Substituted aminothiazoles as DGKZETA inhibitors for immune activation

Abstract

The present invention relates to aminothiazole compounds of general formula (I), wherein R 1 , R 2 , R 3 and R 4 as defined herein, and also relates to methods for preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds as a single agent or in combination with other active ingredients in the preparation of pharmaceutical compositions for the treatment and / or prevention of diseases, in particular diseases regulated by diacylglycerol kinase ζ (DGKζ).

Description

Technical Field

[0001] The present invention relates to substituted aminothiazole compounds of general formula (I) as described and defined herein, methods for preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds as a single agent or in combination with other active ingredients in the preparation of pharmaceutical compositions for the treatment or prevention of diseases, in particular diseases regulated by diacylglycerol kinase ζ (DGKzeta, DGKζ).

[0002] The compounds of general formula (I) inhibit DGKζ and thereby enhance T cell-mediated immune responses. This is a new strategy for using the patient's own immune system to overcome the immune escape strategies exploited by many tumor diseases (various cancers) and thereby enhance anti-tumor immunity. In addition, the compounds are particularly useful for treating diseases such as viral infections or disorders of immune response or other diseases associated with abnormal DGKζ signal transduction.

[0003] The present invention also relates to the use of the compounds of general formula (I) in the preparation of pharmaceutical compositions for enhancing T cell-mediated immune responses.

[0004] The present invention also relates to the use of the compounds of general formula (I) in the preparation of pharmaceutical compositions for the treatment of cancer.

[0005] The present invention also relates to the use of the compounds of general formula (I) in the preparation of pharmaceutical compositions for the treatment or prevention of viral infections, lymphoproliferative diseases, asthma, eye diseases and type 2 diabetes / insulin resistance. Background Art

[0006] 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 forms downstream of the T cell receptor (TCR) after activation of the gamma-1 subtype of phospholipase C (PLCγ1) and cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into DAG and an additional second messenger, inositol 1,4,5-trisphosphate (IP3) (S. Krishna and X.-P. Zhong, Front. Immunol. 2013, 4, 178). However, IP3 is important in promoting the release of calcium from the endoplasmic reticulum, while DAG interacts with other proteins important for TCR signal transduction, such as protein kinase C theta (E.J. Quann et al., Nat. Immunol. 2011, 12(7), 647-654) and the Ras activator RasGRP1 (S. Krishna and X.-P. Zhong, Front. Immunol. 2013, 4, 178). Although three DGK subtypes [DGKα (DGKalpha), DGKδ (DGKdelta), and DGKζ (DGKzeta)] are known to be present in T cells, only two (DGKα and DGKζ) are thought to play important roles in promoting DAG metabolism downstream of the TCR (R.P. 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 using chemical inhibitors results in enhanced and sustained signal transduction downstream of T cells, which can be assessed by the prolonged phosphorylation of downstream molecules such as extracellular signal-related kinases 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 results in enhanced production of effector cytokines (such as IL2, IFNγ) and enhanced proliferation (X.-P. Zhong et al., Nat. Immunol. 2003, 4, 882 - 890; BAOlenchock et al., Nat. Immunol. 2006, 7(11), 1174 - 1181; E.M. Riese et al., J. Biol. Chem. 2011, 286, 5254 - 5264).

[0009] Compared with controls, adoptive transfer of DGKζ - deficient T cells reduced leukemia burden after inoculation with C1498.SIY leukemia cells. In addition, DGKζ - deficient T cells were at least partially resistant to PD1 - mediated inhibitory signals (W. Jing et al., Cancer Res. 2017, 77(20), 5676 - 5686). In addition, after orthotopic tumor injection in a pancreatic tumor model, DGKζ - deficient mice had reduced tumor size compared with controls (E.M. Wesley et al., ImmunoHorizons, 2018, 2(4), 107 - 118). In addition, S. Wee et al. inoculated C57BL / 6 mice with multiple syngeneic tumor cell lines - MC38 colon cancer, B16F1 melanoma, and C1498 leukemia - and analyzed survival and tumor growth among DGKζ - deficient mice in the presence or absence of anti - PD1 treatment. DGKζ− / − mice inhibited the growth of subcutaneously implanted tumor cells in three model systems, and the combination of DGKζ - deletion and anti - PD1 had an additive effect on tumor control (S. Wee et al., Proceedings of the American Association for Cancer Research Annual Meeting 2019; Cancer Res. 2019, 79(13Suppl):Abstract nr 936).

[0010] These findings suggest that DGKζ can serve as a useful target for enhancing T - cell anti - tumor activity.

[0011] In addition, compared with wild - type CAR T cells, adoptively transferred DGKζ - deficient CAR (chimeric antigen receptor) - T cells showed higher efficacy in treating murine mesothelioma (M.J. Riese et al., Cancer Res. 2013, 73(12), 3566 - 3577) and in combination with DGKα knockout in a glioblastoma xenograft mouse model (I. - Y. Jung et al., Cancer Res. 2018, 78(16), 4692 - 4703).

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

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

[0014] In addition to immune cell regulation, DGKζ also plays a role in many aspects of cancer cell progression, mediating proliferation, apoptosis, survival, invasion, and tumorigenicity, such as 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] In addition, DGKζ knockout reduces airway inflammation and airway hyperreactivity in mice and also reduces bronchoconstriction in human airway samples in vitro by blocking T helper 2 (TH2) differentiation (B. A. Singh et al., Sci. Signal. 2019, 12:eaax3332).

[0016] Taken together, the results of these studies suggest that inhibiting DGKζ activity in T cells and tumor cells may be beneficial in generating stronger immune responses against pathogens and tumors and in improving Th2-driven (auto)immune diseases (rebalancing the immune system).

[0017] In addition, inhibiting DGKα has the potential to reverse life-threatening Epstein-Barr virus (EBV)-associated immunopathology in patients with X-linked lymphoproliferative disease (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 mode of action, it can be hypothesized that inhibiting DGKζ would have a similar effect.

[0018] DGKα-inhibitor II (R59949) can inhibit retinal neovascularization and protect retinal astrocytes in an oxygen-induced retinopathy model (L. Yang et al., J. Mol. Neurosci. 2015, 56, 78-88). In addition, based on the mode of action, it can be hypothesized that inhibiting DGKζ would produce a similar effect.

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

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

[0021] Prior art

[0022] WO2020 / 006016 and WO2020 / 006018 disclose naphthyridone compounds as T cell activators that inhibit the activity of DGKα and / or DGKζ for the treatment of viral infections and proliferative diseases such as cancer. WO2021 / 041588 discloses pyridopyrimidone compounds as T cell activators that inhibit the activity of DGKα and / or DGKζ for the treatment of viral infections and proliferative diseases such as cancer.

[0023] 2,4,5-Trisubstituted triazole derivatives in which a substituted amino group is 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.

[0024] WO 2014 / 181287 discloses heterocyclic compounds as inhibitors of interleukin 17 and tumor necrosis factor α.

[0025] WO 2014 / 173904 discloses compounds with antibacterial activity.

[0026] WO 2009 / 149054 discloses small molecule inhibitors for the treatment or prevention of dengue infection.

[0027] WO 2007 / 130075 discloses aminothiazole derivatives as inhibitors of human stearoyl-CoA desaturase.

[0028] WO 2012 / 064715 discloses compositions and methods related to heat shock transcription factor activating compounds and their targets.

[0029] WO 2005 / 103022 discloses substituted thiazole and pyrimidine derivatives as melanocortin receptor modulators.

[0030] CN 106109467 discloses the medical use of aromatic compounds including thiazole in the treatment of pyrazinamide-resistant tuberculosis.

[0031] WO 2015 / 199206 discloses compounds derived from six-membered rings as TRPV4 inhibitors.

[0032] WO 2015 / 046193 discloses aromatic heterocyclic amine derivatives as TRPV4 inhibitors.

[0033] CN 103159695 discloses thiazole compounds capable of inhibiting the replication of human immunodeficiency (HIV) virus and effectively combating drug-resistant HIV virus strains.

[0034] WO 2013 / 056684 discloses thiazole derivatives as dihydroorotate dehydrogenase (DHODH) inhibitors.

[0035] WO 2013 / 033037 discloses compounds of various chemical types, especially thiazole derivatives, as anti-prion compounds.

[0036] WO 2012 / 075393 discloses compounds of various chemical types, especially thiazole derivatives, as activators of proteasomal degradation.

[0037] JP 20 11032254 discloses compounds of various chemical types, especially thiazole derivatives, as pest control agents.

[0038] WO 2009 / 041790 discloses 2,4,5-trisubstituted thiazole derivatives as inhibitors of sphingosine phosphocholine (SPC) receptors for the treatment of inflammatory diseases.

[0039] WO 2008 / 090382 discloses thiazole and oxazole derivatives for the treatment of prion diseases, cancer and central nervous system disorders and for regulating stem cells.

[0040] WO 2007 / 022415 discloses substituted 2-aminothiazoles for the treatment of neurodegenerative diseases.

[0041] WO 2006 / 122011 discloses thiazole compounds and methods for the treatment of viral infections, especially hepatitis C virus infection.

[0042] WO 2006 / 078287 discloses derivatives of various 5-membered heteroarenes, especially thiazoles, as inhibitors of phosphodiesterase 4B.

[0043] WO 2005 / 102318, WO 2005 / 102325, WO 2005 / 102326, WO 2005 / 102346, WO 2005 / 102455, WO 2005 / 112920, WO 2005 / 115304, WO 2005 / 115385 all relate to c-Kit inhibitors of various chemical types, including 2-aminothiazole derivatives and their various uses.

[0044] EP 1543824 and US 2005 / 0137239 disclose that thiazole derivatives counteract glycosylation.

[0045] WO 2004 / 014884 discloses thiazole derivatives as neuropeptide Y receptor ligands.

[0046] WO 2019 / 133445 discloses aminothiazole derivatives as Vanin-1 inhibitors.

[0047] WO 2021 / 043966 discloses substituted five-membered nitrogen-containing heteroaryl compounds as inhibitors of the NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3).

[0048] 2,4,5-trisubstituted triazole derivatives are structurally related to the compounds of the present invention, but are structurally different from the compounds disclosed in several scientific publications.

[0049] The general review of the synthesis of thiazoles by D. Kikelj and U. Urleb in Science of Synthesis (2002), 11, 627 - 833. To date, most of the specific compounds disclosed are structurally far from the compounds of the present invention, except for having the same thiazole nucleus as the compounds of the present invention. Several of the individual compounds disclosed therein, namely the compounds disclosed on pages 651, 681 - 683 and 719, including {4-methyl-2-[methyl(phenyl)amino]-1,3-thiazol-5-yl}(phenyl)methanone, are somewhat structurally related to the compounds of the present invention, but are still structurally different.

[0050] 2,4,5-trisubstituted triazole derivatives are structurally related to the compounds of the present invention, but are structurally different from the compounds disclosed in several journal articles.

[0051] The journal articles listed below also disclose some compounds that are somewhat structurally related to the compounds of the present invention but are still structurally different, and none disclose the pharmaceutical use treatment of the compounds disclosed herein.

[0052] The four-component synthesis of 4-hydrazinothiazole derivatives was disclosed by S. Titus et al. in Tetrahedron Lett. 2014, 55, 5465-5467.

[0053] The spectroscopic and chemical studies of 5-acyl and 5-nitroso-2-(N,N-disubstituted amino)thiazoles were disclosed by T. N. Birkinshaw et al. in J. Chem. Soc. Perkin Trans. 1, 1988, 2209-2212.

[0054] The study on the formation of the isomeric 2-(N,N-disubstituted amino)thiazol-5-yl ketones was disclosed by R. A. Funnell et al. in J. Chem. Soc. Perkin Trans. 1, 1987, 2311-2315.

[0055] The conversion of N'-substituted N-acyl and N-iminothioureas into 2-(N,N-disubstituted amino)thiazol-5-yl ketones was disclosed by J. C. Brindley et al. in J. Chem. Soc. Perkin Trans. 1, 1987, 1153-1158.

[0056] The chemical reaction that unexpectedly produces 5-benzoyl-4-methyl-2-(N-methyl-N-phenylamino)thiazole was disclosed by G. D. Meakins et al. in J. Chem. Soc. Chem. Comm. 1984, 837-838.

[0057] The synthesis of certain 2-arylaminothiazoles by the 1,3-cycloaddition of 4-aryl-3-arylimino-5-imino-1,2,4-thiadiazolane (also known as Hector base) and acetylene was disclosed by K. Akiba et al. in Tetrahedron Lett. 1975, 7, 459-462.

[0058] Finally, in the Chemical Abstracts Service (CAS) registry of the database three structures that are structurally somewhat related to the compounds of the present invention but still different in structure were disclosed, all without references and without technical applications, and all have CAS registration numbers 1349635-19-3, 1349215-57-1, and 1348293-02-6.

[0059] However, the prior art does not disclose:

[0060] · The specific substituted aminothiazole compounds of general formula (I) as described and defined herein, i.e., compounds having a 2-aminothiazole nucleus with

[0061] · An optionally substituted 5-membered heteroaroyl group attached to C-5,

[0062] · -NH2 or methyl group connected to C-4,

[0063] · and (i) optionally substituted phenyl or 5- or 6-membered heteroaryl and (ii) an alkyl group laterally substituted by a group -S(=O)2-NH2 or especially -C(=O)-NH2, where both (i) and (ii) are connected to the nitrogen atom linked to C-2, and said laterally substituted alkyl group is essential for effectively inhibiting DGKζ, as shown in the comparative experiments below,

[0064] or its stereoisomers, tautomers, N-oxides, hydrates, solvates, salts or mixtures thereof, as described and defined herein, and hereinafter referred to as "compounds of general formula (I)" or "compounds of the present invention",

[0065] · or their pharmacological activities.

[0066] There is a need to provide new compounds with prophylactic and therapeutic properties.

[0067] Accordingly, an object of the present invention is to provide compounds and pharmaceutical compositions containing these compounds for the prophylactic and therapeutic use in the regulation of DGKζ in a T cell immune-stimulating or immunomodulatory manner. Diseases regulated by DGKζ include diseases with dysregulated immune responses, especially in the immunosuppressive tumor microenvironment in cancer, autoimmune diseases, viral infections, and other diseases associated with abnormal DGKζ signal transduction. The compounds can be used as a single agent or in combination with other active ingredients.

[0068] It has now been found, and this forms the basis of the present invention, that the compounds of the present invention have unexpected and advantageous properties.

[0069] In particular, it has unexpectedly been found that the compounds of the present invention effectively inhibit DGKζ protein and thereby enhance T cell-mediated immunity. Thus, they provide a new structure for treating mammalian diseases, including humans, especially cancer, and can therefore be used for treating or preventing hyperproliferative diseases, such as cancer. Summary of the Invention

[0070] According to a first aspect, the present invention relates to compounds of general formula (I):

[0071]

[0072] Wherein:

[0073] R 1represents a phenyl or 6-membered heteroaryl group optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: 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 ),

[0074] wherein the phenyl in the (phenyl)-(C1-C3-alkyl)- and (phenyl)-(C1-C3-alkoxy)- groups is optionally substituted one or two times, each substituent independently selected from a halogen atom or a group selected from: cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy,

[0075] alternatively, two substituents attached to adjacent carbon atoms of the 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-,

[0076] or

[0077] R 1 represents a 5-membered heteroaryl group optionally substituted one or two times, each substituent independently selected from a halogen atom or a group selected from: cyano, C1-C3-alkyl and C1-C3-alkoxy;

[0078] R 2 represents the group

[0079] wherein “*” represents the point of attachment to the nitrogen atom to which R 2 is attached;

[0080] R 3 represents a group selected from methyl and -NH2;

[0081] R 4 represents a 5-membered heteroaryl group optionally substituted one or two times, each substituent independently selected from a halogen atom or a group selected from: C1-C6-alkyl, ((R 9 )O)-(C1-C3-alkyl)-, ((R 10 )(R 11N)-(C1-C3-alkyl)-, (C3-C7-cycloalkyl)-(C1-C3-alkyl)-, C3-C7-cycloalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 15 )(R 16 ), -C(=O)-OR 17 , phenyl and 5- or 6-membered heteroaryl,

[0082] wherein the phenyl and 5- or 6-membered heteroaryl are optionally substituted one or two times, each substituent independently selected from a halogen atom or a group selected from: cyano, C1-C3-alkyl, C1-C3-haloalkyl, ((R 22 )(R 23 ))N)-C1-C3-alkyl, -OR 9 , -N(R 10 )(R 11 ) and -C(=O)-N(R 15 )(R 16 );

[0083] R 5 and R 6 independently represent a hydrogen atom or a group selected from: C1-C4-alkyl, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl and (phenyl)-(C1-C3-alkyl)-, or

[0084] 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, which is optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: oxo, hydroxy, C1-C4-alkyl, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl and C1-C4-alkoxy;

[0085] R 7 represents a hydrogen atom or C1-C2-alkyl;

[0086] R 8 represents a group selected from -C(=O)-NH2 and -S(=O)2-NH2;

[0087] R 9represents a hydrogen atom or a group selected from the following: C1-C6-alkyl, (C3-C7-cycloalkyl)-(C1-C3-alkyl)-, (phenyl)-(C1-C3-alkyl)-, (5- or 6-membered heteroaryl)-(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 ), C3-C7-cycloalkyl, phenyl and 5- or 6-membered heteroaryl,

[0088] wherein the C3-C7-cycloalkyl in the C3-C7-cycloalkyl and the (C3-C7-cycloalkyl)-(C1-C3-alkyl)- group is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom or a group selected from the following: oxo, cyano, C1-C2-alkyl and C1-C2-haloalkyl,

[0089] and wherein the phenyl in the (phenyl)-(C1-C3-alkyl)- group and the phenyl itself, and the 5- or 6-membered heteroaryl in the (5- or 6-membered heteroaryl)-(C1-C3-alkyl)- group and the 5- or 6-membered heteroaryl itself are optionally substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from the following: cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy;

[0090] R 10 and R 11 independently represent a hydrogen atom or a group selected from the following: 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)-O-C(=O)-, phenyl and 5- or 6-membered heteroaryl,

[0091] wherein the C3-C7-cycloalkyl, and the C3-C7-cycloalkyl within the (C3-C7-cycloalkyl)-(C1-C3-alkyl)- and (C3-C7-cycloalkyl)-C(=O)- groups are optionally substituted one or two times, and each substituent is independently selected from a fluorine atom or a group selected from the following: a cyano group, a C1-C2-alkyl group, and a C1-C2-haloalkyl group,

[0092] and wherein the phenyl and the 5- or 6-membered heteroaryl, and the phenyl within the (phenyl)-(C1-C3-alkyl)-, (phenyl)-(C1-C3-alkyl)-C(=O)-, and (phenyl)-(C1-C3-alkyl)-O-C(=O)- groups are optionally substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from the following: a cyano group, a methyl group, an ethyl group, a trifluoromethyl group, a methoxy group, an ethoxy group, a dimethylamino group, and a trifluoromethoxy group,

[0093] or

[0094] 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 or a bicyclic nitrogen-containing 5- to 11-membered heterocycloalkyl, which is optionally substituted one, two, or three times, and each substituent is independently selected from a halogen atom or a group selected from the following: a cyano group, an oxo group, a hydroxy group, a C1-C4-alkyl group, a C1-C4-haloalkyl group, (C1-C4-alkyl)-C(=O)-, a C3-C7-cycloalkyl group, a C1-C4-alkoxy group, -N(R 22 )(R 23 ) and a monocyclic 4- to 7-membered heterocycloalkyl;

[0095] R 15 and R 16 independently represent a hydrogen atom or a group selected from the following: a C1-C4-alkyl group, a C1-C4-haloalkyl group, a C1-C4-hydroxyalkyl group, (cyano)-C1-C4-alkyl-, (C1-C4-alkoxy)-C2-C3-alkyl-, (C1-C4-haloalkoxy)-C2-C3-alkyl-, (phenoxy)-C2-C3-alkyl-, (C3-C7-cycloalkyl)-(C1-C3-alkyl)-, a C3-C7-cycloalkyl group, a bicyclic C5-C 11 -cycloalkyl group, a monocyclic 4- to 7-membered heterocycloalkyl group, (phenyl)-(C1-C3-alkyl)-, a phenyl group, and a 5- or 6-membered heteroaryl group,

[0096] wherein the C3-C7-cycloalkyl, the C3-C7-cycloalkyl within the (C3-C7-cycloalkyl)-(C1-C3-alkyl)- group, the bicyclic C5-C 11-Cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from the following: oxo, hydroxy, C1-C4-alkyl, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl and C1-C4-alkoxy, and wherein the phenyl and 5- or 6-membered heteroaryl, including the phenyl within the (phenoxy)-C2-C3-alkyl- and (phenyl)-(C1-C3-alkyl)- groups, are optionally substituted one or two times, each substituent independently selected from a halogen atom or a group selected from the following: cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy,

[0097] or

[0098] R 15 and R 16 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl which is optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from the following: oxo, hydroxy, C1-C4-alkyl, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl and C1-C4-alkoxy;

[0099] R 17 represents C1-C4-alkyl;

[0100] R 18 and R 19 independently represent a hydrogen atom or C1-C4-alkyl;

[0101] R 20 represents a hydrogen atom or a group selected from the following: C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C5-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 5- to 11-membered heterocycloalkyl, phenyl, naphthyl and 5- to 10-membered heteroaryl,

[0102] wherein the C1-C6-alkyl is optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from the following: hydroxy, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 )、C3-C7-cycloalkyl, bicyclic C5-C 11- cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 5- to 11-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, where the phenyl and 5- to 10-membered heteroaryl are each optionally substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from: cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino, and trifluoromethoxy, and where C3-C7-cycloalkyl, bicyclic C5-C 11 - cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, and bicyclic 5- to 11-membered heterocycloalkyl are each optionally substituted one, two, or three times, and each substituent is independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C4-alkyl, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl, and C1-C4-alkoxy,

[0103] and where the phenyl, naphthyl, and 5- to 10-membered heteroaryl are each optionally substituted one, two, or three times, and each substituent is independently selected from a halogen atom or a group selected from: 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 ),

[0104] R 21 represents a hydrogen atom or C1-C4-alkyl,

[0105] or

[0106] R 20 and R 21 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl, which is optionally benzo-fused and optionally substituted one, two, or three times, and each substituent is independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C4-alkyl, C1-C4-haloalkyl, (phenyl)-(C1-C3-alkyl)-, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl, C1-C4-alkoxy, C1-C3-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 );

[0107] R 22 and R 23 independently represent a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, and

[0108] R 24 and R 25 each independently represents a hydrogen atom or a C1-C4-alkyl group,

[0109] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0110] Definition

[0111] The term "substituted" means that one or more hydrogen atoms on a specified atom or group are replaced by a substituent selected from the specified group, provided that the normal valence state of the specified atom in the existing situation is not exceeded. Combinations of substituents and / or variables are permitted.

[0112] The term "optionally substituted" means that the number of substituents may be equal to or different from 0. Unless otherwise specified, an optionally substituted group may be substituted with as many optional substituents as possible, which can be accommodated by replacing hydrogen atoms with non-hydrogen substituents on any available carbon or nitrogen atom. Generally, the number of optional substituents (when present) may be 1, 2, 3, or 4, particularly 1, 2, or 3.

[0113] When a group in a compound according to the invention is substituted, unless otherwise specified, the group may be mono-substituted or multi-substituted by a substituent. Within the scope of the invention, the meanings of all recurring groups are independent of each other. A group in a compound according to the invention may be substituted by one, two, or three identical or different substituents, particularly by one substituent.

[0114] As used herein, an oxo substituent represents an oxygen atom that is bonded to a carbon atom or a sulfur atom by a double bond.

[0115] If a compound substituent consists of more than one part, such as (C1-C2-alkoxy)-(C1-C6-alkyl)-, a given part may be attached at any suitable position of the compound substituent. For example, the C1-C2-alkoxy part may be attached to any suitable carbon atom of the C1-C6-alkyl part of the (C1-C2-alkoxy)-(C1-C6-alkyl)- group. A hyphen at the beginning or end of such a compound substituent indicates the point of attachment of the compound substituent to the rest of the molecule. If a ring containing carbon atoms and optionally one or more heteroatoms (such as nitrogen, oxygen, or sulfur atoms) is substituted by a substituent, the substituent may be attached at any suitable position of the ring, either to a suitable carbon atom and / or a suitable heteroatom.

[0116] The term "comprising", when used in the specification, includes "consisting of".

[0117] If any item is referred to in this text as "as described herein", it means that it can be mentioned anywhere in this text.

[0118] The terms mentioned in this text have the following meanings:

[0119] The term "halogen atom" means a fluorine, chlorine, bromine or iodine atom, especially a fluorine, chlorine or bromine atom.

[0120] The term "C1-C6-alkyl" means a straight-chain or branched-chain, saturated monovalent hydrocarbon radical having 1, 2, 3, 4, 5 or 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 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, or an isomer thereof. In particular, the group has 1, 2, 3 or 4 carbon atoms ("C1-C4-alkyl"), such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl or tert-butyl, more particularly 1, 2 or 3 carbon atoms ("C1-C3-alkyl"), such as methyl, ethyl, n-propyl or isopropyl, more particularly 1 or 2 carbon atoms ("C1-C2-alkyl"), such as methyl or ethyl.

[0121] The term "C1-C4-hydroxyalkyl" means a straight-chain or branched-chain, saturated monovalent hydrocarbon radical in which the term "C1-C4-alkyl" is as defined above and in which 1 or 2 hydrogen atoms are replaced by a hydroxy group, such as hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1,2-dihydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-hydroxypropyl, 1-hydroxyprop-2-yl, 2-hydroxyprop-2-yl, 2,3-dihydroxypropyl, 1,3-dihydroxyprop-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, or an isomer thereof.

[0122] The term "C1-C6-haloalkyl" means a straight-chain or branched, saturated monovalent hydrocarbon radical, where the term "C1-C6-alkyl" is as defined above, and where one or more hydrogen atoms are replaced by the same or different halogen atoms. In particular, the halogen atom is a fluorine atom. The C1-C6-haloalkyl 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.

[0123] The term "C1-C6-alkoxy" means a straight-chain or branched, saturated monovalent group of the formula (C1-C6-alkyl)-O-, where the term "C1-C6-alkyl" is as defined above, for example methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, tert-butoxy, pentyloxy, isopentyloxy or n-hexyloxy, or an isomer thereof.

[0124] The term "C1-C6-haloalkoxy" means a straight-chain or branched, saturated monovalent C1-C6-alkoxy as defined above, where one or more hydrogen atoms are replaced by the same or different halogen atoms. In particular, the halogen atom is a fluorine atom. The C1-C6-haloalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy or pentafluoroethoxy.

[0125] The term "C3-C4-alkenyl" means a straight-chain or branched monovalent hydrocarbon radical containing one or two double bonds and containing 3 or 4 carbon atoms. The alkenyl is, for example, prop-2-en-1-yl (or "allyl"), prop-1-en-1-yl, but-3-enyl, but-2-enyl or but-1-enyl.

