bridged heterocycloalkyl group include azabicyclo[2.2.1]heptyl, oxazabicyclo[2.2.1]heptyl, thiazabicyclo[2.2.1]heptyl, diazabicyclo[2.2.1]heptyl, azabicyclo[2.2.2]octyl, diazabicyclo[2.2.2]octyl, oxazabicyclo[2.2.2]octyl, thiazabicyclo[2.2.2]octyl, azabicyclo[3.2.1]octyl, diazabicyclo[3.2.1]octyl, oxazabicyclo[3.2.1]octyl, thiazabicyclo[3.2.1] octyl, azabicyclo[3.3.1]nonyl, diazabicyclo[3.3.1]nonyl, oxazabicyclo[3.3.1]nonyl, thiazabicyclo[3.3.1]nonyl, azabicyclo[4.2.1]nonyl, diazabicyclo[4.2.1]nonyl, oxazabicyclo[4.2.1]nonyl, thiazabicyclo[4.2.1]nonyl, azabicyclo[3.3.2]decyl, diazabicyclo[3.3.2]decyl, oxazabicyclo[3.3.2]decyl, thiazabicyclo[3.3.2]decyl or azabicyclo[4.2.2]decyl.

[0093] The term "bicyclic nitrogen-containing 5-11 membered heterocycloalkyl" means a 5-11 membered heterospirocycloalkyl, a 5-11 membered fused heterocycloalkyl or a 5-11 membered bridged heterocycloalkyl group as defined above, but containing one ring nitrogen atom and optionally one or two additional ring heteroatoms from the N, O and S series; said bicyclic nitrogen-containing 5-11 membered heterocycloalkyl group can be attached to the remainder of the molecule via the nitrogen atom or any one of the carbon atoms, excluding the spiro carbon atom.

[0094] The term "heteroaryl" means a monovalent, monocyclic or bicyclic aromatic ring having 5, 6, 8, 9 or 10 ring atoms (a "5-10 membered heteroaryl" group), which contains at least one ring heteroatom and optionally 1, 2 or 3 additional ring heteroatoms from the series: N, O and / or S, and is bonded via a ring carbon atom or, where valency allows, via a nitrogen atom, e.g., in pyrrol-1-yl.

[0095] The heteroaryl group can be, for example, a 5-membered heteroaryl group such as thienyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, or tetrazolyl; or a 6-membered heteroaryl group such as, for example, pyridinyl (also referred to herein as pyridyl), pyridazinyl, pyrimidinyl, pyrazinyl, or triazinyl; or a 9-membered heteroaryl group such as, for example, benzofuranyl, benzothienyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, benzothiazolyl, benzotriazolyl, thiazolopyridinyl, indazolyl, indolyl, isoindolyl, indolizinyl, or purinyl; or a 10-membered heteroaryl group such as, for example, quinolinyl, quinazolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, or pteridinyl.

[0096] In general, unless otherwise specified, a heteroaryl or heteroarylene group includes all possible isomeric forms thereof, such as tautomers and positional isomers with respect to the point of attachment to the rest of the molecule. Thus, in some illustrative, non-limiting examples, the term pyridinyl includes pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl; or the term thienyl includes thien-2-yl and thien-3-yl.

[0097] The term "C1-C6" as used herein, for example in the context of the definitions of "C1-C6-alkyl", "C1-C6-haloalkyl", "C1-C6-hydroxyalkyl", "C1-C6-alkoxy" or "C1-C6-haloalkoxy", refers to an alkyl group having a finite number of carbon atoms, from 1 to 6, i.e., 1, 2, 3, 4, 5 or 6.

[0098] Furthermore, as used herein, the term "C3-C7" refers to a cycloalkyl group having 3 to 7 carbon atoms, i.e., a finite number of carbon atoms, 3, 4, 5, 6 or 7, as used herein, for example, in the context of the definition "C3-C7-cycloalkyl."

[0099] When a range of values ​​is given, said range includes each value and sub-range within said range.

[0100] for example: "C1-C6" means C1, C2, C3, C4, C5, C6, C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, C2-C6 , C2-C5, C2-C4, C2-C3, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6; "C2-C6" includes C2, C3, C4, C5, C6, C2-C6, C2-C5, C2-C4, C2-C3, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6; "C3-C6" includes C3, C4, C5, C6, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6.

[0101] As used herein, the term "leaving group" refers to an atom or group of atoms that is displaced as a stable species with the bonding electrons in a chemical reaction. In particular, such leaving groups are selected from the group consisting of: halogen atoms, particularly fluorine, chlorine, bromine, or iodine atoms, which are displaced as halides, particularly fluoride, chloride, bromide, or iodide; (methylsulfonyl)oxy, [(trifluoromethyl)sulfonyl]oxy, [(nonafluorobutyl)sulfonyl]oxy, (phenylsulfonyl)oxy, [(4-methylphenyl)sulfonyl]oxy, [(4-bromophenyl)sulfonyl]oxy, [(4-nitrophenyl)sulfonyl]oxy, [(2-nitrophenyl)sulfonyl]oxy, [(4-isopropylphenyl)sulfonyl]oxy, [(2,4,6-triisopropylphenyl)sulfonyl]oxy, [(2,4,6-trimethylphenyl)sulfonyl]oxy, [(4-tert-butylphenyl)sulfonyl]oxy, and [(4-methoxyphenyl)sulfonyl]oxy.

[0102] As used herein, the term "dipolar aprotic solvent" refers to acetone, acetonitrile, propionitrile, dimethyl sulfoxide, diethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N,N-diethylformamide, N,N-diethylacetamide, 1-methyl-2-pyrrolidinone, 1-ethyl-2-pyrrolidinone, 1-methyl-2-piperidinone, and 1-ethyl-2-piperidinone, or mixtures thereof. In particular, the dipolar aprotic solvent is acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, or 1-methyl-2-pyrrolidinone.

[0103] As used herein, the term "room temperature" means a temperature in the range of 15°C to 25°C.

[0104] Compounds of general formula (I) can exist as isotopic variations. Thus, the present invention includes one or more isotopic variations of compounds of general formula (I), particularly deuterium-containing compounds of general formula (I).

[0105] The term "isotopic variant" of a compound or reagent is defined as a compound that exhibits an unnatural proportion of one or more isotopes that constitute such compound. The term "isotopic variant of a compound of general formula (I)" is defined as a compound of general formula (I) that exhibits unnatural proportions of one or more isotopes that constitute such compound.

[0106] The expression "unnatural proportion" means a proportion of such an isotope that is higher than its natural abundance. The natural abundance of an isotope as applied in this context is described in "Isotopic Compositions of Elements 1997", Pure Appl. Chem. 70(1), 217-235, 1998.

[0107] Such isotopes include stable and radioactive isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine, and iodine, for example, 2 H (deuterium), 3 H (tritium), 11 C. 13 C. 14 C. 15 N, 17 O. 18 O. 32 P, 33 P, 33 S, 34 S, 35 S, 36 S, 18 F, 36 Cl, 82 Br, 123 I, 124 I, 125 I, 129 I and 131 I can be mentioned.

[0108] For the treatment and / or prevention of the disorders specified herein, isotopic variants of the compounds of general formula (I) preferably contain deuterium ("deuterium-containing compounds of general formula (I)"). 3 H or 14 Isotopic variations of compounds of general formula (I), into which one or more radioactive isotopes, such as C, are incorporated, are useful, for example, in drug and / or substrate tissue distribution studies. These isotopes are particularly preferred for their ease of incorporation and detectability. 18 F or 11 Positron-emitting isotopes, such as C, can be incorporated into the compounds of general formula (I). These isotopic variants of the compounds of general formula (I) are useful for in vivo imaging applications. Deuterium-containing and 13 C-containing compounds can be used for mass spectrometry in non-clinical or clinical studies.

[0109] Isotopic variants of compounds of general formula (I) can generally be prepared by replacing a reagent with an isotopic variant of the reagent, preferably a deuterium-containing reagent, by methods known to those skilled in the art, such as those described in the schemes and / or examples herein. Depending on the desired deuteration site, deuterium from DO can be incorporated directly into the compound or into a reagent useful for synthesizing such a compound. Deuterium gas is also a useful reagent for incorporating deuterium into molecules. Catalytic deuteration of olefinic and acetylenic bonds is a rapid route for deuterium incorporation. Metal catalysts (i.e., Pd, Pt, and Rh) can be used in the presence of deuterium gas to directly exchange deuterium for hydrogen in hydrocarbon-containing functional groups. A variety of deuterated reagents and synthetic building blocks are commercially available from companies such as, for example, C / D / N Isotopes, Quebec, Canada; Cambridge Isotope Laboratories Inc. Andover, MA, USA; and CombiPhos Catalysts, Inc. Princeton, NJ, USA.

[0110] The term "deuterium-containing compound of general formula (I)" is defined as a compound of general formula (I) in which one or more hydrogen atoms are replaced by one or more deuterium atoms, and the abundance of deuterium at each deuteration position of the compound of general formula (I) is greater than the natural abundance of deuterium (about 0.015%). In particular, in a deuterium-containing compound of general formula (I), the abundance of deuterium at each deuteration position of the compound of general formula (I) is greater than 10%, 20%, 30%, 40%, 50%, 60%, 70%, or 80% at said position, preferably greater than 90%, 95%, 96%, or 97%, and more preferably greater than 98% or 99%. It is understood that the abundance of deuterium at each deuteration position is independent of the abundance of deuterium at other deuteration positions.

[0111] Selective incorporation of one or more deuterium atoms into compounds of general formula (I) can alter the physicochemical properties (e.g., acidity [CL Perrin et al., J. Am. Chem. Soc. 2007, 129, 4490], basicity [CL Perrin et al., J. Am. Chem. Soc. 2005, 127, 9641], lipophilicity [B. Testa et al., Int. J. Pharm. 1984, 19(3), 271], etc.) and / or metabolic profile of the molecule, resulting in a change in the ratio of parent compound to metabolites or the amount of metabolites formed. Such changes can confer certain therapeutic advantages and may therefore be desirable in some situations. A decrease in the rate of metabolism and metabolic switching, resulting in an altered ratio of metabolites, has been reported (AEMutlib et al., Toxicol. Appl. Pharmacol. 2000, 169, 102). These changes in exposure to the parent drug and metabolites can have important consequences for the pharmacodynamics, tolerability, and efficacy of deuterium-containing compounds of general formula (I). In some cases, deuterium substitution reduces or eliminates the formation of undesirable or toxic metabolites and enhances the formation of desirable metabolites (e.g., Nevirapine: AM Sharma et al., Chem. Res. Toxicol. 2013, 26, 410; Efavirenz: AEMutlib et al., Toxicol. Appl. Pharmacol. 2000, 169, 102). In other cases, the primary effect of deuteration is to decrease the rate of systemic clearance, thereby increasing the biological half-life of the compound. Potential clinical benefits include the ability to maintain similar systemic exposure with reduced peak levels and increased trough levels. This may result in fewer side effects and enhanced efficacy, depending on the pharmacokinetic / pharmacodynamic relationship of the particular compound. ML-337 (CJ Wenthur et al., J. Med. Chem. 2013, 56, 5208) and odanacatib (K. Kassahun et al., WO2012 / 112363) are examples of this deuterium effect.Still other cases have been reported in which a decrease in metabolic rate results in increased drug exposure without altering systemic clearance rate (e.g., Rofecoxib: F. Schneider et al., Arzneim. Forsch. / Drug. Res. 2006, 56, 295; Telaprevir: F. Maltais et al., J. Med. Chem. 2009, 52, 7993). Deuterated drugs that exhibit this effect can reduce dosage requirements (e.g., fewer doses or lower doses to achieve the desired effect) and / or produce a lower metabolic burden.

[0112] The compound of general formula (I) may have multiple potential attack sites for metabolism. To optimize the above effects on physicochemical properties and metabolic profiles, a deuterium-containing compound of general formula (I) with one or more specific patterns of deuterium-hydrogen exchange can be selected. In particular, the deuterium atoms of the deuterium-containing compound of general formula (I) are bonded to carbon atoms and / or located at those positions of the compound of general formula (I), and they are, for example, cytochrome P 450 It is the site of attack for metabolic enzymes such as

[0113] In another embodiment, the present invention relates to deuterium-containing compounds of general formula (I) having 1, 2, 3 or 4 deuterium atoms, in particular 1, 2 or 3 deuterium atoms.

[0114] When the plural of the terms compounds, salts, polymorphs, hydrates, solvates, etc. is used herein, this is taken to mean a single compound, salt, polymorph, isomer, hydrate, solvate, etc.

[0115] By "stable compound" or "stable structure" is meant a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.

[0116] The compounds of the present invention may contain one or more asymmetric centers, depending on the position and nature of the various desired substituents.One or more asymmetric carbon atoms may be present in (R) or (S) configuration, and in the case of a single asymmetric center, it may result in a racemic mixture, and in the case of multiple asymmetric centers, it may result in a diastereomeric mixture.In certain cases, asymmetry may also exist due to the restricted rotation around a given bond, for example, the central bond adjacent to the two substituted aromatic rings of a certain compound.

[0117] Preferred isomers are those which result in the more desirable biological activity. These separated, pure, or partially purified isomers or racemic mixtures of the compounds of the present invention are also included within the scope of the present invention. Purification and separation of such materials can be accomplished by standard techniques known in the art.

[0118] Optical isomers can be obtained by resolving racemic mixtures according to conventional methods, for example, by forming diastereomeric salts or covalent diastereomers with optically active acids or bases. Examples of suitable acids are tartaric acid, diacetyltartaric acid, ditoluoyltartaric acid, and camphorsulfonic acid. Diastereomeric mixtures can be separated into their individual diastereomers based on their physical and / or chemical differences by methods known in the art, such as chromatography or fractional crystallization. The optically active base or acid is then liberated from the separated diastereomeric salts. Different methods for separating optical isomers include the use of chiral chromatography (e.g., HPLC columns using chiral phases) with or without conventional derivatization, optimally selected to maximize the separation of enantiomers. Suitable HPLC columns using chiral phases are commercially available, for example, those manufactured by Daicel, such as Chiracel OD and Chiracel OJ, among others, all of which are routinely selectable. Enzymatic separation, with or without derivatization, is also useful. The optically active compounds of this invention can also be obtained by chiral syntheses utilizing optically active starting materials.

[0119] To distinguish different types of isomers from one another, reference is made to IUPAC Rules Section E (Pure Appl Chem 45, 11-30, 1976).

[0120] The present invention includes all possible stereoisomers of the compounds of the present invention, either as a single stereoisomer or as any mixture of said stereoisomers, e.g., as (R)- or (S)-isomers, in any ratio. Isolation of a single stereoisomer of a compound of the present invention, e.g., a single enantiomer or a single diastereomer, is achieved by any suitable state-of-the-art method, such as chromatography, in particular, e.g., chiral chromatography.

[0121] Additionally, some of the compounds of the present invention can exist as tautomers. For example, a compound of the present invention can contain a pyridone moiety and can exist as a pyridone, as a hydroxypyridine, or as a mixture of any amount of the two tautomers, i.e.: [ka]

[0122] The present invention includes all possible tautomers of the compounds of the present invention, either as single tautomers or as any mixture of said tautomers, in any proportion.

[0123] Additionally, the compounds of the present invention can exist as N-oxides, which is defined as at least one nitrogen in a compound of the present invention being oxidized. The present invention includes all such possible N-oxides.

[0124] The present invention also encompasses useful forms of the compounds of the present invention, such as metabolites, hydrates, solvates, prodrugs, salts, particularly pharmaceutically acceptable salts, and / or coprecipitates.

[0125] The compounds of the present invention can exist as hydrates or solvates, and the compounds of the present invention contain polar solvents, particularly water, methanol or ethanol, as structural elements of the crystal lattice of the compounds. The amount of polar solvent, particularly water, can be stoichiometric or non-stoichiometric. In the case of stoichiometric solvates, for example, hydrates, hemi-, (semi-), mono-, sesqui-, di-, tri-, tetra-, penta-, etc. solvates or hydrates are possible. The present invention includes all such hydrates or solvates.

[0126] Furthermore, the compounds of the present invention can exist in free form, for example as a free base, or as a free acid, or as a zwitterion, or in the form of a salt, which may be any salt, organic or inorganic addition salt, in particular any pharmaceutically acceptable organic or inorganic addition salt customarily used in pharmacy or used, for example, to isolate or purify the compounds of the present invention.

