Combinations of diacylglycerol kinase (DGK) inhibitors

Abstract

The present invention encompasses combinations comprising one or more inhibitors of DGKalpha and one or more inhibitors of DGKzeta. Another aspect of the present invention encompasses the use of a combination as described herein for the preparation of a medicament for the treatment or prevention of a disease, particularly a condition with a dysregulated immune response, particularly cancer, or a viral infection or another disorder associated with abnormal DGKalpha and / or DGKzeta signaling.

Description

[Technical Field]

[0001] The present invention encompasses combinations comprising one or more inhibitors of DGKalpha and one or more inhibitors of DGKzeta, particularly combinations comprising one or more DGKalpha inhibitor compounds of general formula (I) as described herein and one or more DGKzeta inhibitor compounds of general formula (II) as described herein, more particularly combinations comprising DGKalpha inhibitor A and DGKzeta inhibitor A' as described herein. Furthermore, the present invention relates to inhibitors of DGKalpha for use in a method for the treatment or prevention of diseases, particularly conditions with a dysregulated immune response, in particular cancer, or viral infection or another disorder associated with aberrant DGKalpha and / or DGKzeta signaling, in mammals, including humans, characterized in that the method of treatment or prevention of said disease comprises administering at least one inhibitor of DGKzeta. Further provided is an inhibitor of DGKzeta for use in a method for the treatment or prevention of a disease, particularly a condition involving a dysregulated immune response, particularly cancer, or another disorder associated with abnormal DGKalpha and / or DGKzeta signaling, or a viral infection, in a mammal, including a human, wherein the method for the treatment or prevention of the disease comprises administering at least one inhibitor of DGKalpha. Another aspect of the invention encompasses the use of the above combination comprising one or more inhibitors of DGKalpha and one or more inhibitors of DGKzeta for the preparation of a medicament for the treatment or prevention of a disease, particularly a condition involving a dysregulated immune response, particularly cancer, or another disorder associated with abnormal DGKalpha and / or DGKzeta signaling, or a viral infection, in a mammal, including a human. [Background technology]

[0002] Cancer is the second leading cause of death in the United States, causing 450,000 deaths annually. Although substantial progress has been made in identifying some of the environmental and genetic causes that contribute to cancer, additional therapeutic modalities that target cancer and related diseases are needed. In particular, there is a need for therapeutic methods to reactivate a patient's immune system, especially exhausted and suppressed T cells, to kill tumors.

[0003] Diacylglycerol kinases (DGKs) represent a family of enzymes that catalyze the phosphorylation of the membrane lipid sn-1,2 diacylglycerol (DAG) to form phosphatidic acid (PA) (T.O. Eichmann and A. Lass, Cell. Mol. Life Sci. 2015, 72, 3931-3952). In T cells, DAG is formed downstream of the T cell receptor (TCR) after activation of the γ1 isoform of phospholipase C (PLCγ1) and cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into DAG and an additional second messenger, inositol 1,4,5-triphosphate (IP3) (S. Krishna and X.-P. Zhong, Front. Immunol. 2013, 4, 178). IP3 is important for promoting calcium release from the endoplasmic reticulum, while DAG interacts with other proteins important in TCR signaling, such as protein kinase CΘ (E.J. Quann et al., Nat. Immunol. 2011, 12(7), 647-654) and the Ras activating protein RasGRP1 (S. Krishna and X.-P. Zhong, Front. Immunol. 2013, 4, 178). Three DGK isoforms are known to exist in T cells: DGKα (DGKalpha), DGKδ (DGKdelta), and DGKzeta (DGKzeta). Two of these, DGKalpha and DGKzeta, are thought to play important roles in promoting DAG metabolism downstream of the TCR (RP Joshi and G.A. Koretzky, Int. J. Mol. Sci. 2013, 14(4), 6649-6673).

[0004] Targeting the activity of DGKalpha or DGKzeta in T cells, either by germline deletion or chemical inhibitors, enhances and sustains downstream signaling in T cells, as assessed by prolonged phosphorylation of downstream molecules such as extracellular signal-related kinase 1 / 2 (ERK1 / 2) and NFκB (X.-P.-Zhong et al., Nat. Immunol. 2003, 4, 882-890; B.A. Olenchock et al., Nat. Immunol. 2006, 7(11), 1174-1181; M.J. Riese et al., J. Biol. Chem. 2011, 286, 5254-5265; E.M. Wesley et al., ImmunoHorizons 2018, 2(4), 107-118).

[0005] Deletion of DGKzeta or DGKalpha in T cells leads to enhanced production of effector cytokines such as IL2 and IFNγ and enhanced proliferation (X.-P. Zhong et al., Nat. Immunol. 2003, 4, 882-890; B.A. Olenchock et al., Nat. Immunol. 2006, 7(11), 1174-1181; E.M. Riese et al., J. Biol. Chem. 2011, 286, 5254-5264). Furthermore, overexpression of DGKalpha induces a state of reduced functional activity resembling an anergic state (Zha et al., Nat. Immunol. 2006, 7, 1166).

[0006] Transplantation of DGKzeta-deficient T cells reduced leukemia burden after inoculation with C1498.SIY leukemia cells compared with controls. DGKzeta-deficient T cells were also at least partially resistant to PD1-mediated inhibitory signals (W. Jing et al., Cancer Res. 2017, 77(20), 5676-5686). Furthermore, DGKzeta-deficient mice exhibited reduced tumor size after orthotopic tumor injection in a pancreatic tumor model compared with controls (E.M. Wesley et al., ImmunoHorizons, 2018, 2(4), 107-118). S. Wee et al. inoculated C57BL / 6 mice with various syngeneic tumor cell lines—MC38 colon carcinoma, B16F1 melanoma, and C1498 leukemia—and analyzed survival and tumor growth in DGKzeta-deficient mice with or without anti-PD1 treatment. DGKzeta- / - mice suppressed the growth of subcutaneously implanted tumor cells in three model systems, and the combination of DGKzeta deficiency and anti-PD1 was additive in tumor control (S. Wee et al., Proceedings of the American Association for Cancer Research Annual Meeting 2019; Cancer Res. 2019, 79(13 Suppl):Abstract nr 936).

[0007] The role of DGKalpha in antitumor responses was also investigated in human tumor-infiltrating CD8+ T cells (CD8-TILs) from patients with renal cell carcinoma (RCC) (Prinz et al., J. Immunol 2012, 188, 5990). RCC-derived CD8-TILs lacked the release of lytic granules and their ability to kill target cells. Although proximal signaling events were intact in response to TCR engagement, CD8-TILs showed reduced ERK phosphorylation compared to non-tumor-infiltrating CD8+ T cells. Treatment of CD8-TILs with an inhibitor of DGKalpha activity restored their ability to kill target cells, increased basal levels of ERK phosphorylation, and increased PMA / ionomycin-stimulated ERK phosphorylation.