[0126] The term "C3-C4-alkynyl" means a straight-chain or branched monovalent hydrocarbon radical containing one triple bond and containing 3 or 4 carbon atoms. The C3-C4-alkynyl is, for example, prop-1-ynyl, prop-2-ynyl (or "propargyl"), but-1-ynyl, but-2-ynyl or but-3-ynyl.

[0127] The term "C3-C7-cycloalkyl" means a saturated, monovalent monocyclic hydrocarbon ring containing 3, 4, 5, 6 or 7 carbon ring atoms ("C3-C7-cycloalkyl"). The C3-C7-cycloalkyl is, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.

[0128] The term "bicyclic C6-C 11 -cycloalkyl" means a spiroalkyl, fused C6-C 10 -cycloalkyl or bridged C7-C 10 -cycloalkyl as defined below:

[0129] The term "spiroalkyl" means a bicyclic, saturated monovalent C5-C 11 hydrocarbyl group in which two rings share a common ring carbon atom and in which the bicyclic hydrocarbyl group contains 5, 6, 7, 8, 9, 10 or 11 carbon atoms, and the spiroalkyl group may be attached to the remainder of the molecule through any one of the carbon atoms other than the spiro carbon atom. The spiroalkyl group is 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.

[0130] The term "fused C6-C 10 -cycloalkyl" means a bicyclic saturated monovalent hydrocarbyl group in which two rings share two adjacent ring atoms, such as bicyclo[4.2.0]octyl, octahydropentalenyl or naphthylalkyl.

[0131] The term "bridged C7-C 10 -cycloalkyl" means a bicyclic saturated monovalent hydrocarbyl group in which two rings share two non-adjacent common ring atoms, such as bicyclo[2.2.1]heptyl (also known as norbornyl).

[0132] The term "bicyclic C5-C 11 -cycloalkyl" means a spiroalkyl, fused C5-C 10 -cycloalkyl or bridged C5-C 10 -cycloalkyl as defined below:

[0133] The term "spiroalkyl" means a bicyclic, saturated monovalent C5-C 11 hydrocarbyl group in which two rings share a common ring carbon atom and in which the bicyclic hydrocarbyl group contains 5, 6, 7, 8, 9, 10 or 11 carbon atoms, and the spiroalkyl group may be attached to the remainder of the molecule through any one of the carbon atoms other than the spiro carbon atom. The spiroalkyl group is 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.

[0134] The term "fused C5-C 10 -cycloalkyl" means a bicyclic, saturated monovalent hydrocarbyl group in which two rings share two adjacent ring atoms, such as bicyclo[4.2.0]octyl, octahydropentaldienyl or naphthylalkyl.

[0135] The term "bridged C5-C 10The term "-cycloalkyl" means a bicyclic, saturated monovalent hydrocarbon group in which the two rings share two non-adjacent common ring atoms, such as bicyclo[1.1.1]pentyl or bicyclo[2.2.1]heptyl (also known as norbornyl).

[0136] The term "monocyclic 4- to 7-membered heteroalkyl" means a monocyclic saturated heterocycle having a total of 4, 5, 6 or 7 ring atoms and containing one or two identical or different ring heteroatoms from the series N, O and S.

[0137] The monocyclic heteroalkyl can be a 4-membered ring, such as azetidinyl, oxetanyl or thietanyl; or a 5-membered ring, such as tetrahydrofuranyl, 1,3-dioxolanyl, thiolanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, 1,1-dioxothiolanyl, 1,2-oxazolidinyl, 1,3-oxazolidinyl or 1,3-thiazolidinyl; or a 6-membered ring, such as tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, 1,3-dioxanyl, 1,4-dioxanyl or 1,2-oxazinyl; or a 7-membered ring, such as azepanyl, 1,4-diazepanyl or 1,4-oxazepanyl, but is not limited thereto.

[0138] The term "monocyclic nitrogen-containing 4- to 7-membered heteroalkyl" means a monocyclic saturated heterocycle having a total of 4, 5, 6 or 7 ring atoms and containing one ring nitrogen atom and optionally one other ring heteroatom from the series N, O and S.

[0139] The monocyclic nitrogen-containing 4- to 7-membered heteroalkyl can be 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, but is not limited thereto.

[0140] The term "optionally benzo-fused monocyclic nitrogen-containing 4- to 7-membered heteroalkyl" means a monocyclic saturated heterocycle having a total of 4, 5, 6 or 7 ring atoms and containing one ring nitrogen atom and optionally one additional ring heteroatom selected from the series N, O and S, wherein two adjacent ring carbon atoms in the heteroalkyl can be shared with an optionally fused benzene ring, and the group is one of the above monocyclic nitrogen-containing 4- to 7-membered heteroalkyls, such as pyrrolidinyl, piperidinyl, etc., or a benzo-condensed group, such as 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.

[0141] The term "bicyclic 6-11 membered heterocycloalkyl" means a 6- to 11-membered heterospiroalkyl, a 6- to 10-membered fused heterocycloalkyl, or a 7- to 10-membered bridged heterocycloalkyl as defined below:

[0142] The term "6- to 11-membered heterospiroalkyl" means a bicyclic saturated heterocycle having a total of 6, 7, 8, 9, 10 or 11 ring atoms, wherein the two rings share a common ring carbon atom, and wherein "heterospiroalkyl" contains one or two identical or different ring heteroatoms: N, O, S; the heterospiroalkyl may be attached to the remainder of the molecule through any one carbon atom other than the spiro carbon atom or a nitrogen atom (if present).

[0143] Examples of the heterospiroalkyl are 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, oxazaspiro[5.5]undecyl, diazaspiro[3.3]heptyl, thiazaspiro[3.3]heptyl, thiazaspiro[4.3]octyl, azaspiro[5.5]undecyl or one of the 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]-.

[0144] 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, wherein the two rings share two adjacent ring atoms, and wherein "fused heterocycloalkyl" contains one or two identical or different ring heteroatoms: N, O, S; the fused heterocycloalkyl may be attached to the remainder of the molecule through any one carbon atom or a nitrogen atom (if present).

[0145] Examples of the fused heterocycloalkyl are 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.

[0146] The term "7- to 10-membered bridged heterocycloalkyl" means a bicyclic saturated heterocycle having a total of 7, 8, 9 or 10 ring atoms, wherein the two rings share two non-adjacent common ring atoms, and wherein "bridged heterocycloalkyl" contains one or two identical or different ring heteroatoms: N, O, S; the bridged heterocycloalkyl may be attached to the remainder of the molecule through any one carbon atom other than the spiro carbon atom or a nitrogen atom (if present).

[0147] The bridged heterocycloalkyl group is, for example, 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]

[0148] decyl, oxazabicyclo[3.3.2]decyl, thiazabicyclo[3.3.2]decyl or azabicyclo[4.2.2]

[0149] decyl.

[0150] The term "bicyclic nitrogen-containing 6-11 membered heterocycloalkyl" means a heterospirocycloalkyl, fused heterocycloalkyl or bridged heterocycloalkyl as defined above, but containing one ring nitrogen atom and optionally one or two additional ring heteroatoms selected from N, O and S; the bicyclic nitrogen-containing 6-11 membered heterocycloalkyl can be attached to the remainder of the molecule through the nitrogen atom or any one carbon atom other than the spiro carbon atom.

[0151] The term "bicyclic 5-11 membered heterocycloalkyl" means a 5-11 membered heterospirocycloalkyl, 5-11 membered fused heterocycloalkyl or 5-11 membered bridged heterocycloalkyl as defined below:

[0152] The term "5-11 membered heterospirocycloalkyl" means a bicyclic saturated heterocycle having a total of 5, 6, 7, 8, 9, 10 or 11 ring atoms, wherein two rings share a common ring carbon atom, and wherein the "heterospirocycloalkyl" contains one or two identical or different ring heteroatoms: N, O, S; the heterospirocycloalkyl can be attached to the remainder of the molecule through any one carbon atom other than the spiro carbon atom or a nitrogen atom (if present).

[0153] The heterospiroalkyl group is, for example, 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, oxazaspiro[5.5]undecyl, diazaspiro[3.3]heptyl, thiazaspiro[3.3]heptyl, thiazaspiro[4.3]octyl, azaspiro[5.5]undecyl or one of other 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]-.

[0154] 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, wherein the two rings share two adjacent ring atoms, and wherein the "fused heterocycloalkyl" contains one or two ring heteroatoms the same or different selected from N, O, S; the fused heterocycloalkyl can be attached to the remainder of the molecule through any one carbon atom or nitrogen atom (if present).

[0155] The fused heterocycloalkyl group is, 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.

[0156] 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, wherein the two rings share two non-adjacent common ring atoms, and wherein the "bridged heterocycloalkyl" contains one or two ring heteroatoms the same or different selected from N, O, S; the bridged heterocycloalkyl can be attached to the remainder of the molecule through any one carbon atom or nitrogen atom (if present) other than a spiro carbon atom.

[0157] The bridged heterocycloalkyl group is, for example, 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.

[0158] The term "bicyclic nitrogen-containing 5-11 membered heterocycloalkyl" means a 5-11 membered heterospiroalkyl, 5-11 membered fused heterocycloalkyl or 5-11 membered bridged heterocycloalkyl as defined above, but which contains one ring nitrogen atom and optionally one or two additional ring heteroatoms selected from N, O and S; the bicyclic nitrogen-containing 5-11 membered heterocycloalkyl can be attached to the remainder of the molecule through the nitrogen atom or any one carbon atom other than a spiro carbon atom.

[0159] The term "heteroaryl" means a monovalent, monocyclic or bicyclic aromatic ring having 5, 6, 8, 9 or 10 ring atoms ("5 to 10 membered heteroaryl" group), which contains at least one ring heteroatom and optionally one, two or three additional ring heteroatoms from N, O and / or S, and which is attached through a ring carbon atom or a nitrogen atom (if valence allows, e.g. in pyrrol-1-yl).

[0160] The heteroaryl can be a 5-membered heteroaryl, such as, for example, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl or tetrazolyl; or a 6-membered heteroaryl, such as, for example, pyridinyl (also referred to herein as pyridyl), pyridazinyl, pyrimidinyl, pyrazinyl or triazinyl; or a 9-membered heteroaryl, such as, for example, benzofuranyl, benzothienyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, benzothiazolyl, benzotriazolyl, thiazolopyridyl, indazolyl, indolyl, isoindolyl, indolizinyl or purinyl; or a 10-membered heteroaryl, such as, for example, quinolinyl, quinazolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinoxalinyl or pteridinyl.

[0161] Generally, unless otherwise stated, heteroaryl or heteroarylene 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, for some illustrative non-limiting examples, the term pyridyl includes pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl; or, the term thienyl includes thien-2-yl and thien-3-yl.

[0162] 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", the term "C1-C6" means an alkyl having from 1 to 6 carbon atoms, i.e., a defined number of 1, 2, 3, 4, 5, or 6 carbon atoms.

[0163] Furthermore, as used herein, as used herein, for example, in the context of the definition of "C3-C7-cycloalkyl", the term "C3-C7" means a cycloalkyl having from 3 to 7 carbon atoms, i.e., a defined number of 3, 4, 5, 6, or 7 carbon atoms.

[0164] When a range of values is given, the range includes each value and sub-range within the range.

[0165] For example:

[0166] "C1-C6" includes 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;

[0167] "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;

[0168] "C3-C6" includes C3, C4, C5, C6, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6.

[0169] As used herein, the term "leaving group" means an atom or group of atoms that is displaced as a stable species with the bonding electrons in a chemical reaction. In particular, the leaving group is selected from the following groups: halogen atoms, especially fluorine, chlorine, bromine or iodine atoms, which are displaced as halides, especially fluorides, chlorides, bromides or iodides; (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.

[0170] As used herein, the term "aprotic dipolar solvent" means a solvent selected from the following: acetone, acetonitrile, propionitrile, dimethyl sulfoxide, diethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N,N-diethylformamide, N,N-diethylacetamide, 1-methyl-2-pyrrolidone, 1-ethyl-2-pyrrolidone, 1-methyl-2-piperidone and 1-ethyl-2-piperidone, or a mixture thereof. Specifically, the aprotic dipolar solvent is acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide or 1-methyl-2-pyrrolidone.

[0171] As used herein, the term "room temperature" means a temperature in the range of 15°C to 25°C.

[0172] The compounds of general formula (I) can exist as isotopic variants. Accordingly, the present invention encompasses one or more isotopic variants of the compounds of general formula (I), especially deuterium-containing compounds of general formula (I).

[0173] The term "isotopic variant" of a compound or reagent is defined as a compound that exhibits a non-natural proportion of one or more isotopes that make up the compound.

[0174] The term "isotopic variant of the compound of general formula (I)" is defined as a compound of general formula (I) that exhibits a non-natural proportion of one or more isotopes that make up the compound.

[0175] The expression "non-natural proportion" means the proportion of the isotope above its natural abundance. The natural abundances of the isotopes applied in the context of this text are recorded in "Isotopic Compositions of the Elements 1997", Pure Appl. Chem., 70(1), 217-235, 1998.

[0176] Examples of such isotopes include the stable and radioactive isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine, and iodine, such as, respectively: 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.

[0177] Regarding the treatment and / or prevention of the diseases described herein, the isotopic variants of the compounds of formula (I) preferably contain deuterium ("deuterium-containing compounds of formula (I)"). The isotopic variants of the compounds of formula (I) - into which one or more radioactive isotopes are incorporated, such as 3 H or 14 C - can be used, for example, in drug and / or substrate tissue distribution studies. These isotopes are particularly preferred because they are easy to incorporate and are detectable. Positron-emitting isotopes such as 18 F or 11 C can be incorporated into the compounds of formula (I). These isotopic variants of the compounds of formula (I) can be used in in vivo imaging applications. The deuterium-containing and 13 C-containing compounds of formula (I) can be used in mass spectrometry in the context of preclinical or clinical studies.

[0178] Isotope variants of the compounds of formula (I) can generally be prepared by methods known to those skilled in the art, such as those described in the schemes and / or examples herein, by substituting the reagents with their isotope variants, preferably deuterated reagents. Depending on the deuteration site required, in some cases, deuterium from D2O can be directly incorporated into the compound or into the reagents used to synthesize such compounds. Deuterium gas is also a useful reagent for incorporating deuterium into molecules. Catalytic deuteration of olefinic and acetylenic bonds is a rapid route for incorporating deuterium. Metal catalysts (i.e., Pd, Pt, and Rh) in the presence of deuterium gas can be used to directly exchange the hydrogen in hydrocarbon functional groups with deuterium. A variety of deuterated reagents and synthetic building blocks are commercially available from companies such as C / D / N Isotopes, Quebec, Canada; Cambridge Isotope Laboratories Inc., Andover, MA, USA; and CombiPhos Catalysts, Inc., Princeton, NJ, USA.

[0179] The term "deuterium-containing compound of formula (I)" is defined as a compound of formula (I) in which one or more hydrogen atoms are replaced by one or more deuterium atoms, and in which the deuterium abundance at each deuterated position of the compound of formula (I) is higher than the natural abundance of deuterium (about 0.015%). Specifically, in the deuterium-containing compound of formula (I), the deuterium abundance at each deuterated position of the compound of formula (I) is higher than 10%, 20%, 30%, 40%, 50%, 60%, 70%, or 80%, preferably higher than 90%, 95%, 96%, or 97%, and even more preferably higher than 98% or 99%. It should be understood that the deuterium abundance at each deuterated position is different from the deuterium abundance at other deuterated positions.

[0180] The selective incorporation of one or more deuterium atoms into a compound of formula (I) may alter the physicochemical properties (e.g., acidity [C.L. Perrin, et al., J. Am. Chem. Soc., 2007, 129, 4490], basicity [C.L. Perrin et al., J. Am. Chem. Soc., 2005, 127, 9641], lipophilicity [B. Testa et al., Int. J. Pharm., 1984, 19(3), 271]) and / or the metabolic profile of the molecule and may result in a change in the ratio of the parent compound to metabolites or the amount of metabolites formed. Such changes may confer certain therapeutic advantages and may thus be preferred in certain cases. Reduced metabolic rates and metabolic turnover rates have been reported, where the ratio of metabolites has changed (A.E. Mutlib et al., Toxicol. Appl. Pharmacol., 2000, 169, 102). These changes in exposure to the parent drug and metabolites may have important implications for the pharmacodynamics, tolerability, and efficacy of the deuterium-containing compounds of formula (I). In some cases, deuterium substitution reduces or eliminates the formation of undesired or toxic metabolites and enhances the formation of desired metabolites (e.g., Nevirapine: A.M. Sharma et al., Chem. Res. Toxicol., 2013, 26, 410; Efavirenz: A.E. Mutlib et al., Toxicol. Appl. Pharmacol., 2000, 169, 102). In other cases, the main effect of deuteration is to reduce the systemic clearance. Consequently, the biological half-life of the compound is increased. Potential clinical benefits would include the ability to maintain a similar systemic exposure by reducing peak levels and increasing trough levels. Depending on the pharmacokinetic / pharmacodynamic relationship of the particular compound, this may result in lower side effects and enhanced efficacy. ML-337 (C.J. Wenthur et al., J. Med. Chem., 2013, 56, 5208) and Odanacatib (K. Kassahun et al., WO2012 / 112363) are examples of such deuterium effects. Other cases have also been reported where a reduced metabolic rate leads to increased drug exposure without changing the systemic clearance (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 showing such an effect may have reduced dose requirements (e.g., reduced dose or reduced dose to achieve the desired effect) and / or may produce a lower metabolite burden.

[0181] Compounds of formula (I) may have multiple potential metabolic attack sites. To optimize the above effects on physicochemical properties and metabolic profiles, deuterated compounds of formula (I) with one or more deuterium-hydrogen exchanges in a certain pattern can be selected. In particular, the deuterium atoms of the deuterated compounds of formula (I) are attached to carbon atoms and / or are located at those positions of the compounds of formula (I) which are the attack sites of metabolic enzymes such as cytochrome P 450 .

[0182] In another embodiment, the invention relates to deuterated compounds of formula (I) having 1, 2, 3 or 4 deuterium atoms, particularly having 1, 2 or 3 deuterium atoms.

[0183] When the plural forms of the terms compound, salt, polymorph, hydrate, solvate, etc. are used herein, this also means a single compound, salt, polymorph, isomer, hydrate, solvate, etc.

[0184] A "stable compound" or "stable structure" means a compound that is sufficiently robust to be isolated in useful purity from a reaction mixture and formulated into an effective therapeutic agent.

[0185] The compounds of the invention optionally contain one or more asymmetric centers, depending on the position and nature of the various substituents required. One or more asymmetric carbon atoms may be present in the (R) or (S) configuration, which may give rise to a racemic mixture in the case of a single asymmetric center and a mixture of diastereoisomers in the case of multiple asymmetric centers. In some cases, asymmetry may also exist due to restricted rotation about a given bond, for example, the central bond adjacent to two substituted aromatic rings of a specified compound.

[0186] Preferred isomers are those that produce more desirable biological activity. These isolated, pure or partially purified isomers or racemic mixtures of the compounds of the invention are also included within the scope of the invention. The purification and separation of these materials can be accomplished by standard techniques known in the art.

[0187] Optical isomers can be obtained by resolving a racemic mixture according to conventional methods, for example, by forming diastereomeric salts or covalent diastereomers using an optically active acid or base. Examples of suitable acids are tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, and camphorsulfonic acid. Based on their physical and / or chemical differences, the mixture of diastereomers can be separated into their respective diastereomers by methods known in the art (e.g., by chromatography or fractional crystallization). Then the optically active base or acid is liberated from the separated diastereomeric salts. Different methods for separating enantiomers involve using chiral chromatography (e.g., HPLC columns with chiral phases), with or without conventional derivatization, and the best method is selected to maximize the separation of enantiomers. Suitable HPLC columns with chiral phases are commercially available, such as those manufactured by Daicel, e.g., Chiracel OD and Chiracel OJ, which are all conventionally selectable. Enzymatic separation with or without derivatization is also useful. The optically active compounds of the present invention can also be obtained by chiral synthesis using optically active starting materials.

[0188] To distinguish between different types of isomers, reference is made to IUPAC Rules Section E (Pure Appl Chem 45, 11 - 30, 1976).

[0189] The present invention includes all possible stereoisomers of the compounds of the present invention, as a single stereoisomer, or as any mixture of said stereoisomers, e.g., in any ratio of (R)- or (S)-isomers. The separation of a single stereoisomer of the compounds of the present invention, e.g., a single enantiomer or a single diastereomer, is achieved by any suitable prior art method such as chromatography, especially chiral chromatography.

[0190] Furthermore, some compounds of the present invention may exist in tautomeric forms. For example, the compounds of the present invention may contain a pyridone moiety and may exist as pyridone, or as hydroxypyridine, or even as a mixture of the two tautomers in any amount, i.e.:

[0191]

[0192] The present invention includes all possible tautomers of the compounds of the present invention, as a single tautomer, or as any mixture of said tautomers in any ratio.

[0193] In addition, the compounds of the present invention may exist as N-oxides, which are defined as at least one nitrogen of the compounds of the present invention being oxidized. The present invention includes all such possible N-oxides.

[0194] The present invention also relates to useful forms of the compounds of the present invention, such as metabolites, hydrates, solvates, prodrugs, salts, in particular pharmaceutically acceptable salts and / or co-precipitates.

[0195] The compounds of the present invention may exist as hydrates or solvates, wherein the compounds of the present invention contain a polar solvent, in particular water, methanol or ethanol, for example as a structural element of the compound lattice. The amount of the polar solvent, in particular water, may be present in a stoichiometric or non-stoichiometric ratio. In the case of stoichiometric solvates, such as hydrates, hemi-, (semi-), mono-, sesqui-, di-, tri-, tetra-, penta-solvates or hydrates, etc. are possible. The present invention includes all such hydrates or solvates.

[0196] Furthermore, the compounds of the present invention may exist in free form, such as as a free base, or as a free acid, or as a zwitterion, or in the form of a salt. The salt may be any salt, an organic or inorganic addition salt, in particular any pharmaceutically acceptable organic or inorganic addition salt, which is commonly used in pharmacy, or for example for separating or purifying the compounds of the present invention.

[0197] The term "pharmaceutically acceptable salt" refers to an inorganic or organic acid addition salt of the compounds of the present invention. See, for example, S.M. Berge et al., "Pharmaceutical Salts," J. Pharm. Sci. 1977, 66, 1-19.

[0198] Suitable pharmaceutically acceptable salts of the compounds of the present invention may be, for example, acid addition salts of the compounds of the present invention having a nitrogen atom (with sufficient basicity) in the chain or ring, such as acid addition salts with inorganic or mineral acids, such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfamic acid, bisulfate, phosphoric acid or nitric acid; or acid addition salts with 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, nicotinic acid, pamoic acid, pectic acid, 3-phenylpropionic acid, pivalic acid, 2-hydroxyethanesulfonic acid, itaconic acid, trifluoromethanesulfonic acid, dodecylsulfuric acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic 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, glucoheptonic acid, glycerophosphoric acid, aspartic acid, sulfosalicylic acid or thiocyanic acid.

[0199] In addition, another suitable pharmaceutically acceptable salt of the compounds of the present invention (which have sufficient acidity) is an alkali metal salt, such as a sodium or potassium salt, an alkaline earth metal salt, such as a calcium, magnesium or strontium salt, or an aluminum or zinc salt, or a salt derived from ammonia or an organic primary, secondary or tertiary amine having 1 to 20 carbon atoms, such as ethylamine, diethylamine, triethylamine, ethyldiisopropylamine, monoethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, dimethylaminoethanol, diethylaminoethanol, tris(hydroxymethyl)methylamine, procaine, dibenzylamine, N-methylmorpholine, arginine, lysine, 1,2-ethylenediamine, N-methylpiperidine, N-methylglucamine, N,N-dimethylglucamine, N-ethylglucamine, 1,6-hexanediamine, glucamine, sarcosine, serinol, 2-amino-1,3-propanediol, 3-amino-1,2-propanediol, 4-amino-1,2,3-butanetriol ammonium salts, or a quaternary ammonium ion 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 chloride salts.

[0200] Those skilled in the art will further recognize that the acid addition salts of the claimed compounds can be prepared by reaction of the compounds with a suitable inorganic or organic acid by any of a variety of known methods. Alternatively, the alkali metal and alkaline earth metal salts of the acidic compounds of the present invention are prepared by reacting the compounds of the present invention with a suitable base by various known methods.

[0201] The present invention includes all possible salts of the compounds of the present invention, as a single salt or as any mixture of said salts in any proportion.

[0202] In the present text, particularly in the "Experimental Section", for the synthesis of intermediates and in the examples of the present invention, when the compounds are mentioned in the form of salts with the corresponding bases or acids, the exact stoichiometric composition of the salt forms obtained through the respective preparation and / or purification processes is mostly unknown in most cases.

[0203] Unless otherwise specified, suffixes in chemical names or structural formulas related to salts, such as "hydrochloride", "trifluoroacetate", "sodium salt" or "×HCl", "×CF3COOH", "×Na + " mean a salt form in which the stoichiometry of the salt form is not specifically specified.

[0204] This similarly applies to the case where a synthetic intermediate or an example compound or its salt is obtained as a solvate, such as a hydrate, having an unknown stoichiometric composition (if defined) through the said preparation and / or purification method.

[0205] In addition, 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 more than one polymorph in any proportion.

[0206] In addition, the present invention also includes prodrugs of the compounds according to the present invention. The term "prodrug" as used herein means a compound which may itself be bioactive or inactive, but which is converted (e.g., metabolized or hydrolyzed) during its residence in the body into a compound of the present invention.

[0207] The present invention also includes all possible cyclodextrin inclusion compounds, namely α-, β- or γ-cyclodextrin, hydroxypropyl-β-cyclodextrin, methyl-β-cyclodextrin.