[0127] The term "pharmaceutically acceptable salt" refers to an inorganic or organic acid addition salt of a compound of the present invention. See, for example, S. M. Berge et al., "Pharmaceutical Salts," J. Pharm. Sci. 1977, 66, 1-19.

[0128] Suitable pharmaceutically acceptable salts of the compounds of the present invention are, for example, acid addition salts of the compounds of the present invention which have a nitrogen atom in the chain or in the ring and which are sufficiently basic, for example, inorganic acids, or "mineral acids", such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfamic acid, bisulfuric acid, phosphoric acid, or nitric acid, for example, organic acids such as formic acid, acetic acid, acetoacetic acid, pyruvic acid, trifluoroacetic acid, propionic acid, butyric acid, hexanoic acid, heptanoic acid, undecanoic acid, lauric acid, benzoic acid, salicylic acid, 2-(4-hydroxybenzoyl)-benzoic acid, camphoric acid, cinnamic acid, cyclopentanepropionic acid, digluconic acid, 3-hydroxy-2-naphthoic acid, nicotine Acid addition salts with acetic acid, pamoic acid, pectinic acid, 3-phenylpropionic acid, pivalic acid, 2-hydroxyethanesulfonic acid, itaconic acid, trifluoromethanesulfonic acid, dodecylsulfuric acid, ethanesulfonic acid, benzenesulfonic acid, paratoluenesulfonic acid, methanesulfonic acid, 2-naphthalenesulfonic acid, naphthalenedisulfonic acid, camphorsulfonic acid, citric acid, tartaric acid, stearic acid, lactic acid, oxalic acid, malonic acid, succinic acid, malic acid, adipic acid, alginic acid, maleic acid, fumaric acid, D-gluconic acid, mandelic acid, ascorbic acid, glucoheptanoic acid, glycerophosphate, aspartic acid, sulfosalicylic acid, and thiocyanic acid.

[0129] Further, other stable pharmaceutically acceptable salts of the compounds of the present invention that are sufficiently acidic are alkali metal salts, such as sodium or potassium salts, alkaline earth metal salts, such as calcium, magnesium or strontium salts, or aluminum or zinc salts, from ammonia or organic primary, secondary or tertiary amines having 1 to 20 carbon atoms, such as ethylamine, diethylamine, triethylamine, ethyldiisopropylamine, monoethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, dimethylaminoethanol, diethylaminoethanol, tris(hydroxymethyl)aminomethane, procaine, dibenzylamine, N-methyl amine, Ammonium salts derived from holin, arginine, lysine, 1,2-ethylenediamine, N-methylpiperidine, N-methylglucamine, N,N-dimethylglucamine, N-ethylglucamine, 1,6-hexanediamine, glucosamine, sarcosine, serinol, 2-amino-1,3-propanediol, 3-amino-1,2-propanediol, 4-amino-1,2,3-butanetriol, or salts with quaternary ammonium ions having 1 to 20 carbon atoms, such as tetramethylammonium, tetraethylammonium, tetra(n-propyl)ammonium, tetra(n-butyl)ammonium, N-benzyl-N,N,N-trimethylammonium, choline, or benzalkonium.

[0130] Those skilled in the art will further recognize that acid addition salts of the claimed compounds can be prepared by reacting the compounds with the appropriate inorganic or organic acid via any of a number of known methods. Alternatively, alkali metal and alkaline earth metal salts of acidic compounds of the invention are prepared by reacting the compounds with the appropriate base via a variety of known methods.

[0131] The present invention includes all possible salts of the compounds of the present invention, either as a single salt or as any mixture of said salts in any ratio.

[0132] When compounds are referred to in the present text, particularly in the "Experimental Part", for the synthesis of intermediates and examples of the present invention in the form of salts with the corresponding bases or acids, the exact stoichiometry of said salt forms obtained by the respective preparation and / or purification process is in most cases unknown.

[0133] Unless otherwise specified, the term "hydrochloride salt," "trifluoroacetate salt," "sodium salt," or "xHCl," "xCF3COOH," "xNa + A suffix to a chemical name or structural formula for a salt, such as "," for example, refers to the salt form, and does not specify the stoichiometry of that salt form.

[0134] This also applies if a synthetic intermediate or an example compound or a salt thereof is obtained by the described preparation and / or purification process as a solvate, such as a hydrate, with unknown stoichiometry (if defined).

[0135] Furthermore, the present invention includes all possible crystalline forms or polymorphs of the compounds of the present invention, either as a single polymorph or as a mixture of two or more polymorphs in any ratio.

[0136] Furthermore, the present invention also includes prodrugs of compounds according to the present invention. The term "prodrug" as used herein means compounds which may themselves be biologically active or inactive, but which are converted (e.g., metabolically or hydrolytically) into compounds according to the present invention during their residence in the body.

[0137] The present invention further includes all possible cyclodextrin inclusion compounds, namely alpha-, beta-, or gamma-cyclodextrin, hydroxypropyl-beta-cyclodextrin, methyl beta-cyclodextrin.