[0008] Therefore, DGKzeta and DGKalpha may be useful targets for enhancing the antitumor activity of T cells.

[0009] Furthermore, transplantation of CAR (chimeric antigen receptor)-T cells deficient in DGKzeta and / or DGKalpha showed increased efficacy compared to wild-type CAR T cells in treating mouse mesothelioma (M.J. Riese et al., Cancer Res. 2013, 73(12), 3566-3577) and glioblastoma xenograft mouse models in combination with DGKalpha knockout (I.-Y. Jung et al., Cancer Res. 2018, 78(16), 4692-4703).

[0010] Furthermore, DGK inhibitors not only promoted Ras / ERK signaling but also AP-1 (activator protein-1) transcription, promoted DGKalpha membrane localization, reduced the need for costimulation, and cooperated in enhancing activation after DGKzeta silencing / deletion. In contrast to the enhanced activation induced by pharmacological inhibition, DGKalpha silencing / genetic deletion inhibited Lck (lymphocyte-specific protein tyrosine kinase) activation and limited the costimulatory response. (Arranz-Nicolas et al., Canc Immun, Immunother 2018, 67(6), 965)

[0011] Furthermore, DGKalpha - / - and DGKzeta - / - Antigen-specific CD8+ T cells from mice exhibit increased proliferation and cytokine production after lymphocytic choriomeningitis virus infection (Shin et al., J. Immunol., 2012). Furthermore, DGKzeta-deficient mice exhibited a stronger immune response to lymphocytic choriomeningitis virus infection than wild-type mice (X.-P. Zhong et al., Nat. Immunol., 2003, 4, 882-890).

[0012] DGKzeta is also associated with natural killer (NK) cells. Upon stimulation through multiple activating receptors, NK cells from mice lacking DGKzeta exhibit increased cytokine production and degranulation in an ERK-dependent manner. Furthermore, they have improved cytotoxicity against tumor cell lines (E. Yang et al., J. Immunol. 2016, 197(3), 934-41).

[0013] Apart from immune cell regulation, DGKzeta also plays a role in cancer, mediating many aspects of cancer cell progression, including proliferation, apoptosis, survival, invasion, and tumorigenicity, 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). DGKalpha also plays a role in cancer, mediating many aspects of cancer cell progression, including cancer cell survival (Bacchiocchi et al., Blood, 2005, 106(6), 2175; Yanagisawa et al., Biochim Biophys Acta 2007, 1771, 462), cancer cell migration and invasion (Baldanzi et al., Oncogene 2008, 27, 942; Filligheddu et al., Anticancer Res 2007, 27, 1489; Rainero et al., J Cell Biol 2012, 196(2):277). In particular, DGKalpha has been reported to be overexpressed in hepatocellular carcinoma (Takeishi et al., J Hepatol 2012, 57, 77) and melanoma cells (Yanagisawa et al., Biochim Biophys Acta 2007, 1771, 462). Meanwhile, other reports have shown that the proliferation of colon and breast cancer cell lines was significantly inhibited by DGKalpha-siRNA16, suggesting that the DGKalpha / atypical PKC / b1 integrin signaling pathway is important for matrix invasion of breast cancer cells (Rainero et al., PLoS One 2014, 9(6):e97144). Additionally, its expression is higher in lymph node metastases than in primary breast tumors (Hao et al., Cancer 2004, 100, 1110).

[0014] Furthermore, a study examining the importance of DGKalpha in glioblastoma multiforme (GBM) cells found that co-administration of the relatively nonspecific DGKalpha inhibitor R59022 resulted in reduced growth of intracranially injected GBM tumors (Dominguez et al., Cancer Discov 2013, 3(7):782).

[0015] Additionally, DGKalpha promotes the progression of esophageal squamous cell carcinoma (ESCC), supporting DGKalpha as a potential target for ESCC treatment (Chen et al., Oncogene, 2019, 38(14)2533).

[0016] In addition, pharmacological inhibition of DGK reduces both airway inflammation and airway hyperresponsiveness in mice, and also reduces T helper 2 (T H 2) Blocking differentiation reduced bronchoconstriction in human airway samples in vitro (Singh et al., Sci Signal. 2019, 12, eaax3332).

[0017] Furthermore, inhibition of DGKalpha has the potential to reverse the life-threatening Epstein-Barr virus (EBV)-associated immunopathology that occurs in patients with X-linked lymphoproliferative disease 1 (XLP-1) (Ruffo et al., Sci Transl Med. 2016, 13, 8, 321; Velnati et al., Eur J Med Chem. 2019, 164, 378).

[0018] Furthermore, DGKalpha exacerbates cardiac injury after ischemia / reperfusion heart disease (Sasaki et al., Heart Vessels, 2014, 29, 110).

[0019] Collectively, these findings suggest that suppressing DGKzeta and / or DGKalpha activity in T cells and tumor cells may prove useful in generating more vigorous immune responses against tumors and ameliorating Th2-driven (auto)immune diseases (rebalancing the immune system). Furthermore, inhibiting DGKzeta and / or DGKalpha activity has therapeutic potential not only in directly targeting tumors but also in addressing fibrotic disorders, conditions associated with viral infections, cardiac disease, and lymphoproliferative disorders.

[0020] Inhibitors of DGK have been previously disclosed, e.g., aminoquinolone inhibitors of DGKalpha, see WO2021 / 105115, WO2021 / 105116 and WO2021 / 105117, and aminothiazole inhibitors of DGKzeta, see WO2021 / 214019 and WO2021 / 214020.

[0021] Further inhibitors of DGKalpha are disclosed in WO2021 / 130638, WO2022 / 271650, WO2022 / 271659, WO2022 / 271677, WO2022 / 271684, WO2022 / 114812, WO2023 / 165504, WO2023 / 165509 and WO2023 / 165525.

[0022] Further inhibitors of DGKzeta are disclosed in WO2021 / 132422 and WO2022 / 114164.

[0023] Inhibitors of DGKalpha and / or DGKzeta are disclosed in WO2020 / 006016, WO2020 / 006018, WO2021 / 041588, WO2021 / 133748, WO2021 / 133749, WO2021 / 133750, WO2021 / 133751, WO2021 / 13375 2, WO2021 / 258010, WO2022 / 133083, WO2022 / 171745, WO2023 / 011456, WO2023 / 122772, WO2023 / 122777, WO2023 / 122778, WO2023 / 184327, and WO2023 / 186060.

[0024] Still further inhibitors / modulators of DGK activity are disclosed in WO2023 / 023376, WO2023 / 023664, WO2023 / 150186, CN116969943 and CN117088874.