[0208] According to a second embodiment of the first aspect, the present invention relates to a compound of the above general formula (I), wherein:

[0209] R 1 represents phenyl or pyridyl optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: 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 ),

[0210] wherein the phenyl in the (phenyl)-(C1-C2-alkyl)- and (phenyl)-(C1-C2-alkoxy)- groups is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: methyl, trifluoromethyl and methoxy,

[0211] or two substituents attached to adjacent carbon atoms of the phenyl or pyridyl 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-,

[0212] or

[0213] R 1 represents pyrazolyl optionally substituted one or two times, each substituent independently selected from a halogen atom or a group selected from: cyano, C1-C2-alkyl and C1-C2-alkoxy;

[0214] R 2 represents a group

[0215] wherein "*" represents the point of attachment of the nitrogen atom linked to R 2 ;

[0216] R 3 represents a group selected from methyl and -NH2;

[0217] R 4 represents a 5 - membered heteroaryl selected from oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, and oxadiazolyl, which is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from the following: C1 - C4 - alkyl, ((R 9 )O)-(C1 - C3 - alkyl)-, ((R 10 )(R 11 )N)-(C1 - C3 - alkyl)-, (C3 - C7 - cycloalkyl)-(C1 - C3 - alkyl)-, C3 - C7 - cycloalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 15 )(R 16 ), -C(=O)-OR 17 , phenyl, and 5 - or 6 - membered heteroaryl, wherein the phenyl and 5 - or 6 - membered heteroaryl are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from the following: cyano, C1 - C2 - alkyl, C1 - C2 - haloalkyl, -OR 9 , -N(R 10 )(R 11 ), and -C(=O)-N(R 15 )(R 16 );

[0218] R 5 and R 6 independently represent a hydrogen atom or a group selected from C1 - C2 - alkyl and (C1 - C2 - alkyl)-C(=O)-,

[0219] or

[0220] 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, which is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from the following: oxo, hydroxy, C1 - C2 - alkyl, and (C1 - C2 - alkyl)-C(=O)-;

[0221] R 7 represents a hydrogen atom or C1 - C2 - alkyl;

[0222] R 8 represents a -C(=O)-NH2 group;

[0223] R 9 represents a hydrogen atom or a group selected from: C1-C4-alkyl, (C3-C7-cycloalkyl)-(C1-C2-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(=O)-N(R 20 )(R 21 ), C3-C7-cycloalkyl and phenyl,

[0224] wherein the C3-C7-cycloalkyl in the C3-C7-cycloalkyl and the (C3-C7-cycloalkyl)-(C1-C2-alkyl)- group is optionally substituted one or two times, each substituent independently selected from a fluorine atom or a group selected from oxo and methyl,

[0225] and wherein the phenyl in the (phenyl)-(C1-C2-alkyl)- group and the phenyl itself are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: cyano, methyl, trifluoromethyl and methoxy;

[0226] R 10 and R 11 independently represent a hydrogen atom or a group selected from: 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)-O-C(=O)-,

[0227] wherein the C3-C7-cycloalkyl, and the C3-C7-cycloalkyl in the (C3-C7-cycloalkyl)-(C1-C2-alkyl)- and (C3-C7-cycloalkyl)-C(=O)- groups is optionally substituted one or two times, each substituent independently selected from a fluorine atom or a group selected from: cyano, C1-C2-alkyl and C1-C2-haloalkyl,

[0228] and wherein the phenyl group within the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(═O)-, and (phenyl)-(C1-C2-alkyl)-O-C(═O)- groups is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or from the group consisting of: methyl, trifluoromethyl, and methoxy,

[0229] or

[0230] 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 or a bicyclic nitrogen-containing 5- to 11-membered heterocycloalkyl, which is optionally substituted one, two, or three times, each substituent independently selected from a halogen atom or from the group consisting of: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-haloalkyl, (C1-C2-alkyl)-C(═O)-, C1-C2-alkoxy, -N(R 22 )(R 23 ) and a monocyclic 4- to 7-membered heterocycloalkyl;

[0231] R 15 and R 16 independently represent a hydrogen atom or from the group consisting of: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-hydroxyalkyl, (cyano)-C1-C4-alkyl-, (C1-C4-alkoxy)-C2-C3-alkyl-, (C1-C4-haloalkoxy)-C2-C3-alkyl-, (C3-C7-cycloalkyl)-(C1-C3-alkyl)-, C3-C7-cycloalkyl, bicyclic C5-C 11 -cycloalkyl, a monocyclic 4- to 7-membered heterocycloalkyl, (phenyl)-(C1-C3-alkyl)-, phenyl, and a 5- or 6-membered heteroaryl,

[0232] wherein the C3-C7-cycloalkyl, the C3-C7-cycloalkyl within the (C3-C7-cycloalkyl)-(C1-C3-alkyl)- group, the bicyclic C5-C 11 -cycloalkyl, and the monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one or two times, each substituent independently selected from a halogen atom or from the group consisting of: oxo, C1-C2-alkyl, (C1-C2-alkyl)-C(═O)-, and cyclopropyl,

[0233] and wherein the phenyl and the 5- or 6-membered heteroaryl, including the phenyl within the (phenyl)-(C1-C3-alkyl)- group, are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or from the group consisting of: methyl, trifluoromethyl, and methoxy,

[0234] or

[0235] R 15 and R 16 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl which is optionally substituted one or twice, each substituent independently selected from a halogen atom or a group selected from: oxo, C1-C2-alkyl, and (C1-C2-alkyl)-C(=O)-;

[0236] R 17 represents C1-C4-alkyl;

[0237] R 20 represents a hydrogen atom or a group selected from: C1-C6-alkyl, C3-C7-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl, and 5- to 6-membered heteroaryl,

[0238] wherein the C1-C6-alkyl is optionally substituted one, two, or three times, each substituent independently selected from a halogen atom or a group selected from: hydroxy, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl, and 5- to 6-membered heteroaryl, and the phenyl and 5- to 6-membered heteroaryl substituents themselves are optionally substituted one or twice, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from: methyl, trifluoromethyl, and methoxy,

[0239] and wherein the C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one, two, or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl, and (C1-C2-alkyl)-C(=O)-,

[0240] and wherein the phenyl and 5- to 6-membered heteroaryl are optionally substituted one, two, or three times, each substituent independently selected from a halogen atom or a group selected from: 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 ),

[0241] R 21 represents a hydrogen atom or C1-C2-alkyl,

[0242] or

[0243] R 20 and R 21Together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl which is optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-haloalkyl, (phenyl)-(C1-C2-alkyl)-, (C1-C2-alkyl)-C(=O)-, C3-C4-cycloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 );

[0244] R 22 and R 23 independently represent a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, and

[0245] R 24 and R 25 independently represent a hydrogen atom or C1-C2-alkyl,

[0246] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0247] According to the third embodiment of the first aspect, the present invention relates to a compound of the above general formula (I), wherein:

[0248] R 1 represents a phenyl or pyridyl group which is optionally substituted one, two or three times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: hydroxy, cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C2-fluoroalkoxy and -N(R 5 )(R 6 ),

[0249] alternatively, two substituents attached to adjacent carbon atoms of the phenyl or pyridyl group together form a divalent group selected from –(CH2)3-, -O-CH2-O- and -O-CF2-O-, or

[0250] R 1 represents a pyrazolyl group which is optionally substituted by a methyl group;

[0251] R 2 represents a group

[0252] wherein “*” represents the point of attachment to the nitrogen atom to which R 2 is attached;

[0253] R 3 represents a group selected from methyl and -NH2;

[0254] R 4 represents a group selected from the group of,

[0255] wherein "#" represents the point of attachment of the carbonyl group attached to R 4 ;

[0256] and wherein

[0257] R 4a and R 4b each independently represent a fluorine atom, a chlorine atom or a bromine atom, or a group selected from: C1-C4-alkyl, ((R 9 )O)-(C1-C2-alkyl)-, ((R 10 )(R 11 )N)-(C1-C2-alkyl)-, (C3-C7-cycloalkyl)-(C1-C2-alkyl)-, C3-C7-cycloalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 15 )(R 16 ), -C(=O)-OR 17 , phenyl and a 5- or 6-membered heteroaryl selected from oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl,

[0258] wherein the phenyl and the 5- or 6-membered heteroaryl selected from oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl are optionally substituted one or two times, each substituent independently selected from a fluorine atom and a chlorine atom, or a group selected from: cyano, C1-C2-alkyl, -OR 9 , -N(R 10 )(R 11 ) and -C(=O)-N(R 15 )(R 16 );

[0259] R 5 and R 6 each independently represent a hydrogen atom or C1-C2-alkyl,

[0260] or

[0261] R 5 and R 6together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl which is optionally substituted one or two times, each substituent independently selected from a fluorine atom or a group selected from a hydroxyl group and C1-C2-alkyl;

[0262] R 7 represents a hydrogen atom or C1-C2-alkyl;

[0263] R 8 represents a -C(=O)-NH2 group;

[0264] R 9 represents a hydrogen atom or a group selected from: C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, C2-hydroxyalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(=O)-N(R 20 )(R 21 ) and phenyl,

[0265] wherein the phenyl in the benzyl and the phenyl itself are optionally substituted one or two times, each substituent independently selected from a fluorine atom and a chlorine atom, or a group selected from a cyano group and a methyl group;

[0266] R 10 and R 11 independently represent a hydrogen atom or a group selected from: C1-C2-alkyl, C1-C2-fluoroalkyl, (C3-C5-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)-O-C(=O)-,

[0267] wherein the C3-C7-cycloalkyl and the C3-C5-cycloalkyl within the (C3-C5-cycloalkyl)-(C1-C2-alkyl)- group and the C3-C7-cycloalkyl within the (C3-C7-cycloalkyl)-C(=O)- group are optionally substituted one or two times, each substituent independently selected from a fluorine atom or a group selected from a cyano group, C1-C2-alkyl and C1-C2-fluoroalkyl,

[0268] and wherein the phenyl within the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-O-C(=O)- groups is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group,

[0269] or

[0270] 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 which is optionally substituted one, two or three times, each substituent independently selected from a fluorine atom or a group selected from: cyano, oxo, C1-C2-alkyl, C1-C2-fluoroalkyl and (C1-C2-alkyl)-C(=O)-;

[0271] R 15 and R 16 independently represent a hydrogen atom or a group selected from: C1-C4-alkyl, C1-C3-fluoroalkyl, (cyano)-C1-C2-alkyl-, (C1-C4-alkoxy)-C2-C3-alkyl-, (C1-C2-fluoroalkoxy)-C2-C3-alkyl-, (C3-C7-cycloalkyl)-(C1-C2-alkyl)-, C3-C5-cycloalkyl, phenyl and a 5- or 6-membered heteroaryl selected from pyrazolyl, pyridyl and pyrimidinyl, wherein the C3-C5-cycloalkyl within the C3-C5-cycloalkyl and the (C3-C5-cycloalkyl)-(C1-C2-alkyl)- group is optionally substituted one or two times, each substituent independently selected from a fluorine atom or a group selected from methyl and cyclopropyl,

[0272] and wherein the phenyl and the 5- or 6-membered heteroaryl selected from pyrazolyl, pyridyl and pyrimidinyl are optionally substituted one or two times, each substituent independently selected from a fluorine atom and a chlorine atom, or a group selected from: methyl, trifluoromethyl and methoxy, or

[0273] R 15 and R 16 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl which is optionally substituted once by a fluorine atom or a group selected from oxo, C1-C2-alkyl and CH3-C(=O)-;

[0274] R 17 represents C1-C2-alkyl;

[0275] R 20 represents a hydrogen atom or a group selected from C1-C3-alkyl and phenyl,

[0276] wherein the C1-C3-alkyl is optionally substituted one or two times, each substituent independently selected from a fluorine atom or a group selected from: hydroxy, C1-C3-alkoxy and phenyl, and the phenyl itself is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and methyl,

[0277] and wherein said phenyl is optionally substituted one, two or three times, each substituent independently selected from a fluorine atom and a chlorine atom or from the group consisting of: methyl, trifluoromethyl, methoxy and trifluoromethoxy,

[0278] R 21 represents a hydrogen atom or a C1-C2-alkyl group,

[0279] or

[0280] R 20 and R 21 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, which is optionally substituted one or two times, each substituent independently selected from a halogen atom or from the group consisting of: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-fluoroalkyl, benzyl, (C1-C2-alkyl)-C(=O)- and C3-C4-cycloalkyl,

[0281] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0282] According to a fourth embodiment of the first aspect, the present invention relates to a compound of the above general formula (I), wherein:

[0283] R 1 represents a phenyl or pyridyl group optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or 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 pyridyl group together form a divalent group -O-CF2-O-;

[0284] R 2 represents the group

[0285] wherein "*" represents the point of attachment to the nitrogen atom to which R 2 is attached;

[0286] R 3 represents a group selected from methyl and -NH2;

[0287] R 4 represents the group

[0288] wherein "#" represents the point of attachment to the carbonyl group to which R 4 is attached,

[0289] and wherein

[0290] R 4arepresents a chlorine atom or a bromine atom, or a group selected from the following: ((R 9 )O)-(C1-C2-alkyl)-, ((R 10 )(R 11 )N)-(C1-C2-alkyl)-, (C3-C5-cycloalkyl)-(C1-C2-alkyl)-, C3-C5-cycloalkyl, -OR 9 , -C(=O)-N(R 15 )(R 16 ) and phenyl,

[0291] wherein the phenyl is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom and a methyl group,

[0292] or

[0293] R 4 represents the group

[0294] wherein "#" represents the point of attachment of the carbonyl group attached to R 4 ;

[0295] and wherein

[0296] R 4b represents a group selected from the following: C1-C4-alkyl, C3-C5-cycloalkyl, -C(=O)-N(R 15 )(R 16 ) and phenyl,

[0297] wherein the phenyl is optionally substituted one or two times, each substituent is independently selected from a fluorine atom and a chlorine atom, or a group selected from the following: cyano, C1-C2-alkyl and -OR 9 ;

[0298] R 7 represents a hydrogen atom or C1-C2-alkyl;

[0299] R 8 represents the -C(=O)-NH2 group;

[0300] R 9 represents a hydrogen atom or a group selected from the following: C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(=O)-N(R 20 )(R 21 ) and phenyl,

[0301] wherein the phenyl group within the benzyl group and the phenyl group itself are each optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, or a group selected from a cyano group and a methyl group;

[0302] R 10 and R 11 independently represent a hydrogen atom or a group selected from: C1-C2-alkyl, (C3-C5-cycloalkyl)-(C1-C2-alkyl)-, C3-C7-cycloalkyl, and (phenyl)-(C1-C2-alkyl)-O-C(=O)-,

[0303] wherein the C3-C7-cycloalkyl and the C3-C5-cycloalkyl within the (C3-C5-cycloalkyl)-(C1-C2-alkyl)- group are each optionally substituted one or two times, and each substituent is independently selected from a fluorine atom or a group selected from a cyano group, a methyl group, and a C1-fluoroalkyl group,

[0304] and wherein the phenyl group within the (phenyl)-(C1-C2-alkyl)-O-C(=O)- group is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[0305] or

[0306] 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, which is optionally substituted one, two, or three times, and each substituent is independently selected from a fluorine atom or a group selected from a cyano group, a methyl group, and a C1-fluoroalkyl group;

[0307] R 15 and R 16 independently represent a hydrogen atom or a group selected from: C1-C4-alkyl, C1-C2-fluoroalkyl, (C1-C4-alkoxy)-C2-C3-alkyl-, (C1-C2-fluoroalkoxy)-C2-C3-alkyl-, (C3-C5-cycloalkyl)-(C1-C2-alkyl)-, C3-C5-cycloalkyl, phenyl, and pyridyl,

[0308] wherein the C3-C5-cycloalkyl and the C3-C5-cycloalkyl within the (C3-C5-cycloalkyl)-(C1-C2-alkyl)- group are each optionally substituted one or two times, and each substituent is independently selected from a fluorine atom and a methyl group,

[0309] and wherein the phenyl and pyridyl groups are each optionally substituted one or two times, and each substituent is independently selected from a fluorine atom and a chlorine atom, or a group selected from a methyl group, a trifluoromethyl group, and a methoxy group;

[0310] R 20represents a group selected from benzyl and phenyl,

[0311] wherein the phenyl group in said phenyl and said benzyl is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group, and

[0312] R 21 represents a hydrogen atom or a methyl group,

[0313] or a stereoisomer, tautomer, N - oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0314] According to the fifth embodiment of the first aspect, the present invention relates to a compound of the above general formula (I), wherein:

[0315] R 1 represents a group

[0316] wherein "**" represents the point of attachment to the nitrogen atom to which R 1 is attached;

[0317] R 2 represents a group

[0318] wherein "*" represents the point of attachment to the nitrogen atom to which R 2 is attached;

[0319] R 3 represents a group selected from methyl and - NH2;

[0320] R 4 represents a group

[0321] wherein "#" represents the point of attachment to the carbonyl group to which R 4 is attached,

[0322] and wherein

[0323] R 4a represents a chlorine atom or a bromine atom, or a group selected from: ((R 9 )O)-(C1 - alkyl)-, ((R 10 )(R 11 )N)-(C1 - alkyl)-, (C3 - C5 - cycloalkyl)-(C1 - alkyl)-, C3 - C5 - cycloalkyl, - OR 9 , - C(=O)-N(R 15 )(R 16 ) and phenyl,

[0324] wherein the phenyl group is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[0325] or

[0326] R 4 represents a group

[0327] wherein "#" represents the point of attachment of the carbonyl group attached to R 4 and wherein

[0328] and wherein

[0329] R 4b represents a group selected from: C1-C4-alkyl, C3-C5-cycloalkyl and phenyl, wherein the phenyl is optionally substituted one or two times, each substituent independently selected from a fluorine atom and a chlorine atom, or a group selected from: cyano, C1-C2-alkyl and -OR 9 ;

[0330] R 7 represents a hydrogen atom or C1-C2-alkyl;

[0331] R 8 represents a -C(=O)-NH2 group;

[0332] R 9 represents a hydrogen atom or a group selected from: C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl- and phenyl,

[0333] wherein the phenyl in the benzyl and the phenyl itself are optionally substituted one or two times, each substituent independently selected from a fluorine atom and a chlorine atom, or a group selected from cyano and methyl;

[0334] R 10 and R 11 independently represent a hydrogen atom or a group selected from: C1-C2-alkyl, C3-C7-cycloalkyl and (benzyl)-O-C(=O)-,

[0335] wherein the C3-C7-cycloalkyl is optionally substituted one or two times, each substituent independently selected from a fluorine atom or a group selected from methyl and trifluoromethyl,

[0336] and wherein the phenyl in the (benzyl)-O-C(=O)- group is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group,

[0337] or

[0338] 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, which is optionally substituted one, two or three times, each substituent independently selected from a fluorine atom or a group selected from: cyano, methyl and trifluoromethyl;

[0339] R 15 and R 16 independently represent a hydrogen atom or a group selected from: C1-C4-alkyl, C1-C2-fluoroalkyl, (C1-C4-alkoxy)-C2-alkyl-, (C1-C2-fluoroalkoxy)-C2-alkyl-, C3-C5-cycloalkyl, phenyl and pyridyl,

[0340] wherein the C3-C5-cycloalkyl is optionally substituted one or two times, each substituent independently selected from a fluorine atom and methyl;

[0341] Y 1 represents -C(H)=, -C(F)=, -C(Cl)=, -C(CN)= or -N=, and

[0342] 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,

[0343] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt, or a mixture thereof.

[0344] According to the sixth embodiment of the first aspect, the present invention relates to a compound of the above general formula (I), wherein:

[0345] R 1 represents a group

[0346] wherein "**" represents the point of attachment to the nitrogen atom to which R 1 is attached;

[0347] R 2 represents a group

[0348] wherein "*" represents the point of attachment to the nitrogen atom to which R 2 is attached;

[0349] R 3 represents a group selected from methyl and -NH2;

[0350] R 4 represents a group

[0351] wherein "#" represents the point of attachment to the carbonyl group to which R 4 is attached,

[0352] and wherein

[0353] R 4a represents a chlorine atom or a bromine atom, or a group selected from: ((R 9 )O)-(C1-alkyl)-, C3-C5-cycloalkyl, -OR 9 and -C(=O)-N(R 15 )(R 16 ),

[0354] or

[0355] R 4 represents the group

[0356] wherein "#" represents the point of attachment of the carbonyl group attached to R 4 ;

[0357] and wherein

[0358] R 4b represents a group selected from: C1-C4-alkyl, C3-C5-cycloalkyl and phenyl,

[0359] wherein the phenyl is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group;

[0360] R 7 represents a hydrogen atom or C1-C2-alkyl;

[0361] R 8 represents the -C(=O)-NH2 group;

[0362] R 9 represents a hydrogen atom or a group selected from: C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl and phenyl,

[0363] wherein the phenyl in the benzyl and the phenyl itself are optionally substituted one or two times, each substituent independently selected from a fluorine atom and a chlorine atom, or a group selected from a cyano group and a methyl group;

[0364] R 15 and R 16 independently represent a hydrogen atom or a group selected from: C1-C2-alkyl, C3-C5-cycloalkyl, phenyl and pyridyl,

[0365] wherein the C3-C5-cycloalkyl is optionally substituted one or two times, each substituent independently selected from a fluorine atom and a methyl group;

[0366] Y 1 represents -C(H)=, -C(F)=, -C(Cl)= or -N=, and

[0367] R 26 represents a fluorine atom, a chlorine atom or a bromine atom, or a group selected from: difluoromethyl, methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy,

[0368] or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture thereof.

[0369] According to the seventh embodiment of the first aspect, the present invention relates to a compound of the above general formula (I), wherein:

[0370] R 1 represents a group

[0371] wherein "**" represents the point of attachment to the nitrogen atom to which R 1 is attached;

[0372] R 2 represents a group

[0373] wherein "*" represents the point of attachment to the nitrogen atom to which R 2 is attached;

[0374] R 3 represents the group -NH2;

[0375] R 4 represents a group

[0376] wherein "#" represents the point of attachment to the carbonyl group to which R 4 is attached,

[0377] and wherein

[0378] R 4a represents a chlorine atom or a bromine atom, or a group selected from: ((R 9 )O)-(C1-alkyl)-, C3-C5-cycloalkyl, -OR 9 and -C(=O)-N(R 15 )(R 16 ),

[0379] or

[0380] R 4 represents a group

[0381] wherein "#" represents the point of attachment to the carbonyl group to which R 4 is attached,

[0382] and wherein

[0383] R4b represents a group selected from: C1-C4-alkyl, C3-C5-cycloalkyl and phenyl, wherein the phenyl is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom and a methyl group;

[0384] R 7 represents methyl;

[0385] R 8 represents a -C(=O)-NH2 group;

[0386] R 9 represents a hydrogen atom or a group selected from: C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl and phenyl,

[0387] wherein the phenyl in the benzyl and the phenyl itself are optionally substituted one or two times, and each substituent is independently selected from a fluorine atom and a chlorine atom, or a group selected from a cyano group and a methyl group;

[0388] R 15 and R 16 independently represent a hydrogen atom or a group selected from: C1-C2-alkyl, C3-C5-cycloalkyl, phenyl and pyridyl,

[0389] wherein the C3-C5-cycloalkyl is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom and a methyl group;

[0390] Y 1 represents -C(H)=, -C(F)=, -C(Cl)= or -N=, and

[0391] R 26 represents a fluorine atom, a chlorine atom or a bromine atom, or a group selected from: difluoromethyl, methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy,

[0392] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0393] According to the eighth embodiment of the first aspect, the present invention relates to a compound of the above general formula (I), wherein:

[0394] R 1 represents a phenyl or 6-membered heteroaryl optionally substituted one, two or three times, and each substituent is independently selected from a halogen atom or a group selected from: 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), wherein the phenyl group in the (phenyl)-(C1-C3-alkyl)- and (phenyl)-(C1-C3-alkoxy)- groups is optionally substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from the following: cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino, and trifluoromethoxy,

[0395] Alternatively, two substituents attached to adjacent carbon atoms of the phenyl group or 6-membered heteroaryl group together form a divalent group selected from the following: -(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-,

[0396] Or

[0397] R 1 represents a 5-membered heteroaryl group optionally substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from the following: cyano, C1-C3-alkyl, and C1-C3-alkoxy;

[0398] R 2 represents the group

[0399] wherein "*" represents the point of attachment to the nitrogen atom to which R 2 is attached;

[0400] R 3 represents a group selected from methyl and -NH2;

[0401] R 4 represents a 5-membered heteroaryl group optionally substituted one or two times, and each substituent is independently

[0402] selected from a halogen atom or a group selected from the following: C1-C3-alkyl, -N(R 10 )(R 11 ), -C(=O)-N(R 15 )(R 16 ), -C(=O)-OR 17 , phenyl, and 5- or 6-membered heteroaryl,

[0403] wherein the phenyl and 5- or 6-membered heteroaryl are optionally substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from the following: cyano, C1-C3-alkyl, C1-C3-haloalkyl, ((R 22 )(R 23 )N)-C1-C3-alkyl, -OR 9, -N(R 10 )(R 11 ) and -C(=O)-N(R 15 )(R 16 );

[0404] R 5 and R 6 independently represent a hydrogen atom or a group selected from: C1-C4-alkyl, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl, and (phenyl)-(C1-C3-alkyl)-,

[0405] or

[0406] 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, which is optionally substituted one, two, or three times, each substituent independently selected from a halogen atom or a group selected from: oxo, hydroxy, C1-C4-alkyl, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl, and C1-C4-alkoxy;

[0407] R 7 represents a hydrogen atom or C1-C2-alkyl;

[0408] R 8 represents a group selected from -C(=O)-NH2 and -S(=O)2-NH2;

[0409] R 9 represents a hydrogen atom or a group selected from: 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,

[0410] wherein the phenyl group within the (phenyl)-(C1-C3-alkyl)- group and the phenyl group itself are optionally substituted one or two times, each substituent independently selected from a halogen atom or a group selected from: cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino, and trifluoromethoxy;

[0411] R 10 and R 11independently represents a hydrogen atom or a group selected from the following: 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)-O-C(=O)-,

[0412] wherein the phenyl group in the (phenyl)-(C1-C3-alkyl)-, (phenyl)-(C1-C3-alkyl)-C(=O)-, and (phenyl)-(C1-C3-alkyl)-O-C(=O)- groups is optionally substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from the following: cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino, and trifluoromethoxy,

[0413] or

[0414] 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 or a bicyclic nitrogen-containing 6- to 11-membered heterocycloalkyl, which is optionally substituted one, two, or three times, and each substituent is independently selected from a halogen atom or a group selected from the following: cyano, oxo, hydroxy, C1-C4-alkyl, C1-C4-haloalkyl, (C1-C4-alkyl)-C(=O)-, C3-C7-cycloalkyl, C1-C4-alkoxy, -N(R 22 )(R 23 ) and monocyclic 4- to 7-membered heterocycloalkyl;

[0415] R 15 and R 16 independently represent a hydrogen atom or a group selected from the following: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-hydroxyalkyl, (C1-C3-alkoxy)-C2-C3-alkyl-, C3-C7-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl, and (phenyl)-(C1-C3-alkyl)-,

[0416] wherein the C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one, two, or three times, and each substituent is independently selected from a halogen atom or a group selected from the following: oxo, hydroxy, C1-C4-alkyl, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl, and C1-C4-alkoxy,

[0417] or

[0418] R 15 and R 16 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, which is optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from the following: oxo, hydroxy, C1-C4-alkyl, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl and C1-C4-alkoxy;

[0419] R 17 represents C1-C4-alkyl;

[0420] R 18 and R 19 independently represent a hydrogen atom or C1-C4-alkyl;

[0421] R 20 represents a hydrogen atom or a group selected from the following: C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 11-membered heterocycloalkyl, phenyl, naphthyl and 5- to 10-membered heteroaryl,

[0422] wherein the C1-C6-alkyl is optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from the following: hydroxy, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 11-membered heterocycloalkyl, phenyl and 5- to 10-membered heteroaryl, and the phenyl and 5- to 10-membered heteroaryl substituents themselves are optionally substituted one or two times, each substituent independently selected from a halogen atom or a group selected from the following: cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy, wherein 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, each substituent independently selected from a halogen atom or a group selected from the following: cyano, oxo, hydroxy, C1-C4-alkyl, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl and C1-C4-alkoxy,

[0423] and wherein said phenyl, naphthyl and 5- to 10-membered heteroaryl are optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: 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 ),