[0138] According to a second embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1is a halogen atom or hydroxy, cyano, nitro, C1-C4-alkyl, (phenyl)-(C1-C2-alkyl)-, C1-C4-haloalkyl, C1-C4-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C4-haloalkoxy, -N(R) 5 (R 6 phenyl or pyridinyl group, optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)- and (phenyl)-(C1-C2-alkoxy)- groups is optionally substituted once or twice by fluorine, chlorine and bromine atoms or by substituents independently selected from the group consisting of methyl, trifluoromethyl and methoxy, or two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O- and -O-CF2-O-; or R 1 represents a pyrazolyl group, optionally substituted one or two times with a halogen atom or with substituents independently selected from the group consisting of cyano, C1-C2-alkyl and C1-C2-alkoxy; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a group selected from methyl and -NH; R 4is a halogen atom or cyano, nitro, C1-C4-alkyl, (phenyl)-(C1-C2-alkyl)-, (5-membered heteroaryl)-(C1-C2-alkyl)-, (C3-C7-cycloalkyl)-(C1-C2-alkyl)-, ((R 9 )O)-(C1-C4-alkyl)-, C1-C4-haloalkyl, C3-C7-cycloalkyl, -OR 9 , -N(R 10 )(R 11 ), ((R 10 )(R 11 )N)-(C1-C3-alkyl)-, -C(=O)-N(R 12 )(R 13 ), S(=O) n -R 14 , -C(=O)R 14 , -C(=O)-OR 17 and a 5-membered heteroaryl group which may itself be substituted by one or two methyl groups; or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O- and -O-CF2-O-; R 5 and R 6 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl and (C-C-alkyl)-C(=O)-, or R 5 and R 6 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one or two times with fluorine, chlorine and bromine atoms or with substituents independently selected from the group consisting of oxo, hydroxy, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; R 9 represents a hydrogen atom or C1-C4-alkyl, (phenyl)-(C1-C2-alkyl)-, C1-C4-haloalkyl, C2-C3-hydroxyalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(R 18 )(R 19 )-C(=O)-OR 17 , -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ), -C(=O)-N(R 20 )(R 21 ) and phenyl, wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)- group and the phenyl group itself may be substituted one or two times with fluorine, chlorine and bromine atoms or with substituents independently selected from the group selected from cyano, methyl, trifluoromethyl and methoxy; R 10 and R 11 is independently in each occurrence a hydrogen atom or C1-C2-alkyl, C1-C2-haloalkyl, C2-C3-hydroxyalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((R 22 )(R 23 )N)—C2-alkyl, (C3-C7-cycloalkyl)-(C1-C2-alkyl)-, (C1-C2-alkyl)-C(═O)-, C3-C7-cycloalkyl, (C3-C7-cycloalkyl)-C(═O)-, (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(═O)- and (phenyl)-(C1-C2-alkyl)-OC(═O)-, wherein C3-C7-cycloalkyl, and C3-C7-cycloalkyl in the (C3-C7-cycloalkyl)-(C1-C2-alkyl)- and (C3-C7-cycloalkyl)-C(=O)- groups, are optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group selected from cyano, C1-C2-alkyl and C1-C2-haloalkyl, and the phenyl group in said (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-OC(=O)- groups may be substituted one or two times by fluorine, chlorine and bromine atoms or by substituents independently selected from groups selected from methyl, trifluoromethyl and methoxy, or R 10 and R 11 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group or a bicyclic nitrogen-containing 5- to 10-membered heterocycloalkyl group, which may be selected from the group consisting of halogen atoms or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (C-C-alkyl)-C(=O)-, C-C-alkoxy, -N(R 22 )(R 23 ), and monocyclic 4- to 7-membered heterocycloalkyl groups; R 12 and R 13 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-haloalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-C-alkyl-, (C-C-haloalkoxy)-C-C-alkyl-, (phenoxy)-C-C-alkyl-, C-C-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one or two times by each substituent independently selected from halogen atoms or groups selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, and the phenyl group in the (phenoxy)-C2-C3-alkyl group and the (phenyl)-(C1-C3-alkyl)- group may be substituted one or two times by fluorine, chlorine and bromine atoms or by substituents independently selected from the group consisting of cyano, methyl, trifluoromethyl and methoxy, or R 12 and R 13 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one or two times with a halogen atom or with substituents independently selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 14 represents a group selected from C1-C2-alkyl, C1-C2-haloalkyl and phenyl, wherein the phenyl group is optionally substituted one or two times with fluorine, chlorine and bromine atoms, or with substituents independently selected from the group selected from methyl, trifluoromethyl and methoxy; R 17 represents a C1-C4-alkyl group; R 18 and R 19 represents, independently in each occurrence, a hydrogen atom or a C1-C2-alkyl group; R 20 is a hydrogen atom or a C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C5-C 11 -represents a group selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 5- to 10-membered heterocycloalkyl, phenyl, naphthyl, and 5- to 10-membered heteroaryl; wherein the C1-C6-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, bicyclic C5-C 11 -optionally substituted one, two or three times with substituents independently selected from groups selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 5- to 10-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted one or two times with substituents independently selected from groups selected from fluorine, chlorine and bromine atoms, or methyl, trifluoromethyl and methoxy; and C3-C7-cycloalkyl, bicyclic C5-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 5- to 10-membered heterocycloalkyl may be optionally substituted 1, 2 or 3 times by halogen atoms or substituents independently selected from cyano, oxo, hydroxy, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; and the phenyl, naphthyl and 5-10 membered heteroaryl groups are each independently selected from the group consisting of a halogen atom or cyano, C1-C2-alkyl, C1-C2-haloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and optionally substituted one, two or three times with each substituent independently selected from the group R 21 represents a hydrogen atom or a C1-C2-alkyl group, or R 20 and R 21may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (phenyl)-(C-C-alkyl)-, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of: R 22 and R 23 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 24 and R 25 represents, independently of each occurrence, a hydrogen atom or a C1-C2-alkyl group, and n represents an integer of 0, 1, or 2. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0139] According to a third embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 represents fluorine, chlorine and bromine atoms, or hydroxy, cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C2-fluoroalkoxy and -N(R 5 )(R 6 phenyl or pyridinyl group, optionally substituted one, two or three times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form a divalent group selected from —(CH)—, —O—CH—O—, and —O—CF—O—; or R 1 represents a pyrazolyl group optionally substituted with one methyl group; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a group selected from methyl and -NH; R 4 is a halogen atom or cyano, C1-C3-alkyl, ((R 9 )O)—(C1-C3-alkyl)-, C1-C3-fluoroalkyl, —OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ), S(=O) n -R 14 and -C(=O)-OR 17 represents a phenyl or pyridinyl group optionally substituted 1, 2 or 3 times with substituents independently selected from the group and two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-; R 5 and R 6 represents, independently at each occurrence, a hydrogen atom or a C1-C2-alkyl group, or R 5 and R 6together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one or two times with a fluorine atom or with substituents independently selected from groups selected from hydroxy and C1-C2-alkyl; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; R 9 is a hydrogen atom or C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, C2-hydroxyalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(R 18 )(R 19 )-C(=O)-OR 17 , -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ), -C(=O)-N(R 20 )(R 21 ) and phenyl, wherein the phenyl group within said benzyl group and said phenyl group itself may be substituted one or two times with each substituent independently selected from fluorine and chlorine atoms, or a group selected from cyano and methyl; R 10 and R 11 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, (C-C-cycloalkyl)-(C-C-alkyl)- (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-cycloalkyl-(C=O)-, (phenyl)-(C-C-alkyl)-, (phenyl)-(C-C-alkyl)-C(=O)- and (phenyl)-(C-C-alkyl)-OC(=O)-, wherein C3-C7-cycloalkyl, and C3-C5-cycloalkyl in said (C3-C5-cycloalkyl)-(C1-C2-alkyl)-, and C3-C7-cycloalkyl in the C3-C7-cycloalkyl-(C=O)- group, are optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group selected from cyano, C1-C2-alkyl and C1-C2-fluoroalkyl, and the phenyl group in said (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-OC(=O)- groups may be substituted one or two times by each substituent independently selected from fluorine atoms, chlorine atoms and methyl groups, or R 10 and R 11 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group consisting of cyano, oxo, C-C-alkyl, C-C-fluoroalkyl and (C-C-alkyl)-C(=O)-; R 12 and R 13 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-C-alkyl-, (C-C-fluoroalkoxy)-C-C-alkyl-, (phenoxy)-C-C-alkyl-, C-C-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one or two times by a fluorine atom or by each substituent independently selected from the group selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, and the phenyl group in the (phenoxy)-C2-C3-alkyl group and the (phenyl)-(C1-C2-alkyl)- group may be substituted one or two times by fluorine and chlorine atoms or by substituents independently selected from the group consisting of methyl, trifluoromethyl and methoxy, or R 12 and R 13 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one or two times with a halogen atom or with substituents independently selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 14 represents a group selected from methyl and trifluoromethyl; R 17 represents a C1-C2-alkyl group; R 18 and R 19 represents, independently at each occurrence, a hydrogen atom or a methyl group; R 20 represents a hydrogen atom or a group selected from optionally substituted C1-C3-alkyl, unsubstituted C4-C6-alkyl, prop-2-ynyl, methoxy, C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl and 5- to 10-membered heteroaryl, wherein the C1-C3-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted 1- to 2-times with substituents independently selected from fluorine atoms, chlorine atoms, and methyl groups; and the C3-C6-cycloalkyl, adamantyl and monocyclic 4- to 7-membered heterocycloalkyl groups are optionally substituted one, two or three times by fluorine atoms or by substituents independently selected from the group consisting of oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, and the phenyl and 5- to 10-membered heteroaryl groups are substituted with fluorine and chlorine atoms, or with cyano, C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and optionally substituted one, two or three times with each substituent independently selected from the group R 21 represents a hydrogen atom or a C1-C2-alkyl group, or R 20 and R 21 may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-fluoroalkyl, benzyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-fluoroalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of: R 22 and R 23 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 24 and R 25 represents, independently of each occurrence, a hydrogen atom or a C1-C2-alkyl group, and n represents the integer 2. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0140] According to a fourth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 represents a phenyl or pyridinyl group optionally substituted one or two times by a fluorine atom, a chlorine atom, or a bromine atom, or by substituents independently selected from the group consisting of cyano, methyl, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy, and trifluoromethoxy; or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form the divalent group -O-CF2-O-; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a group selected from methyl and -NH; R 4 is a halogen atom or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ) and -C(=O)-OR 17 represents a phenyl or pyridinyl group optionally substituted one or two times with substituents independently selected from the group consisting of: R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; R 9is a hydrogen atom or C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ), -C(=O)-N(R 20 )(R 21 ) and phenyl, wherein the phenyl group within said benzyl group and said phenyl group itself may be substituted one or two times with each substituent independently selected from fluorine and chlorine atoms, or a group selected from cyano and methyl; R 10 and R 11 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, (C-C-cycloalkyl)-(C-C-alkyl)-, C-C-cycloalkyl and (phenyl)-(C-C-alkyl)-OC(=O)-, wherein C3-C7-cycloalkyl, and C3-C5-cycloalkyl within said (C3-C5-cycloalkyl)-(C1-C2-alkyl)- group, is optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group selected from cyano, methyl and C1-fluoroalkyl, and the phenyl group in said (phenyl)-(C1-C2-alkyl)-OC(=O)- group is optionally substituted one or two times with each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group, or R 10 and R 11 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted one or two times with a fluorine atom or with substituents independently selected from groups selected from cyano, methyl, and C1-fluoroalkyl; R 12 and R 13represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-C-alkyl-, (C-C-fluoroalkoxy)-C-C-alkyl-, (phenoxy)-C-C-alkyl, C-C-cycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl is optionally substituted one or two times with each substituent independently selected from a fluorine atom or a methyl group, and the phenyl group in said (phenoxy)-C2-C3-alkyl group and said (phenyl)-(C1-C2-alkyl)- group may be substituted one or two times with a fluorine atom and a chlorine atom or with each substituent independently selected from methyl, trifluoromethyl and methoxy; R 17 represents a C1-C2-alkyl group; R 18 and R 19 represents, independently at each occurrence, a hydrogen atom or a methyl group; R 20 represents a hydrogen atom or a group selected from C1-C3-alkyl and phenyl, wherein the C1-C3-alkyl group is optionally substituted one or two times with a fluorine atom or with a substituent independently selected from the group consisting of hydroxy, C1-C3-alkoxy and phenyl, and the phenyl itself is optionally substituted one or two times with a substituent independently selected from the group consisting of a fluorine atom, a chlorine atom and a methyl group, and the phenyl group is optionally substituted one, two or three times with fluorine and chlorine atoms or with substituents independently selected from groups selected from methyl, trifluoromethyl, methoxy and trifluoromethoxy, and R 21 represents a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0141] According to a fifth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 represents a phenyl or pyridinyl group optionally substituted one or two times by a fluorine atom, a chlorine atom, or a bromine atom, or by substituents independently selected from the group consisting of cyano, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy, and trifluoromethoxy; or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form the divalent group -O-CF2-O-; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a group selected from methyl and -NH; R 4 is a halogen atom or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ) and -C(=O)-OR 17 represents a phenyl or pyridinyl group optionally substituted one or two times with substituents independently selected from the group consisting of: R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; R 9is a hydrogen atom or C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ), -C(=O)-N(R 20 )(R 21 ) and phenyl, wherein the phenyl group within said benzyl group and said phenyl group itself may be substituted one or two times with each substituent independently selected from fluorine and chlorine atoms, or a group selected from cyano and methyl; R 10 and R 11 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, (C-C-cycloalkyl)-(C-C-alkyl)-, C-C-cycloalkyl and (phenyl)-(C-C-alkyl)-OC(=O)-, wherein C3-C7-cycloalkyl, and C3-C5-cycloalkyl within said (C3-C5-cycloalkyl)-(C1-C2-alkyl)- group, is optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group selected from cyano, methyl and C1-fluoroalkyl, and the phenyl group in said (phenyl)-(C1-C2-alkyl)-OC(=O)- group is optionally substituted one or two times with each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group, or R 10 and R 11 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted one or two times with a fluorine atom or with substituents independently selected from groups selected from cyano, methyl, and C1-fluoroalkyl; R 12 and R 13represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-C-alkyl-, (C-C-fluoroalkoxy)-C-C-alkyl-, (phenoxy)-C-C-alkyl-, C-C-cycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl is optionally substituted one or two times with each substituent independently selected from a fluorine atom or a methyl group, and the phenyl group in said (phenoxy)-C2-C3-alkyl-group and said (phenyl)-(C1-C2-alkyl)-group may be substituted one or two times with fluorine and chlorine atoms or with substituents independently selected from groups selected from methyl, trifluoromethyl and methoxy; R 17 represents a C1-C2-alkyl group; R 18 and R 19 represents, independently at each occurrence, a hydrogen atom or a methyl group; R 20 represents a hydrogen atom or a group selected from C1-C3-alkyl and phenyl, wherein the C1-C3-alkyl group is optionally substituted one or two times with a fluorine atom or with a substituent independently selected from the group consisting of hydroxy, C1-C3-alkoxy and phenyl, and the phenyl itself is optionally substituted one or two times with a substituent independently selected from the group consisting of a fluorine atom, a chlorine atom and a methyl group, and the phenyl group is optionally substituted one, two or three times with fluorine and chlorine atoms or with substituents independently selected from groups selected from methyl, trifluoromethyl, methoxy and trifluoromethoxy, and R 21 represents a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0142] According to a sixth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a group selected from methyl and -NH; R 4 is the base [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; R 9 is a hydrogen atom or C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ), -C(=O)-N(R 20 )(R 21) and phenyl, wherein the phenyl group within said benzyl group and said phenyl group itself may be substituted one or two times with each substituent independently selected from fluorine and chlorine atoms, or a group selected from cyano and methyl; R 10 and R 11 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl, C3-C7-cycloalkyl and (benzyl)-OC(=O)-, wherein C3-C7-cycloalkyl is optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group selected from methyl and trifluoromethyl, and the phenyl group in the (benzyl)-OC(=O)- group is optionally substituted once or twice with each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group; or R 10 and R 11 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted one or two times with a fluorine atom or with substituents independently selected from groups selected from cyano, methyl, and trifluoromethyl; R 12 and R 13 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-alkyl-, (C-C-fluoroalkoxy)-C-alkyl-, (phenoxy)-C-alkyl-, C-C-cycloalkyl and (phenyl)-(C-C-alkyl)-, wherein the phenyl group in said (phenoxy)-C2-alkyl-group and said (phenyl)-(C1-C2-alkyl)-group may be substituted one or two times with fluorine and chlorine atoms or with substituents independently selected from the group consisting of methyl, trifluoromethyl and methoxy; R 17 represents a C1-C2-alkyl group; R 18 and R 19 represents, independently at each occurrence, a hydrogen atom or a methyl group; R 20 represents a group selected from benzyl and phenyl, wherein the phenyl group and the phenyl group in the benzyl group are optionally substituted once or twice with each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group; R 21 represents a hydrogen atom or a methyl group, Y 1 represents -C(H)=, -C(F)=, -C(Cl)=, -C(CN)= or -N=; Y 2 represents -C(H)= or -N=; Y 3 is -C(R 27 )= or -N=, However, Y 2 If represents -N=, then Y 3 -C(R 27 )=, Y 3 If represents -N=, then Y 2 represents -C(H)=; R 26 represents a fluorine, chlorine or bromine atom or a group selected from methyl, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy, and R 27 is a halogen atom or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ) and -C(=O)-OR 17 represents a group selected from the group and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0143] According to a seventh embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a group selected from methyl and -NH; R 4 is the base [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; R 9 represents a hydrogen atom or a group selected from C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl and phenyl, wherein the phenyl group within said benzyl group and said phenyl group itself may be substituted one or two times with each substituent independently selected from fluorine and chlorine atoms, or a group selected from cyano and methyl; R 10 and R 11 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (benzyl)-OC(=O)-, and wherein the phenyl group in said (benzyl)-OC(=O)- group is optionally substituted one or two times with each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group; or R 10 and R 11 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted one or two times with a fluorine atom or with substituents independently selected from groups selected from cyano, methyl, and trifluoromethyl; R 12 and R 13 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, (C-C-alkoxy)-C-alkyl-, (C-C-fluoroalkoxy)-C-alkyl-, (phenoxy)-C-alkyl-, C-C-cycloalkyl and (phenyl)-(C-C-alkyl)-; Y 1 represents -C(H)=, -C(F)=, -C(Cl)= or -N=; Y 2 represents -C(H)= or -N=; Y 3 is -C(R 27 )= or -N=, However, Y 2 If represents -N=, then Y 3 -C(R 27 )=, Y 3 If represents -N=, then Y 2 represents -C(H)=; R 26 represents a fluorine, chlorine or bromine atom or a group selected from difluoromethyl, methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy, and R 27 is a halogen atom or -OR 9 , -N(R 10 )(R 11 ) and -C(=O)-N(R 12 )(R13 represents a group selected from and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0144] According to an eighth embodiment of the first aspect, the present invention provides a compound of general formula (I), wherein: R 1 is a halogen atom or cyano, nitro, C1-C6-alkyl, (phenyl)-(C1-C3-alkyl)-, C1-C6-haloalkyl, C1-C6-alkoxy, (phenyl)-(C1-C3-alkoxy)-, C1-C6-haloalkoxy, -N(R) 5 (R 6 phenyl or 6-membered heteroaryl group, optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of wherein the phenyl group in the (phenyl)-(C1-C3-alkyl)- and (phenyl)-(C1-C3-alkoxy)- groups is optionally substituted once or twice by a halogen atom or by a substituent independently selected from the group consisting of cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy, or two substituents attached to adjacent carbon atoms of said phenyl or 6-membered heteroaryl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -(CH2)2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O-, -O-CF2-O-, -O-CH2-CF2-O-, and -O-CF2-CF2-O-; or R 1 represents a 5-membered heteroaryl group optionally substituted one or two times with a halogen atom or with substituents independently selected from the group consisting of cyano, C1-C3-alkyl, and C1-C3-alkoxy; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a group selected from methyl and -NH; R 4 is a halogen atom or cyano, nitro, C1-C6-alkyl, (phenyl)-(C1-C3-alkyl)-, (5-membered heteroaryl)-(C1-C3-alkyl)-, C1-C6-hydroxyalkyl, C1-C6-haloalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ), S(=O) n -R 14 and a 5-membered heteroaryl group which may itself be substituted by one or two methyl groups; or two substituents attached to adjacent carbon atoms of said phenyl group or 6-membered heteroaryl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -(CH2)2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O-, -O-CF2-O-, -O-CH2-CF2-O-, and -O-CF2-CF2-O-; R 5 and R 6 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl and (phenyl)-(C-C-alkyl)-, or R 5 and R 6together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one, two or three times with halogen atoms or with substituents independently selected from the group consisting of oxo, hydroxy, C1-C4-alkyl, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl and C1-C4-alkoxy; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a group selected from -C(=O)-NH2 and -S(=O)2-NH2; R 9 represents a hydrogen atom or C1-C6-alkyl, (phenyl)-(C1-C3-alkyl)-, C1-C6-haloalkyl, C2-C4-hydroxyalkyl, (C1-C3-alkoxy)-C2-C3-alkyl-, ((C1-C3-alkyl)-C(=O)-O)-C2-C3-alkyl-, -C(R 18 )(R 19 )-C(=O)-OR 17 , -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ) and phenyl, wherein the phenyl group in the (phenyl)-(C1-C3-alkyl)- group and the phenyl group itself may be substituted one or two times with a halogen atom or a substituent independently selected from the group selected from cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy; R 10 and R 11 is independently in each occurrence a hydrogen atom or C1-C4-alkyl, C1-C4-haloalkyl, C2-C4-hydroxyalkyl, (C1-C3-alkoxy)-C2-C3-alkyl-, ((R 22 )(R 23)N)—C2-C3-alkyl, (C1-C4-alkyl)-C(═O)—, C3-C7-cycloalkyl, (C3-C7-cycloalkyl)-C(═O)—, (phenyl)-(C1-C3-alkyl)-, (phenyl)-(C1-C3-alkyl)-C(═O)— and (phenyl)-(C1-C3-alkyl)-OC(═O)—, wherein the phenyl group in said (phenyl)-(C1-C3-alkyl)-, (phenyl)-(C1-C3-alkyl)-C(=O)- and (phenyl)-(C1-C3-alkyl)-OC(=O)- groups is optionally substituted one or two times by a halogen atom or by a substituent independently selected from the group consisting of cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy, or R 10 and R 11 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group or a bicyclic nitrogen-containing 6- to 11-membered heterocycloalkyl group, which may be selected from the group consisting of halogen atoms or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, -N(R 22 )(R 23 ), and monocyclic 4- to 7-membered heterocycloalkyl groups; R 12 and R 13 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-haloalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-C-alkyl-, C-C-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one, two or three times by halogen atoms or by substituents independently selected from oxo, hydroxy, C1-C4-alkyl, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl and C1-C4-alkoxy, or R 12 and R 13 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one, two or three times with halogen atoms or with substituents independently selected from the group consisting of oxo, hydroxy, C1-C4-alkyl, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl and C1-C4-alkoxy; R 14 represents a group selected from C1-C4-alkyl and C1-C4-haloalkyl; R 17 represents a C1-C4-alkyl group; R 18 and R 19 represents, independently in each occurrence, a hydrogen atom or a C1-C4-alkyl group; R 20 is a hydrogen atom or C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C6-C 11 -represents a group selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 11-membered heterocycloalkyl, phenyl, naphthyl, and 5- to 10-membered heteroaryl; wherein the C1-C6-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, bicyclic C6-C 11-optionally substituted one, two or three times with substituents independently selected from groups selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 11-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted one or two times with halogen atoms or substituents independently selected from groups selected from cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino, and trifluoromethoxy; where C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl and bicyclic 6- to 11-membered heterocycloalkyl are optionally substituted one, two or three times by halogen atoms or by substituents independently selected from cyano, oxo, hydroxy, C-C-alkyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl and C-C-alkoxy; and the phenyl, naphthyl and 5-10 membered heteroaryl groups are each independently selected from the group consisting of a halogen atom or cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and optionally substituted one, two or three times with each substituent independently selected from the group R 21 represents a hydrogen atom or a C1-C4-alkyl group, or R 20 and R 21 may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (phenyl)-(C-C-alkyl)-, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-haloalkoxy, -N(R22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of: R 22 and R 23 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 24 and R 25 represents, independently at each occurrence, a hydrogen atom or a C1-C4-alkyl group, and n represents an integer of 0, 1, or 2. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0145] According to a ninth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 is a halogen atom or cyano, nitro, C1-C4-alkyl, (phenyl)-(C1-C2-alkyl)-, C1-C4-haloalkyl, C1-C4-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C4-haloalkoxy, -N(R) 5 (R 6 phenyl or pyridinyl group, optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)- and (phenyl)-(C1-C2-alkoxy)- groups is optionally substituted once or twice by fluorine, chlorine and bromine atoms or by substituents independently selected from the group consisting of methyl, trifluoromethyl and methoxy, or two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O- and -O-CF2-O-; or R 1 represents a pyrazolyl group, optionally substituted one or two times with a halogen atom or with substituents independently selected from the group consisting of cyano, C1-C2-alkyl and C1-C2-alkoxy; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a group selected from methyl and -NH; R 4 is a halogen atom or cyano, nitro, C1-C4-alkyl, (phenyl)-(C1-C2-alkyl)-, (5-membered heteroaryl)-(C1-C2-alkyl)-, C1-C4-hydroxyalkyl, C1-C4-haloalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ), S(=O) n -R 14 and a 5-membered heteroaryl group which may itself be substituted by one or two methyl groups; or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O- and -O-CF2-O-; R 5 and R 6 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl and (C-C-alkyl)-C(=O)-, or R 5 and R 6 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one or two times with fluorine, chlorine and bromine atoms or with substituents independently selected from the group consisting of oxo, hydroxy, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; R 9 is a hydrogen atom or C1-C4-alkyl, (phenyl)-(C1-C2-alkyl)-, C1-C4-haloalkyl, C2-C3-hydroxyalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(R 18 )(R 19 )-C(=O)-OR 17 , -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ) and phenyl, wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)- group and the phenyl group itself may be substituted one or two times with fluorine, chlorine and bromine atoms or with substituents independently selected from the group selected from methyl, trifluoromethyl and methoxy; R 10 and R 11 is independently in each occurrence a hydrogen atom or C1-C2-alkyl, C1-C2-haloalkyl, C2-C3-hydroxyalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((R 22 )(R 23 )N)—C2-alkyl, (C1-C2-alkyl)-C(═O)—, C3-C5-cycloalkyl, (C3-C5-cycloalkyl)-C(═O)—, (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(═O)— and (phenyl)-(C1-C2-alkyl)-OC(═O)—, wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-OC(=O)- groups is optionally substituted one or two times by a fluorine atom, a chlorine atom and a bromine atom or by a group selected from methyl, trifluoromethyl and methoxy, or R 10 and R 11 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group or a bicyclic nitrogen-containing 6- to 10-membered heterocycloalkyl group, which may be selected from the group consisting of halogen atoms or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (C-C-alkyl)-C(=O)-, C-C-alkoxy, -N(R 22 )(R 23 ), and monocyclic 4- to 7-membered heterocycloalkyl groups; R 12 and R13 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-haloalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-C-alkyl-, C-C-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one or two times by each substituent independently selected from halogen atoms or groups selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, or R 12 and R 13 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one or two times with a halogen atom or with substituents independently selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 14 represents a group selected from C1-C2-alkyl and C1-C2-haloalkyl; R 17 represents a C1-C4-alkyl group; R 18 and R 19 represents, independently in each occurrence, a hydrogen atom or a C1-C2-alkyl group; R 20 is a hydrogen atom or C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C6-C 11 -represents a group selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, naphthyl, and 5- to 10-membered heteroaryl; wherein the C1-C6-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23), C3-C7-cycloalkyl, bicyclic C6-C 11 -optionally substituted one, two or three times with substituents independently selected from groups selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted one or two times with substituents independently selected from groups selected from fluorine, chlorine and bromine atoms, or methyl, trifluoromethyl and methoxy; where C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl are optionally substituted one, two or three times by halogen atoms or by substituents independently selected from cyano, oxo, hydroxy, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; and the phenyl, naphthyl and 5-10 membered heteroaryl groups are each independently selected from the group consisting of a halogen atom or cyano, C1-C2-alkyl, C1-C2-haloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and optionally substituted one, two or three times with each substituent independently selected from the group R 21 represents a hydrogen atom or a C1-C2-alkyl group, or R 20 and R 21 may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (phenyl)-(C-C-alkyl)-, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-haloalkoxy, -N(R 22)(R 23 ) and -C(=O)-N(R 24 )(R 25 a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of: R 22 and R 23 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 24 and R 25 represents, independently of each occurrence, a hydrogen atom or a C1-C2-alkyl group, and n represents an integer of 0, 1, or 2. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0146] According to a tenth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 represents fluorine, chlorine and bromine atoms, or cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy, -N(R) 5 (R 6 phenyl or pyridinyl group, optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form a divalent group selected from —(CH)—, —O—CH—O—, and —O—CF—O—; or R 1 represents a pyrazolyl group optionally substituted with one methyl group, R 2 is the base [ka] [wherein "*" represents R2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a group selected from methyl and -NH; R 4 represents fluorine, chlorine and bromine atoms, or cyano, C1-C3-alkyl, C1-C3-hydroxyalkyl, C1-C3-fluoroalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ) and S(=O) n -R 14 represents a phenyl or pyridinyl group optionally substituted 1, 2 or 3 times with substituents independently selected from the group or two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-; R 5 and R 6 represents, independently at each occurrence, a hydrogen atom or a C1-C2-alkyl group, or R 5 and R 6 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one or two times with a fluorine atom or with substituents independently selected from groups selected from hydroxy and C1-C2-alkyl; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; R 9 is a hydrogen atom or C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(R 18 )(R 19)-C(=O)-OR 17 , -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ) and phenyl, wherein the phenyl group within said benzyl group and said phenyl group itself may be substituted once or twice with each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group; R 10 and R 11 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, (C-C-alkyl)-C(=O)-, (phenyl)-(C-C-alkyl)-, (phenyl)-(C-C-alkyl)-C(=O)- and (phenyl)-(C-C-alkyl)-OC(=O)-, wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-OC(=O)- groups is optionally substituted once or twice by each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group, or R 10 and R 11 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4-7-membered heterocycloalkyl group, optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group consisting of oxo, C-C-alkyl, C-C-fluoroalkyl and (C-C-alkyl)-C(=O)-; R 12 and R 13 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, C-C-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one or two times by a fluorine atom or by each substituent independently selected from the group selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, or R 12 and R 13 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one or two times with a halogen atom or with substituents independently selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 14 represents a group selected from methyl and trifluoromethyl; R 17 represents a C1-C2-alkyl group; R 18 and R 19 represents, independently at each occurrence, a hydrogen atom or a methyl group; R 20 represents a hydrogen atom or a group selected from optionally substituted C1-C3-alkyl, unsubstituted C4-C6-alkyl, prop-2-ynyl, methoxy, C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl and 5- to 10-membered heteroaryl, wherein the C1-C3-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted 1- to 2-times with substituents independently selected from fluorine atoms, chlorine atoms, and methyl groups; the C3-C6-cycloalkyl, adamantyl and monocyclic 4- to 7-membered heterocycloalkyl groups are optionally substituted one, two or three times by fluorine atoms or by substituents independently selected from the group consisting of oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; and the phenyl and 5- to 10-membered heteroaryl groups are substituted with fluorine and chlorine atoms or cyano, C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and optionally substituted one, two or three times with each substituent independently selected from the group R 21 represents a hydrogen atom or a C1-C2-alkyl group, or R 20 and R 21 may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-fluoroalkyl, benzyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of: R 22 and R 23 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 24 and R 25 represents, independently of each occurrence, a hydrogen atom or a C1-C2-alkyl group, and n represents the integer 2. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0147] According to an eleventh embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 represents a phenyl or pyridinyl group, optionally substituted one or two times by fluorine and chlorine atoms or by substituents independently selected from the group consisting of cyano, C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a group selected from methyl and -NH; R 4 represents fluorine and chlorine atoms, or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 represents a phenyl or pyridinyl group optionally substituted one or two times with substituents independently selected from the group consisting of: R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a —C(═O)—NH group, and R 9 represents a group selected from C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl- and phenyl, wherein the phenyl group within the benzyl group and the phenyl group itself may be substituted once or twice with each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0148] According to a twelfth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 represents a phenyl or pyridinyl group, optionally substituted one or two times by fluorine and chlorine atoms or by substituents independently selected from the group consisting of cyano, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a group selected from methyl and -NH; R 4 represents fluorine and chlorine atoms, or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 represents a phenyl or pyridinyl group optionally substituted one or two times with substituents independently selected from the group consisting of: R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a —C(═O)—NH group, and R 9 represents a group selected from C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl- and phenyl, wherein the phenyl group within the benzyl group and the phenyl group itself may be substituted once or twice with each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0149] According to a thirteenth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a group selected from methyl and -NH; R 4 is the base [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; Y 1 represents -C(H)=, -C(F)=, -C(Cl)=, -C(CN)= or -N=; Y 2 represents -C(H)= and -N=; Y 3 is -C(R 27 )= and -N=, However, Y 2 If represents -N=, then Y 3 -C(R27 )=, Y 3 If represents -N=, then Y 2 represents -C(H)=; R 26 represents a fluorine atom, a chlorine atom or a group selected from C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy and C1-C2-fluoroalkoxy, and R 27 represents a fluorine atom, a chlorine atom or a group selected from C1-C2-alkoxy, benzyloxy and C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0150] According to a fourteenth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a group selected from methyl and -NH; R 4 is the base [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; Y 1 represents -C(H)=, -C(F)=, -C(Cl)=, -C(CN)= or -N=; Y 2 represents -C(H)= or -N=; Y 3 is -C(R 27 )= or -N=, However, Y 2 If represents -N=, then Y 3 -C(R 27 )=, Y 3 If represents -N=, then Y 2 represents -C(H)=; R 26 represents a fluorine atom, a chlorine atom or a group selected from C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy and C1-C2-fluoroalkoxy, and R 27 represents a fluorine atom, a chlorine atom or a group selected from C1-C2-alkoxy, benzyloxy and C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0151] According to a fifteenth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a group selected from methyl and -NH; R 4 is the base [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; Y 1 represents -C(H)=, -C(F)= or -N=; Y 2 represents -C(H)= and -N=; Y 3 is -C(R 27 )= and -N=, However, Y 2 If represents -N=, then Y 3 -C(R 27 )=, Y 3 If represents -N=, then Y 2 represents -C(H)=; R 26 represents a fluorine atom, a chlorine atom or a group selected from methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy, and R 27 represents a chlorine atom or a group selected from methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0152] According to a sixteenth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a group selected from methyl and -NH; R 4 is the base [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; Y 1 represents -C(H)=, -C(F)= or -N=; Y 2 represents -C(H)= or -N=; Y 3 is -C(R 27 )= or -N=, However, Y 2 If represents -N=, then Y 3 -C(R 27 )=, Y 3 If represents -N=, then Y 2 represents -C(H)=; R 26 represents a fluorine atom, a chlorine atom or a group selected from methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy, and R 27represents a chlorine atom or a group selected from methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0153] According to a seventeenth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents an -NH2 group; R 4 is the base [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; Y 1 represents -C(H)=, -C(F)=, -C(Cl)=, -C(CN)= or -N=; Y 2 represents -C(H)= and -N=; Y 3 is -C(R 27 )= and -N=, However, Y 2 If represents -N=, then Y 3 -C(R 27 )=, Y 3 If represents -N=, then Y 2 represents -C(H)=; R 26 represents a fluorine atom, a chlorine atom or a group selected from C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy and C1-C2-fluoroalkoxy, and R 27 represents a fluorine atom, a chlorine atom or a group selected from C1-C2-alkoxy, benzyloxy and C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0154] According to an eighteenth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents an -NH2 group; R 4 is the base [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents; R7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; Y 1 represents -C(H)=, -C(F)=, -C(Cl)=, -C(CN)= or -N=; Y 2 represents -C(H)= or -N=; Y 3 is -C(R 27 )= or -N=, However, Y 2 If represents -N=, then Y 3 -C(R 27 )=, Y 3 If represents -N=, then Y 2 represents -C(H)=; R 26 represents a fluorine atom, a chlorine atom or a group selected from C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy and C1-C2-fluoroalkoxy, and R 27 represents a fluorine atom, a chlorine atom or a group selected from C1-C2-alkoxy, benzyloxy and C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0155] According to a nineteenth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; R 2 is the base [ka] [wherein "*" represents R2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents an -NH2 group; R 4 is the base [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; Y 1 represents -C(H)=, -C(F)= or -N=; Y 2 represents -C(H)= and -N=; Y 3 is -C(R 27 )= and -N=, However, Y 2 If represents -N=, then Y 3 -C(R 27 )=, Y 3 If represents -N=, then Y 2 represents -C(H)=; R 26 represents a fluorine atom, a chlorine atom or a group selected from methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy, and R 27 represents a chlorine atom or a group selected from methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0156] According to a twentieth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents an -NH2 group; R 4 is the base [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; Y 1 represents -C(H)=, -C(F)= or -N=; Y 2 represents -C(H)= or -N=; Y 3 is -C(R 27 )= or -N=, However, Y 2 If represents -N=, then Y 3 -C(R 27 )=, Y 3 If represents -N=, then Y 2 represents -C(H)=; R 26 represents a fluorine atom, a chlorine atom or a group selected from methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy, and R 27represents a chlorine atom or a group selected from methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0157] According to a twenty-first embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents or R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a group selected from methyl and -NH; R 4 teeth, [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents a group selected from: R 7 represents a methyl group; R 8 represents a -C(=O)-NH group; Y 1 represents -C(H)= or -C(F)=; R 26 represents a fluorine atom, a chlorine atom, or a group selected from difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy; R 28 represents a group selected from methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0158] According to a twenty-second embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents or R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents an -NH2 group; R 4 teeth, [ka] TIFF0007663603000051.tif53157 [where "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents a group selected from: R 7 represents a methyl group; R 8 represents a -C(=O)-NH group; Y 1 represents -C(H)= or -C(F)=; R 26 represents a fluorine atom, a chlorine atom, or a group selected from difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy; R 28 represents a group selected from methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0159] According to a twenty-third embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents or R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a methyl group; R 4 teeth, [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents a group selected from: R 7 represents a methyl group; R 8 represents a -C(=O)-NH group; Y 1 represents -C(H)= or -C(F)=; R 26 represents a fluorine atom, a chlorine atom, or a group selected from difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy; R 28 represents a group selected from methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0160] According to a twenty-fourth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 teeth, [ka] TIFF0007663603000057.tif102158 [where "**" indicates R 1 indicates the point of attachment to the nitrogen atom to which represents a group selected from: R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents an -NH2 group; R 4 teeth, [ka] TIFF0007663603000060.tif52157 [where "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents a group selected from: R 7 represents a methyl group; R 8 represents a -C(=O)-NH group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0161] According to a twenty-fifth embodiment of the first aspect, the present invention provides a compound of general formula (I) above, wherein: R 1 teeth, [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents a group selected from: R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 3 represents a methyl group; R 4 teeth, [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents a group selected from: R 7 represents a methyl group; R 8 represents a -C(=O)-NH group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0162] Further embodiments of the first aspect of the invention In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 is a halogen atom or hydroxy, cyano, nitro, C1-C4-alkyl, (phenyl)-(C1-C2-alkyl)-, C1-C4-haloalkyl, C1-C4-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C4-haloalkoxy, -N(R) 5 (R 6 phenyl or pyridinyl group, optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)- and (phenyl)-(C1-C2-alkoxy)- groups is optionally substituted once or twice by fluorine, chlorine and bromine atoms or by substituents independently selected from the group consisting of methyl, trifluoromethyl and methoxy, or two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O- and -O-CF2-O-; or R 1represents a halogen atom or a pyrazolyl group, each of which may be substituted one or two times by substituents independently selected from the group consisting of cyano, C1-C2-alkyl, and C1-C2-alkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0163] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 is a halogen atom or hydroxy, cyano, nitro, C1-C4-alkyl, (phenyl)-(C1-C2-alkyl)-, C1-C4-haloalkyl, C1-C4-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C4-haloalkoxy, -N(R) 5 (R 6 phenyl or pyridinyl group, optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)- and (phenyl)-(C1-C2-alkoxy)- groups is optionally substituted once or twice by fluorine, chlorine and bromine atoms or by substituents independently selected from the group consisting of methyl, trifluoromethyl and methoxy, or two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O- and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0164] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1is a halogen atom or hydroxy, cyano, nitro, (phenyl)-(C1-C2-alkyl)-, C1-C4-haloalkyl, C1-C4-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C4-haloalkoxy, -N(R) 5 (R 6 phenyl or pyridinyl group, optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)- and (phenyl)-(C1-C2-alkoxy)- groups is optionally substituted once or twice by fluorine, chlorine and bromine atoms or by substituents independently selected from the group consisting of methyl, trifluoromethyl and methoxy, or two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O- and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0165] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 is a halogen atom or cyano, nitro, C1-C4-alkyl, (phenyl)-(C1-C2-alkyl)-, C1-C4-haloalkyl, C1-C4-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C4-haloalkoxy, -N(R) 5 (R 6 phenyl or pyridinyl group, optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)- and (phenyl)-(C1-C2-alkoxy)- groups is optionally substituted once or twice by fluorine, chlorine and bromine atoms or by substituents independently selected from the group consisting of methyl, trifluoromethyl and methoxy, or two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O- and -O-CF2-O-; or R 1 represents a halogen atom or a pyrazolyl group, each of which may be substituted one or two times by substituents independently selected from the group consisting of cyano, C1-C2-alkyl, and C1-C2-alkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0166] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 is a halogen atom or cyano, nitro, C1-C4-alkyl, (phenyl)-(C1-C2-alkyl)-, C1-C4-haloalkyl, C1-C4-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C4-haloalkoxy, -N(R) 5 (R 6 phenyl or pyridinyl group, optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)- and (phenyl)-(C1-C2-alkoxy)- groups is optionally substituted once or twice by fluorine, chlorine and bromine atoms or by substituents independently selected from the group consisting of methyl, trifluoromethyl and methoxy, or two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O- and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0167] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 is a halogen atom or cyano, nitro, (phenyl)-(C1-C2-alkyl)-, C1-C4-haloalkyl, C1-C4-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C4-haloalkoxy, -N(R) 5 (R 6 phenyl or pyridinyl group, optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)- and (phenyl)-(C1-C2-alkoxy)- groups is optionally substituted once or twice by fluorine, chlorine and bromine atoms or by substituents independently selected from the group consisting of methyl, trifluoromethyl and methoxy, or