[0025] A combination of a DGK inhibitor and an immune checkpoint antagonist is disclosed in WO2021 / 127554.

[0026] The combination of T cell therapy with a DGK inhibitor is disclosed in WO2022 / 187406.

[0027] Wichroski et al., Sci. Transl. Med. 15, eadh1892 (2023) 25 October 2023, discloses a study on a dual DGKalpha / zeta inhibitor in combination with aPD-(L)1.

[0028] Chupak et al., ACS Med. Chem. Lett. 2023, 14, 929-935, disclose the discovery of dual DGKalpha / zeta inhibitors. [Prior art documents] [Patent documents]

[0029] [Patent Document 1] International Publication No. 2021 / 105115 Brochure [Patent Document 2] International Publication No. 2021 / 105116 Brochure [Patent Document 3] International Publication No. 2021 / 105117 Brochure [Patent Document 4] International Publication No. 2021 / 214019 Brochure [Patent Document 5] International Publication No. 2021 / 214020 Brochure [Patent Document 6] International Publication No. 2021 / 130638 Brochure [Patent Document 7] International Publication No. 2022 / 271650 Brochure [Patent Document 8] International Publication No. 2022 / 271659 Brochure [Patent Document 9] International Publication No. 2022 / 271677 Brochure [Patent Document 10] International Publication No. 2022 / 271684 Brochure [Patent Document 11] International Publication No. 2022 / 114812 Brochure [Patent Document 12] International Publication No. 2023 / 165504 Brochure [Patent Document 13] International Publication No. 2023 / 165509 Brochure [Patent Document 14] International Publication No. 2023 / 165525 Brochure [Patent Document 15] International Publication No. 2021 / 132422 Brochure [Patent Document 16] International Publication No. 2022 / 114164 Brochure [Patent Document 17] International Publication No. 2020 / 006016 Brochure [Patent Document 18] International Publication No. 2020 / 006018 Brochure [Patent Document 19] International Publication No. 2021 / 041588 Brochure [Patent Document 20] International Publication No. 2021 / 133748 Brochure [Patent Document 21] International Publication No. 2021 / 133749 Brochure [Patent Document 22] International Publication No. 2021 / 133750 Brochure [Patent Document 23] International Publication No. 2021 / 133751 Brochure [Patent Document 24] International Publication No. 2021 / 133752 Brochure [Patent Document 25] International Publication No. 2021 / 258010 Brochure [Patent Document 26] International Publication No. 2022 / 133083 Brochure [Patent Document 27] International Publication No. 2022 / 171745 Brochure [Patent Document 28] International Publication No. 2023 / 011456 Brochure [Patent Document 29] International Publication No. 2023 / 122772 Brochure [Patent Document 30] International Publication No. 2023 / 122777 Brochure [Patent Document 31] International Publication No. 2023 / 122778 Brochure [Patent Document 32] International Publication No. 2023 / 184327 Brochure [Patent Document 33] International Publication No. 2023 / 186060 Brochure [Patent Document 34] International Publication No. 2023 / 023376 Brochure [Patent Document 35] International Publication No. 2023 / 023664 Brochure [Patent Document 36] International Publication No. 2023 / 150186 Brochure [Patent Document 37] China Patent Publication No. 116969943 [Patent Document 38] China Patent Publication No. 117088874 [Patent Document 39] International Publication No. 2021 / 127554 Brochure [Patent Document 40] International Publication No. 2022 / 187406 Brochure [Non-patent literature]

[0030] [Non-Patent Document 1] T. Eichmann and A. Lass, Cell. Mol. Life Sci. 2015, 72, 3931-3952 [Non-patent document 2] S. Krishna and X.-P. Zhong, Front. Immunol. 2013, 4, 178 [Non-patent document 3] EJ Quann et al., Nat. Immunol. 2011, 12(7), 647-654 [Non-patent document 4] RP Joshi and GA Koretzky, Int. J. Mol. Sci. 2013, 14(4), 6649-6673 [Non-patent document 5] X.-P.-Zhong et al., Nat. Immunol. 2003, 4, 882-890 [Non-patent document 6] BAO Lenchock et al., Nat. Immunol. 2006, 7(11), 1174-1181 [Non-Patent Document 7] MJ Riese et al., J. Biol. Chem. 2011, 286, 5254-5265 [Non-patent document 8] EM Wesley et al., ImmunoHorizons 2018, 2(4), 107-118 [Non-Patent Document 9] EMRiese et al., J. Biol. Chem. 2011, 286, 5254-5264 [Non-Patent Document 10] Zha et al., Nat Immunol 2006,7,1166 [Non-Patent Document 11] W. Jing et al., Cancer Res. 2017, 77(20), 5676-5686 [Non-Patent Document 12] S. Wee et al., Proceedings of American Association for Cancer Research Annual Meeting 2019;Cancer Res.2019,79(13 Suppl):Abstract nr 936 [Non-Patent Document 13] Prinz et al., J. Immunol 2012, 188, 5990 [Non-Patent Document 14] MJ Riese et al., Cancer Res. 2013, 73(12), 3566-3577 [Non-Patent Document 15] I.-Y. Jung et al., Cancer Res. 2018, 78(16), 4692-4703 [Non-Patent Document 16] Arranz-Nicolas et al., Canc Immun, Immunother 2018, 67(6), 965 [Non-Patent Document 17] Shin et al., J. Immunol, 2012 [Non-Patent Document 18] E. Yang et al., J. Immunol. 2016, 197(3), 934-41 [Non-Patent Document 19] W. Yu et al., Front. Oncol. 2019, 8:655 [Non-Patent Document 20] K. Cai et al., BMC Cancer 2014, 14:208 [Non-Patent Document 21] J. Diao et al., Mol. Neurobiol.2016;53, 5425-35 [Non-Patent Document 22] H. Li et al., Pharmazie 2019, 74(7):418-422 [Non-Patent Document 23] Bacchiocchi et al., Blood, 2005, 106(6), 2175 [Non-Patent Document 24] Yanagisawa et al. Biochim Biophys Acta 2007,1771,462 [Non-Patent Document 25] Baldanzi et al., Oncogene 2008,27,942 [Non-Patent Document 26] Filigheddu et al.,Anticancer Res 2007,27,1489 [Non-Patent Document 27] Rainero et al., J Cell Biol 2012, 196(2):277 [Non-patent document 28] Takeishi et al., J Hepatol 2012,57,77 [Non-Patent Document 29] Rainero et al., PLoS One 2014,9(6):e97144 [Non-Patent Document 30] Hao et al., Cancer 2004, 100, 1110 [Non-Patent Document 31] Dominguez et al. Cancer Discov 2013, 3(7):782 [Non-Patent Document 32] Chen et al., Oncogene, 2019, 38(14)2533 [Non-Patent Document 33] Singh et al., Sci Signal. 2019, 12, eaax3332 [Non-Patent Document 34] Ruffo et al., Sci Transl Med.2016,13,8,321 [Non-Patent Document 35] Velnati et al., Eur J Med Chem.2019,164,378 [Non-Patent Document 36] Sasaki et al., Heart Vessels, 2014, 29, 110 [Non-Patent Document 37] Wichroski et al., Sci.Transl.Med.15, eadh1892(2023) October 25, 2023 [Non-Patent Document 38] Chupak et al., ACS Med.Chem.Lett.2023,14,929-935 Summary of the Invention

[0031] When a DGKalpha inhibitor was administered in combination with a DGKzeta inhibitor, surprising effects were observed in in vitro and in vivo tumor models.