[0424] R 21 represents a hydrogen atom or C1-C4-alkyl,

[0425] or

[0426] R 20 and R 21 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl which is optionally benzo-fused and optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C4-alkyl, C1-C4-haloalkyl, (phenyl)-(C1-C3-alkyl)-, (C1-C4-alkyl)-C(=O)-, C3-C4-cycloalkyl, C1-C4-alkoxy, C1-C3-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 );

[0427] R 22 and R 23 independently represent a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, and

[0428] R 24 and R 25 independently represent a hydrogen atom or C1-C4-alkyl,

[0429] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0430] According to the ninth embodiment of the first aspect, the present invention relates to a compound of the above general formula (I), wherein:

[0431] R 1represents phenyl or pyridyl optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: 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 ),

[0432] wherein the phenyl in the (phenyl)-(C1-C2-alkyl)- and (phenyl)-(C1-C2-alkoxy)- groups is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: methyl, trifluoromethyl and methoxy,

[0433] alternatively, two substituents attached to adjacent carbon atoms of the phenyl or pyridyl 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-,

[0434] or

[0435] R 1 represents pyrazolyl optionally substituted one or two times, each substituent independently selected from a halogen atom or a group selected from: cyano, C1-C2-alkyl and C1-C2-alkoxy;

[0436] R 2 represents the group

[0437] wherein "*" represents the point of attachment to the nitrogen atom to which R 2 is attached;

[0438] R 3 represents a group selected from methyl and -NH2;

[0439] R 4 represents a 5-membered heteroaryl selected from oxazolyl, isoxazolyl, thiazolyl and isothiazolyl, optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: C1-C3-alkyl, -N(R 10 )(R 11 ), -C(=O)-N(R 15 )(R 16 ), -C(=O)-OR 17 , phenyl and 5- or 6-membered heteroaryl,

[0440] wherein the phenyl group and the 5- or 6-membered heteroaryl group are each optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from the following: a cyano group, a C1-C2-alkyl group, a C1-C2-fluoroalkyl group, -OR 9 、-N(R 10 )(R 11 ) and -C(=O)-N(R 15 )(R 16 );

[0441] R 5 and R 6 each independently represents a hydrogen atom or a group selected from a C1-C2-alkyl group and a (C1-C2-alkyl)-C(=O)- group,

[0442] or

[0443] 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, which is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from the following: an oxo group, a hydroxy group, a C1-C2-alkyl group, and a (C1-C2-alkyl)-C(=O)- group;

[0444] R 7 represents a hydrogen atom or a C1-C2-alkyl group;

[0445] R 8 represents a -C(=O)-NH2 group;

[0446] R 9 represents a hydrogen atom or a group selected from the following: a C1-C4-alkyl group, a (phenyl)-(C1-C2-alkyl)- group, a C1-C4-haloalkyl group, a C2-C3-hydroxyalkyl group, a (C1-C2-alkoxy)-C2-alkyl- group, a ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl- group, -C(R 18 )(R 19 )-C(=O)-OR 17 、-C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ) and a phenyl group,

[0447] wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)- group and the phenyl group itself are each optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from the following: a methyl group, a trifluoromethyl group, and a methoxy group;

[0448] R 10and R 11 each independently represents a hydrogen atom or a group selected from: 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)-O-C(=O)-,

[0449] wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)-, and (phenyl)-(C1-C2-alkyl)-O-C(=O)- groups is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from: methyl, trifluoromethyl, and methoxy,

[0450] or

[0451] 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 or a bicyclic nitrogen-containing 6- to 10-membered heterocycloalkyl, which is optionally substituted one, two, or three times, and each substituent is independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-haloalkyl, (C1-C2-alkyl)-C(=O)-, C1-C2-alkoxy, -N(R 22 )(R 23 ) and a monocyclic 4- to 7-membered heterocycloalkyl;

[0452] R 15 and R 16 each independently represents a hydrogen atom or a group selected from: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-hydroxyalkyl, (C1-C2-alkoxy)-C2-C3-alkyl-, C3-C7-cycloalkyl, a monocyclic 4- to 7-membered heterocycloalkyl, and (phenyl)-(C1-C3-alkyl)-,

[0453] wherein the C3-C7-cycloalkyl and the monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from: oxo, C1-C2-alkyl, and (C1-C2-alkyl)-C(=O)-,

[0454] or

[0455] R15 and R 16 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl which is optionally substituted one or twice, each substituent independently selected from a halogen atom or a group selected from: oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-;

[0456] R 17 represents C1-C4-alkyl;

[0457] R 18 and R 19 independently represent a hydrogen atom or C1-C2-alkyl;

[0458] R 20 represents a hydrogen atom or a group selected from: C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, naphthyl and 5- to 10-membered heteroaryl,

[0459] wherein the C1-C6-alkyl is optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: hydroxy, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl and 5- to 10-membered heteroaryl, and the phenyl and 5- to 10-membered heteroaryl substituents themselves are optionally substituted one or twice, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: methyl, trifluoromethyl and methoxy,

[0460] wherein C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl and bicyclic 6- to 10-membered heterocycloalkyl are optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-,

[0461] and wherein the phenyl, naphthyl and 5- to 10-membered heteroaryl are optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, C1-C2-alkyl, C1-C2-haloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 ),

[0462] R 21 represents a hydrogen atom or a C1-C2-alkyl group,

[0463] or

[0464] R 20 and R 21 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, which is optionally benzo-fused and optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-haloalkyl, (phenyl)-(C1-C2-alkyl)-, (C1-C2-alkyl)-C(=O)-, C3-C4-cycloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 );

[0465] R 22 and R 23 independently represent a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, and

[0466] R 24 and R 25 independently represent a hydrogen atom or a C1-C2-alkyl group,

[0467] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0468] According to the tenth embodiment of the first aspect, the present invention relates to a compound of the above general formula (I), wherein:

[0469] R 1 represents a phenyl or pyridyl group optionally substituted one, two or three times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy, -N(R 5 )(R 6 ),

[0470] Alternatively, two substituents attached to adjacent carbon atoms of the phenyl or pyridyl group together form a divalent group selected from: -(CH2)3-, -O-CH2-O-, and -O-CF2-O-

[0471] or

[0472] R 1 represents a pyrazolyl group optionally substituted with a methyl group;

[0473] R 2 represents the group

[0474] wherein "*" represents the point of attachment to the nitrogen atom to which R 2 is attached;

[0475] R 3 represents a group selected from methyl and -NH2;

[0476] R 4 represents the group

[0477] wherein "#" represents the point of attachment to the carbonyl group to which R 4 is attached,

[0478] and wherein

[0479] R 4a represents a group selected from: -N(R 10 )(R 11 ), -C(=O)-N(R 15 )(R 16 ), -C(=O)-OR 17 , phenyl, and 5- or 6-membered heteroaryl selected from oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, and pyridazinyl,

[0480] wherein the phenyl and the 5- or 6-membered heteroaryl selected from oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, and pyridazinyl are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, or a group selected from: cyano, C1-C2-alkyl, -OR 9 , -N(R 10 )(R 11 ) and -C(=O)-N(R 15 )(R 16 );

[0481] R 5 and R 6 independently represent a hydrogen atom or C1-C2-alkyl,

[0482] or

[0483] 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 which is optionally substituted one or two times, each substituent independently selected from a fluorine atom or a group selected from a hydroxyl group and a C1-C2-alkyl group;

[0484] R 7 represents a hydrogen atom or a C1-C2-alkyl group;

[0485] R 8 represents a -C(=O)-NH2 group;

[0486] R 9 represents a hydrogen atom or a group selected from the following: 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,

[0487] wherein the phenyl group in the benzyl and the phenyl itself are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group;

[0488] R 10 and R 11 independently represent a hydrogen atom or a group selected from the following: C1-C2-alkyl, C1-C2-fluoroalkyl, (C1-C2-alkyl)-C(=O)-, (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-O-C(=O)-,

[0489] wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-O-C(=O)- groups is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group, or

[0490] R 10 and R 11Together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl which is optionally substituted one or twice, each substituent independently selected from a fluorine atom or a group selected from the following: oxo, C1-C2-alkyl, C1-C2-fluoroalkyl, and (C1-C2-alkyl)-C(=O)-;

[0491] R 15 and R 16 independently represent a hydrogen atom or a group selected from the following: C1-C3-alkyl, C1-C3-fluoroalkyl, and C3-C5-cycloalkyl,

[0492] or

[0493] R 15 and R 16 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl which is optionally substituted once by a fluorine atom or a group selected from oxo, C1-C2-alkyl, and CH3-C(=O)-;

[0494] R 17 represents C1-C2-alkyl;

[0495] R 18 and R 19 independently represent a hydrogen atom or a methyl group;

[0496] R 20 represents a hydrogen atom or a group selected from the following: 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,

[0497] wherein the C1-C3-alkyl is optionally substituted one, two, or three times, each substituent independently selected from a halogen atom or a group selected from the following: hydroxy, 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, and the phenyl and 5- to 10-membered heteroaryl substituents themselves are optionally substituted one or twice, each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[0498] wherein the C3-C6-cycloalkyl, adamantyl, and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one, two, or three times, each substituent independently selected from a fluorine atom or a group selected from the following: oxo, C1-C2-alkyl, and (C1-C2-alkyl)-C(=O)-,

[0499] and wherein said phenyl and 5- to 10-membered heteroaryl are optionally substituted one, two or three times, each substituent independently selected from a fluorine atom and a chlorine atom or from the group consisting of: 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 ),

[0500] R 21 represents a hydrogen atom or C1-C2-alkyl,

[0501] or

[0502] R 20 and R 21 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl which is optionally benzo-fused and which is optionally substituted one, two or three times, each substituent independently selected from a halogen atom or from the group consisting of: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-fluoroalkyl, benzyl, (C1-C2-alkyl)-C(=O)-, C3-C4-cycloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 );

[0503] R 22 and R 23 independently represent a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-, and

[0504] R 24 and R 25 independently represent a hydrogen atom or C1-C2-alkyl,

[0505] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0506] A further embodiment of the first aspect of the invention

[0507] In another embodiment of the first aspect, the invention relates to a compound of formula (I) above, wherein:

[0508] R 1represents a phenyl or pyridyl group optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: hydroxyl, 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 ),

[0509] wherein the phenyl in the (phenyl)-(C1-C2-alkyl)- and (phenyl)-(C1-C2-alkoxy)- groups is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: methyl, trifluoromethyl and methoxy,

[0510] or two substituents attached to adjacent carbon atoms of the phenyl or pyridyl 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-,

[0511] or

[0512] R 1 represents a pyrazolyl group optionally substituted one or two times, each substituent independently selected from a halogen atom or a group selected from: cyano, C1-C2-alkyl and C1-C2-alkoxy,

[0513] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0514] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0515] R 1 represents a phenyl or pyridyl group optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: hydroxyl, 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 ),

[0516] wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)- and (phenyl)-(C1-C2-alkoxy)- groups is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from the following: methyl, trifluoromethyl, and methoxy,

[0517] alternatively, two substituents attached to adjacent carbon atoms of the phenyl or pyridyl group together form a divalent group selected from the following: -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O-, and -O-CF2-O-,

[0518] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0519] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0520] R 1 represents a phenyl or pyridyl group optionally substituted one, two, or three times, and each substituent is independently selected from a halogen atom or a group selected from the following: 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 ),

[0521] wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)- and (phenyl)-(C1-C2-alkoxy)- groups is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from the following: methyl, trifluoromethyl, and methoxy,

[0522] alternatively, two substituents attached to adjacent carbon atoms of the phenyl or pyridyl group together form a divalent group selected from the following: –(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O-, and -O-CF2-O-,

[0523] or

[0524] R 1 represents a pyrazolyl group optionally substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from the following: cyano, C1-C2-alkyl, and C1-C2-alkoxy,

[0525] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0526] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0527] R 1 represents phenyl or pyridyl optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: 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 ),

[0528] wherein the phenyl in the (phenyl)-(C1-C2-alkyl)- and (phenyl)-(C1-C2-alkoxy)- groups is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: methyl, trifluoromethyl and methoxy,

[0529] or, two substituents attached to adjacent carbon atoms of the phenyl or pyridyl 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-,

[0530] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0531] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0532] R 1 represents phenyl or pyridyl optionally substituted one, two or three times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: hydroxy, cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C2-fluoroalkoxy and -N(R 5 )(R 6 ),

[0533] Alternatively, two substituents attached to adjacent carbon atoms of the phenyl or pyridyl group together form a divalent group selected from: -(CH2)3-, -O-CH2-O-, and -O-CF2-O-

[0534] or

[0535] R 1 represents a pyrazolyl group optionally substituted with one methyl group

[0536] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0537] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0538] R 1 represents a phenyl or pyridyl group optionally substituted one, two or three times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: hydroxy, cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C2-fluoroalkoxy and -N(R 5 )(R 6 ),

[0539] Alternatively, two substituents attached to adjacent carbon atoms of the phenyl or pyridyl group together form a divalent group selected from: –(CH2)3-, -O-CH2-O- and -O-CF2-O-,

[0540] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0541] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0542] R 1 represents a phenyl or pyridyl group optionally substituted one, two or three times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy, -N(R 5 )(R 6 ),

[0543] Alternatively, two substituents attached to adjacent carbon atoms of the phenyl or pyridyl group together form a divalent group selected from: –(CH2)3-, -O-CH2-O- and -O-CF2-O-,

[0544] or

[0545] R 1 represents a pyrazolyl group optionally substituted with one methyl group,

[0546] or a stereoisomer, tautomer, N - oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0547] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0548] R 1 represents a phenyl or pyridyl group optionally substituted one, two, or three times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or from the following groups: cyano, C1 - C4 - alkyl, C1 - C2 - fluoroalkyl, C1 - C2 - alkoxy, C1 - C2 - fluoroalkoxy, and -N(R 5 )(R 6 ),

[0549] alternatively, two substituents attached to adjacent carbon atoms of the phenyl or pyridyl group together form a divalent group selected from the following: –(CH2)3 -, -O - CH2 - O -, and -O - CF2 - O -,

[0550] or a stereoisomer, tautomer, N - oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0551] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0552] R 1 represents a phenyl group optionally substituted one, two, or three times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or from the following groups: hydroxyl, cyano, C1 - C4 - alkyl, C1 - C2 - fluoroalkyl, C1 - C2 - alkoxy, (phenyl)-(C1 - C2 - alkoxy)-, C1 - C2 - fluoroalkoxy, and -N(R 5 )(R 6 ),

[0553] alternatively, two substituents attached to adjacent carbon atoms of the phenyl group together form a divalent group selected from the following: –(CH2)3 -, -O - CH2 - O -, and -O - CF2 - O -,

[0554] or a stereoisomer, tautomer, N - oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0555] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0556] R 1 represents a pyridyl group optionally substituted one, two or three times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or from the following groups: hydroxyl, cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, (phenyl)-(C1-C2-alkoxy)-, C1-C2-fluoroalkoxy and -N(R 5 )(R 6 ),

[0557] alternatively, two substituents attached to adjacent carbon atoms of the pyridyl group together form a divalent group selected from the following: –(CH2)3-, -O-CH2-O- and -O-CF2-O-,

[0558] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0559] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0560] R 1 represents a phenyl group optionally substituted one, two or three times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or from the following groups: cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy, -N(R 5 )(R 6 ),

[0561] alternatively, two substituents attached to adjacent carbon atoms of the phenyl or pyridyl group together form a divalent group selected from the following: –(CH2)3-, -O-CH2-O- and -O-CF2-O-,

[0562] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0563] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0564] R 1 represents a pyridyl group optionally substituted one, two or three times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or from the following groups: cyano, C1-C4-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy, -N(R 5 )(R 6 ),

[0565] Alternatively, two substituents attached to adjacent carbon atoms of the phenyl or pyridyl group together form a divalent group selected from: –(CH2)3-, -O-CH2-O- and -O-CF2-O-

[0566] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0567] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0568] R 1 represents a phenyl or pyridyl group optionally substituted one or twice, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from: methyl, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy, and trifluoromethoxy, or two substituents attached to adjacent carbon atoms of the phenyl or pyridyl group together form a divalent group -O-CF2-O-

[0569] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0570] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0571] R 1 represents a phenyl group optionally substituted one or twice, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from: methyl, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy, and trifluoromethoxy

[0572] or two substituents attached to adjacent carbon atoms of the phenyl group together form a divalent group -O-CF2-O-

[0573] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0574] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0575] R 1 represents a pyridyl group optionally substituted one or twice, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from: methyl, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy, and trifluoromethoxy

[0576] or two substituents attached to adjacent carbon atoms of the pyridyl group together form a divalent group -O-CF2-O-

[0577] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0578] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0579] R 1 represents phenyl or pyridyl optionally substituted one or twice, each substituent independently selected from a fluorine atom and a chlorine atom, or from the following groups: C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy,

[0580] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0581] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0582] R 1 represents phenyl optionally substituted one or twice, each substituent independently selected from a fluorine atom and a chlorine atom, or from the following groups: cyano, C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy,

[0583] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0584] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0585] R 1 represents phenyl optionally substituted one or twice, each substituent independently selected from a fluorine atom and a chlorine atom, or from the following groups: C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy,

[0586] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0587] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0588] R 1represents a pyridyl group optionally substituted one or two times, each substituent independently selected from a fluorine atom and a chlorine atom, or from the following groups: C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-fluoroalkoxy,

[0589] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0590] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0591] R 1 represents the group

[0592] wherein "**" represents the point of attachment to the nitrogen atom to which R 1 is attached;

[0593] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0594] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0595] R 1 represents the group

[0596] wherein "**" represents the point of attachment to the nitrogen atom to which R 1 is attached;

[0597] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0598] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0599] R 1 represents the group

[0600] wherein "**" represents the point of attachment to the nitrogen atom to which R 1 is attached;

[0601] Y 1 represents -C(H)=, -C(F)=, -C(Cl)=, -C(CN)= or -N=, and

[0602] R 26 represents a fluorine atom, a chlorine atom or a bromine atom, or a group selected from the following: methyl, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy,

[0603] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0604] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0605] R 1 represents a group

[0606] wherein "**" represents the point of attachment to the nitrogen atom to which R 1 is attached;

[0607] Y 1 represents -C(H)=, -C(F)=, -C(Cl)= or -N=, and

[0608] R 26 represents a fluorine atom, a chlorine atom or a bromine atom, or a group selected from: difluoromethyl, methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy,

[0609] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0610] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0611] R 1 represents a group

[0612] wherein "**" represents the point of attachment to the nitrogen atom to which R 1 is attached;

[0613] Y 1 represents -C(H)=, -C(F)= or -N=, and

[0614] 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,

[0615] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0616] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0617] R 1 represents a group

[0618] wherein "**" represents the point of attachment of the nitrogen atom linked to R 1 the point of attachment;

[0619] Y 1 represents -C(H)= or -N=, and

[0620] R 26 represents a fluorine atom, a chlorine atom, or a group selected from: difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy, and trifluoromethoxy,

[0621] or its stereoisomers, tautomers, N-oxides, hydrates, solvates, or salts, or mixtures thereof.

[0622] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0623] R 1 represents the group

[0624] wherein "**" represents the point of attachment of the nitrogen atom linked to R 1 the point of attachment, and

[0625] R 28 represents a group selected from: methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy, and trifluoromethoxy,

[0626] or its stereoisomers, tautomers, N-oxides, hydrates, solvates, or salts, or mixtures thereof.

[0627] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0628] R 1 represents a group selected from:

[0629]

[0630]

[0631] wherein "**" represents the point of attachment of the nitrogen atom linked to R 1 the point of attachment,

[0632] or its stereoisomers, tautomers, N-oxides, hydrates, solvates, or salts, or mixtures thereof.

[0633] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0634] R 1represents a group selected from the following:

[0635]

[0636] wherein "**" represents the point of attachment of the nitrogen atom linked to R 1 and the point of attachment of the nitrogen atom to which it is attached,

[0637] or its stereoisomers, tautomers, N-oxides, hydrates, solvates, or salts, or mixtures thereof.

[0638] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0639] R 2 represents a group

[0640] wherein "*" represents the point of attachment of the nitrogen atom linked to R 2 and the point of attachment of the nitrogen atom to which it is attached;

[0641] R 7 represents a hydrogen atom or C1-C2-alkyl;

[0642] R 8 represents a -C(=O)-NH2 group,

[0643] or its stereoisomers, tautomers, N-oxides, hydrates, solvates, or salts, or mixtures thereof.

[0644] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0645] R 2 represents a group

[0646] wherein "*" represents the point of attachment of the nitrogen atom linked to R 2 and the point of attachment of the nitrogen atom to which it is attached;

[0647] R 7 represents C1-C2-alkyl;

[0648] R 8 represents a -C(=O)-NH2 group,

[0649] or its stereoisomers, tautomers, N-oxides, hydrates, solvates, or salts, or mixtures thereof.

[0650] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0651] R 2 represents a group

[0652] wherein "*" represents the point of attachment of the nitrogen atom linked to R 2 ;

[0653] R 7 represents a C1-C2-alkyl group;

[0654] R 8 represents a -C(=O)-NH2 group,

[0655] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0656] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0657] R 2 represents a group

[0658] wherein "*" represents the point of attachment of the nitrogen atom linked to R 2 ;

[0659] R 7 represents a C1-C2-alkyl group;

[0660] R 8 represents a -C(=O)-NH2 group,

[0661] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0662] In another embodiment of the first aspect, the present invention relates to a mixture of isomers of a compound of formula (I) above, wherein:

[0663] R 2 represents a group in a ratio of about 99:1 or higher, with the higher proportion being

[0664] wherein "*" represents the point of attachment of the nitrogen atom linked to R 2 ;

[0665] R 7 represents a C1-C2-alkyl group;

[0666] R 8 represents a -C(=O)-NH2 group,

[0667] or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0668] In another embodiment of the first aspect, the present invention relates to an isomer mixture of the compound of formula (I) above, wherein:

[0669] R 2 represents a group in a ratio of about 98:2 or higher, with the higher proportion being

[0670] wherein "*" represents the point of attachment of the nitrogen atom connected to R 2 ;

[0671] R 7 represents C1-C2-alkyl;

[0672] R 8 represents a -C(=O)-NH2 group,

[0673] or its tautomer, N-oxide, hydrate, solvate, or salt, or a mixture thereof.

[0674] In another embodiment of the first aspect, the present invention relates to an isomer mixture of the compound of formula (I) above, wherein:

[0675] R 2 represents a group in a ratio of about 95:5 or higher, with the higher proportion being

[0676] wherein "*" represents the point of attachment of the nitrogen atom connected to R 2 ;

[0677] R 7 represents C1-C2-alkyl;

[0678] R 8 represents a -C(=O)-NH2 group,

[0679] or its tautomer, N-oxide, hydrate, solvate, or salt, or a mixture thereof.

[0680] In another embodiment of the first aspect, the present invention relates to an isomer mixture of the compound of formula (I) above, wherein:

[0681] R 2 represents a group in a ratio of about 90:10 or higher, with the higher proportion being

[0682] wherein "*" represents the point of attachment of the nitrogen atom connected to R 2 ;

[0683] R 7represents a C1-C2-alkyl group;

[0684] R 8 represents a -C(=O)-NH2 group,

[0685] or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0686] In another embodiment of the first aspect, the present invention relates to a mixture of isomers of the compound of formula (I) above, wherein:

[0687] R 2 represents a group in a ratio of about 80:20 or higher, with the higher proportion being

[0688] wherein "*" represents the point of attachment to the nitrogen atom to which R 2 is attached;

[0689] R 7 represents a C1-C2-alkyl group;

[0690] R 8 represents a -C(=O)-NH2 group,

[0691] or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0692] In another embodiment of the first aspect, the present invention relates to a mixture of isomers of the compound of formula (I) above, wherein:

[0693] R 2 represents a group in a ratio of about 50:50, i.e., a racemic mixture in the absence of other chiral elements in the compound,

[0694] wherein "*" represents the point of attachment to the nitrogen atom to which R 2 is attached;

[0695] R 7 represents a C1-C2-alkyl group;

[0696] R 8 represents a -C(=O)-NH2 group,

[0697] or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0698] In another embodiment of the first aspect, the present invention relates to the compound of formula (I) above, wherein:

[0699] R 2 represents a group

[0700] wherein "*" represents the point of attachment of the nitrogen atom linked to R 2 the point of attachment;

[0701] R 7 represents methyl;

[0702] R 8 represents a -C(=O)-NH2 group,

[0703] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0704] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0705] R 2 represents the group

[0706] wherein "*" represents the point of attachment of the nitrogen atom linked to R 2 the point of attachment;

[0707] R 7 represents methyl;

[0708] R 8 represents a -C(=O)-NH2 group,

[0709] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0710] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0711] R 2 represents the group

[0712] wherein "*" represents the point of attachment of the nitrogen atom linked to R 2 the point of attachment;

[0713] R 7 represents methyl;

[0714] R 8 represents a -C(=O)-NH2 group,

[0715] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0716] In another embodiment of the first aspect, the present invention relates to a mixture of isomers of a compound of formula (I) above, wherein:

[0717] R 2 represents a group The ratio is about 99:1 or higher, and the one with a higher proportion is

[0718] wherein "*" represents the connection point of the nitrogen atom connected to R 2 the connection point;

[0719] R 7 represents methyl;

[0720] R 8 represents a -C(=O)-NH2 group,

[0721] or its tautomer, N-oxide, hydrate, solvate, or salt, or a mixture thereof.

[0722] In another embodiment of the first aspect, the present invention relates to a mixture of isomers of the compound of formula (I) above, wherein:

[0723] R 2 represents a group The ratio is about 98:2 or higher, and the one with a higher proportion is

[0724] wherein "*" represents the connection point of the nitrogen atom connected to R 2 the connection point;

[0725] R 7 represents methyl;

[0726] R 8 represents a -C(=O)-NH2 group,

[0727] or its tautomer, N-oxide, hydrate, solvate, or salt, or a mixture thereof.

[0728] In another embodiment of the first aspect, the present invention relates to a mixture of isomers of the compound of formula (I) above, wherein:

[0729] R 2 represents a group The ratio is about 95:5 or higher, and the one with a higher proportion is

[0730] wherein "*" represents the connection point of the nitrogen atom connected to R 2 the connection point;

[0731] R 7 represents methyl;

[0732] R 8 represents a -C(=O)-NH2 group,

[0733] or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0734] In another embodiment of the first aspect, the present invention relates to a mixture of isomers of a compound of formula (I) above, wherein:

[0735] R 2 represents a group in a ratio of about 90:10 or higher, with the higher proportion being

[0736] wherein "*" represents the point of attachment of the nitrogen atom to which R is attached; 2 the nitrogen atom to which R is attached;

[0737] R 7 represents methyl;

[0738] R 8 represents a -C(=O)-NH2 group,

[0739] or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0740] In another embodiment of the first aspect, the present invention relates to a mixture of isomers of a compound of formula (I) above, wherein:

[0741] R 2 represents a group in a ratio of about 80:20 or higher, with the higher proportion being

[0742] wherein "*" represents the point of attachment of the nitrogen atom to which R is attached; 2 the nitrogen atom to which R is attached;

[0743] R 7 represents methyl;

[0744] R 8 represents a -C(=O)-NH2 group,

[0745] or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0746] In another embodiment of the first aspect, the present invention relates to a mixture of isomers of a compound of formula (I) above, wherein:

[0747] R 2 represents a group in a ratio of about 50:50, i.e., a racemic mixture in the absence of other chiral elements in the compound,

[0748] wherein "*" represents the point of attachment of the nitrogen atom to which R is attached2 The attachment point of the attached nitrogen atom;

[0749] R 7 represents methyl;

[0750] R 8 represents a -C(=O)-NH2 group,

[0751] or its tautomer, N-oxide, hydrate, solvate, or salt, or a mixture thereof.