two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O- and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0168] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents fluorine, chlorine and bromine atoms, or hydroxy, cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C2-fluoroalkoxy and -N(R 5 )(R 6 phenyl or pyridinyl group, optionally substituted one, two or three times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form a divalent group selected from —(CH)—, —O—CH—O—, and —O—CF—O—; or R 1 represents a pyrazolyl group optionally substituted with one methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0169] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents fluorine, chlorine and bromine atoms, or hydroxy, cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C2-fluoroalkoxy and -N(R 5 )(R 6 phenyl or pyridinyl group, optionally substituted one, two or three times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0170] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents fluorine, chlorine and bromine atoms, or hydroxy, cyano, C-C-fluoroalkyl, C-C-alkoxy, (phenyl)-(C-C-alkoxy)-, C-C-fluoroalkoxy and -N(R 5 )(R 6 phenyl or pyridinyl group, optionally substituted one, two or three times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0171] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents fluorine, chlorine and bromine atoms, or hydroxy, cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C2-fluoroalkoxy and -N(R 5 )(R 6 phenyl, which may be substituted one, two or three times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of said phenyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0172] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents fluorine, chlorine and bromine atoms, or hydroxy, cyano, C-C-fluoroalkyl, C-C-alkoxy, (phenyl)-(C-C-alkoxy)-, C-C-fluoroalkoxy and -N(R 5 )(R 6 phenyl, which may be substituted one, two or three times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of said phenyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0173] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents fluorine, chlorine and bromine atoms, or hydroxy, cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C2-fluoroalkoxy and -N(R 5 )(R 6 a pyridinyl group optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of the pyridinyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0174] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1represents fluorine, chlorine and bromine atoms, or cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy, -N(R) 5 (R 6 phenyl or pyridinyl group, optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form a divalent group selected from —(CH)—, —O—CH—O—, and —O—CF—O—; or R 1 represents a pyrazolyl group optionally substituted with one methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0175] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents fluorine, chlorine and bromine atoms, or cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy, -N(R) 5 (R 6 phenyl or pyridinyl group, optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0176] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1represents fluorine, chlorine and bromine atoms, or cyano, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy, -N(R) 5 (R) 6 represents a phenyl group or a pyridinyl group which may be substituted one, two or three times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0177] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents fluorine, chlorine and bromine atoms, or cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy, -N(R) 5 (R 6 phenyl, optionally substituted one, two or three times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0178] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents fluorine, chlorine and bromine atoms, or cyano, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy, -N(R) 5 (R) 6represents a phenyl group optionally substituted one, two or three times with substituents independently selected from the group consisting of or two substituents on adjacent carbon atoms of said phenyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0179] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents fluorine, chlorine and bromine atoms, or cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy, -N(R) 5 (R 6 a pyridinyl group optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0180] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents a fluorine atom, a chlorine atom, or a phenyl or pyridinyl group, each of which may be substituted one or two times by substituents independently selected from the group consisting of C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0181] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents a fluorine atom and a chlorine atom, or a phenyl or pyridinyl group, each of which may be substituted one or two times by substituents independently selected from the group consisting of C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0182] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents a fluorine atom, a chlorine atom, or a phenyl group which may be substituted one or two times by substituents independently selected from the group consisting of cyano, C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0183] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents a phenyl group, which may be substituted one or two times by fluorine and chlorine atoms or by substituents independently selected from the group consisting of C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0184] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1represents a fluorine atom, a chlorine atom, or a phenyl group which may be substituted one or two times by substituents independently selected from the group consisting of cyano, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0185] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents a phenyl group which may be substituted one or two times by fluorine and chlorine atoms or by substituents independently selected from the group consisting of C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0186] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents a pyridinyl group, optionally substituted one or two times by fluorine and chlorine atoms or by substituents independently selected from the group consisting of C-C-alkyl, C-C-fluoroalkyl, C-C-alkoxy, C-C-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0187] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1represents a phenyl or pyridinyl group optionally substituted one or two times by a fluorine atom, a chlorine atom, or a bromine atom, or by substituents independently selected from the group consisting of cyano, methyl, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy, and trifluoromethoxy; or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form the divalent group -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0188] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents a phenyl or pyridinyl group optionally substituted one or two times by a fluorine atom, a chlorine atom, or a bromine atom, or by substituents independently selected from the group consisting of cyano, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy, and trifluoromethoxy; or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form the divalent group -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0189] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents a phenyl group which may be substituted one or two times with a fluorine atom, a chlorine atom, or a bromine atom, or with substituents independently selected from the group consisting of cyano, methyl, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy, and trifluoromethoxy; or two substituents attached to adjacent carbon atoms of said phenyl group together form the divalent group -O-CF-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0190] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents a phenyl group optionally substituted one or two times with a fluorine atom, a chlorine atom, or a bromine atom, or with substituents independently selected from the group consisting of cyano, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy, and trifluoromethoxy; or two substituents attached to adjacent carbon atoms of said phenyl group together form the divalent group -O-CF-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0191] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents a pyridinyl group optionally substituted one or two times with a fluorine atom, a chlorine atom, or a bromine atom, or with substituents independently selected from the group consisting of cyano, methyl, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy, and trifluoromethoxy; or two substituents attached to adjacent carbon atoms of the pyridinyl group, taken together, form the divalent group -O-CF-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0192] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1represents a phenyl or pyridinyl group optionally substituted one or two times by a fluorine atom, a chlorine atom, a bromine atom, or by substituents independently selected from the group consisting of methyl, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy; or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form the divalent group -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0193] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents a phenyl or pyridinyl group optionally substituted one or two times by a fluorine atom, a chlorine atom, a bromine atom, or by substituents independently selected from difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy; or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form the divalent group -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0194] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents a phenyl group optionally substituted one or two times with a fluorine atom, a chlorine atom, or a bromine atom, or with substituents independently selected from the group consisting of methyl, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy, and trifluoromethoxy; or two substituents attached to adjacent carbon atoms of said phenyl group together form the divalent group -O-CF-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0195] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents a phenyl group optionally substituted one or two times with a fluorine atom, a chlorine atom, or a bromine atom, or with substituents independently selected from difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy, and trifluoromethoxy; or two substituents attached to adjacent carbon atoms of said phenyl group together form the divalent group -O-CF-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0196] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 represents a pyridinyl group optionally substituted one or two times by a fluorine atom, a chlorine atom, a bromine atom, or by substituents independently selected from the group consisting of methyl, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy, and trifluoromethoxy; or two substituents attached to adjacent carbon atoms of the pyridinyl group, taken together, form the divalent group -O-CF-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0197] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R1 indicates the point of attachment to the nitrogen atom to which represents] and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0198] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; Y 1 represents -C(H)=, -C(F)=, -C(Cl)=, -C(CN)= or -N=; R 26 represents a fluorine atom, a chlorine atom or a bromine atom, or a group selected from methyl, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0199] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; Y 1 represents -C(H)=, -C(F)=, -C(Cl)=, -C(CN)= or -N=; R 26represents a fluorine atom, a chlorine atom or a bromine atom, or a group selected from difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0200] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; Y 1 represents -C(H)=, -C(F)= or -N=; R 26 represents a fluorine atom, a chlorine atom or a group selected from C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy and C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0201] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; Y 1 represents -C(H)=, -C(F)= or -N=; R 26represents a fluorine atom, a chlorine atom or a group selected from C1-C2-fluoroalkyl, C1-C2-alkoxy and C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0202] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents; Y 1 represents -C(H)=, -C(F)=, -C(Cl)= or -N=; R 26 represents a fluorine atom, a chlorine atom or a bromine atom, or a group selected from difluoromethyl, methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0203] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents Y 1 represents -C(H)= or -C(F)=, and R 26represents a fluorine atom, a chlorine atom, or a group selected from difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0204] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 is the base [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents R 28 represents a group selected from methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0205] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1 teeth, [ka] TIFF0007663603000073.tif48159 [where "**" indicates R 1 indicates the point of attachment to the nitrogen atom to which represents a group selected from the group and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0206] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 1teeth, [ka] [wherein "**" represents R 1 indicates the point of attachment to the nitrogen atom to which represents a group selected from the group and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0207] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0208] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0209] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0210] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0211] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] is expressed in a ratio of about 99:1 or greater, preferably [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group. and isomeric mixtures of the compounds of formula (I) and tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0212] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] in a ratio of about 98:2 or greater, preferably [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group. and isomeric mixtures of the compounds of formula (I) and tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0213] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] is expressed in a ratio of about 95:5 or more, preferably [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group. and isomeric mixtures of the compounds of formula (I) and tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0214] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] in a ratio of about 90:10 or greater, preferably [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group. and isomeric mixtures of the compounds of formula (I) and tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0215] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] in a ratio of about 80:20 or greater, preferably [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group. and isomeric mixtures of the compounds of formula (I) and tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0216] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which in a ratio of approximately 50:50, i.e., representing a racemic mixture in the case of compounds not characterized by an additional element of chirality; R 7 represents a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group. and isomeric mixtures of the compounds of formula (I) and tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0217] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a methyl group; R 8 represents a -C(=O)-NH group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0218] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a methyl group; R 8 represents a -C(=O)-NH group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0219] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a methyl group; R 8 represents a -C(=O)-NH group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0220] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] is expressed in a ratio of about 99:1 or greater, preferably [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a methyl group; R 8 represents a -C(=O)-NH group. and isomeric mixtures of the compounds of formula (I) and tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0221] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] in a ratio of about 98:2 or greater, preferably [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a methyl group; R 8 represents a -C(=O)-NH group. and isomeric mixtures of the compounds of formula (I) and tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0222] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] in a ratio of about 95:5 or greater, preferably [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a methyl group; R 8 represents a -C(=O)-NH group. and isomeric mixtures of the compounds of formula (I) and tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0223] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] in a ratio of about 90:10 or greater, preferably [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a methyl group; R 8 represents a -C(=O)-NH group. and isomeric mixtures of the compounds of formula (I) and tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0224] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] in a ratio of about 80:20 or greater, preferably [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which represents; R 7 represents a methyl group; R 8 represents a -C(=O)-NH group. and isomeric mixtures of the compounds of formula (I) and tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0225] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 2 is the base [ka] [wherein "*" represents R 2 indicates the point of attachment to the nitrogen atom to which in a ratio of approximately 50:50, i.e., representing a racemic mixture in the case of compounds not characterized by an additional element of chirality; R 7 represents a methyl group; R 8 represents a -C(=O)-NH group. and isomeric mixtures of the compounds of formula (I) and tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0226] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 3 represents a group selected from methyl and —NH and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0227] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 3 represents an -NH group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0228] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 3 represents a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0229] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 is a halogen atom or cyano, nitro, C1-C4-alkyl, (phenyl)-(C1-C2-alkyl)-, (5-membered heteroaryl)-(C1-C2-alkyl)-, (C3-C7-cycloalkyl)-(C1-C2-alkyl)-, ((R 9 )O)-(C1-C4-alkyl)-, C1-C4-haloalkyl, C3-C7-cycloalkyl, -OR 9 , -N(R 10 )(R 11 ), ((R 10 )(R 11 )N)-(C1-C3-alkyl)-, -C(=O)-N(R 12 )(R 13 ), S(=O) n -R 14 , -C(=O)R 14 , -C(=O)-OR 17 or a 5-membered heteroaryl group which may itself be substituted by one or two methyl groups; or two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O- and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0230] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 is a halogen atom or cyano, nitro, C1-C4-alkyl, (phenyl)-(C1-C2-alkyl)-, (5-membered heteroaryl)-(C1-C2-alkyl)-, C1-C4-hydroxyalkyl, C1-C4-haloalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ), S(=O) n -R 14 and a 5-membered heteroaryl group which may itself be substituted by one or two methyl groups; or two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O- and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0231] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R4 is a halogen atom or cyano, C1-C3-alkyl, ((R 9 )O)—(C1-C3-alkyl)-, C1-C3-fluoroalkyl, —OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ), S(=O) n -R 14 and -C(=O)-OR 17 represents a phenyl or pyridinyl group optionally substituted 1, 2 or 3 times with substituents independently selected from the group or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0232] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 is a halogen atom or cyano, C1-C3-alkyl, ((R 9 )O)—(C1-C3-alkyl)-, C1-C3-fluoroalkyl, —OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ), S(=O) n -R 14 and -C(=O)-OR 17 represents a phenyl group optionally substituted one, two or three times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0233] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 is a halogen atom or cyano, C1-C3-alkyl, ((R 9 )O)—(C1-C3-alkyl)-, C1-C3-fluoroalkyl, —OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ), S(=O) n -R 14 and -C(=O)-OR 17 represents a pyridinyl group optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0234] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 represents fluorine, chlorine and bromine atoms, or cyano, C1-C3-alkyl, C1-C3-hydroxyalkyl, C1-C3-fluoroalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ) and S(=O) n -R 14 represents a phenyl group optionally substituted one, two or three times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of said phenyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0235] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 represents fluorine, chlorine and bromine atoms, or cyano, C1-C3-alkyl, C1-C3-hydroxyalkyl, C1-C3-fluoroalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ) and S(=O) n -R 14 represents a pyridinyl group optionally substituted 1, 2 or 3 times with substituents independently selected from the group consisting of or two substituents attached to adjacent carbon atoms of the pyridinyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0236] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 represents fluorine and chlorine atoms, or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 represents a phenyl or pyridinyl group optionally substituted one or two times with substituents independently selected from the group consisting of: R 9represents a group selected from C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl- and phenyl, wherein the phenyl group within the benzyl group and the phenyl group itself may be substituted once or twice with each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0237] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 is a halogen atom or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ) and -C(=O)-OR 17 represents a phenyl or pyridinyl group which may be substituted one or two times with substituents independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0238] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 is a halogen atom or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ) and -C(=O)-OR 17 represents a phenyl group which may be substituted one or two times with substituents independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0239] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 is a halogen atom or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ) and -C(=O)-OR 17 represents a pyridinyl group which may be substituted one or two times with substituents independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0240] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 represents fluorine and chlorine atoms, or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 represents a phenyl or pyridinyl group which may be substituted one or two times with substituents independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0241] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 represents fluorine and chlorine atoms, or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 represents a phenyl group optionally substituted one or two times with substituents independently selected from the group consisting of: R 9is selected from C-C-alkyl, benzyl, C-C-fluoroalkyl, (C-C-alkoxy)-C-alkyl- and phenyl, wherein the phenyl group within the benzyl group and the phenyl group itself may be substituted once or twice with each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0242] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 represents fluorine and chlorine atoms, or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 represents a phenyl group which may be substituted one or two times with substituents independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0243] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 represents fluorine and chlorine atoms, or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 represents a pyridinyl group optionally substituted one or two times with substituents independently selected from the group consisting of: R 9 represents a group selected from C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl- and phenyl, wherein the phenyl group within the benzyl group and the phenyl group itself may be substituted once or twice with each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0244] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 represents fluorine and chlorine atoms, or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 represents a pyridinyl group which may be substituted one or two times with substituents independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0245] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 is the base [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents; Y 2 represents -C(H)= or -N=; Y 3 is -C(R 27 )= or -N=, However, Y 2 If represents -N=, then Y 3 -C(R 27 )=, Y 3 If represents -N=, then Y 2 represents -C(H)=; R 27 is a halogen atom or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ) and -C(=O)-OR 17represents a group selected from the group and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0246] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 is the base [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents; Y 2 represents -C(H)= or -N=; Y 3 is -C(R 27 )= or -N=, However, Y 2 If represents -N=, then Y 3 -C(R 27 )=, Y 3 If represents -N=, then Y 2 represents -C(H)=; R 27 represents a fluorine atom, a chlorine atom or a group selected from C1-C2-alkoxy, benzyloxy and C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0247] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 is the base [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents; Y 2 represents -C(H)= and -N=; Y 3 is -C(R 27 )= and -N=, However, Y 2 If represents -N=, then Y 3 -C(R 27 )=, Y 3 If represents -N=, then Y 2 represents -C(H)=; R 27 represents a fluorine atom, a chlorine atom or a group selected from C1-C2-alkoxy, benzyloxy and C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0248] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 is the base [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents; R 27 represents a fluorine atom, a chlorine atom or a group selected from C1-C2-alkoxy, benzyloxy and C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0249] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 is the base [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents; R27 represents a fluorine atom, a chlorine atom or a group selected from C1-C2-alkoxy, benzyloxy and C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0250] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 teeth, [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents a group selected from the group and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0251] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 4 teeth, [ka] [wherein "#" represents R 4 indicates the point of attachment to the carbonyl group to which represents a group selected from the group and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0252] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 5 and R 6 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl and (C-C-alkyl)-C(=O)-, or R5 and R 6 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted one or two times with fluorine, chlorine and bromine atoms, or with substituents independently selected from oxo, hydroxy, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0253] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 5 and R 6 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0254] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 5 and R 6 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted one or two times with fluorine, chlorine and bromine atoms, or with substituents independently selected from oxo, hydroxy, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0255] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 5 and R 6represents, independently at each occurrence, a hydrogen atom or a C1-C2-alkyl group, or R 5 and R 6 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one or two times with a fluorine atom or with substituents independently selected from groups selected from hydroxy and C1-C2-alkyl. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0256] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 5 and R 6 represents, independently in each occurrence, a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0257] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 5 and R 6 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one or two times with a fluorine atom or with substituents independently selected from groups selected from hydroxy and C1-C2-alkyl. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0258] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 7 represents a hydrogen atom. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0259] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 7 represents a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0260] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 7 represents an ethyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0261] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 7 represents a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0262] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 9 is a hydrogen atom or C1-C4-alkyl, (phenyl)-(C1-C2-alkyl)-, C1-C4-haloalkyl, C2-C3-hydroxyalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(R 18 )(R 19 )-C(=O)-OR 17 , -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ), -C(=O)-N(R20 )(R 21 ) and phenyl, wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)- group and the phenyl group itself may be substituted one or two times with fluorine, chlorine and bromine atoms or with substituents independently selected from the group consisting of cyano, methyl, trifluoromethyl and methoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0263] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 9 is a hydrogen atom or C1-C4-alkyl, (phenyl)-(C1-C2-alkyl)-, C1-C4-haloalkyl, C2-C3-hydroxyalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(R 18 )(R 19 )-C(=O)-OR 17 , -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ) and phenyl, wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)- group and the phenyl group itself may be substituted one or two times with fluorine, chlorine and bromine atoms, or with substituents independently selected from groups selected from methyl, trifluoromethyl and methoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0264] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 9is a hydrogen atom or C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, C2-hydroxyalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(R 18 )(R 19 )-C(=O)-OR 17 , -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ), -C(=O)-N(R 20 )(R 21 ) and phenyl, wherein the phenyl group within the benzyl group and the phenyl group itself may be substituted once or twice with each substituent independently selected from fluorine and chlorine atoms, or a group selected from cyano and methyl. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0265] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 9 is a hydrogen atom or C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(R 18 )(R 19 )-C(=O)-OR 17 , -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ) and phenyl, wherein the phenyl group within the benzyl group and the phenyl group itself may be substituted once or twice with each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0266] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 9 represents a group selected from C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl- and phenyl, wherein the phenyl group within the benzyl group and the phenyl group itself may be substituted once or twice with each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0267] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 9 is a hydrogen atom or C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ), -C(=O)-N(R 20 )(R 21 ) and phenyl, wherein the phenyl group within the benzyl group and the phenyl group itself may be substituted once or twice with each substituent independently selected from fluorine and chlorine atoms, or a group selected from cyano and methyl. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0268] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 9represents a hydrogen atom or a group selected from C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl and phenyl, wherein the phenyl group within the benzyl group and the phenyl group itself may be substituted once or twice with each substituent independently selected from fluorine and chlorine atoms, or a group selected from cyano and methyl. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0269] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11 is independently in each occurrence a hydrogen atom or C1-C2-alkyl, C1-C2-haloalkyl, C2-C3-hydroxyalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((R 22 )(R 23 )N)—C2-alkyl, (C3-C7-cycloalkyl)-(C1-C2-alkyl)-, (C1-C2-alkyl)-C(═O)-, C3-C7-cycloalkyl, (C3-C7-cycloalkyl)-C(═O)-, (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(═O)- and (phenyl)-(C1-C2-alkyl)-OC(═O)-, wherein C3-C7-cycloalkyl, and C3-C7-cycloalkyl in the (C3-C7-cycloalkyl)-(C1-C2-alkyl)- and (C3-C7-cycloalkyl)-C(=O)- groups, are optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group selected from cyano, C1-C2-alkyl and C1-C2-haloalkyl, and the phenyl group in said (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-OC(=O)- groups may be substituted one or two times by fluorine, chlorine and bromine atoms or by substituents independently selected from groups selected from methyl, trifluoromethyl and methoxy, or R 10 and R 11 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group or a bicyclic nitrogen-containing 5- to 10-membered heterocycloalkyl group, which may be selected from the group consisting of halogen atoms or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (C-C-alkyl)-C(=O)-, C-C-alkoxy, -N(R 22 )(R 23 ), and monocyclic 4- to 7-membered heterocycloalkyl groups, each of which may be substituted one, two, or three times with each substituent independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0270] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11 is independently in each occurrence a hydrogen atom or C1-C2-alkyl, C1-C2-haloalkyl, C2-C3-hydroxyalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((R 22 )(R 23 )N)—C2-alkyl, (C3-C7-cycloalkyl)-(C1-C2-alkyl)-, (C1-C2-alkyl)-C(═O)-, C3-C7-cycloalkyl, (C3-C7-cycloalkyl)-C(═O)-, (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(═O)- and (phenyl)-(C1-C2-alkyl)-OC(═O)-, wherein C3-C7-cycloalkyl, and C3-C7-cycloalkyl in the (C3-C7-cycloalkyl)-(C1-C2-alkyl)- and (C3-C7-cycloalkyl)-C(=O)- groups, are optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group selected from cyano, C1-C2-alkyl and C1-C2-haloalkyl, and the phenyl group in said (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-OC(=O)- groups may be substituted one or two times by fluorine, chlorine and bromine atoms or by substituents independently selected from groups selected from methyl, trifluoromethyl and methoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0271] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group or a bicyclic nitrogen-containing 5- to 10-membered heterocycloalkyl group, which may be selected from the group consisting of halogen atoms or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (C-C-alkyl)-C(=O)-, C-C-alkoxy, -N(R 22 )(R 23 ), and monocyclic 4- to 7-membered heterocycloalkyl groups, each of which may be substituted one, two, or three times with each substituent independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0272] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R10 and R 11 is independently in each occurrence a hydrogen atom or C1-C2-alkyl, C1-C2-haloalkyl, C2-C3-hydroxyalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((R 22 )(R 23 )N)—C2-alkyl, (C1-C2-alkyl)-C(═O)—, C3-C5-cycloalkyl, (C3-C5-cycloalkyl)-C(═O)—, (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(═O)— and (phenyl)-(C1-C2-alkyl)-OC(═O)—, wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-OC(=O)- groups is optionally substituted one or two times by a fluorine atom, a chlorine atom and a bromine atom or by a group selected from methyl, trifluoromethyl and methoxy, or R 10 and R 11 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group or a bicyclic nitrogen-containing 6- to 10-membered heterocycloalkyl group, which may be selected from the group consisting of halogen atoms or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (C-C-alkyl)-C(=O)-, C-C-alkoxy, -N(R 22 )(R 23 ), and monocyclic 4- to 7-membered heterocycloalkyl groups, each of which may be substituted one, two, or three times with each substituent independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0273] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R11 is independently in each occurrence a hydrogen atom or C1-C2-alkyl, C1-C2-haloalkyl, C2-C3-hydroxyalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((R 22 )(R 23 )N)—C2-alkyl, (C1-C2-alkyl)-C(═O)—, C3-C5-cycloalkyl, (C3-C5-cycloalkyl)-C(═O)—, (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(═O)— and (phenyl)-(C1-C2-alkyl)-OC(═O)—, wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-OC(=O)- groups may be substituted once or twice with a fluorine atom, a chlorine atom, a bromine atom, or a group selected from methyl, trifluoromethyl, and methoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0274] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group or a bicyclic nitrogen-containing 6- to 10-membered heterocycloalkyl group, which may be selected from the group consisting of halogen atoms or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (C-C-alkyl)-C(=O)-, C-C-alkoxy, -N(R 22 )(R 23 ), and monocyclic 4- to 7-membered heterocycloalkyl groups, each of which may be substituted one, two, or three times with each substituent independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0275] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, (C-C-cycloalkyl)-(C-C-alkyl)-, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-cycloalkyl-(C=O)-, (phenyl)-(C-C-alkyl)-, (phenyl)-(C-C-alkyl)-C(=O)- and (phenyl)-(C-C-alkyl)-OC(=O)-, wherein C3-C7-cycloalkyl, and C3-C5-cycloalkyl in said (C3-C5-cycloalkyl)-(C1-C2-alkyl)-, and C3-C7-cycloalkyl in the C3-C7-cycloalkyl-(C=O)- group, are optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group selected from cyano, C1-C2-alkyl and C1-C2-fluoroalkyl, and the phenyl group in said (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-OC(=O)- groups may be substituted one or two times by each substituent independently selected from fluorine atoms, chlorine atoms and methyl groups, or R 10 and R 11 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group consisting of cyano, oxo, C-C-alkyl, C-C-fluoroalkyl and (C-C-alkyl)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0276] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11 represents, independently in each occurrence, a hydrogen atom and a group selected from C-C-alkyl, C-C-fluoroalkyl, (C-C-cycloalkyl)-(C-C-alkyl)-, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-cycloalkyl-(C=O)-, (phenyl)-(C-C-alkyl)-, (phenyl)-(C-C-alkyl)-C(=O)- and (phenyl)-(C-C-alkyl)-OC(=O)-, wherein C3-C7-cycloalkyl, and C3-C5-cycloalkyl in said (C3-C5-cycloalkyl)-(C1-C2-alkyl)-, and C3-C7-cycloalkyl in the C3-C7-cycloalkyl-(C=O)- group, are optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group selected from cyano, C1-C2-alkyl and C1-C2-fluoroalkyl, and the phenyl group in said (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-OC(=O)- groups may be substituted one or two times by each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0277] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group consisting of cyano, oxo, C-C-alkyl, C-C-fluoroalkyl and (C-C-alkyl)-C(=O)-. and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0278] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, (C-C-alkyl)-C(=O)-, (phenyl)-(C-C-alkyl)-, (phenyl)-(C-C-alkyl)-C(=O)- and (phenyl)-(C-C-alkyl)-OC(=O)-, wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-OC(=O)- groups is optionally substituted once or twice by each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group, or R 10 and R 11 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one or two times by a fluorine atom or by substituents independently selected from oxo, C-C-alkyl, C-C-fluoroalkyl and (C-C-alkyl)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0279] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, (C-C-alkyl)-C(=O)-, (phenyl)-(C-C-alkyl)-, (phenyl)-(C-C-alkyl)-C(=O)- and (phenyl)-(C-C-alkyl)-OC(=O)-, wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-OC(=O)- groups may be substituted once or twice with each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0280] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one or two times by a fluorine atom or by substituents independently selected from oxo, C-C-alkyl, C-C-fluoroalkyl and (C-C-alkyl)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0281] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, (C-C-cycloalkyl)-(C-C-alkyl)-, C-C-cycloalkyl and (phenyl)-(C-C-alkyl)-OC(=O)-, wherein C3-C7-cycloalkyl, and C3-C5-cycloalkyl within said (C3-C5-cycloalkyl)-(C1-C2-alkyl)- group, is optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group selected from cyano, methyl and C1-fluoroalkyl, and the phenyl group in said (phenyl)-(C1-C2-alkyl)-OC(=O)- group is optionally substituted one or two times with each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group, or R 10 and R 11 together with the nitrogen atom to which they are attached, represent a fluorine atom or a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group which may be substituted one or two times with substituents independently selected from groups selected from cyano, methyl and C1-fluoroalkyl. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0282] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, (C-C-cycloalkyl)-(C-C-alkyl)-, C-C-cycloalkyl and (phenyl)-(C-C-alkyl)-OC(=O)-, wherein C3-C7-cycloalkyl, and C3-C5-cycloalkyl within said (C3-C5-cycloalkyl)-(C1-C2-alkyl)- group, is optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group selected from cyano, methyl and C1-fluoroalkyl, and the phenyl group in said (phenyl)-(C1-C2-alkyl)-OC(=O)- group may be substituted one or two times with each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0283] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11 together with the nitrogen atom to which they are attached, represent a fluorine atom or a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group which may be substituted one or two times with substituents independently selected from groups selected from cyano, methyl, and C1-fluoroalkyl. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0284] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl, C3-C7-cycloalkyl and (benzyl)-OC(=O)-, wherein C3-C7-cycloalkyl is optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group selected from methyl and trifluoromethyl, and the phenyl group in the (benzyl)-OC(=O)- group is optionally substituted once or twice with each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group; or R 10 and R 11 together with the nitrogen atom to which they are attached, represent a fluorine atom or a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group which may be substituted one or two times with substituents independently selected from groups selected from cyano, methyl and trifluoromethyl. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0285] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl, C3-C7-cycloalkyl and (benzyl)-OC(=O)-, wherein C3-C7-cycloalkyl is optionally substituted one or two times by a fluorine atom or by substituents independently selected from the group selected from methyl and trifluoromethyl, and the phenyl group in the (benzyl)-OC(=O)- group may be substituted once or twice with each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0286] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11together with the nitrogen atom to which they are attached, represent a fluorine atom or a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group which may be substituted one or two times with substituents independently selected from groups selected from cyano, methyl and trifluoromethyl. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0287] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (benzyl)-OC(=O)-, wherein the phenyl group in the (benzyl)-OC(=O)- group is optionally substituted once or twice with each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group; or R 10 and R 11 together with the nitrogen atom to which they are attached, represent a fluorine atom or a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group which may be substituted one or two times with substituents independently selected from groups selected from cyano, methyl and trifluoromethyl. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0288] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 10 and R 11 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (benzyl)-OC(=O)-, and wherein the phenyl group in the (benzyl)-OC(=O)- group is optionally substituted once or twice with each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0289] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 12 and R 13 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-haloalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-C-alkyl-, (C-C-haloalkoxy)-C-C-alkyl-, (phenoxy)-C-C-alkyl-, C-C-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one or two times by each substituent independently selected from halogen atoms or groups selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, and the phenyl group in the (phenoxy)-C2-C3-alkyl- group and the (phenyl)-(C1-C3-alkyl)- group may be substituted one or two times by fluorine, chlorine and bromine atoms or by substituents independently selected from the group consisting of cyano, methyl, trifluoromethyl and methoxy, or R 12 and R 13 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one or two times with a halogen atom or with substituents independently selected from oxo, C-C-alkyl and (C-C-alkyl)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0290] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 12 and R 13 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-haloalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-C-alkyl-, (C-C-haloalkoxy)-C-C-alkyl-, (phenoxy)-C-C-alkyl-, C-C-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one or two times by each substituent independently selected from halogen atoms or groups selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, and the phenyl group in the (phenoxy)-C2-C3-alkyl- group and the (phenyl)-(C1-C3-alkyl)- group may be substituted one or two times with fluorine, chlorine and bromine atoms or with substituents independently selected from the group consisting of cyano, methyl, trifluoromethyl and methoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0291] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 12 and R 13together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted one or two times with a halogen atom or with substituents independently selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0292] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 12 and R 13 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-haloalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-C-alkyl-, C-C-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one or two times by each substituent independently selected from halogen atoms or groups selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, or R 12 and R 13 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted one or two times with a halogen atom or with substituents independently selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0293] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 12 and R13 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-haloalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-C-alkyl-, C-C-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl may be substituted one or two times by a halogen atom or by substituents independently selected from the group consisting of oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0294] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 12 and R 13 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted one or two times with a halogen atom or with substituents independently selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0295] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 12 and R 13represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-C-alkyl-, (C-C-fluoroalkoxy)-C-C-alkyl-, (phenoxy)-C-C-alkyl-, C-C-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one or two times by a fluorine atom or by each substituent independently selected from the group selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, and the phenyl group in the (phenoxy)-C2-C3-alkyl group and the (phenyl)-(C1-C2-alkyl)- group may be substituted one or two times by fluorine and chlorine atoms or by substituents independently selected from the group consisting of methyl, trifluoromethyl and methoxy, or R 12 and R 13 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted one or two times with a halogen atom or with substituents independently selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0296] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 12 and R 13represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-C-alkyl-, (C-C-fluoroalkoxy)-C-C-alkyl-, (phenoxy)-C-C-alkyl-, C-C-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one or two times by a fluorine atom or by each substituent independently selected from the group selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, and the phenyl group in the (phenoxy)-C2-C3-alkyl- group and the (phenyl)-(C1-C2-alkyl)- group may be substituted one or two times by fluorine and chlorine atoms or by substituents independently selected from the group consisting of methyl, trifluoromethyl and methoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0297] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 12 and R 13 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, C-C-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one or two times by a fluorine atom or by each substituent independently selected from the group selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, or R 12 and R13 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted one or two times with a halogen atom or with substituents independently selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0298] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 12 and R 13 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, C-C-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl may be substituted one or two times by a fluorine atom or by substituents independently selected from the group consisting of oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0299] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 12 and R 13 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted one or two times with a halogen atom or with substituents independently selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0300] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 12 and R 13 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-C-alkyl-, (C-C-fluoroalkoxy)-C-C-alkyl-, (phenoxy)-C-C-alkyl-, C-C-cycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl is optionally substituted one or two times with each substituent independently selected from a fluorine atom or a methyl group, and the phenyl group in the (phenoxy)-C2-C3-alkyl group and the (phenyl)-(C1-C2-alkyl)- group may be substituted one or two times by fluorine and chlorine atoms or by substituents independently selected from the group consisting of methyl, trifluoromethyl and methoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0301] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 12 and R 13 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-alkyl-, (C-C-fluoroalkoxy)-C-alkyl-, (phenoxy)-C-alkyl-, C-C-cycloalkyl and (phenyl)-(C-C-alkyl)-, wherein the phenyl group in the (phenoxy)-C2-alkyl group and the (phenyl)-(C1-C2-alkyl)- group may be substituted once or twice with a fluorine atom and a chlorine atom, or with a group selected from methyl, trifluoromethyl and methoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0302] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 12 and R 13 represents, independently at each occurrence, a hydrogen atom or a group selected from C-C-alkyl, (C-C-alkoxy)-C-alkyl-, (C-C-fluoroalkoxy)-C-alkyl-, (phenoxy)-C-alkyl-, C-C-cycloalkyl and (phenyl)-(C-C-alkyl)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0303] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 14 represents a group selected from C1-C2-alkyl, C1-C2-haloalkyl and phenyl, wherein the phenyl group may be substituted once or twice with a fluorine atom, a chlorine atom, or a bromine atom, or with each substituent independently selected from the group selected from methyl, trifluoromethyl, and methoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0304] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 14represents a group selected from C1-C2-alkyl, C1-C2-haloalkyl and phenyl, wherein the phenyl group may be substituted once or twice with a fluorine atom, a chlorine atom, or a bromine atom, or with each substituent independently selected from the group selected from methyl, trifluoromethyl, and methoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0305] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 14 represents a group selected from C1-C2-alkyl and C1-C2-haloalkyl. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0306] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 14 represents a group selected from methyl and trifluoromethyl. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0307] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 14 represents a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0308] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 17 represents a C1-C4 alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0309] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 17 represents a C1-C3 alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0310] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 17 represents a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0311] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 17 represents a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0312] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 17 represents an ethyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0313] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 18 and R 19 represents, independently in each occurrence, a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0314] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 18 and R 19 represents, independently at each occurrence, a hydrogen atom or a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0315] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 18 and R 19 and both represent a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0316] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 18 and R 19 Both represent hydrogen atoms. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0317] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 18 represents a hydrogen atom, and R 19 represents a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0318] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20is a hydrogen atom or C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C6-C 11 -represents a group selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, naphthyl, and 5- to 10-membered heteroaryl; wherein the C1-C6-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, bicyclic C6-C 11 -optionally substituted one, two or three times with substituents independently selected from groups selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted one or two times with substituents independently selected from groups selected from fluorine, chlorine and bromine atoms, or methyl, trifluoromethyl and methoxy; C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl are optionally substituted one, two or three times by halogen atoms or by substituents independently selected from cyano, oxo, hydroxy, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; and the phenyl, naphthyl and 5-10 membered heteroaryl groups are each independently selected from the group consisting of a halogen atom or cyano, C1-C2-alkyl, C1-C2-haloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and optionally substituted one, two or three times with each substituent independently selected from the group R21 represents a hydrogen atom or a C1-C2-alkyl group, or R 20 and R 21 may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (phenyl)-(C-C-alkyl)-, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of: R 22 and R 23 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 24 and R 25 represents, independently in each occurrence, a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0319] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 is a hydrogen atom or C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C6-C 11 -represents a group selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, naphthyl, and 5- to 10-membered heteroaryl; wherein the C1-C6-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, bicyclic C6-C 11 -optionally substituted one, two or three times with substituents independently selected from groups selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted one or two times with substituents independently selected from groups selected from fluorine, chlorine and bromine atoms, or methyl, trifluoromethyl and methoxy; C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl are optionally substituted one, two or three times by halogen atoms or by substituents independently selected from cyano, oxo, hydroxy, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; and the phenyl, naphthyl and 5-10 membered heteroaryl groups are each independently selected from the group consisting of a halogen atom or cyano, C1-C2-alkyl, C1-C2-haloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and optionally substituted one, two or three times with each substituent independently selected from the group R 21 represents a hydrogen atom or a C1-C2-alkyl group, R 22 and R 23 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 24 and R 25represents, independently in each occurrence, a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0320] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 and R 21 may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (phenyl)-(C-C-alkyl)-, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of: R 22 and R 23 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 24 and R 25 represents, independently in each occurrence, a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0321] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 is a hydrogen atom or a C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C5-C 11-represents a group selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 5- to 10-membered heterocycloalkyl, phenyl, naphthyl, and 5- to 10-membered heteroaryl; wherein the C1-C6-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, bicyclic C5-C 11 -optionally substituted one, two or three times with substituents independently selected from groups selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 5- to 10-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted one or two times with substituents independently selected from groups selected from fluorine, chlorine and bromine atoms, or methyl, trifluoromethyl and methoxy; and C3-C7-cycloalkyl, bicyclic C5-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 5- to 10-membered heterocycloalkyl may be optionally substituted one, two or three times by halogen atoms or by substituents independently selected from cyano, oxo, hydroxy, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; and the phenyl, naphthyl and 5-10 membered heteroaryl groups are each independently selected from the group consisting of a halogen atom or cyano, C1-C2-alkyl, C1-C2-haloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 ), and R 21 represents a hydrogen atom or a C1-C2-alkyl group, or R 20 and R21 may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (phenyl)-(C-C-alkyl)-, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and represents a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0322] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 is a hydrogen atom or a C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C5-C 11 -represents a group selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 5- to 10-membered heterocycloalkyl, phenyl, naphthyl, and 5- to 10-membered heteroaryl; wherein the C1-C6-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, bicyclic C5-C 11-optionally substituted one, two or three times with substituents independently selected from groups selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 5- to 10-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted one or two times with substituents independently selected from groups selected from fluorine, chlorine and bromine atoms, or methyl, trifluoromethyl and methoxy; and C3-C7-cycloalkyl, bicyclic C5-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 5- to 10-membered heterocycloalkyl may be optionally substituted one, two or three times by halogen atoms or by substituents independently selected from cyano, oxo, hydroxy, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; and the phenyl, naphthyl and 5-10 membered heteroaryl groups are each independently selected from the group consisting of a halogen atom or cyano, C1-C2-alkyl, C1-C2-haloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 ), and R 21 represents a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0323] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 is a hydrogen atom or C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C6-C 11-represents a group selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, naphthyl, and 5- to 10-membered heteroaryl; wherein the C1-C6-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, bicyclic C6-C 11 -optionally substituted one, two or three times with substituents independently selected from groups selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted one or two times with substituents independently selected from groups selected from fluorine, chlorine and bromine atoms, or methyl, trifluoromethyl and methoxy; C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl are optionally substituted one, two or three times by halogen atoms or by substituents independently selected from cyano, oxo, hydroxy, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; and the phenyl, naphthyl and 5-10 membered heteroaryl groups are each independently selected from the group consisting of a halogen atom or cyano, C1-C2-alkyl, C1-C2-haloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and optionally substituted one, two or three times with each substituent independently selected from the group R 21 represents a hydrogen atom or a C1-C2-alkyl group, or R 20 and R 21may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (phenyl)-(C-C-alkyl)-, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and represents a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0324] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 is a hydrogen atom or C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C6-C 11 -represents a group selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, naphthyl, and 5- to 10-membered heteroaryl; wherein the C1-C6-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, bicyclic C6-C 11-optionally substituted one, two or three times with substituents independently selected from groups selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted one or two times with substituents independently selected from groups selected from fluorine, chlorine and bromine atoms, or methyl, trifluoromethyl and methoxy; C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl are optionally substituted one, two or three times by halogen atoms or by substituents independently selected from cyano, oxo, hydroxy, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; and the phenyl, naphthyl and 5-10 membered heteroaryl groups are each independently selected from the group consisting of a halogen atom or cyano, C1-C2-alkyl, C1-C2-haloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and optionally substituted one, two or three times with each substituent independently selected from the group R 21 represents a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0325] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 and R 21may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (phenyl)-(C-C-alkyl)-, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and represents a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0326] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 represents a hydrogen atom or a group selected from optionally substituted C1-C3-alkyl, unsubstituted C4-C6-alkyl, prop-2-ynyl, methoxy, C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl and 5- to 10-membered heteroaryl, wherein the C1-C3-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted 1- to 2-times with substituents independently selected from fluorine atoms, chlorine atoms, and methyl groups; the C3-C6-cycloalkyl, adamantyl and monocyclic 4- to 7-membered heterocycloalkyl groups are optionally substituted one, two or three times by fluorine atoms or by substituents independently selected from the group consisting of oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; and the phenyl and 5- to 10-membered heteroaryl groups are substituted with fluorine and chlorine atoms or cyano, C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and optionally substituted one, two or three times with each substituent independently selected from the group R 21 represents a hydrogen atom or a C1-C2-alkyl group, or R 20 and R 21 may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-fluoroalkyl, benzyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of: R 22 and R 23 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 24 and R 25 represents, independently in each occurrence, a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof. In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 represents a hydrogen atom or a group selected from optionally substituted C1-C3-alkyl, unsubstituted C4-C6-alkyl, prop-2-ynyl, methoxy, C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl and 5- to 10-membered heteroaryl, wherein the C1-C3-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted 1- to 2-times with substituents independently selected from fluorine atoms, chlorine atoms, and methyl groups; the C3-C6-cycloalkyl, adamantyl and monocyclic 4- to 7-membered heterocycloalkyl groups are optionally substituted one, two or three times by fluorine atoms or by substituents independently selected from the group consisting of oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; and the phenyl and 5- to 10-membered heteroaryl groups are substituted with fluorine and chlorine atoms or cyano, C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and optionally substituted one, two or three times with each substituent independently selected from the group R 21 represents a hydrogen atom or a C1-C2-alkyl group, R22 and R 23 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 24 and R 25 represents, independently in each occurrence, a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0327] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 and R 21 may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-fluoroalkyl, benzyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of: R 22 and R 23 represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 24 and R 25 represents, independently in each occurrence, a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0328] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 represents a hydrogen atom or a group selected from optionally substituted C1-C3-alkyl, unsubstituted C4-C6-alkyl, prop-2-ynyl, methoxy, C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl and 5- to 10-membered heteroaryl, wherein the C1-C3-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted 1- to 2-times with substituents independently selected from fluorine atoms, chlorine atoms, and methyl groups; the C3-C6-cycloalkyl, adamantyl and monocyclic 4- to 7-membered heterocycloalkyl groups are optionally substituted one, two or three times by fluorine atoms or by substituents independently selected from the group consisting of oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; and the phenyl and 5- to 10-membered heteroaryl groups are substituted with fluorine and chlorine atoms or cyano, C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and optionally substituted one, two or three times with each substituent independently selected from the group R 21 represents a hydrogen atom or a C1-C2-alkyl group, or R 20 and R 21may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-fluoroalkyl, benzyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and represents a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0329] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 represents a hydrogen atom or a group selected from optionally substituted C1-C3-alkyl, unsubstituted C4-C6-alkyl, prop-2-ynyl, methoxy, C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl and 5- to 10-membered heteroaryl, wherein the C1-C3-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted 1- to 2-times with substituents independently selected from fluorine atoms, chlorine atoms, and methyl groups; the C3-C6-cycloalkyl, adamantyl and monocyclic 4- to 7-membered heterocycloalkyl groups are optionally substituted one, two or three times by fluorine atoms or by substituents independently selected from the group consisting of oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; and the phenyl and 5- to 10-membered heteroaryl groups are substituted with fluorine and chlorine atoms or cyano, C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and optionally substituted one, two or three times with each substituent independently selected from the group R 21 represents a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0330] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 and R 21 may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-fluoroalkyl, benzyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and represents a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0331] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 represents a hydrogen atom or a group selected from optionally substituted C1-C3-alkyl, unsubstituted C4-C6-alkyl, prop-2-ynyl, methoxy, C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl and 5- to 10-membered heteroaryl, wherein the C1-C3-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted 1- to 2-times with substituents independently selected from fluorine atoms, chlorine atoms, and methyl groups; and the C3-C6-cycloalkyl, adamantyl and monocyclic 4- to 7-membered heterocycloalkyl groups are optionally substituted one, two or three times by fluorine atoms or by substituents independently selected from the group consisting of oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, and the phenyl and 5-10 heteroaryl groups are substituted with fluorine and chlorine atoms or cyano, C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and optionally substituted one, two or three times with each substituent independently selected from the group R 21 represents a hydrogen atom or a C1-C2-alkyl group, or R 20 and R 21may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-fluoroalkyl, benzyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-fluoroalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and represents a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0332] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 represents a hydrogen atom or a group selected from optionally substituted C1-C3-alkyl, unsubstituted C4-C6-alkyl, prop-2-ynyl, methoxy, C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl and 5- to 10-membered heteroaryl, wherein the C1-C3-alkyl group is a halogen atom or a hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein the phenyl and 5- to 10-membered heteroaryl substituents are themselves optionally substituted 1- to 2-times with substituents independently selected from fluorine atoms, chlorine atoms, and methyl groups; and the C3-C6-cycloalkyl, adamantyl and monocyclic 4- to 7-membered heterocycloalkyl groups are optionally substituted one, two or three times by fluorine atoms or by substituents independently selected from the group consisting of oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, and the phenyl and 5- to 10-membered heteroaryl groups are substituted with fluorine and chlorine atoms or cyano, C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and optionally substituted one, two or three times with each substituent independently selected from the group R 21 represents a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0333] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 and R 21 may be benzo-fused together with the nitrogen atom to which they are attached and may be a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-fluoroalkyl, benzyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-fluoroalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 and represents a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group optionally substituted 1, 2, or 3 times with substituents independently selected from the group consisting of and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0334] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 represents a hydrogen atom or a group selected from C1-C3-alkyl and phenyl, wherein the C1-C3-alkyl group is optionally substituted one or two times with a fluorine atom or with a substituent independently selected from the group consisting of hydroxy, C1-C3-alkoxy and phenyl, and the phenyl itself is optionally substituted one or two times with a substituent independently selected from the group consisting of a fluorine atom, a chlorine atom and a methyl group, and said phenyl group is optionally substituted one, two or three times with fluorine and chlorine atoms or with substituents independently selected from groups selected from methyl, trifluoromethyl, methoxy and trifluoromethoxy; R 21 represents a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0335] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 20 represents a group selected from benzyl and phenyl, wherein the phenyl group and the phenyl group in the benzyl group are optionally substituted once or twice with each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group; R 21 represents a hydrogen atom or a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0336] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 22 and R 23represents, independently at each occurrence, a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0337] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 22 and R 23 represents, independently at each occurrence, a hydrogen atom or a group selected from methyl and (CH3)-C(=O)-. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof. In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 24 and R 25 represents, independently in each occurrence, a hydrogen atom or a C1-C2-alkyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0338] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 24 and R 25 represents, independently at each occurrence, a hydrogen atom or a methyl group. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0339] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 26 represents a fluorine atom, a chlorine atom or a group selected from C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy and C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0340] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 26 represents a fluorine atom, a chlorine atom or a bromine atom, or a group selected from methyl, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0341] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 26 represents a fluorine atom, a chlorine atom, or a group selected from methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0342] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 26 represents a fluorine atom, a chlorine atom or a bromine atom, or a group selected from difluoromethyl, methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0343] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 26represents a fluorine atom, a chlorine atom, or a group selected from difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0344] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 27 is a halogen atom or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ) and -C(=O)-OR 17 represents a group selected from the group and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0345] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 27 represents a fluorine atom, a chlorine atom or a group selected from C1-C2-alkoxy, benzyloxy and C1-C2-fluoroalkoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0346] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 27 is a halogen atom or -OR 9 , -N(R 10 )(R 11 ) and -C(=O)-N(R 12 )(R 13 represents a group selected from and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0347] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: R 27 represents a chlorine atom or a group selected from methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0348] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: n represents an integer of 0, 1, or 2. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0349] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: n represents an integer of 0 or 2. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0350] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: n represents the integer 0. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0351] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: n represents the integer 2. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0352] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: Y 1 represents -C(H)=, -C(F)=, -C(Cl)=, -C(CN)= or -N=. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0353] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: Y 1 represents -C(H)=, -C(F)=, -C(Cl)= or -N=. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0354] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: Y 1 represents -C(H)=, -C(F)= or -N=. and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0355] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: Y 1 represents -C(H)= or -C(F)= and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0356] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: Y 1 represents -C(H)= and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0357] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: Y 1 represents -C(Cl)= and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0358] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: Y 1 represents -C(F)= and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0359] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: Y 1 represents -N= and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0360] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: Y 2 represents -C(H)= or -N=, Y 3 is -C(R 27 )= or -N=, However, Y 2 If represents -N=, then Y 3 -C(R 27 )=, Y 3 If represents -N=, then Y 2 represents -C(H)= and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0361] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: Y 2 represents -C(H)= and -N=, Y 3 is -C(R 27 )= and -N=, However, Y 2 If represents -N=, then Y 3 -C(R 27 )=, Y 3 If represents -N=, then Y 2 represents -C(H)= and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0362] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: Y 2 represents -N=; Y 3 is -C(R 27 ) = represents and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0363] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: Y 2 represents -C(H)=; Y 3 represents -N= and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0364] In a further embodiment of the first aspect, the present invention provides a compound of formula (I) above, wherein: Y 2 represents -C(H)=; Y 3 is -C(R 27 ) = represents and the stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures thereof.