[0032] According to a first aspect, the present invention provides a combination comprising one or more inhibitors of DGKalpha and one or more inhibitors of DGKzeta.

[0033] According to a second aspect, the present invention provides a method for producing a method for manufacturing a semiconductor device comprising: one DGKalpha inhibitor compound of general formula (I) as described herein, more particularly DGKalpha inhibitor A, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof; One DGKzeta inhibitor compound of general formula (II) as described herein, more specifically DGKzeta inhibitor A', or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof. A kit comprising:

[0034] According to a third aspect, the present invention provides a pharmaceutical composition comprising a combination of one or more DGKalpha inhibitors and one or more DGKzeta inhibitors, together with one or more pharmaceutically acceptable excipients.

[0035] According to a fourth aspect, as described above, there is provided an inhibitor of DGKalpha for use in a method for the treatment or prevention of a disease, preferably a condition with a dysregulated immune response, in particular cancer, or another disorder associated with a viral infection or abnormal DGKalpha and / or DGKzeta signaling in a mammal, including a human, characterized in that the method comprises administering at least one inhibitor of DGKzeta.

[0036] According to a fifth aspect, as described above, there is provided an inhibitor of DGKzeta for use in a method for the treatment or prevention of a disease, preferably a condition with a dysregulated immune response, in particular cancer, or another disorder associated with a viral infection or abnormal DGKalpha and / or DGKzeta signaling in a mammal, including a human, characterized in that the method comprises administering at least one inhibitor of DGKalpha.

[0037] According to a sixth aspect, the present invention provides a combination of the invention as described above for use in the treatment or prevention of a disease, preferably a condition with a dysregulated immune response, in particular cancer, or another disorder associated with viral infection or abnormal DGKalpha and / or DGKzeta signaling, in a mammal, including a human, as described below.

[0038] According to a seventh aspect, the present invention provides a kit as described above for use in the treatment or prevention of a disease, preferably a condition with a dysregulated immune response, particularly cancer, or another disorder associated with viral infection or abnormal DGKalpha and / or DGKzeta signaling, in a mammal, including a human, as described below.

[0039] According to an eighth aspect, the present invention provides a pharmaceutical composition as described above for use in the treatment or prevention of a disease, preferably a condition with a dysregulated immune response, particularly cancer, or another disorder associated with viral infection or abnormal DGKalpha and / or DGKzeta signaling, in a mammal, including a human, as described below.

[0040] According to a ninth aspect, the present invention provides a method for producing a medicament for the treatment of a pulmonary arthritis, comprising: a) administering a DGKalpha inhibitor A described herein, or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof; and b) administering a DGKzeta inhibitor A' described herein, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof. The present invention provides a method for treating or preventing a disease in a patient, preferably a condition with a dysregulated immune response, particularly cancer, or another disorder associated with viral infection or aberrant DGKalpha and / or DGKzeta signaling, in a mammal, including a human, comprising: [Problem to be solved by the invention]

[0041] technical issues While there has been significant clinical success in treating cancer by stimulating immune cells to act against tumors, for example, by treatment with humanized antibodies targeting the PD-1 / PD-L1 axis in a portion of each patient population, many patients' tumors develop resistance to treatment, and many others do not respond at all. Therefore, there is a need for further improvements in cancer treatments, including those that act by activating immune cells against each tumor. Furthermore, there is a need to provide solutions to prevent tumor recurrence, such as the formation of metastases. As outlined above, there is a large body of evidence supporting that inhibition of several DGK isoforms, particularly DGKalpha and DGKzeta, can provide such stimulation, and multiple clinical studies have been initiated, including with inhibitors of DGKalpha, DGKzeta, and dual DGKalpha / zeta inhibitors. However, little is known about how the effects of inhibiting DGKalpha and DGKzeta are best balanced, and "further studies using DGKalpha and DGKzeta selective inhibitors are needed to elucidate how components of these DGK isozymes contribute to T cell signaling and tumor immunity" (Wichroski et al., Sci. Transl. Med. 15, eadh1892 (2023) October 25, 2023). [Means for solving the problem]

[0042] Resolving the issue Surprisingly, it has now been found in preclinical experiments that combined treatment with a DGKalpha inhibitor and a DGKzeta inhibitor results in advantageous and surprising technical effects. In syngeneic mouse tumor models (e.g., EMT6, MC38, Hepa1-6), combined treatment with a DGKalpha inhibitor and a DGKzeta inhibitor has been found to significantly reduce tumor growth, which clearly exceeds the additive effects of monotherapy with each DGKalpha inhibitor and each DGKzeta inhibitor alone. Furthermore, combined treatment with a DGKalpha inhibitor and a DGKzeta inhibitor has been found to increase survival in the MC38 syngeneic mouse tumor model compared to either monotherapy, and surviving animals were re-inoculated with MC38 cells after recovery from the experiment described in Example 6, without substantial tumor growth.

[0043] As with any drug, increasing the dose may at some point reach dose-limiting toxicity, so replacing part of the anti-tumor effect of a given dose of a DGKzeta inhibitor with combined treatment at reduced doses of a DGKzeta inhibitor and a DGKalpha inhibitor results in a reduction in DGKzeta inhibitor-associated toxicity while efficacy remains at least unchanged, and vice versa, i.e., replacing part of the anti-tumor effect of a given dose of a DGKalpha inhibitor with combined treatment at reduced doses of a DGKalpha inhibitor and a DGKzeta inhibitor results in a reduction in DGKalpha inhibitor-associated toxicity while efficacy remains at least unchanged.

[0044] Further advantages of combined treatment with an inhibitor of DGKalpha and an inhibitor of DGKzeta, compared to treatment with a single dual DGKalpha / zeta inhibitor, include the option to flexibly administer them independently of each other, allowing for tracking of individual patient responses to treatment in terms of dosage and in terms of the sequence and timing of their respective administration, thereby enabling optimized treatment for individual patients, maximizing beneficial effects from inhibition of either DGK isoform while minimizing potential undesirable effects. DETAILED DESCRIPTION OF THE INVENTION

[0045] Detailed Description of the Invention definition general definition Unless otherwise defined, all scientific and technical terms used in the specification, drawings, and claims have their ordinary meanings as commonly understood by those skilled in the art. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. If two or more documents incorporated by reference contain conflicting and / or inconsistent disclosure, the document having the later effective date will control. The materials, methods, and examples are illustrative only and are not intended to be limiting. Unless otherwise specified, the following terms used in this document, including the specification and claims, have the definitions set forth below.