[0752] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0753] R 3 represents a group selected from methyl and -NH2;

[0754] or its stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt, or a mixture thereof.

[0755] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0756] R 3 represents an -NH2 group;

[0757] or its stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt, or a mixture thereof.

[0758] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0759] R 3 represents methyl;

[0760] or its stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt, or a mixture thereof.

[0761] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0762] R 4 represents a 5-membered heteroaryl selected from oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, and oxadiazolyl, which is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from: C1-C4-alkyl, ((R 9 )O)-(C1-C3-alkyl)-, ((R 10 )(R 11)-(C1-C3-alkyl)-, (C3-C7-cycloalkyl)-(C1-C3-alkyl)-, C3-C7-cycloalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 15 )(R 16 ), -C(=O)-OR 17 , phenyl and 5- or 6-membered heteroaryl, where the phenyl and 5- or 6-membered heteroaryl are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or from the following groups: cyano, C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 , -N(R 10 )(R 11 ) and -C(=O)-N(R 15 )(R 16 );

[0763] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0764] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0765] R 4 represents a 5-membered heteroaryl selected from oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl, which is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or from the following groups: C1-C3-alkyl, -N(R 10 )(R 11 ), -C(=O)-N(R 15 )(R 16 ), -C(=O)-OR 17 , phenyl and 5- or 6-membered heteroaryl, where the phenyl and 5- or 6-membered heteroaryl are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or from the following groups: cyano, C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 , -N(R 10 )(R 11 ) and -C(=O)-N(R 15 )(R 16 );

[0766] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0767] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0768] R 4 represents a group selected from ,

[0769] wherein "#" represents the point of attachment of the carbonyl group attached to R 4 ,

[0770] and wherein

[0771] R 4a and R 4b each independently represents a fluorine atom, a chlorine atom or a bromine atom, or a group selected from: C1-C4-alkyl, ((R 9 )O)-(C1-C2-alkyl)-, ((R 10 )(R 11 )N)-(C1-C2-alkyl)-, (C3-C7-cycloalkyl)-(C1-C2-alkyl)-, C3-C7-cycloalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 15 )(R 16 ), -C(=O)-OR 17 , phenyl and 5- or 6-membered heteroaryl selected from oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl,

[0772] wherein phenyl and 5- or 6-membered heteroaryl selected from oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl are optionally substituted one or two times, each substituent independently selected from a fluorine atom and a chlorine atom, or a group selected from: cyano, C1-C2-alkyl, -OR 9 , -N(R 10 )(R 11 ) and -C(=O)-N(R 15 )(R 16 ),

[0773] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0774] In another embodiment of the first aspect, the invention relates to a compound of formula (I) above, wherein:

[0775] R 4 represents the group

[0776] wherein "#" represents the point of attachment of the carbonyl group attached to R 4 ,

[0777] and wherein

[0778] R 4a represents a fluorine atom, a chlorine atom or a bromine atom, or a group selected from: C1-C4-alkyl, ((R 9 ))O)-(C1-C2-alkyl)-, ((R 10 )(R 11 ))N)-(C1-C2-alkyl)-, (C3-C7-cycloalkyl)-(C1-C2-alkyl)-, C3-C7-cycloalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 15 )(R 16 ), -C(=O)-OR 17 , phenyl and a 5- or 6-membered heteroaryl selected from oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl,

[0779] wherein the phenyl and the 5- or 6-membered heteroaryl selected from oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl are optionally substituted one or two times, each substituent independently selected from a fluorine atom and a chlorine atom, or a group selected from: cyano, C1-C2-alkyl, -OR 9 , -N(R 10 )(R 11 ) and -C(=O)-N(R 15 )(R 16 ),

[0780] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0781] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0782] R 4 represents a group

[0783] wherein "#" represents the point of attachment of the carbonyl group attached to R 4 ,

[0784] and wherein

[0785] R 4b represents a fluorine atom, a chlorine atom or a bromine atom, or a group selected from: C1-C4-alkyl, ((R 9 ))O)-(C1-C2-alkyl)-, ((R 10 )(R 11)-(C1-C2-alkyl)-, (C3-C7-cycloalkyl)-(C1-C2-alkyl)-, C3-C7-cycloalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 15 )(R 16 ), -C(=O)-OR 17 , phenyl and 5- or 6-membered heteroaryl selected from oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl,

[0786] wherein phenyl and 5- or 6-membered heteroaryl selected from oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl are optionally substituted one or two times, each substituent independently selected from a fluorine atom and a chlorine atom, or a group selected from the following: cyano, C1-C2-alkyl, -OR 9 , -N(R 10 )(R 11 ), and -C(=O)-N(R 15 )(R 16 ),

[0787] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0788] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0789] R 4 represents a group

[0790] wherein "#" represents the point of attachment of the carbonyl group to which R 4 is attached,

[0791] and wherein

[0792] R 4a represents a group selected from: -N(R 10 )(R 11 ), -C(=O)-N(R 15 )(R 16 ), -C(=O)-OR 17 , phenyl and 5- or 6-membered heteroaryl selected from oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl,

[0793] wherein the phenyl group and a 5- or 6-membered heteroaryl group selected from oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, and pyridazinyl are optionally substituted one or two times, each substituent independently selected from a fluorine atom and a chlorine atom, or a group selected from the following: cyano, C1-C2-alkyl, -OR 9 、-N(R 10 )(R 11 ) and -C(=O)-N(R 15 )(R 16 ),

[0794] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0795] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0796] R 4 represents isoxazolyl substituted with one phenyl group,

[0797] wherein the phenyl group is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, or a methyl group,

[0798] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0799] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0800] R 4 represents the group

[0801] wherein "#" represents the point of attachment of the carbonyl group to which R 4 is attached,

[0802] and wherein

[0803] R 4a represents a chlorine atom or a bromine atom, or a group selected from the following: ((R 9 )O)-(C1-C2-alkyl)-, ((R 10 )(R 11 )N)-(C1-C2-alkyl)-, (C3-C5-cycloalkyl)-(C1-C2-alkyl)-, C3-C5-cycloalkyl, -OR 9 、-C(=O)-N(R 15 )(R 16 ) and phenyl,

[0804] wherein the phenyl group is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[0805] or

[0806] R 4 represents a group

[0807] wherein "#" represents the point of attachment of the carbonyl group to R 4 to which it is attached,

[0808] and wherein

[0809] R 4b represents a group selected from: C1-C4-alkyl, C3-C5-cycloalkyl, -C(=O)-N(R 15 )(R 16 ), and phenyl,

[0810] wherein the phenyl group is optionally substituted one or two times, each substituent being independently selected from a fluorine atom and a chlorine atom, or a group selected from: cyano, C1-C2-alkyl, and -OR 9 ,

[0811] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0812] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0813] R 4 represents a group

[0814] wherein "#" represents the point of attachment of the carbonyl group to R 4 to which it is attached,

[0815] and wherein

[0816] R 4a represents a chlorine atom or a bromine atom, or a group selected from: ((R 9 )O)-(C1-C2-alkyl)-, ((R 10 )(R 11 )N)-(C1-C2-alkyl)-, (C3-C5-cycloalkyl)-(C1-C2-alkyl)-, C3-C5-cycloalkyl, -OR 9 , -C(=O)-N(R 15 )(R 16 ), and phenyl,

[0817] wherein the phenyl group is optionally substituted one or two times, each substituent being independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[0818] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0819] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0820] R 4 represents a group

[0821] wherein "#" represents the point of attachment of the carbonyl group attached to R 4 and wherein

[0822] and wherein

[0823] R 4a represents a group selected from: C1-C4-alkyl, C3-C5-cycloalkyl, -C(=O)-N(R 15 )(R 16 ), and phenyl,

[0824] wherein the phenyl is optionally substituted one or two times, each substituent independently selected from a fluorine atom and a chlorine atom, or from a group selected from: a cyano group, C1-C2-alkyl, and -OR 9 ,

[0825] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0826] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0827] R 4 represents a group

[0828] wherein "#" represents the point of attachment of the carbonyl group attached to R 4 and wherein

[0829] and wherein

[0830] R 4a represents a chlorine atom or a bromine atom, or a group selected from: ((R 9 )O)-(C1-alkyl)-, ((R 10 )(R 11 )N)-(C1-alkyl)-, (C3-C5-cycloalkyl)-(C1-alkyl)-, C3-C5-cycloalkyl, -OR 9 , -C(=O)-N(R 15 )(R 16 ), and phenyl,

[0831] wherein the phenyl group is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[0832] or

[0833] R 4 represents a group

[0834] wherein "#" represents the point of attachment of the carbonyl group attached to R 4 and wherein

[0835] and wherein

[0836] R 4b represents a group selected from: C1-C4-alkyl, C3-C5-cycloalkyl, and phenyl,

[0837] wherein the phenyl group is optionally substituted one or two times, each substituent is independently selected from a fluorine atom and a chlorine atom, or a group selected from: cyano, C1-C2-alkyl, and -OR 9 ,

[0838] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0839] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0840] R 4 represents a group

[0841] wherein "#" represents the point of attachment of the carbonyl group attached to R 4 and wherein

[0842] and wherein

[0843] R 4a represents a chlorine atom or a bromine atom, or a group selected from: ((R 9 )O)-(C1-alkyl)-, ((R 10 )(R 11 )N)-(C1-alkyl)-, (C3-C5-cycloalkyl)-(C1-alkyl)-, C3-C5-cycloalkyl, -OR 9 , -C(=O)-N(R 15 )(R 16 ) and phenyl,

[0844] wherein the phenyl group is optionally substituted one or two times, each substituent is independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[0845] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0846] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0847] R 4 represents the group

[0848] wherein "#" represents the point of attachment of the carbonyl group attached to R 4 and wherein

[0849] and wherein

[0850] R 4b represents a group selected from: C1-C4-alkyl, C3-C5-cycloalkyl, and phenyl,

[0851] wherein the phenyl is optionally substituted one or two times, each substituent independently selected from a fluorine atom and a chlorine atom, or from the group consisting of: a cyano group, C1-C2-alkyl, and -OR 9 ,

[0852] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0853] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0854] R 4 represents the group

[0855] wherein "#" represents the point of attachment of the carbonyl group attached to R 4 and wherein

[0856] and wherein

[0857] R 4a represents a chlorine atom or a bromine atom, or a group selected from: ((R 9 )O)-(C1-alkyl)-, C3-C5-cycloalkyl, -OR 9 and -C(=O)-N(R 15 )(R 16 ),

[0858] or

[0859] R 4 represents the group

[0860] wherein "#" represents the point of attachment of the carbonyl group attached to R 4 and wherein

[0861] and wherein

[0862] R 4b represents a group selected from: C1-C4-alkyl, C3-C5-cycloalkyl and phenyl,

[0863] wherein the phenyl is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group,

[0864] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0865] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0866] R 4 represents the group

[0867] wherein "#" represents the point of attachment of the carbonyl group attached to R 4 and wherein

[0868] and wherein

[0869] R 4a represents a chlorine atom or a bromine atom, or a group selected from: ((R 9 )O)-(C1-alkyl)-, C3-C5-cycloalkyl, -OR 9 and -C(=O)-N(R 15 )(R 16 ),

[0870] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0871] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0872] R 4 represents the group

[0873] wherein "#" represents the point of attachment of the carbonyl group attached to R 4 and wherein

[0874] and wherein

[0875] R 4b represents a group selected from: C1-C4-alkyl, C3-C5-cycloalkyl and phenyl,

[0876] wherein the phenyl is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group,

[0877] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0878] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0879] R 5 and R 6 independently represent a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-,

[0880] or

[0881] 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 which is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from the following: oxo, hydroxy, C1-C2-alkyl, and (C1-C2-alkyl)-C(=O)-,

[0882] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0883] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0884] R 5 and R 6 independently represent a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-,

[0885] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0886] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0887] 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 which is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from the following: oxo, hydroxy, C1-C2-alkyl, and (C1-C2-alkyl)-C(=O)-,

[0888] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0889] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0890] R 5 and R 6 independently represent a hydrogen atom or a C1-C2-alkyl group,

[0891] or

[0892] 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, which is optionally substituted one or two times, each substituent independently selected from a fluorine atom or a group selected from a hydroxyl group and a C1-C2-alkyl group,

[0893] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0894] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0895] R 5 and R 6 independently represent a hydrogen atom or a C1-C2-alkyl group,

[0896] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0897] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0898] 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, which is optionally substituted one or two times, each substituent independently selected from a fluorine atom or a group selected from a hydroxyl group and a C1-C2-alkyl group,

[0899] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0900] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0901] R 7 represents a hydrogen atom,

[0902] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0903] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0904] R 7 represents methyl,

[0905] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0906] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0907] R 7 represents ethyl,

[0908] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0909] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0910] R 7 represents a hydrogen atom or a C1-C2-alkyl group,

[0911] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0912] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0913] R 9 represents a hydrogen atom or a group selected from: C1-C4-alkyl, (C3-C7-cycloalkyl)-(C1-C2-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(=O)-N(R 20 )(R 21 ), C3-C7-cycloalkyl, and phenyl,

[0914] wherein the C3-C7-cycloalkyl in the C3-C7-cycloalkyl and the (C3-C7-cycloalkyl)-(C1-C2-alkyl)- group is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom or a group selected from oxo and methyl,

[0915] and wherein the phenyl group within the (phenyl)-(C1-C2-alkyl)- group and the phenyl itself are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or from the following groups: a cyano group, a methyl group, a trifluoromethyl group, and a methoxy group,

[0916] or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture thereof.

[0917] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0918] R 9 represents a hydrogen atom or a group selected from the following: 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,

[0919] wherein the phenyl group within the (phenyl)-(C1-C2-alkyl)- group and the phenyl itself are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or from the following groups: a methyl group, a trifluoromethyl group, and a methoxy group,

[0920] or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture thereof.

[0921] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0922] R 9 represents a hydrogen atom or a group selected from the following: C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, C2-hydroxyalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(=O)-N(R 20 )(R 21 ) and phenyl,

[0923] wherein the phenyl group within the benzyl and the phenyl itself are optionally substituted one or two times, each substituent independently selected from a fluorine atom and a chlorine atom, or from the groups of a cyano group and a methyl group,

[0924] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0925] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0926] R 9 represents a hydrogen atom or a group selected from: 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,

[0927] wherein the phenyl in the benzyl and the phenyl itself are optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[0928] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0929] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0930] R 9 represents a hydrogen atom or a group selected from: C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(=O)-N(R 20 )(R 21 ), and phenyl,

[0931] wherein the phenyl in the benzyl and the phenyl itself are optionally substituted one or two times, and each substituent is independently selected from a fluorine atom and a chlorine atom, or a group selected from a cyano group and a methyl group,

[0932] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0933] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0934] R 9represents a group selected from: C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl-, and phenyl,

[0935] wherein the phenyl group within the benzyl group and the phenyl group itself are optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[0936] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0937] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0938] R 9 represents a hydrogen atom or a group selected from: C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, and phenyl,

[0939] wherein the phenyl group within the benzyl group and the phenyl group itself are optionally substituted one or two times, and each substituent is independently selected from a fluorine atom and a chlorine atom, or a group selected from a cyano group and a methyl group;

[0940] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0941] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0942] R 9 represents a hydrogen atom or a group selected from: C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, and phenyl,

[0943] wherein the phenyl group within the benzyl group and the phenyl group itself are optionally substituted one or two times, and each substituent is independently selected from a fluorine atom and a chlorine atom, or a group selected from a cyano group and a methyl group;

[0944] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0945] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0946] R 10 and R 11independently represents a hydrogen atom or a group selected from the following: 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)-O-C(=O)-,

[0947] wherein the C3-C7-cycloalkyl, and the C3-C7-cycloalkyl within the (C3-C7-cycloalkyl)-(C1-C2-alkyl)- and (C3-C7-cycloalkyl)-C(=O)- groups are optionally substituted one or two times, and each substituent is independently selected from a fluorine atom or a group selected from the following: cyano, C1-C2-alkyl, and C1-C2-haloalkyl,

[0948] and wherein the phenyl within the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)-, and (phenyl)-(C1-C2-alkyl)-O-C(=O)- groups is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from the following: methyl, trifluoromethyl, and methoxy,

[0949] or

[0950] 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 or a bicyclic nitrogen-containing 5- to 10-membered heterocycloalkyl, which is optionally substituted one, two, or three times, and each substituent is independently selected from a halogen atom or a group selected from the following: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-haloalkyl, (C1-C2-alkyl)-C(=O)-, C1-C2-alkoxy, -N(R 22 )(R 23 ) and a monocyclic 4- to 7-membered heterocycloalkyl,

[0951] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0952] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0953] R 10 and R11 independently represents a hydrogen atom or a group selected from: 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)-O-C(=O)-,

[0954] wherein the C3-C7-cycloalkyl, and the C3-C7-cycloalkyl within the (C3-C7-cycloalkyl)-(C1-C2-alkyl)- and (C3-C7-cycloalkyl)-C(=O)- groups is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom or a group selected from: cyano, C1-C2-alkyl and C1-C2-haloalkyl,

[0955] and wherein the phenyl within the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-O-C(=O)- groups is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: methyl, trifluoromethyl and methoxy,

[0956] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt, or a mixture thereof.

[0957] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0958] 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 or a bicyclic nitrogen-containing 5- to 10-membered heterocycloalkyl, which is optionally substituted one, two or three times, and each substituent is independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-haloalkyl, (C1-C2-alkyl)-C(=O)-, C1-C2-alkoxy, -N(R 22 )(R 23 ) and a monocyclic 4- to 7-membered heterocycloalkyl,

[0959] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt, or a mixture thereof.

[0960] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0961] R 10 and R 11 independently represent a hydrogen atom or a group selected from: 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)-O-C(=O)-,

[0962] wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-O-C(=O)- groups is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: methyl, trifluoromethyl and methoxy,

[0963] or

[0964] 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 or a bicyclic nitrogen-containing 6- to 10-membered heterocycloalkyl, which is optionally substituted one, two or three times, and each substituent is independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-haloalkyl, (C1-C2-alkyl)-C(=O)-, C1-C2-alkoxy, -N(R 22 )(R 23 ) and a monocyclic 4- to 7-membered heterocycloalkyl,

[0965] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0966] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0967] R 10 and R 11independently represents a hydrogen atom or a group selected from the following: 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)-O-C(═O)-,

[0968] wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(═O)- and (phenyl)-(C1-C2-alkyl)-O-C(═O)- groups is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from the following: methyl, trifluoromethyl and methoxy,

[0969] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0970] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0971] 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 or a bicyclic nitrogen-containing 6- to 10-membered heterocycloalkyl, which is optionally substituted one, two or three times, and each substituent is independently selected from a halogen atom or a group selected from the following: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-haloalkyl, (C1-C2-alkyl)-C(═O)-, C1-C2-alkoxy, -N(R 22 )(R 23 ) and a monocyclic 4- to 7-membered heterocycloalkyl,

[0972] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0973] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0974] R 10 and R 11independently represent a hydrogen atom or a group selected from: C1-C2-alkyl, C1-C2-fluoroalkyl, (C3-C5-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)-O-C(=O)-,

[0975] wherein the C3-C7-cycloalkyl, the C3-C5-cycloalkyl within the (C3-C5-cycloalkyl)-(C1-C2-alkyl)- group, and the C3-C7-cycloalkyl within the (C3-C7-cycloalkyl)-C(=O)- group are optionally substituted one or two times, and each substituent is independently selected from a fluorine atom or a group selected from: cyano, C1-C2-alkyl, and C1-C2-fluoroalkyl,

[0976] and wherein the phenyl within the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)-, and (phenyl)-(C1-C2-alkyl)-O-C(=O)- groups is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[0977] or

[0978] 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, which is optionally substituted one, two, or three times, and each substituent is independently selected from a fluorine atom or a group selected from: cyano, oxo, C1-C2-alkyl, C1-C2-fluoroalkyl, and (C1-C2-alkyl)-C(=O)-,

[0979] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0980] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0981] R 10 and R 11independently represents a hydrogen atom or a group selected from: C1-C2-alkyl, C1-C2-fluoroalkyl, (C3-C5-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)-O-C(=O)-,

[0982] wherein the C3-C7-cycloalkyl, the C3-C5-cycloalkyl within the (C3-C5-cycloalkyl)-(C1-C2-alkyl)- group, and the C3-C7-cycloalkyl within the (C3-C7-cycloalkyl)-C(=O)- group are optionally substituted one or two times, and each substituent is independently selected from a fluorine atom or a group selected from: cyano, C1-C2-alkyl, and C1-C2-fluoroalkyl,

[0983] and wherein the phenyl within the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)-, and (phenyl)-(C1-C2-alkyl)-O-C(=O)- groups is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[0984] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0985] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0986] 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 which is optionally substituted one, two, or three times, and each substituent is independently selected from a fluorine atom or a group selected from: cyano, oxo, C1-C2-alkyl, C1-C2-fluoroalkyl, and (C1-C2-alkyl)-C(=O)-,

[0987] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0988] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0989] R 10 and R 11independently represents a hydrogen atom or a group selected from: C1-C2-alkyl, C1-C2-fluoroalkyl, (C1-C2-alkyl)-C(=O)-, (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)-, and (phenyl)-(C1-C2-alkyl)-O-C(=O)-,

[0990] wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)-, and (phenyl)-(C1-C2-alkyl)-O-C(=O)- groups is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[0991] or

[0992] 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, which is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom or a group selected from: oxo, C1-C2-alkyl, C1-C2-fluoroalkyl, and (C1-C2-alkyl)-C(=O)-,

[0993] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0994] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0995] R 10 and R 11 independently represent a hydrogen atom or a group selected from: C1-C2-alkyl, C1-C2-fluoroalkyl, (C1-C2-alkyl)-C(=O)-, (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)-, and (phenyl)-(C1-C2-alkyl)-O-C(=O)-,

[0996] wherein the phenyl group in the (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)-, and (phenyl)-(C1-C2-alkyl)-O-C(=O)- groups is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[0997] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0998] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[0999] 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, which is optionally substituted one or two times, each substituent independently selected from a fluorine atom or a group selected from the following: oxo, C1-C2-alkyl, C1-C2-fluoroalkyl, and (C1-C2-alkyl)-C(=O)-,

[1000] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1001] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1002] R 10 and R 11 independently represent a hydrogen atom or a group selected from the following: C1-C2-alkyl, (C3-C5-cycloalkyl)-(C1-C2-alkyl)-, C3-C7-cycloalkyl, and (phenyl)-(C1-C2-alkyl)-O-C(=O)-,

[1003] wherein the C3-C7-cycloalkyl and the C3-C5-cycloalkyl within the (C3-C5-cycloalkyl)-(C1-C2-alkyl)- group are optionally substituted one or two times, each substituent independently selected from a fluorine atom or a group selected from the following: cyano, methyl, and C1-fluoroalkyl,

[1004] and wherein the phenyl within the (phenyl)-(C1-C2-alkyl)-O-C(=O)- group is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and methyl,

[1005] or

[1006] 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, which is optionally substituted one, two, or three times, each substituent independently selected from a fluorine atom or a group selected from the following: cyano, methyl, and C1-fluoroalkyl,

[1007] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1008] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1009] R 10 and R 11independently represents a hydrogen atom or a group selected from: C1-C2-alkyl, (C3-C5-cycloalkyl)-(C1-C2-alkyl)-, C3-C7-cycloalkyl, and (phenyl)-(C1-C2-alkyl)-O-C(=O)-,

[1010] wherein the C3-C7-cycloalkyl and the C3-C5-cycloalkyl within the (C3-C5-cycloalkyl)-(C1-C2-alkyl)- group are optionally substituted one or two times, and each substituent is independently selected from a fluorine atom or a group selected from: cyano, methyl, and C1-fluoroalkyl,

[1011] and wherein the phenyl within the (phenyl)-(C1-C2-alkyl)-O-C(=O)- group is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and methyl,

[1012] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1013] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1014] 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, which is optionally substituted one, two, or three times, and each substituent is independently selected from a fluorine atom or a group selected from: cyano, methyl, and C1-fluoroalkyl,

[1015] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1016] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1017] R 10 and R 11 independently represent a hydrogen atom or a group selected from: C1-C2-alkyl, C3-C7-cycloalkyl, and (benzyl)-O-C(=O)-,

[1018] wherein the C3-C7-cycloalkyl is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom or a group selected from methyl and trifluoromethyl,

[1019] and wherein the phenyl within the (benzyl)-O-C(=O)- group is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and methyl,

[1020] Or

[1021] 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 which is optionally substituted one, two or three times, each substituent independently selected from a fluorine atom or a group selected from: cyano, methyl and trifluoromethyl,

[1022] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1023] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1024] R 10 and R 11 independently represent a hydrogen atom or a group selected from: C1-C2-alkyl, C3-C7-cycloalkyl and (benzyl)-O-C(=O)-,

[1025] wherein the C3-C7-cycloalkyl is optionally substituted one or two times, each substituent independently selected from a fluorine atom or a group selected from methyl and trifluoromethyl,

[1026] and wherein the phenyl group within the (benzyl)-O-C(=O)- group is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and methyl,

[1027] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1028] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1029] 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 which is optionally substituted one, two or three times, each substituent independently selected from a fluorine atom or a group selected from: cyano, methyl and trifluoromethyl,

[1030] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1031] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1032] R 15 and R 16independently represent a hydrogen atom or a group selected from: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-hydroxyalkyl, (cyano)-C1-C4-alkyl-, (C1-C4-alkoxy)-C2-C3-alkyl-, (C1-C4-haloalkoxy)-C2-C3-alkyl-, (C3-C7-cycloalkyl)-(C1-C3-alkyl)-, C3-C7-cycloalkyl, bicyclic C5-C 11 -cycloalkyl, monocyclic 4- to 7-membered heteroalkyl, (phenyl)-(C1-C3-alkyl)-, phenyl and 5- or 6-membered heteroaryl,

[1033] wherein the C3-C7-cycloalkyl, the C3-C7-cycloalkyl within the (C3-C7-cycloalkyl)-(C1-C3-alkyl)- group, the bicyclic C5-C 11 -cycloalkyl and the monocyclic 4- to 7-membered heteroalkyl are optionally substituted one or two times, each substituent independently selected from a halogen atom or a group selected from: oxo, C1-C2-alkyl, (C1-C2-alkyl)-C(=O)- and cyclopropyl,

[1034] and wherein the phenyl and 5- or 6-membered heteroaryl, including the phenyl within the (phenyl)-(C1-C3-alkyl)- group, are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: methyl, trifluoromethyl and methoxy,

[1035] or

[1036] R 15 and R 16 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heteroalkyl, which is optionally substituted one or two times, each substituent independently selected from a halogen atom or a group selected from: oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-,