[0365] In certain further embodiments of the first aspect, the invention encompasses combinations of two or more of the above embodiments entitled "Further Embodiments of the First Aspect of the Invention."

[0366] The present invention includes any subcombination of compounds of general formula (I) above within any embodiment or aspect of the invention.

[0367] The present invention includes compounds of general formula (I) disclosed in the Examples section of the text below.

[0368] The compound of the present invention represented by general formula (I) can be converted into any salt described herein, preferably a pharmaceutically acceptable salt, by any method known to those skilled in the art.Similarly, any salt of the compound of the present invention represented by general formula (I) can be converted into the free compound by any method known to those skilled in the art. The compounds of general formula (I) of the present invention exhibit an unexpectedly beneficial pharmacological spectrum of action. The compounds of the present invention have surprisingly been found to effectively inhibit DGKζ, and therefore can be used to treat or prevent diseases in mammals, including humans, preferably conditions with a dysregulated immune response, in particular cancer, or other disorders associated with abnormal DGKζ signaling.

[0369] Disorders and conditions particularly suitable for treatment with the DGKζ inhibitors of the present invention include liquid and solid tumors, such as cancers of the breast, respiratory tract, brain, reproductive organs, gastrointestinal tract, urinary tract, eye, liver, skin, head and neck, thyroid, parathyroid, etc., and their distant metastases. These disorders also include lymphomas, sarcomas, and leukemias.

[0370] Examples of breast cancer include, but are not limited to, triple-negative breast cancer, invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, and lobular carcinoma in situ.

[0371] Examples of cancers of the respiratory tract include, but are not limited to, small-cell and non-small-cell lung carcinoma, as well as bronchial adenoma and pleuropulmonary blastoma.

[0372] Examples of brain tumors include, but are not limited to, brain stem and hypothalamic glioma, cerebellar and cerebral astrocytoma, glioblastoma, medulloblastoma, ependymoma, as well as neuroectodermal and pineal tumor.

[0373] Tumors of the male reproductive organs include, but are not limited to, prostate and testicular cancer.

[0374] Tumors of the female reproductive organs include, but are not limited to, endometrial, cervical, ovarian, vaginal, and vulvar cancer, as well as sarcoma of the uterus.

[0375] Examples of ovarian cancer include, but are not limited to, serous tumor, endometrioid tumor, mucinous cystadenocarcinoma, granulosa cell tumor, Sertoli-Leydig cell tumor, and arenoblastoma.

[0376] Examples of cervical cancer include, but are not limited to, squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, small cell carcinoma, neuroendocrine tumors, hyaline cell carcinoma, and chorioalveolar adenocarcinoma.

[0377] Tumors of the digestive tract include, but are not limited to, anal, colon, colorectal, esophageal, gallbladder, gastric, pancreatic, rectal, small intestine, and salivary gland cancer.

[0378] Examples of esophageal cancer include, but are not limited to, esophageal carcinoma and adenocarcinoma, as well as squamous cell carcinoma, leiomyosarcoma, malignant melanoma, rhabdomyosarcoma, and lymphoma.

[0379] Examples of gastric cancer include, but are not limited to, intestinal-type and diffuse-type gastric adenocarcinoma.

[0380] Examples of pancreatic cancer include, but are not limited to, ductal adenocarcinoma, adenosquamous carcinoma, and pancreatic endocrine tumors.

[0381] Tumors of the urinary tract include, but are not limited to, bladder, penile, kidney, renal pelvis, ureter, urethral, ​​and human papillary renal carcinoma.

[0382] Examples of renal cancer include, but are not limited to, renal cell carcinoma, urothelial cell carcinoma, juxtaglomerular cell tumor (reninoma), angiomyolipoma, renal oncocytoma, Bellini duct carcinoma, clear cell sarcoma of the kidney, mesoblastic nephroma, and Wilms' tumor.

[0383] Examples of bladder cancer include, but are not limited to, transitional cell carcinoma, squamous cell carcinoma, adenocarcinoma, sarcoma, and small cell carcinoma.

[0384] Eye cancers include, but are not limited to intraocular melanoma and retinoblastoma.

[0385] Examples of liver cancer include, but are not limited to, hepatocellular carcinoma (hepatocellular carcinoma with or without the fibrolamellar variant), cholangiocarcinoma (intrahepatic cholangiocarcinoma), and mixed hepatocellular-cholangiocarcinoma.

[0386] Skin cancers include, but are not limited to squamous cell carcinoma, Kaposi's sarcoma, malignant melanoma, Merkel cell skin cancer, and non-melanoma skin cancer.

[0387] Head and neck cancers include, but are not limited to, squamous cell carcinoma of the head and neck, laryngeal, hypopharyngeal, nasopharyngeal, oropharyngeal cancer, salivary gland cancer, lip and oral cavity cancer, and squamous cell.

[0388] Lymphomas include, but are not limited to, AIDS-related lymphoma, non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, Burkitt lymphoma, Hodgkin's disease, and lymphoma of the central nervous system.

[0389] Sarcomas include, but are not limited to, sarcoma of the soft tissue, osteosarcoma, malignant fibrous histiocytoma, lymphosarcoma, and rhabdomyosarcoma.

[0390] Leukemias include, but are not limited to acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, and hairy cell leukemia.

[0391] The terms "treat" or "treatment" as used throughout this document are conventionally used for the management or care of a subject for the purposes of combating, alleviating, reducing, relieving, or improving the condition of a disease or disorder, e.g., cancer.

[0392] The compounds of the present invention can be used in particular in the treatment and prevention, ie prophylaxis, of tumor growth and metastasis, especially in solid tumors of all indications and stages with or without prior treatment of tumor growth.

[0393] In general, the use of chemotherapeutic and / or anti-cancer agents in combination with the compounds or pharmaceutical compositions of the present invention involves: 1. Provides better efficacy in reducing tumor growth or eliminating tumors compared with administration of either agent alone; 2. Providing for the administration of smaller amounts of administered chemotherapy agents; 3. Providing chemotherapy treatments that are well tolerated in patients with fewer adverse pharmacological complications than those observed with single-agent chemotherapy and certain other combination therapies; 4. To provide treatment for a wider variety of different cancers in mammals, particularly humans; 5. Increase response rates in treated patients 6. Extends survival of treated patients compared to standard chemotherapy; 7. Increased time to tumor progression, and / or 8. Produce efficacy and tolerability results at least comparable to those of the agents used alone compared with known instances where other anticancer drug combinations produce antagonistic effects.

[0394] Furthermore, the compounds of general formula (I) of the present invention can also be used in combination with radiotherapy and / or surgical intervention. In a further embodiment of the present invention, the compounds of general formula (I) of the present invention are used in combination with radiation: radiation therapy sensitizes cancer to anti-tumor immune responses by inducing tumor cell death and subsequently presenting tumor neoantigens to tumor-reactive T cells. Because DGKζ enhances antigen-specific activation of T cells, the overall effect is much stronger in attacking cancer cells compared to radiation therapy alone.

[0395] Thus, the present invention also provides methods of killing tumors in which conventional radiation therapy is used prior to administering one or more of the compounds of the present invention.

[0396] The compound of the present invention can be administered as the sole pharmaceutical agent or in combination with one or more other pharmaceutically active ingredients, and this combination does not cause unacceptable adverse effects.The present invention also encompasses such pharmaceutical combinations.For example, the compound of the present invention can be combined with: 131I-chTNT, abarelix, abemaciclib, abiraterone, acalabrutinib, aclarubicin, adalimumab, ado-trastuzumab emtansine, afatinib, aflibercept, aldesleukin, alectinib, alemtuzumab, alendronate, alitretinoin, alpharadin, altretamine, amifostine, aminoglutethimide, hexylaminolevulinate, amrubicin, amsacrine, anastrozole, ancestim, anetholethiourethion, anethumab ravtansine, angiotensin II, antithrombin III, apalutamide, aprepitant, arcitumomab, aruglavin, arsenic trioxide, asparaginase, atezolizumab, avelumab, axicabtagene Ciloreucel, axitinib, azacitidine, basiliximab, belotecan, bendamustine, besilesomab, belinostat, bevacizumab, bexarotene, bicalutamide, bisantrene, bleomycin, blinatumomab, bortezomib, bosutinib, buserelin, brentuximab vedotin, brigatinib, busulfan, cabazitaxel, cabozantinib , calcitonin, calcium folinate, calcium levofolinate, capecitabine, capromab, carbamazepine, carboplatin, carboquone, carfilzomib, carmofur, carmustine, catumaxomab, celecoxib, celmoleukin, cemiplimab, ceritinib, cetuximab, chlorambucil, chlormadinone, chlormethine, cidofovir, cina Calcet, cisplatin, cladribine, clodronate, clofarabine, cobimetinib, copanlisib, crisantaspase, crizotinib, cyclophosphamide, cyproterone, cytarabine, dacarbazine, dactinomycin, daratumumab, darbepoetin alfa, dabrafenib, dasatinib, daunorubicin, decitabine, degarelix, denileukin diftitox, denosumab, depreotide, deslorelin, dianhydrogalactitol, dexrazoxane, dibrospidium chloride, dianhydrogalactitol, diclofenac, dinutuximab, docetaxel, dolasetron, doxifluridine, doxorubicin, doxorubicin + estrone, dronabinol, durvalumab, eculizumab, edrecolomab,Elimsertib (BAY1895344), elliptinium acetate, elotuzumab, eltrombopag, enasidenib, endostatin, enocitabine, enzalutamide, epirubicin, epithiostanol, epoetin alfa, epoetin beta, epoetin zeta, eptaplatin, eribulin, erlotinib, esomeprazole, estradiol, estramustine, ethinyl estradiol, etoposide, everolimus, exemestane, fadrozole, fentanyl, filgrastim, fluoxymesterone, floxuridine, fluoxetine Darabine, fluorouracil, flutamide, folinic acid, formestane, fosaprepitant, fotemustine, fulvestrant, gadobutrol, gadoteridol, gadoterate meglumine, gadoversetamide, gadoxetic acid, gallium nitrate, ganirelix, gefitinib, gemcitabine, gemtuzumab, glucarpidase, glutoxime, GM-CSF, goserelin, granisetron, granulocyte colony-stimulating factor, histamine dihydrochloride, histrelin, hydroxycarbamide, I-125 seed, lansoprazole, ibandronate, ibritumomab, tiuxetan, ibrutinib, idarubicin, ifosfamide, imatinib, imiquimod, improsulfan, indisetron, incadronic acid, ingenol mebutate, inotuzumab Ozogamicin, interferon alpha, interferon beta, interferon gamma, iobitridol, iobenguane (123I), iomeprol, ipilimumab, irinotecan, itraconazole, ixabepilone, ixazomib, lanreotide, lansoprazole, lapatinib, lasocolin, lenalidomide, lenvatinib, lenograstim, lentinan, letrozole, leuprorelin, levamisole , levonorgestrel, levothyroxine sodium, lisuride, lobaplatin, lomustine, lonidamine, lutetium Lu177 dotatate, masoprocol, medroxyprogesterone, megestrol, melarsoprol, melphalan, mepitiostane, mercaptopurine, mesna, methadone, methotrexate, methoxsalen, methyl aminolevulinate, methylprednisolone, methyltestosterone, metyrosine, midostaurin, mifamurtide,Miltefosine, miriplatin, mitobronitol, mitoguazone, mitolactol, mitomycin, mitotane, mitoxantrone, mogamulizumab, molgramostim, mopidamol, morphine hydrochloride, morphine sulfate, MVAS1 (bevacizumab-awwb), nabilone, nabiximols, nafarelin, naloxone + pentazocine, naltrexone, nartograstim, necitumumab, nedaplatin, nelarabine, neratinib, neridronic acid, netupitant / palonosetron, nivolumab, pentetreotide, nilotinib, nilutamide, nimorazole , nimotuzumab, nimustine, nintedanib, niraparib, nitracrine, nivolumab, obinutuzumab, octreotide, ofatumumab, olaparib, olaratumab, omacetaxine mepesuccinate, omeprazole, ondansetron, oprelvekin, orgotein, orilotimod, osimertinib, oxaliplatin, oxycodone, oxymetholone, ozogamicin, p53 gene therapy, paclitaxel, palbociclib, palifermin, palladium-103 seed, palonosetron, pamidronate, panitumumab, panobistat, pan Toprazole, pazopanib, pegaspargase, PEG-epoetin beta (methoxyPEG-epoetin beta), pembrolizumab, pegfilgrastim, peginterferon alfa-2b, pemetrexed, pentazocine, pentostatin, peplomycin, perflubutane, perfosfamide, pertuzumab, picibanil, pilocarpine, pirarubicin, pixantrone, plerixafor, pli...

Claims

【Request 1】 【Chemistry 1】 or a stereoisomer thereof, a hydrate or solvate thereof, or a pharma- ceutically acceptable salt of any of the above.

2. The compound is 【Chemistry 2】 2. The compound of claim 1, wherein:

3. The compound is 【Chemistry 3】 2. The compound of claim 1 ,

4. 10. A pharmaceutical composition comprising a compound according to claim 1, or a hydrate or solvate thereof, or a pharma- ceutically acceptable salt of any of the above, and at least one pharma- ceutically acceptable excipient.

5. 10. A pharmaceutical composition comprising a compound according to claim 2, or a hydrate or solvate thereof, and at least one pharma- ceutically acceptable excipient.

6. A pharmaceutical composition comprising a compound of claim 3 and at least one pharma- ceutically acceptable excipient.

7. A pharmaceutical composition for treating or preventing a disease or condition associated with a dysregulated immune response or abnormal DGKζ signaling in a mammal, comprising an effective amount of a compound according to claim 1, or a hydrate or solvate thereof, or a pharma- ceutically acceptable salt of either of the above.

8. The pharmaceutical composition of claim 7, wherein the mammal is a human.

9. The pharmaceutical composition according to claim 7, wherein the disease is cancer.

10. The pharmaceutical composition according to claim 7 , wherein the compound or a pharma- ceutically acceptable salt thereof exerts its effect via T cell activation.

11. 8. The pharmaceutical composition of claim 7, wherein the disease is non-small cell lung cancer (NSCLC), gastric cancer, esophageal adenocarcinoma, skin cancer, or colorectal cancer.

12. The pharmaceutical composition according to claim 7, wherein the disease is non-small cell lung cancer.

13. The pharmaceutical composition according to claim 7, wherein the disease is gastric cancer.

14. The pharmaceutical composition according to claim 7, wherein the disease is esophageal adenocarcinoma.

15. The pharmaceutical composition according to claim 7, wherein the disease is skin cancer.

16. The pharmaceutical composition of claim 15, wherein the skin cancer is malignant melanoma.

17. The pharmaceutical composition according to claim 7, wherein the disease is colorectal cancer.

18. A pharmaceutical composition for treating or preventing a disease or condition associated with a dysregulated immune response or abnormal DGKζ signaling in a mammal, comprising an effective amount of a compound according to claim 3.

19. 20. The pharmaceutical composition of claim 18, wherein the mammal is a human.

20. The pharmaceutical composition of claim 18, wherein the disease is cancer.

21. 20. The pharmaceutical composition of claim 18, wherein the compound exerts its effect via T cell activation.

22. 19. The pharmaceutical composition of claim 18, wherein the disease is non-small cell lung cancer (NSCLC), gastric cancer, esophageal adenocarcinoma, skin cancer, or colorectal cancer.

23. The pharmaceutical composition according to claim 18, wherein the disease is non-small cell lung cancer.

24. The pharmaceutical composition according to claim 18, wherein the disease is gastric cancer.

25. The pharmaceutical composition of claim 18, wherein the disease is esophageal adenocarcinoma.

26. The pharmaceutical composition of claim 18, wherein the disease is skin cancer.

27. 27. The pharmaceutical composition of claim 26, wherein the skin cancer is malignant melanoma.

28. 19. The pharmaceutical composition of claim 18, wherein the disease is colorectal cancer.

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