[0046] The terms "about" or "~" as used herein refer to a value that is within an acceptable error range of a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, "about" can mean within one standard deviation or more than one standard deviation, according to the convention in the art. The term "about" is also used to indicate that the quantity or value in question may be the specified value or some other value that is approximately the same. This phrase is intended to convey that similar values ​​will promote comparable results or effects as described herein. In this context, "about" can refer to a range above and / or below, up to 10%. Whenever the term "about" is specified for a particular assay or embodiment, that definition prevails in the particular context.

[0047] Unless otherwise defined, the term "approximately" means + / - 10% of the value provided.

[0048] Terms such as "comprising," "including," "containing," "having," and the like are to be interpreted expansively or open-endedly and without limitation. As used herein, the term "including" includes "consisting of."

[0049] In the text, when any item is referred to as "mentioned herein" or "described herein", it means that it may be mentioned anywhere in the text.

[0050] Singular forms such as "a," "an," or "the" include plural references unless the context clearly dictates otherwise. Thus, for example, reference to a "monoclonal antibody" includes a single monoclonal antibody as well as multiple monoclonal antibodies, whether the same or different. Similarly, reference to a "cell" includes a single cell as well as multiple cells.

[0051] Unless otherwise specified, the term "at least" preceding a series of elements should be understood to refer to every element in the series. The terms "at least one" and "at least one of" include, for example, 1, 2, 3, 4, 5, or more elements.

[0052] It is further understood that slight variations above and below the stated ranges can achieve substantially the same results as values ​​within the range, and unless otherwise indicated, the disclosure of ranges is intended as a continuous range, including every value between the minimum and maximum values.

[0053] As used herein, the term "amino acid" or "amino acid residue" typically refers to a naturally occurring amino acid. Single-letter codes are used herein to refer to each amino acid. As used herein, a "charged amino acid" is a negatively or positively charged amino acid. "Negatively charged amino acids" are aspartic acid (D) and glutamic acid (E). "Positively charged amino acids" are arginine (R), lysine (K), and histidine (H). "Polar amino acids" are all amino acids that form hydrogen bonds as donors or acceptors. These are all charged amino acids, as well as asparagine (N), glutamine (Q), serine (S), threonine (T), tyrosine (Y), and cysteine ​​(C). "Polar uncharged amino acids" are asparagine (N), glutamine (Q), serine (S), threonine (T), tyrosine (Y), and cysteine ​​(C). "Amphoteric amino acids" are tryptophan (W), tyrosine (Y), and methionine (M). "Aromatic amino acids" are phenylalanine (F), tyrosine (Y), and tryptophan (W). "Hydrophobic amino acids" are glycine (G), alanine (A), valine (V), leucine (L), isoleucine (I), proline (P), phenylalanine (F), methionine (M), and cysteine. "Small amino acids" are glycine (G), alanine (A), serine (S), proline (P), threonine (T), aspartic acid (D), and asparagine (N).

[0054] The term "DGK" also refers to the diacylglycerol kinase family, a family of enzymes that catalyze the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). Family members use ATP as a phosphate source. DGKs can be classified into five groups: type 1 DGKs include DGK-α, DGK-β, and DGK-γ, whose members contain an EF-hand motif and a recoverin homology domain; type 2 DGKs include DGK-δ and DGK-η, whose members contain a pleckstrin homology domain; type 3 DGKs include DGK-ε, which has specificity for arachidonic acid-containing DAG; and type 4 DGKs include DGK-ζ and DGK-ι, whose members contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localization signal, and a PDZ-binding motif. The type 5 DGK group includes DGK-θ, which contains a third cysteine-rich domain, a pleckstrin homology domain, and a proline-rich region. DGK inhibitors are inhibitors of at least one member of the DGK family. For example, DGK inhibitors can be inhibitors of one or more of DGK-α, DGK-β, DGK-γ, DGK-δ, DGK-η, DGK-ε, DGK-ζ, DGK-ι, and DGK-θ.

[0055] The term "DGKalpha," also DGK-α or DGKα, refers to diacylglycerol kinase alpha, a member of the DGK family. The DGKalpha protein is encoded by the gene DGKA (DAGK, DAGK1, NCBI gene ID 1606). Synonyms for DGKalpha include DAG kinase alpha, 80 kDa diacylglycerol kinase, and diglyceride kinase alpha, among others. DGKalpha proteins include human, mouse, rat, rhesus monkey, and additional mammalian and non-mammalian homologs. The sequence of human DGKalpha is accessible via the UniProt identifier P23743 (DGKA_HUMAN), e.g., human isoforms P23743-1 or P23743-2, or P23743-3 (UniProt, February 1, 2023). Different isoforms and variants may exist in different species, and all are encompassed by the term DGKalpha. In addition, synthetic mutants of DGKalpha protein can be produced and are included in the term DGKalpha. Protein DGKalpha can also undergo various modifications, such as synthetic or naturally occurring modifications, such as post-translational modifications. DGKalpha inhibitors are compounds or antibodies that at least partially inhibit the functional activity of at least one isoform of DGKalpha.

[0056] The term "DGKzeta," also known as DGK-zeta or DGKzeta, refers to the DGK family member diacylglycerol kinase zeta. The DGKzeta protein is encoded by the gene DGKZ (DAGK6, DAGK5, DGK-ZETA, hDGKzeta, NCBI gene ID 8525). Synonyms for DGKzeta include DAG kinase zeta and diglyceride kinase zeta, among others. The DGKzeta protein includes homologs from humans, mice, rats, rhesus monkeys, and other mammals and non-mammals. The sequence of human DGKzeta is accessible via the UniProt identifier Q13574 (DGKZ_HUMAN), e.g., the standard human isoform Q13574-2 (UniProt, February 1, 2023). Different isoforms and variants exist in different species, and all are encompassed by the term DGKzeta. Furthermore, synthetic variants of DGKzeta protein can be produced and are included in the term DGKzeta.DGKzeta protein can also undergo various modifications, such as synthetic or naturally occurring modifications, such as post-translational modifications.DGKzeta inhibitors are compounds or antibodies that at least partially inhibit the functional activity of at least one isoform of DGKzeta.

[0057] An "isotype control" is an antibody or fragment that does not bind to a target but has the same class and type as a reference antibody or fragment that recognizes a target.