[1037] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1038] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1039] R 15 and R 16independently represents a hydrogen atom or a group selected from the following: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-hydroxyalkyl, (cyano)-C1-C4-alkyl-, (C1-C4-alkoxy)-C2-C3-alkyl-, (C1-C4-haloalkoxy)-C2-C3-alkyl-, (C3-C7-cycloalkyl)-(C1-C3-alkyl)-, C3-C7-cycloalkyl, bicyclic C5-C 11 -cycloalkyl, monocyclic 4- to 7-membered heteroalkyl, (phenyl)-(C1-C3-alkyl)-, phenyl and 5- or 6-membered heteroaryl,

[1040] wherein the C3-C7-cycloalkyl, the C3-C7-cycloalkyl within the (C3-C7-cycloalkyl)-(C1-C3-alkyl)- group, the bicyclic C5-C 11 -cycloalkyl and the monocyclic 4- to 7-membered heteroalkyl are optionally substituted one or two times, each substituent independently selected from a halogen atom or a group selected from the following: oxo, C1-C2-alkyl, (C1-C2-alkyl)-C(=O)- and cyclopropyl,

[1041] and wherein the phenyl and 5- or 6-membered heteroaryl, including the phenyl within the (phenyl)-(C1-C3-alkyl)- group, are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from the following: methyl, trifluoromethyl and methoxy,

[1042] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1043] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1044] R 15 and R 16 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heteroalkyl which is optionally substituted one or two times, each substituent independently selected from a halogen atom or a group selected from the following: oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-,

[1045] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1046] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1047] R 15 and R 16independently represent a hydrogen atom or a group selected from the following: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-hydroxyalkyl, (C1-C2-alkoxy)-C2-C3-alkyl-, C3-C7-cycloalkyl, monocyclic 4- to 7-membered heteroalkyl, and (phenyl)-(C1-C3-alkyl)-,

[1048] wherein the C3-C7-cycloalkyl and the monocyclic 4- to 7-membered heteroalkyl are optionally substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from the following: oxo, C1-C2-alkyl, and (C1-C2-alkyl)-C(=O)-,

[1049] or

[1050] R 15 and R 16 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heteroalkyl, which is optionally substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from the following: oxo, C1-C2-alkyl, and (C1-C2-alkyl)-C(=O)-,

[1051] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1052] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1053] R 15 and R 16 independently represent a hydrogen atom or a group selected from the following: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-hydroxyalkyl, (C1-C2-alkoxy)-C2-C3-alkyl-, C3-C7-cycloalkyl, monocyclic 4- to 7-membered heteroalkyl, and (phenyl)-(C1-C3-alkyl)-,

[1054] wherein the C3-C7-cycloalkyl and the monocyclic 4- to 7-membered heteroalkyl are optionally substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from the following: oxo, C1-C2-alkyl, and (C1-C2-alkyl)-C(=O)-,

[1055] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1056] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1057] R 15 and R 16Together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl, which is optionally substituted one or twice, each substituent independently selected from a halogen atom or a group selected from: oxo, C1-C2-alkyl, and (C1-C2-alkyl)-C(=O)-,

[1058] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1059] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1060] R 15 and R 16 independently represent a hydrogen atom or a group selected from: C1-C4-alkyl, C1-C3-fluoroalkyl, (cyano)-C1-C2-alkyl-, (C1-C4-alkoxy)-C2-C3-alkyl-, (C1-C2-fluoroalkoxy)-C2-C3-alkyl-, (C3-C5-cycloalkyl)-(C1-C2-alkyl)-, C3-C5-cycloalkyl, phenyl, and a 5- or 6-membered heteroaryl selected from pyrazolyl, pyridyl, and pyrimidinyl,

[1061] wherein the C3-C5-cycloalkyl in the C3-C5-cycloalkyl and the (C3-C5-cycloalkyl)-(C1-C2-alkyl)- groups is optionally substituted one or twice, each substituent independently selected from a fluorine atom or a group selected from methyl and cyclopropyl,

[1062] and wherein the phenyl and the 5- or 6-membered heteroaryl selected from pyrazolyl, pyridyl, and pyrimidinyl are optionally substituted one or twice, each substituent independently selected from a fluorine atom and a chlorine atom, or a group selected from methyl, trifluoromethyl, and methoxy,

[1063] or

[1064] R 15 and R 16 Together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl, which is optionally substituted once by a fluorine atom or a group selected from oxo, C1-C2-alkyl, and CH3-C(=O)-,

[1065] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1066] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1067] R 15 and R 16independently represent a hydrogen atom or a group selected from: C1-C4-alkyl, C1-C3-fluoroalkyl, (cyano)-C1-C2-alkyl-, (C1-C4-alkoxy)-C2-C3-alkyl-, (C1-C2-fluoroalkoxy)-C2-C3-alkyl-, (C3-C5-cycloalkyl)-(C1-C2-alkyl)-, C3-C5-cycloalkyl, phenyl and a 5- or 6-membered heteroaryl selected from pyrazolyl, pyridyl and pyrimidinyl,

[1068] wherein the C3-C5-cycloalkyl in the C3-C5-cycloalkyl and the (C3-C5-cycloalkyl)-(C1-C2-alkyl)- group is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom or a group selected from methyl and cyclopropyl,

[1069] and wherein the phenyl and the 5- or 6-membered heteroaryl selected from pyrazolyl, pyridyl and pyrimidinyl are optionally substituted one or two times, and each substituent is independently selected from a fluorine atom and a chlorine atom, or a group selected from: methyl, trifluoromethyl and methoxy,

[1070] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1071] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1072] R 15 and R 16 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl, which is optionally substituted once by a fluorine atom or a group selected from oxo, C1-C2-alkyl and CH3-C(=O)-,

[1073] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1074] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1075] R 15 and R 16 independently represent a hydrogen atom or a group selected from: C1-C3-alkyl, C1-C3-fluoroalkyl and C3-C5-cycloalkyl,

[1076] or

[1077] R 15 and R 16Together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl which is optionally substituted once by a fluorine atom or a group selected from oxo, C1-C2-alkyl and CH3-C(=O)-,

[1078] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1079] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1080] R 15 and R 16 independently represent a hydrogen atom or a group selected from: C1-C3-alkyl, C1-C3-fluoroalkyl and C3-C5-cycloalkyl,

[1081] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1082] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1083] R 15 and R 16 Together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl which is optionally substituted once by a fluorine atom or a group selected from oxo, C1-C2-alkyl and CH3-C(=O)-,

[1084] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1085] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1086] R 15 and R 16 Together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl which is optionally substituted once by a group selected from oxo, methyl and CH3-C(=O)-,

[1087] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1088] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1089] R 15 and R 16independently represents a hydrogen atom or a group selected from the following: C1-C4-alkyl, C1-C2-fluoroalkyl, (C1-C4-alkoxy)-C2-C3-alkyl-, (C1-C2-fluoroalkoxy)-C2-C3-alkyl-, (C3-C5-cycloalkyl)-(C1-C2-alkyl)-, C3-C5-cycloalkyl, phenyl and pyridyl,

[1090] wherein the C3-C5-cycloalkyl in the C3-C5-cycloalkyl and the (C3-C5-cycloalkyl)-(C1-C2-alkyl)- group is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom and a methyl group,

[1091] and wherein the phenyl and pyridyl are optionally substituted one or two times, and each substituent is independently selected from a fluorine atom and a chlorine atom, or a group selected from the following: methyl, trifluoromethyl and methoxy,

[1092] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1093] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1094] R 15 and R 16 independently represents a hydrogen atom or a group selected from the following: C1-C4-alkyl, C1-C2-fluoroalkyl, (C1-C4-alkoxy)-C2-alkyl-, (C1-C2-fluoroalkoxy)-C2-alkyl-, C3-C5-cycloalkyl, phenyl and pyridyl,

[1095] wherein the C3-C5-cycloalkyl is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom and a methyl group,

[1096] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1097] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1098] R 15 and R 16 independently represents a hydrogen atom or a group selected from the following: C1-C2-alkyl, C3-C5-cycloalkyl, phenyl and pyridyl,

[1099] wherein the C3-C5-cycloalkyl is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom and a methyl group,

[1100] or its stereoisomers, tautomers, N-oxides, hydrates, solvates, or salts, or mixtures thereof.

[1101] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1102] R 17 represents C1-C4-alkyl,

[1103] or its stereoisomers, tautomers, N-oxides, hydrates, solvates, or salts, or mixtures thereof.

[1104] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1105] R 17 represents C1-C3-alkyl,

[1106] or its stereoisomers, tautomers, N-oxides, hydrates, solvates, or salts, or mixtures thereof.

[1107] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1108] R 17 represents C1-C2-alkyl,

[1109] or its stereoisomers, tautomers, N-oxides, hydrates, solvates, or salts, or mixtures thereof.

[1110] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1111] R 17 represents methyl,

[1112] or its stereoisomers, tautomers, N-oxides, hydrates, solvates, or salts, or mixtures thereof.

[1113] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1114] R 17 represents ethyl,

[1115] or its stereoisomers, tautomers, N-oxides, hydrates, solvates, or salts, or mixtures thereof.

[1116] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1117] R18 and R 19 independently represent a hydrogen atom or a C1-C2-alkyl group,

[1118] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1119] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1120] R 18 and R 19 independently represent a hydrogen atom or a methyl group,

[1121] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1122] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1123] R 18 and R 19 both represent methyl groups,

[1124] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1125] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1126] R 18 and R 19 both represent hydrogen atoms,

[1127] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1128] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1129] R 18 represents a hydrogen atom and R 19 represents a methyl group,

[1130] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1131] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1132] R 20represents a hydrogen atom or a group selected from the following: C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, naphthyl, and 5- to 10-membered heteroaryl,

[1133] wherein the C1-C6-alkyl is optionally substituted one, two, or three times, and each substituent is independently selected from a halogen atom or a group selected from the following: hydroxy, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, and the phenyl and 5- to 10-membered heteroaryl substituents themselves are optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from the following: methyl, trifluoromethyl, and methoxy,

[1134] wherein the C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl is optionally substituted one, two, or three times, and each substituent is independently selected from a halogen atom or a group selected from the following: cyano, oxo, hydroxy, C1-C2-alkyl, and (C1-C2-alkyl)-C(=O)-,

[1135] and wherein the phenyl, naphthyl, and 5- to 10-membered heteroaryl are optionally substituted one, two, or three times, and each substituent is independently selected from a halogen atom or a group selected from the following: cyano, C1-C2-alkyl, C1-C2-haloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ), and

[1136] -C(=O)-N(R 24 )(R 25 ),

[1137] R 21 represents a hydrogen atom or C1-C2-alkyl,

[1138] or

[1139] R 20 and R 21Together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, which is optionally benzo-fused and optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-haloalkyl, (phenyl)-(C1-C2-alkyl)-, (C1-C2-alkyl)-C(=O)-, C3-C4-cycloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ), and -C(=O)-N(R 24 )(R 25 );

[1140] R 22 and R 23 independently represent a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-;

[1141] R 24 and R 25 independently represent a hydrogen atom or C1-C2-alkyl,

[1142] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1143] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1144] R 20 represents a hydrogen atom or a group selected from: C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, naphthyl, and 5- to 10-membered heteroaryl,

[1145] wherein the C1-C6-alkyl is optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: hydroxy, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, and the phenyl and 5- to 10-membered heteroaryl substituents themselves are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from: methyl, trifluoromethyl, and methoxy,

[1146] wherein the C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heteroalkyl, bicyclic 6- to 10-membered heteroalkyl are optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl and (C1-C2-alkyl)-C(═O)-,

[1147] and wherein the phenyl, naphthyl and 5- to 10-membered heteroaryl are optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: 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 ),

[1148] R 21 represents a hydrogen atom or C1-C2-alkyl,

[1149] R 22 and R 23 independently represent a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(═O)-;

[1150] R 24 and R 25 independently represent a hydrogen atom or C1-C2-alkyl,

[1151] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1152] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1153] R 20 and R 21 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heteroalkyl, which is optionally benzo-fused and optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-haloalkyl, (phenyl)-(C1-C2-alkyl)-, (C1-C2-alkyl)-C(═O)-, C3-C4-cycloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(═O)-N(R24 )(R 25 );

[1154] R 22 and R 23 each independently represents a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-;

[1155] R 24 and R 25 each independently represents a hydrogen atom or C1-C2-alkyl,

[1156] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1157] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1158] R 20 represents a hydrogen atom or a group selected from: C1-C6-alkyl, C3-C7-cycloalkyl, monocyclic 4- to 7-membered heteroalkyl, phenyl, and 5- to 6-membered heteroaryl,

[1159] wherein said C1-C6-alkyl is optionally substituted one, two, or three times, each substituent independently selected from a halogen atom or a group selected from: hydroxy, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, monocyclic 4- to 7-membered heteroalkyl, phenyl, and 5- to 6-membered heteroaryl, and said phenyl and 5- to 6-membered heteroaryl substituents themselves are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from: methyl, trifluoromethyl, and methoxy,

[1160] and wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heteroalkyl are optionally substituted one, two, or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl, and (C1-C2-alkyl)-C(=O)-,

[1161] and wherein said phenyl and 5- to 6-membered heteroaryl are optionally substituted one, two, or three times, each substituent independently selected from a halogen atom or a group selected from: 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 ),

[1162] R 21 represents a hydrogen atom or a C1-C2-alkyl group,

[1163] or

[1164] R 20 and R 21 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, which is substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-haloalkyl, (phenyl)-(C1-C2-alkyl)-, (C1-C2-alkyl)-C(=O)-, C3-C4-cycloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ), and -C(=O)-N(R 24 )(R 25 ),

[1165] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1166] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1167] R 20 represents a hydrogen atom or a group selected from: C1-C6-alkyl, C3-C7-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl and 5- to 6-membered heteroaryl,

[1168] wherein said C1-C6-alkyl is optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: hydroxy, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl and 5- to 6-membered heteroaryl, and said phenyl and 5- to 6-membered heteroaryl substituents themselves are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: methyl, trifluoromethyl and methoxy,

[1169] and wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-,

[1170] and wherein said phenyl and 5- to 6-membered heteroaryl are optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: 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 wherein

[1171] R 21 represents a hydrogen atom or C1-C2-alkyl,

[1172] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1173] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1174] R 20 and R 21 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl which is substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-haloalkyl, (phenyl)-(C1-C2-alkyl)-, (C1-C2-alkyl)-C(=O)-, C3-C4-cycloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 ),

[1175] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1176] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1177] R 20 represents a hydrogen atom or a group selected from: C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, naphthyl and 5- to 10-membered heteroaryl,

[1178] wherein the C1-C6-alkyl is optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: hydroxyl, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl and 5- to 10-membered heteroaryl, the phenyl and 5- to 10-membered heteroaryl substituents themselves being optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a bromine atom, or a group selected from: methyl, trifluoromethyl and methoxy,

[1179] wherein the C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl is optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxyl, C1-C2-alkyl and (C1-C2-alkyl)-C(═O)-,

[1180] and wherein the phenyl, naphthyl and 5- to 10-membered heteroaryl are optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: 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 ),

[1181] R 21 represents a hydrogen atom or C1-C2-alkyl,

[1182] or

[1183] R 20 and R 21 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl, which is optionally benzo-fused and optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxyl, C1-C2-alkyl, C1-C2-haloalkyl, (phenyl)-(C1-C2-alkyl)-, (C1-C2-alkyl)-C(═O)-, C3-C4-cycloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ), and -C(═O)-N(R 24 )(R25 )

[1184] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1185] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1186] R 20 represents a hydrogen atom or a group selected from: C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, naphthyl, and 5- to 10-membered heteroaryl,

[1187] wherein said C1-C6-alkyl is optionally substituted one, two, or three times, each substituent independently selected from a halogen atom or a group selected from: hydroxy, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, bicyclic C6-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 6- to 10-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, and said phenyl and 5- to 10-membered heteroaryl substituents themselves are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a bromine atom, or a group selected from: methyl, trifluoromethyl, and methoxy,

[1188] wherein 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, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl, and (C1-C2-alkyl)-C(=O)-,

[1189] and wherein said phenyl, naphthyl, and 5- to 10-membered heteroaryl are optionally substituted one, two, or three times, each substituent independently selected from a halogen atom or a group selected from: 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 ),

[1190] R 21represents a hydrogen atom or a C1-C2-alkyl group,

[1191] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1192] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1193] R 20 and R 21 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, which is optionally benzo-fused and optionally substituted one, two, or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-haloalkyl, (phenyl)-(C1-C2-alkyl)-, (C1-C2-alkyl)-C(=O)-, C3-C4-cycloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 ),

[1194] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1195] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1196] R 20 represents a hydrogen atom or a group selected from C1-C3-alkyl and phenyl,

[1197] wherein the C1-C3-alkyl is optionally substituted one or two times, each substituent independently selected from a fluorine atom or a group selected from: hydroxy, C1-C3-alkoxy, and phenyl, and the phenyl itself is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[1198] and wherein the phenyl is optionally substituted one, two, or three times, each substituent independently selected from a fluorine atom and a chlorine atom or a group selected from: methyl, trifluoromethyl, methoxy, and trifluoromethoxy,

[1199] R 21 represents a hydrogen atom or a C1-C2-alkyl group,

[1200] or

[1201] R 20 and R 21Together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, which is optionally substituted one or twice, each substituent independently selected from a halogen atom or a group selected from the following: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-fluoroalkyl, benzyl, (C1-C2-alkyl)-C(=O)-, and C3-C4-cycloalkyl,

[1202] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1203] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1204] R 20 represents a hydrogen atom or a group selected from C1-C3-alkyl and phenyl,

[1205] wherein the C1-C3-alkyl is optionally substituted one or twice, each substituent independently selected from a fluorine atom or a group selected from the following: hydroxy, C1-C3-alkoxy, and phenyl, and the phenyl itself is optionally substituted one or twice, each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[1206] and wherein the phenyl is optionally substituted one, two, or three times, each substituent independently selected from a fluorine atom and a chlorine atom or a group selected from the following: methyl, trifluoromethyl, methoxy, and trifluoromethoxy, and wherein

[1207] R 21 represents a hydrogen atom or C1-C2-alkyl,

[1208] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1209] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1210] R 20 and R 21 Together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, which is optionally substituted one or twice, each substituent independently selected from a halogen atom or a group selected from the following: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-fluoroalkyl, benzyl, (C1-C2-alkyl)-C(=O)-, and C3-C4-cycloalkyl,

[1211] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1212] In another embodiment of the first aspect, the invention relates to a compound of formula (I) above, wherein:

[1213] R 20 represents a group selected from benzyl and phenyl,

[1214] wherein the phenyl in said phenyl and said benzyl is optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group, and wherein

[1215] R 21 represents a hydrogen atom or a methyl group,

[1216] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1217] In another embodiment of the first aspect, the invention relates to a compound of formula (I) above, wherein:

[1218] 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,

[1219] wherein said C1-C3-alkyl is optionally substituted one, two, or three times, each substituent independently selected from a halogen atom or a group selected from: hydroxy, 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, and the phenyl and 5- to 10-membered heteroaryl substituents themselves are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[1220] wherein said C3-C6-cycloalkyl, adamantyl, and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one, two, or three times, each substituent independently selected from a fluorine atom or a group selected from: oxo, C1-C2-alkyl, and (C1-C2-alkyl)-C(=O)-,

[1221] and wherein said phenyl and 5- to 10-membered heteroaryl are optionally substituted one, two, or three times, each substituent independently selected from a fluorine atom and a chlorine atom or a group selected from: cyano, C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R25 ),

[1222] R 21 represents a hydrogen atom or a C1-C2-alkyl group,

[1223] or

[1224] R 20 and R 21 , together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, which is optionally benzo-fused and optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-fluoroalkyl, benzyl, (C1-C2-alkyl)-C(=O)-, C3-C4-cycloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 );

[1225] R 22 and R 23 independently represent a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-;

[1226] R 24 and R 25 independently represent a hydrogen atom or a C1-C2-alkyl group,

[1227] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1228] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1229] 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,

[1230] wherein said C1-C3-alkyl is optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: hydroxy, cyano, C1-C3-alkoxy, -N(R 22 )(R 23)、C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heteroalkyl, phenyl, and 5- to 10-membered heteroaryl, where the phenyl and 5- to 10-membered heteroaryl are each optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[1231] wherein the C3-C6-cycloalkyl, adamantyl, and monocyclic 4- to 7-membered heteroalkyl are each optionally substituted one, two, or three times, and each substituent is independently selected from a fluorine atom or a group selected from the following: oxo, C1-C2-alkyl, and (C1-C2-alkyl)-C(=O)-,

[1232] and wherein the phenyl and 5- to 10-membered heteroaryl are each optionally substituted one, two, or three times, and each substituent is independently selected from a fluorine atom, a chlorine atom, or a group selected from the following: 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 ),

[1233] R 21 represents a hydrogen atom or C1-C2-alkyl,

[1234] R 22 and R 23 independently represent a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-;

[1235] R 24 and R 25 independently represent a hydrogen atom or C1-C2-alkyl,

[1236] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1237] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1238] R 20 and R 21 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heteroalkyl, which is optionally benzocondensed and optionally substituted one, two, or three times, and each substituent is independently selected from a halogen atom or a group selected from the following: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-fluoroalkyl, benzyl, (C1-C2-alkyl)-C(=O)-, C3-C4-cycloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22)(R 23 ) and -C(=O)-N(R 24 )(R 25 );

[1239] R 22 and R 23 each independently represents a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-;

[1240] R 24 and R 25 each independently represents a hydrogen atom or C1-C2-alkyl,

[1241] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1242] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1243] 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,

[1244] wherein the C1-C3-alkyl is optionally substituted one, two, or three times, each substituent independently selected from a halogen atom or a group selected from: hydroxy, 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, and the phenyl and 5- to 10-membered heteroaryl substituents themselves are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom, and a methyl group,

[1245] wherein the C3-C6-cycloalkyl, adamantyl, and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one, two, or three times, each substituent independently selected from a fluorine atom or a group selected from: oxo, C1-C2-alkyl, and (C1-C2-alkyl)-C(=O)-,

[1246] and wherein the phenyl and 5- to 10-membered heteroaryl are optionally substituted one, two, or three times, each substituent independently selected from a fluorine atom and a chlorine atom or a group selected from: cyano, C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R24 )(R 25 ),

[1247] R 21 represents a hydrogen atom or a C1-C2-alkyl group,

[1248] or

[1249] R 20 and R 21 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, which is optionally benzo-fused and optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-fluoroalkyl, benzyl, (C1-C2-alkyl)-C(=O)-, C3-C4-cycloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 ),

[1250] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1251] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1252] 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,

[1253] wherein the C1-C3-alkyl is optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: hydroxy, 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, and the phenyl and 5- to 10-membered heteroaryl substituents themselves are optionally substituted one or two times, each substituent independently selected from a fluorine atom, a chlorine atom and a methyl group,

[1254] wherein the C3-C6-cycloalkyl, adamantyl and monocyclic 4- to 7-membered heterocycloalkyl are optionally substituted one, two or three times, each substituent independently selected from a fluorine atom or a group selected from: oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-,

[1255] and wherein said phenyl and 5- to 10-membered heteroaryl are optionally substituted one, two or three times, each substituent independently selected from a fluorine atom, a chlorine atom or a group selected from: 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 ), R 21 representing a hydrogen atom or C1-C2-alkyl,

[1256] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1257] In another embodiment of the first aspect, the invention relates to a compound of formula (I) above, wherein:

[1258] R 20 and R 21 together with the nitrogen atom to which they are attached represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl which is optionally benzo-fused and which is optionally substituted one, two or three times, each substituent independently selected from a halogen atom or a group selected from: cyano, oxo, hydroxy, C1-C2-alkyl, C1-C2-fluoroalkyl, benzyl, (C1-C2-alkyl)-C(=O)-, C3-C4-cycloalkyl, C1-C2-alkoxy, C1-C2-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 ),

[1259] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1260] In another embodiment of the first aspect, the invention relates to a compound of formula (I) above, wherein:

[1261] R 22 and R 23 independently represent a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-,

[1262] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1263] In another embodiment of the first aspect, the invention relates to a compound of formula (I) above, wherein:

[1264] R 22 and R 23 independently represent a hydrogen atom or a group selected from methyl and (CH3)-C(=O)-,

[1265] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1266] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1267] R 24 and R 25 independently represent a hydrogen atom or a C1-C2-alkyl group,

[1268] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1269] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1270] R 24 and R 25 independently represent a hydrogen atom or a methyl group,

[1271] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1272] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1273] R 26 represents a fluorine atom, a chlorine atom, or a group selected from the following: C1-C2-alkyl, C1-C2-fluoroalkyl, C1-C2-alkoxy, and C1-C2-fluoroalkoxy,

[1274] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1275] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1276] R 26 represents a fluorine atom, a chlorine atom, or a group selected from the following: methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy, and trifluoromethoxy,

[1277] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1278] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1279] R 26 represents a fluorine atom, a chlorine atom, or a group selected from: difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy, and trifluoromethoxy,

[1280] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1281] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1282] Y 1 represents -C(H)=, -C(F)=, -C(Cl)=, -C(CN)= or -N=,

[1283] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1284] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1285] Y 1 represents -C(H)=, -C(F)= or -N=,

[1286] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1287] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1288] Y 1 represents -C(H)= or -C(F)=,

[1289] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1290] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1291] Y 1 represents -C(H)=,

[1292] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1293] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1294] Y 1 represents -C(F)=,

[1295] or a stereoisomer, tautomer, N - oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1296] In another embodiment of the first aspect, the present invention relates to a compound of formula (I) above, wherein:

[1297] Y 1 represents -N=,

[1298] or a stereoisomer, tautomer, N - oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[1299] In another specific embodiment of the first aspect, the present invention encompasses the combination of two or more of the above - mentioned embodiments under the title "Another Embodiment of the First Aspect of the Present Invention".

[1300] The present invention encompasses any sub - combination of the compounds of general formula (I) above in any embodiment or aspect of the present invention.

[1301] The present invention encompasses the compounds of general formula (I) disclosed in the Examples section below.

[1302] The compounds of general formula (I) of the present invention can be converted into any of the salts described herein, preferably pharmaceutically acceptable salts, by any method known to those skilled in the art. Similarly, any salt of the compounds of general formula (I) of the present invention can be converted into the free compound by any method known to those skilled in the art.

[1303] The compounds of general formula (I) of the present invention exhibit a valuable pharmacological activity profile, which is not predictable. Unexpectedly, it has been found that the compounds of the present invention effectively inhibit DGKζ, and thus the compounds can be used for treating or preventing diseases in mammals including humans, preferably disorders of immune response dysregulation, particularly cancer or other disorders associated with abnormal DGKζ signal transduction.

[1304] Diseases and disorders particularly suitable for treatment with the DGKζ inhibitors of the present invention are liquid and solid tumors, such as breast cancer, respiratory cancer, brain cancer, cancer of the reproductive organs, cancer of the digestive tract, cancer of the urinary tract, eye cancer, liver cancer, skin cancer, head and neck cancer, thyroid cancer, parathyroid cancer, and their distant metastases. These diseases also include lymphoma, sarcoma, and leukemia.

[1305] 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.

[1306] Examples of respiratory tract cancers include, but are not limited to, small cell lung cancer and non-small cell lung cancer, as well as bronchial adenoma and pleuropulmonary blastoma.

[1307] Examples of brain cancers include, but are not limited to, brainstem and hypothalamic gliomas, cerebellar and cerebral astrocytomas, glioblastoma multiforme, medulloblastoma, ependymoma, and neuroectodermal and pineal tumors.

[1308] Tumors of the male reproductive organs include, but are not limited to, prostate cancer and testicular cancer.

[1309] Tumors of the female reproductive organs include, but are not limited to, endometrial cancer, cervical cancer, ovarian cancer, vaginal cancer, and vulvar cancer, as well as uterine sarcoma.

[1310] Examples of ovarian cancers include, but are not limited to, serous tumors, endometrioid tumors, mucinous cystadenocarcinomas, granulosa cell tumors, sertoli-leydig cell tumors, and dysgerminomas.

[1311] Examples of cervical cancers include, but are not limited to, squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, small cell carcinoma, neuroendocrine tumors, clear cell carcinoma, and villoglandular adenocarcinoma.

[1312] Digestive tract tumors include, but are not limited to, anal cancer, colon cancer, colorectal cancer, esophageal cancer, gallbladder cancer, gastric cancer, pancreatic cancer, rectal cancer, small intestine cancer, and salivary gland cancer.

[1313] Examples of esophageal cancers include, but are not limited to, esophageal cell carcinoma and adenocarcinoma, as well as squamous cell carcinoma, leiomyosarcoma, malignant melanoma, rhabdomyosarcoma, and lymphoma.

[1314] Examples of gastric cancers include, but are not limited to, intestinal type and diffuse gastric adenocarcinoma.

[1315] Examples of pancreatic cancers include, but are not limited to, ductal adenocarcinoma, adenosquamous carcinoma, and pancreatic endocrine tumors.

[1316] Urinary tract tumors include, but are not limited to, bladder cancer, penile cancer, kidney cancer, renal pelvic cancer, ureteral cancer, urethral cancer, and papillary renal cell carcinoma.

[1317] Examples of kidney cancers include, but are not limited to, renal cell carcinoma, urothelial cell carcinoma, juxtaglomerular cell tumor (nephroma), angiomyolipoma, renal oncocytoma, Bellini duct carcinoma, renal clear cell sarcoma, mesoblastic nephroma, and Wilms tumor.

[1318] Examples of bladder cancers include, but are not limited to, transitional cell carcinoma, squamous cell carcinoma, adenocarcinoma, sarcoma, and small cell carcinoma.

[1319] Eye cancers include, but are not limited to, intraocular melanoma and retinoblastoma.

[1320] Examples of liver cancer include, but are not limited to, hepatocellular carcinoma (with or without fibrolamellar variant), cholangiocarcinoma (intrahepatic cholangiocarcinoma), and combined hepatocellular cholangiocarcinoma.

[1321] Skin cancers include, but are not limited to, squamous cell carcinoma, Kaposi's sarcoma, malignant melanoma, Merkel cell carcinoma of the skin, and non-melanoma skin cancers.

[1322] Head and neck cancers include, but are not limited to, head and neck squamous cell carcinoma, laryngeal cancer, hypopharyngeal cancer, nasopharyngeal cancer, oropharyngeal cancer, salivary gland cancer, lip cancer, and oral cancer, as well as squamous cell carcinoma.

[1323] Lymphomas include, but are not limited to, AIDS-related lymphoma, non-Hodgkin lymphoma, cutaneous T-cell lymphoma, Burkitt lymphoma, Hodgkin disease, and central nervous system lymphoma.

[1324] Sarcomas include, but are not limited to, soft tissue sarcoma, osteosarcoma, malignant fibrous histiocytoma, lymphosarcoma, and rhabdomyosarcoma.

[1325] Leukemias include, but are not limited to, acute myeloid leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and hairy cell leukemia.

[1326] As used throughout this text, the terms "treatment" or "treating" are used conventionally, for example, to administer or care for a subject in order to combat, mitigate, reduce, alleviate, or improve the condition of a disease or disorder (such as cancer).

[1327] The compounds of the present invention can be particularly useful for treating and preventing (i.e., prophylaxis) tumor growth and metastasis, especially in solid tumors at all indications and stages, with or without pretreatment of tumor growth.

[1328] Generally, the use of chemotherapeutic agents and / or anti-cancer agents in combination with the compounds or pharmaceutical compositions of the present invention will contribute to:

[1329] 1. Produce better efficacy in reducing tumor growth and even eliminating tumors compared to administering either agent alone.

[1330] 2. Provide a smaller amount of the chemotherapeutic agent administered.

[1331] 3. Provide a chemotherapy treatment that is well tolerated in patients, with fewer harmful pharmacological complications compared to single-agent chemotherapy and certain other combination therapies.

[1332] 4. Provide treatment for a wider variety of different cancer types in mammals, especially humans.

[1333] 5. Provide a higher response rate in treated patients,

[1334] 6. Provide a longer survival time in treated patients compared to standard chemotherapy treatment,

[1335] 7. Provide a longer time to tumor progression, and / or

[1336] 8. Produce efficacy and tolerability results at least as good as the drugs used alone compared to known cases of antagonistic effects when combined with other cancer drugs.

[1337] In addition, the compounds of general formula (I) of the present invention can also be used in combination with radiotherapy and / or surgery.

[1338] In another embodiment of the present invention, the compounds of general formula (I) of the present invention are used in combination with radiation: namely, radiotherapy sensitizes cancer to the anti-tumor immune response by inducing tumor cell death and subsequent presentation of tumor neoantigens to tumor-reactive T cells. Since DGKζ enhances the antigen-specific activation of T cells, the overall effect results in a stronger attack on cancer cells compared to radiotherapy alone.

[1339] Therefore, the present invention also provides a method for killing tumors, wherein conventional radiotherapy is employed before administering one or more compounds of the present invention.

[1340] The compounds of the present invention can be administered as a single agent or in combination with one or more other pharmaceutically active ingredients, provided that the combination does not cause unacceptable side effects. The present invention also relates to such pharmaceutical combinations. For example, the compounds of the present invention can be used in combination with the following drugs:

[1341] 131I-chTNT, abarelix, abemaciclib, abiraterone, acalabrutinib, aclarubicin, adalimumab, ado-trastuzumab emtansine, afatinib, aflibercept, aldesleukin, alectinib, alemtuzumab, alendronic acid, alitretinoin, alpharadin, altretamine, amifostine, aminoglutethimide, hexyl aminolevulinate, amrubicin, amsacrine, anastrozole, anceslim, anethole dithiolethione, anetumab ravtansine, angiotensin II, antithrombin III, apalutamide, aprepitant, arcitumomab, arglabin, arsenic trioxide, asparaginase, atezolizumab, avelumab, axicabtageneciloleucel), axitinib, azacitidine, basiliximab, belotecan, bendamustine, besilesomab, belinostat, bevacizumab, bexarotene, bicalutamide, bisantrene, bleomycin, blinatumomab, bortezomib, bosutinib, buserelin, brentuximab vedotin, brigatinib, busulfan, cabazitaxel, cabozantinib, calcitonine, calcium folinate, calciumlevofolinate, capecitabine, capromab, carbamazepine carboplatin, carboquone, carfilzomib, carmofur, carmustine, catumaxomab, celecoxib, celmoleukin, cemiplimab, ceritinib, cetuximab, chlorambucil, chlormadinone, chlormethine, cidofovir, cinacalcet, cisplatin, cladribine, clodronicacid), 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, elimusertib (BAY1895344), elliptinium acetate, elotuzumab, eltrombopag, enasidenib, endostatin, enocitabine, enzalutamide, epirubicin, epitiostanol, epoetin alfa, epoetinbeta, epoetin ζ (epoetinzeta), eptaplatin, eribulin, erlotinib, esomeprazole, estradiol, estramustine, ethinylestradiol, etoposide, everolimus, exemestane, fadrozole, fentanyl, filgrastim, fluoxymesterone, floxuridine, fludarabine, fluorouracil, flutamide, folinic acid, formestane, fosaprepitant, fotemustine, fulvestrant, gadobutrol, gadoteridol, gadoteric acid meglumine, gadoversetamide, gadoxetic acid, gallium nitrate, ganirelix, gefitinib, gemcitabine, gemtuzumab, Glucarpidase, glutoxim, GM-CSF, goserelin, granisetron, granulocyte colony stimulating factor, histamine dihydrochloride, histrelin, hydroxycarbamide, I-125 seeds, lansoprazole, ibandronic acid, ibritumomab tiuxetan, ibrutinib, idarubicin, ifosfamide, imatinib, imiquimod, improsulfan, indisetron, incadronicacid), ingenol mebutate, inotuzumab ozogamicin, interferon alfa, interferon beta, interferon gamma, iobitridol, iobenguane (123I), iomeprol, ipilimumab, irinotecan, Itraconazole, ixabepilone, ixazomib, lanreotide, lansoprazole, lapatinib, Iasocholine, lenalidomide, lenvatinib, lenograstim, lentinan, letrozole, leuprorelin, levamisole, levonorgestrel, levothyroxine sodium, lisuride, lobaplatin, lomustine, lonidamine, lutetium Lu 177dotatate), masoprocol, medroxyprogesterone, megestrol, melarsoprol, melphalan, mepitiostane, mercaptopurine, mesna, methadone, methotrexate, methoxsalen, methylaminolevulinate, methylprednisolone, methyltestosterone, metirosine, midostaurin, mifamurtide, miltefosine, miriplatin, mitobronitol, mitoguazone, mitolactol, mitomycin, mitotane, mitoxantrone, mogamulizumab, molgramostim, mopidamol, morphine hydrochloride, morphine sulfate, mvasi, nabilone, nabiximols, nafarelin, naloxone + pentazocine, naltrexone, nartograstim, necitumumab, nedaplatin, nelarabine, neratinib, neridronicacid), 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, ozogamicine, p53 gene therapy, paclitaxel, palbociclib, palifermin, palladium-103 seed, palonosetron, pamidronic acid, panitumumab, panobinostat, pantoprazole, pazopanib, pegaspargase, PEG-epoetin beta (methoxy PEG-epoetin beta), pembrolizumab, pegfilgrastim, peginterferon alpha-2b (peginterferonalfa-2b), pemetrexed, pentazocine, pentostatin, peplomycin, Perflubutane, perfosfamide, Pertuzumab, picibanil, pilocarpine, pirarubicin, pixantrone, plerixafor, plicamycin, poliglusam, polyestradiol phosphate, polyvinylpyrrolidone + sodium hyaluronate, polysaccharide-K, pomalidomide, ponatinib, porfimer sodium, pralatrexate, prednimustine, prednisone, procarbazine, procodazole, propranolol, quinagolide, rabeprazole, racotumomab, radium-223 chloride, radotinib, raloxifene, raltitrexed, ramosetron, ramucirumab, ranimustine, rasburicase, razoxane, refametinib, regorafenib, ribociclib, risedronicacid), rhenium-186 etidronate, rituximab, rolapitant, romidepsin, romiplostim, romurtide, rucaparib, samarium(153Sm) lexidronam, sargramostim, sarilumab, satumomab, secretin, siltuximab, sipuleucel-T, sizofiran, sobuzoxane, sodium glycididazole, sonidegib, sorafenib, stanozolol, streptozocin, sunitinib, talaporfin, talimogene laherparepvec, tamibarotene, tamoxifen, tapentadol, tasonermin, teceleukin, technetium(99mTc) nofetumomab merpentan, 99mTc-HYNIC-[Tyr3]-octreotide, tegafur, tegafur+gimeracil+oteracil, temoporfin, temozolomide, temsirolimus, teniposide, testosterone, tetrofosmin, thalidomide, thiotepa, thymalfasin, thyrotropinalfa), tioguanine, tisagenlecleucel, tislelizumab, tocilizumab, topotecan, toremifene, tositumomab, trabectedin, trametinib, tramadol, trastuzumab, trastuzumab emtansine, treosulfan, tretinoin, trifluridine + tipiracil, trilostane, triptorelin, trametinib, trofosfamide, thrombopoietin, tryptophan, ubenimex, valatinib, valrubicin, vandetanib, vapreotide, vemurafenib, vinblastine, vincristine, vindesine, vinflunine, vinorelbine, vismodegib, vorinostat, vorozole, yttrium-90 glass microspheres, zinostatin, zinostatin stimalamer, zoledronic acid, and zorubicin.

[1342] The compounds of the present invention can be further combined with other reagents targeting the immune system, such as immune checkpoint inhibitors, such as aPD-1 / -L1 axis antagonists.

[1343] PD-1 and its ligands PD-L1 and PD-L2 function as negative regulators of T cell activation. PD-L1 is overexpressed in many cancers, and overexpression of PD-1 often occurs concomitantly in tumor-infiltrating T cells. This results in attenuated T cell activation and escape from immune surveillance, leading to impaired anti-tumor immune responses. (M.E. Keir et al., Annu. Rev. Immunol. 2008, 26, 677-704).

[1344] According to another aspect, the present invention relates to a combination comprising one or more compounds of general formula (I) as described herein or their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts (especially their pharmaceutically acceptable salts), or mixtures thereof, and one or more immune checkpoint inhibitors.

[1345] Preferably, the immune checkpoint inhibitor is an aPD-1 / -L1 axis antagonist.

[1346] The compounds of the present invention can be further combined with DGKα inhibitors, such as those disclosed in WO2020 / 006016, WO2020 / 006018 and WO2021 / 041588. Since DGKα in T cells operates in a manner similar to DGKζ, dual inhibition significantly enhances T cell effector functions compared to cells lacking only the DGK isoform or wild-type cells. (MJRiese et al., Cancer Res. (2013), 73(12); p. 3566-77).

[1347] The compounds of the present invention can be further combined with chimeric antigen receptor T cells (CAR-T cells), such as Axicabtagen-Ciloleucel or Tisagenlecleucel. The activity of CAR-T cells can be inhibited by the tumor microenvironment (TME). Knockout of DGK by techniques such as Crispr has been shown to enhance the activity of CAR-T cells in the inhibitory TME (I.Y. Jung et al., Mol. Cells 2018, 41(8), 717-723).

[1348] According to another aspect, the present invention relates to a combination comprising one or more compounds of general formula (I) as described herein or their stereoisomers, tautomers, N-oxides, hydrates, solvates and salts (especially their pharmaceutically acceptable salts), or mixtures thereof, with chimeric antigen receptor T cells (CAR-T cells), CAR-NKT cells or CAR-NK cells.

[1349] Preferably, the chimeric antigen receptor T cells (CAR-T cells) are Axicabtagen-Ciloleucel or Tisagenlecleucel.

[1350] The present invention further provides the use of a compound according to the present invention for the ex vivo expansion of T cells including CAR-T and tumor infiltrating lymphocytes.

[1351] According to another aspect, the present invention relates to a compound of formula (I) as described herein - or its stereoisomers, tautomers, N-oxides, hydrates, solvates and salts (especially pharmaceutically acceptable salts thereof), or mixtures thereof - for the ex vivo expansion of T cells including CAR-T cells, CAR-NKT cells or CAR-NK cells and tumor infiltrating lymphocytes.

[1352] Accordingly, the present invention also relates to the use of a compound according to the present invention for the ex vivo expansion of T cells including CAR-T cells, CAR-NKT cells or CAR-NK cells and tumor infiltrating lymphocytes.

[1353] The present invention also encompasses an ex vivo method for expanding T cells including CAR-T cells, CAR-NKT cells or CAR-NK cells and tumor infiltrating lymphocytes, which comprises contacting the T cells with a compound according to the present invention.

[1354] The compounds of the present invention can be used to inhibit, block, reduce or decrease DGKζ activity, thereby resulting in dysregulated immune responses, such as blocking immunosuppression and increasing immune cell activation and infiltration in the context of cancer and cancer immunotherapy, which will ultimately lead to reduced tumor growth.

[1355] The method comprises administering to a mammal (including a human) in need thereof a therapeutically effective amount of a compound of the present invention or a pharmaceutically acceptable salt, isomer, polymorph, metabolite, hydrate, solvate or ester thereof.

[1356] The present invention also provides methods for treating a variety of other diseases involving DGKζ, such as but not limited to diseases with dysregulated immune responses, inflammation, infections and cancer vaccination, viral infections, lymphoproliferative diseases, asthma, eye diseases, and type 2 diabetes / insulin resistance.

[1357] These diseases have been well characterized in humans, but similar etiologies also exist in other mammals and can be treated by administering the pharmaceutical compositions of the present invention.

[1358] According to another aspect, the present invention relates to a compound of general formula (I) as described above - or a stereoisomer, tautomer, N-oxide, hydrate, solvate and salt thereof (especially a pharmaceutically acceptable salt thereof), or a mixture thereof - for the treatment or prevention of diseases, especially cancer or disorders of immune response or other diseases associated with abnormal DGKζ signal transduction.

[1359] The pharmaceutical activity of the compounds according to the invention can be explained by their activity as DGKζ inhibitors.

[1360] According to another aspect, the present invention relates to a compound of general formula (I) as described above - or a stereoisomer, tautomer, N-oxide, hydrate, solvate and salt thereof (especially a pharmaceutically acceptable salt thereof), or a mixture thereof - for the treatment or prevention of diseases, especially cancer or disorders of immune response or other diseases associated with abnormal DGKζ signal transduction, especially for the use in liquid and solid tumors.

[1361] According to another aspect, the present invention relates to a compound of general formula (I) as described above - or a stereoisomer, tautomer, N-oxide, hydrate, solvate and salt thereof (especially a pharmaceutically acceptable salt thereof), or a mixture thereof - for the treatment or prevention of diseases, especially cancer or disorders of immune response or other diseases associated with abnormal DGKζ signal transduction, especially liquid and solid tumors.

[1362] According to another aspect, the present invention relates to a compound of general formula (I) as described above - or a stereoisomer, tautomer, N-oxide, hydrate, solvate and salt thereof (especially a pharmaceutically acceptable salt thereof), or a mixture thereof - for use in a method for the treatment or prevention of diseases, especially cancer or disorders of immune response or other diseases associated with abnormal DGKζ signal transduction, especially liquid and solid tumors.

[1363] According to another aspect, the present invention relates to a compound of general formula (I) as described above - or a stereoisomer, tautomer, N-oxide, hydrate, solvate and salt thereof (especially a pharmaceutically acceptable salt thereof), or a mixture thereof - for use in a method for the treatment or prevention of diseases, especially cancer or disorders of immune response or other diseases associated with abnormal DGKζ signal transduction, especially liquid and solid tumors.

[1364] According to another aspect, the present invention relates to the use of a compound of general formula (I) as described above - or its stereoisomers, tautomers, N-oxides, hydrates, solvates and salts (especially pharmaceutically acceptable salts thereof), or mixtures thereof - for the preparation of a pharmaceutical composition, preferably a medicament, said pharmaceutical composition being for the prevention or treatment of a disease, especially a cancer or a disorder of the immune response or other disorders associated with abnormal DGKζ signal transduction, especially liquid and solid tumors.

[1365] According to another aspect, the present invention relates to a method of treating or preventing a disease, especially a cancer or a disorder of the immune response or other diseases associated with abnormal DGKζ signal transduction, especially liquid and solid tumors, using an effective amount of a compound of general formula (I) as described above - or its stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, especially pharmaceutically acceptable salts thereof, or mixtures thereof.

[1366] According to another aspect, the present invention relates to a pharmaceutical composition, preferably a medicament, comprising a compound of general formula (I) as described above - or its stereoisomers, tautomers, N-oxides, hydrates, solvates, salts, especially pharmaceutically acceptable salts thereof, or mixtures thereof - and one or more excipients, especially one or more pharmaceutically acceptable excipients. Conventional procedures for preparing such pharmaceutical compositions in suitable dosage forms can be used.

[1367] The present invention also relates to pharmaceutical compositions, preferably medicaments, comprising at least one compound according to the invention, usually used in combination with one or more pharmaceutically suitable excipients, and to their use for the above-mentioned purposes.

[1368] The compounds according to the invention can have systemic and / or local activity. For this purpose, they can be administered in a suitable manner, for example by oral, parenteral, pulmonary, nasal, sublingual, lingual, buccal, rectal, vaginal, dermal, transdermal, conjunctival, otic routes or as implants or stents.

[1369] For these routes of administration, the compounds according to the invention can be administered in a suitable dosage form.

[1370] For oral administration, the compounds according to the invention can be formulated into dosage forms known in the art for delivering the compounds according to the invention rapidly and / or in an improved manner, such as tablets (uncoated or coated tablets, for example with a delayed dissolution or insoluble enteric or controlled release coating), orally disintegrating tablets, films / thin films, film / freeze-dried products, capsules (e.g., hard or soft gelatin capsules), dragees, granules, pills, powders, emulsions, suspensions, aerosols or solutions. The compounds according to the invention can be incorporated into the dosage forms in crystalline and / or amorphous and / or dissolved form.

[1371] Parenteral administration can be carried out by avoiding absorption steps (e.g., intravenous, intra-arterial, intracardiac, intraspinal or intralumbar) or including absorption (e.g., intramuscular, subcutaneous, intradermal, transdermal or intraperitoneal). Dosage forms suitable for parenteral administration are especially injection and infusion preparations in the form of solutions, suspensions, emulsions, lyophilizates or sterile powders.

[1372] Examples of dosage forms suitable for other routes of administration are pharmaceutical forms for inhalation [especially powder inhalers, nebulizers], nasal drops, nasal solutions, nasal sprays; tablets / films / thins / capsules for lingual, sublingual or oral administration; suppositories; eye drops, eye ointments, eye washes, ocular inserts, ear drops, ear sprays, ear powders, ear washes, ear plugs; vaginal capsules, aqueous suspensions (lotions, mixtures), lipophilic suspensions, emulsions, ointments, creams, transdermal therapeutic systems (e.g., such as patches), milk preparations, pastes, foams, dusting powders, implants or stents.

[1373] The compounds according to the invention can be incorporated into the said dosage forms. This can be achieved in a manner known per se by mixing with pharmaceutically suitable excipients. Pharmaceutically suitable excipients especially include,

[1374] · Fillers and carriers (e.g., cellulose, microcrystalline cellulose (e.g., such as ), lactose, mannitol, starch, calcium phosphate (e.g., such as ),

[1375] · Ointment bases (e.g., petrolatum, paraffin, triglycerides, waxes, lanolin wax, lanolin alcohol, lanolin, hydrophilic ointment, polyethylene glycol),

[1376] · Suppository bases (e.g., polyethylene glycol, cocoa butter, stearin),

[1377] · Solvents (e.g., water, ethanol, isopropanol, glycerol, propylene glycol, medium-chain triglyceride fatty oils, liquid polyethylene glycol, paraffin),

[1378] · Surfactants, emulsifiers, dispersants or wetting agents (e.g., sodium dodecyl sulfate), lecithin, phospholipids, fatty alcohols (e.g., such as ) Sorbitan fatty acid esters (e.g., as ) Polyoxyethylene sorbitan fatty acid esters (e.g., as ) Polyoxyethylene fatty acid glycerol esters (e.g., as ) Polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, glycerol fatty acid esters, poloxamers (e.g., as ),

[1379] · Buffers, acids and bases (e.g., phosphates, carbonates, citric acid, acetic acid, hydrochloric acid, sodium hydroxide solution, ammonium carbonate, tromethamine, triethanolamine),

[1380] · Isotonic agents (e.g., glucose, sodium chloride),

[1381] · Adsorbents (e.g., highly dispersed silica),

[1382] · Viscosity increasing agents, gel forming agents, thickening agents and / or binders (e.g., polyvinylpyrrolidone, methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, starch, carbomer, polyacrylic acid (e.g., as ); alginates, gelatin),

[1383] · Disintegrants (e.g., modified starch, sodium carboxymethylcellulose, sodium starch glycolate (e.g., as ), crosslinked polyvinylpyrrolidone, crosslinked sodium carboxymethylcellulose (e.g., as ))

[1384] · Flow regulators, lubricants, glidants and mold release agents (e.g., magnesium stearate, stearic acid, talc, highly dispersed silica (e.g., as ))

[1385] · Coating materials (e.g., sugar, shellac) and film forming agents for thin films or diffusion films, which can dissolve rapidly or in a modified manner (e.g., polyvinylpyrrolidone (e.g., as ), polyvinyl alcohol, hydroxypropylmethylcellulose, hydroxypropylcellulose, ethylcellulose, methylhydroxypropylphthalate cellulose, cellulose acetate, cellulose acetate phthalate, polyacrylate, polymethacrylate e.g., as ))

[1386] · Capsule materials (e.g., gelatin, hydroxypropylmethylcellulose)

[1387] · Synthetic polymers (e.g., polylactide, polyglycolide, polyacrylate, polymethacrylate (e.g., as ), polyvinylpyrrolidone (e.g., as ), polyvinyl alcohol, polyvinyl acetate, polyethylene oxide, polyethylene glycol and their copolymers and block copolymers)

[1388] · Plasticizers (such as polyethylene glycol, propylene glycol, glycerol, triacetin, triacetyl citrate, dibutyl phthalate),

[1389] · Permeation enhancers,

[1390] · Stabilizers (such as antioxidants, such as ascorbic acid, ascorbyl palmitate, sodium ascorbate, butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate),

[1391] · Preservatives (such as parabens, sorbic acid, thimerosal, benzalkonium chloride, chlorhexidine acetate, sodium benzoate),

[1392] · Colorants (such as inorganic pigments, such as iron oxide, titanium dioxide),

[1393] · Flavoring agents, sweetening agents, flavoring agents and / or odor masking agents.

[1394] The present invention also relates to a pharmaceutical composition comprising at least one compound according to the present invention, usually used in combination with one or more pharmaceutically suitable excipients, and to their use according to the present invention.

[1395] According to another aspect, the present invention relates to a pharmaceutical combination comprising at least one compound of general formula (I) of the present invention and at least one or more other active ingredients, in particular medicaments, in particular for the treatment and / or prevention of cancer or diseases of immune response disorders or other diseases associated with abnormal DGKζ signal transduction, in particular liquid and solid tumors.

[1396] In particular, the present invention relates to a pharmaceutical combination comprising:

[1397] · One or more first active ingredients, in particular a compound of general formula (I) as defined above, and

[1398] · One or more other active ingredients, in particular immune checkpoint inhibitors.

[1399] The term "combination" in the present invention is used as known to those skilled in the art, and said combination can be a fixed combination, a non-fixed combination or a kit-of-parts.

[1400] The "fixed combination" in the present invention is used as known to those skilled in the art and is defined as a combination in which, for example, a first active ingredient (e.g., one or more compounds of general formula (I) of the present invention) and another active ingredient are present together in a unit dose or a single entity. An example of a "fixed combination" is a pharmaceutical composition in which the first active ingredient and the other active ingredient are present in a mixture for simultaneous administration, e.g., in one formulation. Another example of a "fixed combination" is a pharmaceutical combination in which the first active ingredient and the other active ingredient are present in a unit rather than in a mixture.