[0058] "Half-maximal effective concentration" (EC50) refers to the concentration of a drug, antibody, fragment, conjugate, or molecule that induces a response halfway between the baseline and maximum after a specific incubation time. Thus, with respect to antibody binding, EC50 reflects the antibody concentration required for half-maximal binding. EC50 can be determined if the inflection point can be determined by mathematical modeling (e.g., nonlinear regression) of a dose-response curve that describes the relationship between the applied drug, antibody, fragment, conjugate, or molecule concentration and the signal. For example, if the dose-response curve follows a sigmoidal curve, EC50 can be determined. If the response is inhibitory, EC50 is referred to as the half-maximal inhibitory concentration (IC50). EC80 can be determined as needed.

[0059] The term "linker" or "spacer" as used herein refers to any molecule that allows a direct topological connection between two moieties. The moiety can be, among others, a polypeptide, a protein, an antibody, an antibody fragment, a cytotoxic moiety, a binding moiety, a moiety for detection (e.g., a fluorophore), a moiety for immobilization or retrieval (e.g., a bead or magnetic bead), a reactive moiety, or any other molecule. The two moieties can be the same type or different. The linker can be part of the conjugate and contribute to its function. For example, for a conjugate containing a polypeptide and biotin, a spacer of approximately 4 Å (~5 atoms) between the carboxy group of biotin and the first bulky amino acid of the peptide allows biotin to reach the (strept)avidin binding pocket. Various linkers are known in the art and can be selected based on the moieties to be linked. Linker lengths typically range from 4 atoms to over 200 atoms. Linkers longer than 60 atoms generally comprise a population of compounds with an average length.

[0060] In the context of the present invention, the term "treatment" or "treating" includes inhibiting, delaying, controlling, alleviating, attenuating, limiting, reducing, suppressing, warding off, or curing the onset, course, or progression of a disease or condition of such a condition, and / or the symptoms of such a condition. The term "disease" includes, but is not limited to, a condition, disorder, injury, or health problem. The term "therapy" is understood herein to be synonymous with the term "treatment."

[0061] The terms "prevention", "prophylaxis" or "preclusion" are used interchangeably in relation to the present invention and refer to avoiding or reducing the risk of contracting, experiencing, suffering from or having a disease, or the risk of developing or progressing such symptoms and / or the pathology of such a condition.

[0062] The treatment or prevention of a disease may be partial or complete.

[0063] The terms "effective amount" and "therapeutically effective amount" are used interchangeably herein and refer to an amount sufficient to achieve a specific biological result or to regulate or improve symptoms or the time to onset of symptoms in a subject, typically by at least about 10%; usually by at least about 20%, preferably at least about 30%, or more preferably at least about 50%. The effectiveness of the use of antibodies in cancer treatment can be evaluated based on changes in tumor burden. Both tumor shrinkage (objective response) and the time to disease progression are important endpoints in cancer clinical trials. Standardized response criteria known as RECIST (Response Evaluation Criteria in Solid Tumors) were published in 2000. An updated version (RECIST 1.1) was released in 2009. RECIST criteria are typically used in clinical trials where objective response is the primary study endpoint, as well as in trials where stable disease, tumor progression, or time to progression analysis is assessed. This is because these outcome measures are based on the evaluation of anatomical tumor burden and its change during the study period. The effective amount for a specific subject may vary depending on factors such as the symptoms to be treated, the overall health of the subject, the method, route and dosage of administration, and the severity of side effects.When combined, the effective amount is the ratio of the combination of components, and the effect is not limited to only individual components.It is clear to those skilled in the art that whenever an antibody is administered as part of a medical application, the antibody must be administered in an effective amount.

[0064] Unless otherwise defined, a "complete response" (CR) is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a short-axis reduction of <10 mm. For a "partial response" (PR), at least a 30% reduction in the sum of the target lesion diameters must be achieved, relative to the baseline summed diameter. For a "progression" (PD), the sum of the target lesion diameters must increase by at least 20% relative to the study minimum sum (including the baseline sum, if this is the study minimum). In addition to the 20% relative increase, the sum must also show an absolute increase of at least 5 mm. For a "stable disease" (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD is observed, relative to the study minimum summed diameter.

[0065] Secondary outcome measures that can be used to determine the therapeutic benefit of the antibodies of the present invention described herein include the following: "Objective Response Rate" (ORR) is defined as the proportion of subjects achieving a complete response (CR) or partial response (PR). "Progression-Free Survival" (PFS) is defined as the time from the date of first administration of the antibody to disease progression or death, whichever occurs first. "Overall Survival" (OS) is defined as the period from the date of disease diagnosis or treatment initiation during which a patient diagnosed with the disease is still alive. "Duration of Response" (DOR) is defined as the time from a participant's first CR or PR to the time of disease progression. "Depth of Response" (DpR) is defined as the percentage of tumor shrinkage observed at the time of maximum response compared to baseline tumor burden. Both ORR and PFS clinical endpoints can be determined based on the RECIST 1.1 criteria described above.

[0066] When non-human subjects are analyzed, the aforementioned parameters for determining the efficacy and benefits of treatment must be adapted.

[0067] As used herein, the terms "patient" or "subject" are used interchangeably and refer to a mammal, including but not limited to a human or non-human mammal, such as a cow, horse, dog, sheep, or cat. Preferably, the patient is a human.

[0068] As used herein, a "lesion" refers to an area of ​​abnormal tissue. Lesions can be benign or malignant ("cancerous lesions" or "tumor lesions").

[0069] The terms "intra-tumoral," "intratumoral," "tumor-infiltrating," or "neoplastic," with respect to cells, structures, proteins, antibodies, or markers, refer to their localization within tumor tissue.

[0070] Cells that are "positive" or "+" for a particular marker or protein are cells characterized by substantial expression of that marker or protein. Marker or protein expression can be determined and quantified as known in the art, for example, to define different cell populations. For characterization of (immune) cell populations, marker expression can be determined by FACS or using any other technique described herein.

[0071] A "leukocyte" is an immune cell that expresses CD45.

[0072] "CD45+ cells," as used herein, refer to all white blood cells. CD45 can be used as a marker to distinguish between immune and non-immune cells.

[0073] The term "lymphocyte" refers to all immature, mature, undifferentiated, and differentiated white lymphocyte populations, including tissue-specific and specialized variants. This includes, by way of non-limiting example, B cells, T cells, NKT cells, and NK cells. In some embodiments, lymphocytes include all B cell lineages, including pre-B cells, precursor B cells, early pro-B cells, late pro-B cells, large pre-B cells, small pre-B cells, immature B cells, mature B cells, plasma B cells, memory B cells, B-1 cells, B-2 cells, and anergic AN1 / T3 cell populations.

[0074] "T cells" are immune cells that express TCRalphabeta, CD3, and CD8 or CD4. As used herein, the term includes naive T cells, CD4+ T cells, CD8+ T cells, regulatory T cells, memory T cells, activated T cells, anergic T cells, tolerant T cells, chimeric B cells, and antigen-specific T cells, as well as additional T cell populations known in the art. In some embodiments, the presence of a T cell receptor (TCR) on the cell surface distinguishes T cells from other lymphocytes.

[0075] A "CD8+ T cell" (also "cytotoxic T cell," "TC," "cytotoxic T lymphocyte," "CTL," "T killer cell," "cytolytic T cell," "CD8+ T cell," or "killer T cell") is a T cell that expresses CD3, CD45, and CD8. CD8+ T cells can kill cancer cells, infected (especially virally infected) cells, or other damaged cells.

[0076] "CD4+ T cells" (also "T helper cells," "Th cells") are immune cells that express CD3, CD4, and CD45. There are several subsets of T helper cells, including, but not limited to, Th1, Th2, and Th17. CD4+ T cells help suppress or regulate immune responses. They are essential for B cell antibody class switching, activation and proliferation of cytotoxic T cells, and maximizing the bactericidal activity of phagocytes such as macrophages.

[0077] "NK cells" (also natural killer cells) are immune cells that express CD45, CD16, CD56, and NKG2D, but are CD3 negative. NK cells do not require activation to kill cells that lack the MHC class 1 "self" marker. NCR1 (also called CD335 or NKp46) is expressed on NK cells and a subset of NKT cells.

[0078] "Natural killer T (NKT) cells" are a heterogeneous group of T cells that share properties of both T cells and natural killer cells.

[0079] "iNKT cells" (also "invariant natural killer T cells") express the invariant alphaβ TCR (Valpha24-Jalpha18, CD24lo), CD44hi, NK1.1 (mouse), and NKG2D. The invariant TCR recognizes glycoprotein antigens presented by the non-polymorphic MHC class I-like molecule CD1d. These cells can influence immune responses by rapidly producing large amounts of cytokines, namely IFNγ.

[0080] As known in the art, "effector cell" refers to the immune cell that actively supports immune response after stimulation.As used herein, effector cell refers to the immune cell that expresses Fcγ receptor, and therefore can mediate ADCC or ADCP.Non-limiting examples of effector cell are monocytes, neutrophils, mast cells, and preferably macrophages, and natural killer cells.

[0081] The term "chimeric antigen receptor" or "CAR" as used herein refers to an artificial T cell surface receptor that is expressed on immune effector cells and engineered to specifically bind to an antigen. CARs can be used as a therapy involving adoptive cell transfer. Monocytes are removed from patients (blood, tumor, or ascites) and modified to express a receptor specific for a particular form of antigen. In some embodiments, the CAR is specifically expressed against a tumor-associated antigen. The CAR may also include an extracellular domain containing an intracellular activation domain, a transmembrane domain, and a tumor-associated antigen-binding region. In some embodiments, the CAR comprises a fusion of a single-chain variable fragment (scFv)-derived monoclonal antibody fused to a CD3-zeta transmembrane domain and an intracellular domain. The specificity of the CAR design can be derived from the receptor's ligand (e.g., a peptide). In some embodiments, the CAR can target cancer by redirecting monocytes / macrophages expressing the CAR specific for a tumor-associated antigen.

[0082] Unless otherwise specified, administration schemes are abbreviated as known in the art, e.g., every day (QD), every 2 days (Q2D), or every 3 days (Q3D). Accordingly, "QW" means once every week, "Q2W" means once every 2 weeks, "Q3W" means once every 3 weeks, "Q4W" means once every 4 weeks, "Q5W" means once every 5 weeks, and "Q6W" means once every 6 weeks. "BIW" means every 2 weeks, and "BIWx4" means four administrations every 2 weeks, i.e., four administrations in 2 weeks.

[0083] Dose ratios referred to as "dose ratio (mg or mg / kg DGKalpha inhibitor A: mg or mg / kg DGKzeta inhibitor A')" refer either to the ratio of mg DGKalpha inhibitor A: mg DGKzeta inhibitor A' or to mg / kg DGKalpha inhibitor A: mg / kg DGKzeta inhibitor A'.

[0084] A "dosing cycle" or "treatment cycle" is a period of treatment followed by a period of rest (no treatment) that is repeated on a regular schedule. When this cycle is repeated multiple times on a regular schedule, it constitutes a course of treatment.

[0085] An intravenous line or "IV line" is a tube or cannula that can be used for intravenous infusions.

[0086] Definition of DGK inhibitors of formula (I) The terms described herein in connection with the DGK inhibitors of formula (I) have the following meanings: The term "substituted" means that one or more hydrogen atoms on the specified atom or group are replaced with one selected from the specified group, provided that the normal valence of the specified atom under the existing circumstances is not exceeded. Combinations of substituents and / or variables are permissible.

[0087] The term "optionally substituted" means that the number of substituents may be equal to or different from zero. Unless otherwise specified, an optionally substituted group can be substituted with as many optional substituents as can be accommodated by replacing hydrogen atoms on available carbon or nitrogen atoms with non-hydrogen substituents. Generally, if present, the number of optional substituents can be 1, 2, 3 or 4, particularly 1, 2 or 3.

[0088] When the radical in the compound of the present invention is substituted, said radical can be mono- or polysubstituted by substituent unless otherwise specified.Within the scope of the present invention, the meanings of all repeating radicals are independent of each other.The radical of the compound of the present invention can be substituted by 1, 2 or 3 identical or different substituents, particularly 1 substituent.

[0089] As used herein, an oxo substituent represents an oxygen atom that is attached to a carbon or sulfur atom via a double bond.

[0090] When a composite substituent is composed of two or more moieties, such as (C-C-alkoxy)-(C-C-alkyl), a given moiety can be attached to any suitable position on the composite substituent, e.g., a C-C-alkoxy moiety can be attached to any suitable carbon atom on the C-C-alkyl moiety of the (C-C-alkoxy)-(C-C-alkyl) group. The first or last hyphen on such a composite substituent indicates the point of attachment of the composite substituent to the rest of the molecule. For example, when a ring containing carbon atoms and optionally containing one or more heteroatoms, such as nitrogen, oxygen, or sulfur atoms, is substituted with a substituent, the substituent can be attached at any suitable position on the ring and be attached to a suitable carbon atom and / or heteroatom.

[0091] The term "comprising" as used herein includes "consisting of." When any item is referred to as "mentioned herein," it means that it may be mentioned anywhere in the text.

[0092] The terms mentioned herein have the following meanings: The term "halogen atom" means a fluorine, chlorine, bromine or iodine atom, in particular a fluorine, chlorine or bromine atom.