[1401] The non-fixed combination or "kit of parts" in the present invention is used as known to those skilled in the art and is defined as a combination in which the first active ingredient and the other active ingredient are present in more than one unit. An example of a non-fixed combination or kit of parts is a combination in which the first active ingredient and the other active ingredient are present separately. The components of the non-fixed combination or kit of parts can be administered separately, sequentially, jointly, simultaneously or in a time-staggered manner.

[1402] Based on known standard laboratory techniques for evaluating compounds that can be used to treat cancer or disorders of the immune response or other conditions associated with abnormal DGKζ signal transduction, by standard toxicity tests and standard pharmacological assays for determining the treatment of the above mammalian diseases, and by comparing these results with the results of known active ingredients or drugs for treating these conditions, the effective dose of the compounds of the present invention can be easily determined to treat each desired indication. The amount of the active ingredient administered in the treatment of one of these conditions can vary depending on factors such as the specific compound and dosage unit used, the mode of administration, the duration of treatment, the age and sex of the patient, and the nature and extent of the disease being treated.

[1403] The total amount of the active ingredient to be administered is usually about 0.001 mg / kg to about 200 mg / kg body weight per day, preferably about 0.01 mg / kg to about 20 mg / kg body weight per day. Clinically useful dosing regimens range from one to three times a day to once every four weeks. In addition, "drug holidays" - that is, periods during which the patient does not take the drug - may be beneficial for the overall balance between pharmacological effects and tolerance. The unit dose may contain about 0.5 mg to about 1500 mg of the active ingredient and may be administered once or more than once a day or less than once a day. By injection, including intravenous, intramuscular, subcutaneous and parenteral injections and using infusion techniques, the average daily dose to be administered will preferably be 0.01 to 200 mg / kg total body weight. The average daily rectal dosing regimen will preferably be 0.01 to 200 mg / kg total body weight. The average daily vaginal dosing regimen will preferably be 0.01 to 200 mg / kg total body weight. The average daily topical dose regimen will preferably be 0.1 to 200 mg administered 1 to 4 times a day. The transdermal concentration is preferably the concentration required to maintain a daily dose of 0.01 to 200 mg / kg. The average daily inhalation dose regimen will preferably be 0.01 to 100 mg / kg total body weight.

[1404] Of course, the specific initial and continuous dosing regimens for each patient will vary depending on the nature and severity of the condition determined by the attending diagnostician, the activity of the particular compound used, the age and general condition of the patient, the time of administration, the route of administration, the excretion rate of the drug, drug combinations, etc. Those skilled in the art can determine the required treatment modality and number of administrations of the compounds of the present invention or their pharmaceutically acceptable salts or esters or compositions using conventional therapeutic trials.

[1405] General synthesis of the compounds of the present invention

[1406] The compounds according to general formula (I) of the present invention can be prepared according to the following Schemes 1a, 1b, 2, 3, 4, 5 and 6. The schemes and steps described below illustrate the synthetic routes of the compounds of general formula (I) of the present invention and are not intended to be limiting. It will be apparent to those skilled in the art that the order of transformations exemplified in Schemes 1a, 1b, 2, 3, 4, 5 and 6 can be modified in various ways. Therefore, the order of transformations exemplified in these schemes is not intended to be limiting. In addition, any substituent R 1 , R 2 , R 3 or R 4The modification can be achieved before and / or after the exemplary transformation. These modifications can be those known to those skilled in the art, such as the introduction of protecting groups, the cleavage of protecting groups, the reduction or oxidation of functional groups, halogenation, metalation, substitution or coupling reactions, such as amide coupling (coupling of carboxylic acid and amine) or transition metal-catalyzed coupling reactions (such as the well-known Suzuki coupling). These transformations include those that introduce functional groups allowing further modification of substituents. Suitable protecting groups and their introduction and cleavage are well-known to those skilled in the art (see, for example, T.W. Greene and P.G.M. Wuts in Protective Groups in Organic Synthesis, 3rd Edition, Wiley 1999). Specific examples are described in the subsequent paragraphs.

[1407] Suitable routes for preparing the compounds of formula (I-a) and (I-b) - formula (I-a) and (I-b) are subsets of formula (I) and together form formula (I) - and for preparing other subsets (I-c), (I-d), (I-e), (I-f) and (I-g) of formula (I) are described in Schemes 1a, 1b, 2, 3, 4, 5 and 6.

[1408]

[1409] Scheme 1a Route for preparing the compound of formula (I-a) from the isothiocyanate of formula (II) and the ketone of formula (III) (wherein R 3 represents a subset of formula (I) for amino group).

[1410] The compound of formula (I-a) (constituted by a subset of formula (I) where R 3 represents a subset of formula (I) for amino group) can be prepared from the isothiocyanate of formula (II) (where R 1 has the meaning given in formula (I)), and the ketone of formula (III) (where R 4 has the meaning given in formula (I), and wherein LG 1represents a leaving group as defined herein, preferably a chlorine, bromine or iodine atom, more preferably a bromine atom), in the presence of a non-nucleophilic base, preferably 1,8-diazabicyclo(5.4.0)undec-7-ene (also referred to herein as DBU, CAS-RN 6674-22-2), in a dipolar aprotic solvent as defined herein, preferably in acetonitrile, at a temperature range from 0 °C to 50 °C, preferably 15 °C to 30 °C, more preferably at room temperature, for a duration from 1 hour to 100 hours, preferably 1 hour to 10 hours, more preferably 2 hours to 4 hours, by reaction with aminocyanide (IV) to obtain an intermediate compound of formula (V-a). Subsequently, the intermediate compound of formula (V-a) can be reacted with a compound of formula (VI) (wherein R 2 has the meaning given by the general formula (I), and wherein LG 2 represents a leaving group as defined herein, preferably a chlorine, bromine or iodine atom, or (methylsulfonyl)oxy or [(4-methylphenyl)sulfonyl]oxy, more preferably a bromine atom), in a dipolar aprotic solvent as defined herein, preferably in N,N-dimethylformamide, at a temperature range from 60 °C to 120 °C, preferably 80 °C to 100 °C, more preferably 90 °C, for a duration from 30 minutes to 24 hours, preferably 1 hour to 4 hours, more preferably 2 hours, to obtain the compound of the invention of formula (I-a). The conversion of the intermediate compound of formula (V-a) to the compound of the invention of formula (I-a) by reaction with a compound of formula (VI) can also be advantageously carried out in a dipolar aprotic solvent as defined herein, preferably in N,N-dimethylformamide, at a temperature range from 0 °C to 60 °C, preferably 10 °C to 40 °C, more preferably at room temperature as defined herein, for a duration from 6 hours to 48 hours, preferably 12 hours to 24 hours. As pointed out in the introductory paragraph of this section, for example, those substituents attached to R 1 and R 4 can be modified by various methods known to those skilled in the art during this synthetic route or in the final step. Specific examples are described in the experimental section.

[1411]

[1412] Scheme 1b An alternative route for preparing the intermediate compound of formula (V-a) from the isothiocyanate of formula (II) and the ketone of formula (III).

[1413] As shown in Scheme 1b, the conversion of the isothiocyanate of formula (II), the ketone of formula (III) and aminocyanide (IV) to the above-mentioned intermediate compound of formula (V-a) can also be carried out in two steps, wherein the isothiocyanate of formula (II) (wherein R 1has the meaning given by the general formula (I)), in the presence of a base, such as an alkali metal hydroxide, preferably potassium hydroxide, in a fatty alcohol of the formula C1-C4-alkyl-OH, preferably methanol or ethanol, at a temperature range from 0 °C to 60 °C, preferably from 10 °C to 40 °C, more preferably at room temperature as defined herein, for a duration from 15 minutes to 2 hours, preferably 30 minutes, react with ammonia cyanide (IV) to obtain the corresponding carbamimidothioate of the formula (VII) (where M + represents an alkali metal cation), which can be in an aliphatic alcohol of the formula C1-C4-alkyl-OH, preferably methanol or ethanol, at a temperature range from 40 °C to 100 °C, preferably from 60 °C to 90 °C, for a duration from 1 minute to 4 hours, preferably 2 hours, react with a ketone of the formula (III) (where R 4 has the meaning given by the general formula (I), and where LG 1 represents a leaving group as defined herein, preferably a chlorine, bromine or iodine atom, more preferably a bromine atom) to obtain an intermediate compound of the formula (V-a). Specific examples are described in the experimental section.

[1414]

[1415] Scheme 2 Route for preparing a compound of the formula (I-b) (where R 3 represents a subset of the general formula (I) for methyl) from an isothiocyanate of the formula (II) and a ketone of the formula (III).

[1416] The compound of the formula (I-b) (composed of a subset of the general formula (I) where R 3 represents methyl) can be prepared from an isothiocyanate of the formula (II) (where R 1 has the meaning given by the general formula (I)), and a ketone of the formula (III) (where R 4 has the meaning given by the general formula (I), and where LG 1 represents a leaving group as defined herein, preferably a chlorine, bromine or iodine atom, more preferably a bromine atom), in a non-nucleophilic base, preferably in 1,8-diazabicyclo(5.4.0)undec-7-ene (also referred to herein as DBU, CAS-RN 6674-22-2), in a dipolar aprotic solvent as defined herein, preferably in acetonitrile, at a temperature range from 0 °C to 50 °C, preferably from 15 °C to 30 °C, more preferably at room temperature, for a duration from 1 hour to 100 hours, preferably from 1 hour to 10 hours, more preferably from 2 hours to 4 hours, by reacting with a salt of acetamidine of the formula (VIII) (where X -represents a monovalent anion, preferably chlorine, bromine, iodine or acetate, more preferably chlorine) to prepare an intermediate compound of formula (V-b). Subsequently, the intermediate compound of formula (V-b) can be reacted with a compound of formula (VI) (wherein R 2 has the meaning given in general formula (I), and wherein LG 2 represents a leaving group as defined herein, preferably a chlorine, bromine or iodine atom, or (methylsulfonyl)oxy or [(4-methylphenyl)sulfonyl]oxy, more preferably a bromine atom), in a dipolar aprotic solvent as defined herein, preferably in N,N-dimethylformamide, at a temperature range of 60 °C to 120 °C, preferably 80 °C to 100 °C, more preferably 90 °C, for a duration of 30 minutes to 24 hours, preferably 1 hour to 4 hours, more preferably 2 hours, to obtain the compound of formula (I-b) of the present invention.

[1417] The compounds of formulas (II), (III), (IV), (VI) and (VIII) are mainly obtained commercially or can be prepared using methods known to those skilled in the art. See, for example, the isothiocyanate of formula (II) prepared by F. Calderon et al. in Journal of Medicinal Chemistry 2017, 60(16), 6880–6896, or Y. Xing et al. in European Journal of Organic Chemistry 2017, 2017(4), 781–785; the ketone of formula (III) prepared by A. Wu et al. in Tetrahedron 2013, 69(31), 6392–6398; also see the synthetic schemes of intermediates 9, 10 and 11 in the experimental section.

[1418] Alternatively, the compounds of formulas (I-c), (I-d), (I-e), (I-f) and (I-g) (composed of various subsets of general formula (I) wherein R 3 represents an amino group) can be prepared from precursors that do not initially contain the R 4 group (Schemes 3, 4 and 5), or from precursors in which the R 4 group is replaced by a group not involved in the definition of R 4 (such as a carboxyl group), but this allows different R 4 groups to be established from a common precursor (Scheme 6).

[1419]

[1420] Scheme 3 To prepare the compound of formula (I-c) from the isothiocyanate of formula (II) and the silylethynyl ketone of formula (III-a) (wherein R 3represents an amino group and in which R 4 a route that is a subset of general formula (I) representing an isoxazolyl group).

[1421] As shown in Scheme 3, the compound of formula (I-c) (composed of a subset of general formula (I) in which R 3 represents an amino group and in which R 4 represents a subset of general formula (I) representing an isoxazolyl group) can be prepared in a manner somewhat similar to Scheme 1a by reacting an isothiocyanate of formula (II) (in which R 1 has the meaning given in general formula (I)) with aminocyanide (IV), and then with a silylethynyl ketone of formula (III-a) (in which LG 1 represents a leaving group as defined herein, preferably a chlorine, bromine or iodine atom, more preferably a bromine atom), in the presence of a non-nucleophilic base, preferably 1,8-diazabicyclo(5.4.0)undec-7-ene (also referred to herein as DBU, CAS-RN 6674-22-2), in a dipolar aprotic solvent as defined herein, preferably in acetonitrile, at a temperature range of 0 °C to 50 °C, preferably 15 °C to 30 °C, more preferably at room temperature, for a duration of 1 hour to 10 hours, preferably 2 hours to 4 hours, to obtain an intermediate compound of formula (V-c) characterized by a terminal alkyne. Subsequently, the intermediate compound of formula (V-c) can be reacted with a compound of formula (VI) (in which R 2 has the meaning given in general formula (I), and in which LG 2 represents a leaving group as defined herein, preferably a chlorine, bromine or iodine atom, or (methylsulfonyl)oxy or [(4-methylphenyl)sulfonyl]oxy, more preferably a bromine atom), in the presence of a base such as potassium carbonate, in a dipolar aprotic solvent as defined herein, preferably in N,N-dimethylformamide, at a temperature range of 0 °C to 60 °C, preferably 10 °C to 40 °C, more preferably at room temperature as defined herein, for a duration of 6 hours to 48 hours, preferably 12 hours to 24 hours, to obtain an intermediate compound of formula (IX). The intermediate compound of formula (IX) can be converted to the compound of formula (I-c) by reacting with an N-hydroxyimidoyl chloride of formula (X) (in which R 4a has the meaning given in general formula (I)) in a mixture of DMSO, tetrahydrofuran and tert-butanol as a solvent, in the presence of copper(II) sulfate pentahydrate, (+)-ascorbic acid and potassium carbonate, at a temperature range of 0 °C to 50 °C, preferably 20 °C to 40 °C, for a duration of 2 hours to 3 days. Alternatively, this reaction can be carried out in the presence of triethylamine in tetrahydrofuran as a solvent without adding copper salts. Specific examples are given in the experimental section. When the N-hydroxyimidoyl chloride of formula (X) is replaced with an azide, one can obtain in which R 4The compounds of the invention representing substituted 1,2,3-triazolyl. Specific examples are described in the experimental section.

[1422] The order of the last two steps can be reversed, i.e., the alkynyl group present in the intermediate compound of formula (V-c) can first react with the N-hydroxyimidoyl chloride of formula (X) to obtain the intermediate compound of formula (V-d), and then R is introduced by reaction with the compound of formula (VI) as described above. 2 group.

[1423] The silyl ethynyl ketone of formula (III-a) is mainly commercially available or can be prepared using methods known to those skilled in the art. In addition, the N-hydroxyimidoyl chloride of formula (X) is known to those skilled in the art; for the synthetic scheme, see Intermediates 41 and 72-76 in the experimental section below.

[1424]

[1425] Scheme 4 The route for preparing the compound of formula (I-d) (wherein R 3 represents amino and wherein R 4 represents a subset of the general formula (I) of oxadiazolyl) from the isothiocyanate of formula (II) and the pyruvate of formula (III-b).

[1426] As shown in Scheme 4, the compound of formula (I-d) (composed of a subset of the general formula (I) wherein R 3 represents amino and wherein R 4 represents oxadiazolyl) can be prepared in a manner somewhat similar to that of Scheme 1a by reacting the isothiocyanate of formula (II) (wherein R 1 has the meaning given in the general formula (I)) with aminocyanide (IV), and then with the pyruvate of formula (III-b) (wherein LG 1 represents a leaving group as defined herein, preferably a chlorine, bromine or iodine atom, more preferably a bromine atom, and wherein R A represents C1-C4-alkyl, preferably methyl or ethyl) in the presence of a non-nucleophilic base, preferably 1,8-diazabicyclo(5.4.0)undec-7-ene (also referred to herein as DBU, CAS-RN 6674-22-2), in a dipolar aprotic solvent as defined herein, preferably in acetonitrile, at a temperature range of 0 °C to 50 °C, preferably 15 °C to 30 °C, more preferably at room temperature, for a duration of 2 hours to 48 hours, preferably 12 hours to 20 hours, to obtain an intermediate compound of formula (V-e) characterized by a carboxylic acid ester group. Subsequently, the carboxylic acid ester group can be reacted with the N-hydroxyamidine of formula (XI) (wherein R 4bReact with a compound having the meaning given by the general formula (I) to obtain an intermediate compound of formula (V-f). Subsequently, the intermediate compound of formula (V-f) can react with a compound of formula (VI) (wherein R 2 has the meaning given by the general formula (I), and wherein LG 2 represents a leaving group as defined herein, preferably a chlorine, bromine or iodine atom, or (methylsulfonyl)oxy or [(4-methylphenyl)sulfonyl]oxy, more preferably a bromine atom), in the presence of a base such as potassium carbonate, in a dipolar aprotic solvent as defined herein, preferably in N,N-dimethylformamide, at a temperature range of 0 °C to 60 °C, preferably 10 °C to 40 °C, more preferably at room temperature as defined herein, for a duration of 6 hours to 48 hours, preferably 12 hours to 24 hours, to obtain a compound of formula (I-d). Specific examples are described in the experimental section.

[1427] The pyruvate ester of formula (III-b) is mainly obtained commercially or can be prepared using methods known to those skilled in the art. In addition, the N-hydroxyamidine of formula (XI) is known to those skilled in the art; see Intermediates 64 and 67 in the experimental section below for the synthetic scheme.

[1428]

[1429] Scheme 5 Preparation of the compound of formula (I-e) from 2,4-dichlorothiazole (XII) (where R 3 represents amino, where R 4 represents oxadiazolyl, and wherein under the condition that R 8 represents the group -C(=O)-NH2, R 2 ' has the meaning given for R 2 in the general formula (I) of a subset of the general formula (I)) route.

[1430] As shown in Scheme 5, the compound of formula (I-e) (composed of a subset of the general formula (I) where R 3 represents amino, where R 4 represents oxadiazolyl, and wherein under the condition that R 8 represents the group -C(=O)-NH2, R 2 ' has the meaning given for R 2 in the general formula (I)) can be prepared from 2,4-dichlorothiazole (XII) by reaction with a strong base such as lithium diisopropylamide, and then with an oxalate ester of formula (XIII) (where R Aeach independently represents a C1-C4-alkyl group, preferably a methyl or ethyl group), are prepared by reacting in a solvent such as tetrahydrofuran at a temperature range of -80°C to -50°C, preferably at -70°C, to obtain a dichlorothiazole derivative of formula (XIV), which can in turn be reacted in a solvent such as N,N-dimethylformamide with an amine of formula (XV) (wherein R 1 has the meaning given by general formula (I)) to obtain an ester derivative of formula (V-g). The ester group present in the compound of formula (V-g) can be easily saponified by well-known methods, such as with an alkali metal hy...

Claims

1. A compound of formula (I), or a salt thereof, or a mixture thereof: Wherein: R 1 represents a group where "**" represents the connection point of the nitrogen atom connected to R 1 ; R 2 represents a group where "*" represents the connection point of the nitrogen atom connected to R 2 ; R 3 represents -NH2; R 4 represents a group where "#" represents the connection point of the carbonyl group connected to R 4 and the connection point of the carbonyl group connected to And wherein R 4a represents a bromine atom, or a group selected from: C3-C5-cycloalkyl and phenyl, wherein the phenyl is optionally substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, or a group selected from: methyl, methoxy, and trifluoromethoxy Or R 4 represents a group where "#" represents the connection point of the carbonyl group connected to R 4 the connection point of the carbonyl group connected to And wherein R 4b represents a group selected from: C3-C4-alkyl, C3-C5-cycloalkyl and phenyl, where the phenyl is optionally substituted one or two times, each substituent independently selected from a fluorine atom and a chlorine atom, or a group selected from: C1-C2-alkyl and -OR 9 ; R 7 represents methyl; R 8 represents a -C(=O)-NH2 group; R 9 represents a group selected from: C1-C3-alkyl and C1-C2-fluoroalkyl, Y 1 represents -C(H)=, -C(F)= or -C(Cl)=, and R 26 represents a fluorine atom or a chlorine atom.

2. A compound of formula (I), or a salt thereof, or a mixture thereof: Wherein: R 1 represents a group wherein "**" represents the connection point of the nitrogen atom connected to R 1 ; the connection point of the nitrogen atom connected to R 2 represents a group where "*" represents the connection point of the nitrogen atom connected to R 2 ; R 3 represents -NH2; R 4 represents a group where "#" represents the connection point of the carbonyl group connected to R 4 and the connection point of the carbonyl group connected to And wherein R 4a represents the group -OR 9 , R 7 represents methyl; R 8 represents a -C(=O)-NH2 group; R 9 represents a group selected from: C1-C3-alkyl, (C3-C5-cycloalkyl)-(C1-alkyl)-, benzyl, C1-C2-fluoroalkyl, and C3-C6-cycloalkyl, Wherein the C3-C6-cycloalkyl is optionally substituted one or two times, and each substituent is independently selected from the group consisting of a fluorine atom and a methyl group; Y 1 represents -C(H)=, -C(F)= or -C(Cl)=, and R 26 represents a fluorine atom or a chlorine atom.

3. A compound, or a salt thereof, or a mixture thereof, selected from: rac-2-(N-[4-Amino-5-[3-(4-chlorophenyl)-1,2,4-oxadiazole-5-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-Amino-5-(3-benzyloxyisoxazole-5-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-Amino-5-(3-phenylisoxazole-5-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-Amino-5-(3-phenylisoxazole-5-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-Amino-5-[3-(2,4-dichlorophenyl)isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-Amino-5-[3-(4-chlorophenyl)isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-Amino-5-(3-bromoisoxazole-5-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-Amino-5-(3-bromoisoxazole-5-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazol-5-carbonyl]-N-phenyl-isoxazole-3-carboxamide, rac-5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazol-5-carbonyl]-N-(1-cyclopropylcyclopropyl)isoxazole-3-carboxamide, rac-5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazol-5-carbonyl]-N-(2-pyridyl)isoxazole-3-carboxamide, rac-5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazol-5-carbonyl]-N-[2-(trifluoromethoxy)ethyl]isoxazole-3-carboxamide, rac-5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazol-5-carbonyl]-N-(1-methylcyclobutyl)isoxazole-3-carboxamide, (R)-5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilinothiazole-5-carbonyl]-N-(1-methylcyclobutyl)isoxazole-3-carboxamide, rac-5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilinothiazole-5-carbonyl]-N-(3,3-difluorocyclobutyl)isoxazole-3-carboxamide, (R)-5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilinothiazole-5-carbonyl]-N-(3,3-difluorocyclobutyl)isoxazole-3-carboxamide, 5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilinothiazole-5-carbonyl]-N-(3,3-difluorocyclopentyl)isoxazole-3-carboxamide, 5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilinothiazole-5-carbonyl]-N-(2,2-dimethylcyclopentyl)isoxazole-3-carboxamide, rac-5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilinothiazole-5-carbonyl]-N-(1-methylcyclopentyl)isoxazole-3-carboxamide, 5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilinothiazole-5-carbonyl]-N-(3,3-dimethylcyclopentyl)isoxazole-3-carboxamide, rac-5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-3,4-difluoro-anilinothiazole-5-carbonyl]-N-(1-methylcyclobutyl)isoxazole-3-carboxamide, (R)-5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-3,4-difluoro-anilinothiazole-5-carbonyl]-N-(1-methylcyclobutyl)isoxazole-3-carboxamide, rac-5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-3,4-difluoro-anilinothiazole-5-carbonyl]-N-(3,3-difluorocyclobutyl)isoxazole-3-carboxamide, (R)-5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-3,4-difluoro-anilinothiazole-5-carbonyl]-N-(3,3-difluorocyclobutyl)isoxazole-3-carboxamide, rac-5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-3,4-difluoro-anilinothiazole-5-carbonyl]-N-cyclopentyl-isoxazole-3-carboxamide, (R)-5-[4-Amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-3,4-difluoro-anilinothiazole-5-carbonyl]-N-cyclopentyl-isoxazole-3-carboxamide, rac-2-(N-[4-amino-5-(3-cyclopentylisoxazole-5-carbonyl)thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-amino-5-[3-(difluoromethoxy)isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-amino-5-(3-isopropyl-1,2,4-oxadiazole-5-carbonyl)thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-amino-5-(3-phenyl-1,2,4-oxadiazole-5-carbonyl)thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-amino-5-(3-tert-butyl-1,2,4-oxadiazole-5-carbonyl)thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-amino-5-[3-(3-fluorophenyl)-1,2,4-oxadiazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-amino-5-[3-(2,3-dimethylphenyl)-1,2,4-oxadiazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-amino-5-(3-cyclopropyl-1,2,4-oxadiazole-5-carbonyl)thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-amino-5-(3-cyclopentyl-1,2,4-oxadiazole-5-carbonyl)thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-amino-5-[3-[[cyclopentyl(methyl)amino]methyl]isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-amino-5-[3-[[(1-methylcyclopentyl)amino]methyl]isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-amino-5-[3-(1-piperidinylmethyl) isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-amino-5-[3-[(4-cyanophenoxy)methyl]isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, rac-[5-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoroanilino)thiazole-5-carbonyl]isoxazol-3-yl]methyl N-phenylcarbamate, rac-2-(N-[4-amino-5-[3-(2-fluorophenyl)isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-amino-5-[3-[4-(trifluoromethoxy)phenyl]isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-Amino-5-[3-(2-methoxyphenyl)isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-Amino-5-[3-(6-methoxy-3-pyridyl)isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-Amino-5-[3-[(3,3-difluoroazetidin-1-yl)methyl]isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-Amino-5-[3-[(4,4-difluoro-1-piperidyl)methyl]isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, 2-(N-[4-Amino-5-[3-[(4,4-difluoro-3-methyl-1-piperidyl)methyl]isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-Amino-5-[3-(cyclobutoxy)isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-Amino-5-[3-(cyclobutylmethoxy)isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, rac-2-(N-[4-Amino-5-[3-(4,4-difluorocyclohexyloxy)isoxazole-5-carbonyl]thiazol-2-yl]-4-fluoroanilino)propanamide, and rac-2-(N-[4-Amino-5-(3-isopropoxyisoxazole-5-carbonyl)thiazol-2-yl]-4-fluoroanilino)propanamide.

4. A compound according to any one of claims 1 to 3 for use in the treatment or prevention of a disease.

5. A pharmaceutical composition comprising a compound according to any one of claims 1 to 3 and one or more pharmaceutically acceptable excipients.

6. A pharmaceutical combination comprising: ● one or more compounds according to any one of claims 1 to 3, and ● one or more other active ingredients.

7. The pharmaceutical combination according to claim 6, wherein the one or more other active ingredients are immune checkpoint inhibitors.

8. The pharmaceutical combination according to claim 7, wherein the immune checkpoint inhibitor is an aPD-1 / -L1 axis antagonist.

9. The pharmaceutical combination according to claim 7, wherein the immune checkpoint inhibitor is an inhibitor of DGKα.

10. Use of a compound according to any one of claims 1 to 3 in the manufacture of a medicament for the treatment or prevention of a disease, wherein the disease is a disease associated with abnormal DGKζ signal transduction.

11. The use according to claim 10, wherein the disease is cancer or a disorder of immune response.

12. The use according to claim 10, wherein the disease is selected from liquid and solid tumors.

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