[0093] The term "C1-C6-alkyl" means a straight-chain or branched, saturated, monovalent hydrocarbon radical having 1, 2, 3, 4, 5 or 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neo-pentyl, 1,1-dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2,3-dimethylbutyl, 1,2-dimethylbutyl or 1,3-dimethylbutyl group, or an isomer thereof. In particular, the groups have 1, 2, 3, 4 or 5 carbon atoms ("C-C-alkyl"), such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neo-pentyl, 1,1-dimethylpropyl groups. More particularly, the groups have 1, 2, 3 or 4 carbon atoms ("C-C-alkyl"), such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl or tert-butyl groups, even more particularly 1, 2 or 3 carbon atoms ("C-C-alkyl"), such as methyl, ethyl, n-propyl or isopropyl groups, and even more particularly 1 or 2 carbon atoms ("C-C-alkyl"), such as methyl or ethyl groups.

[0094] The term "C2-C4-alkyl" denotes a straight-chain or branched, saturated, monovalent hydrocarbon radical having 2, 3 or 4 carbon atoms, for example an ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl or tert-butyl radical.

[0095] The term "C1-C6-hydroxyalkyl" means a linear or branched saturated monovalent hydrocarbon radical, in which the term "C1-C6-alkyl" is defined above and in which one or two hydrogen atoms have been replaced by hydroxy groups, such as, for example, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1,2-dihydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-hydroxypropyl, 1-hydroxypropan-2-yl, 2-hydroxypropan-2-yl, 2,3-dihydroxypropyl, 1,3-dihydroxypropyl. hydroxypentyl, 2-hydroxypentyl, 3-hydroxypentyl, 4-hydroxypentyl, 5-hydroxypentyl, 1-hydroxyhexyl, 2-hydroxyhexyl, 3-hydroxyhexyl, 4-hydroxyhexyl, 5-hydroxyhexyl, 6-hydroxyhexyl, or isomers thereof. In particular, the groups have 1, 2, 3 or 4 carbon atoms ("C1-C4-hydroxyalkyl") and include, for example, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1,2-dihydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-hydroxypropyl, 1-hydroxypropan-2-yl, 2-hydroxypropan-2-yl, 2,3-dihydroxypropyl, 1,3-dihydroxypropan-2-yl, 3-hydroxy-2-methyl-propyl, 2-hydroxy-2-methyl-propyl, 1-hydroxy-2-methyl-propyl, 1-hydroxybutyl, 2-hydroxybutyl, 3-hydroxybutyl, 4-hydroxybutyl groups, or isomers thereof.

[0096] The term "C2-C4-hydroxyalkyl" means a straight-chain or branched, saturated, monovalent hydrocarbon radical having 2, 3 or 4 carbon atoms, wherein the term "C2-C4-alkyl" is defined above and in which one or two hydrogen atoms have been replaced by a hydroxy group, such as, for example, 1-hydroxyethyl, 2-hydroxyethyl, 1,2-dihydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-hydroxypropyl, 1-hydroxypropan-2-yl, 2-hydroxypropan-2-yl, 2,3-dihydroxypropyl, 1,3-dihydroxypropan-2-yl, 3-hydroxy-2-methyl-propyl, 2-hydroxy-2-methyl-propyl, 1-hydroxy-2-methyl-propyl, 1-hydroxybutyl, 2-hydroxybutyl, 3-hydroxybutyl or 4-hydroxybutyl radicals, or isomers thereof.

[0097] The term "C1-C6-haloalkyl" means a linear or branched, saturated, monovalent hydrocarbon radical, in which the term "C1-C6-alkyl" is as defined above, and in which one or more hydrogen atoms, identical or different, are replaced by halogen atoms. In particular, said halogen atoms are fluorine atoms. The C1-C6-haloalkyl radical is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3,3,3-trifluoropropyl, 1,3-difluoropropan-2-yl, 4,4,4-trifluorobutyl, 5,5,5-trifluoropentyl or 6,6,6-trifluorohexyl. In particular, the groups have 1, 2, 3 or 4 carbon atoms ("C1-C4-haloalkyl") and include, for example, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3,3,3-trifluoropropyl, 1,3-difluoropropan-2-yl or 4,4,4-trifluorobutyl groups.

[0098] The term "C-C-alkoxy" means a linear or branched, saturated, monovalent radical of the formula (C-C-alkyl)-O-, where the term "C-C-alkyl" is as defined above, such as a methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, tert-butoxy, pentyloxy, isopentyloxy or n-hexyloxy group, or an isomer thereof. In particular, said group has 1, 2, 3 or 4 carbon atoms ("C-C-alkoxy") and includes, for example, a methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy or tert-butoxy group.

[0099] The term "C1-C6-haloalkoxy" means a linear or branched saturated monovalent C1-C6-alkoxy group as defined above, in which one or more hydrogen atoms are replaced by halogen atoms, whether identical or different. In particular, the halogen atoms are fluorine atoms. The C1-C6-haloalkoxy group is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy or pentafluoroethoxy.

[0100] The term "C2-C6-alkenyl" means a straight or branched chain monovalent hydrocarbon radical containing one or two double bonds and having 2, 3, 4, 5 or 6 carbon atoms, although it is understood that if the alkenyl group contains two double bonds, the double bonds can be bonded to each other or form an allene. Examples of alkenyl groups include, for example, ethenyl (or "vinyl"), prop-2-en-1-yl (or "allyl"), prop-1-en-1-yl, but-3-enyl, but-2-enyl, but-1-enyl, pent-4-enyl, pent-3-enyl, pent-2-enyl, pent-1-enyl, hex-5-enyl, hex-4-enyl, hex-3-enyl, hex-2-enyl, hex-1-enyl, prop-1-en-2-yl (also is "isopropenyl"), 2-methylprop-2-enyl, 1-methylprop-2-enyl, 2-methylprop-1-enyl, 1-methylprop-1-enyl, 3-methylbut-3-enyl, 2-methylbut-3-enyl, 1-methylbut-3-enyl, 3-methylbut-2-enyl, 2-methylbut-2-enyl, 1-methylbut-2-enyl, 3-methylbut-1-enyl, 2-methylbut-1-enyl, 1-methylbut-1-enyl, 1,1-Dimethylprop-2-enyl, 1-ethylprop-1-enyl, 1-propyl vinyl, 1-isopropyl vinyl, 4-methylpent-4-enyl, 3-methylpent-4-enyl, 2-methylpent-4-enyl, 1-methylpent-4-enyl, 4-methylpent-3-enyl, 3-methylpent-3-enyl, 2-methylpent-3-enyl, 1-methylpent-3-enyl, 4-methylpent-1-enyl, 3-methylpent-2-enyl, 2-methylpent-2-enyl, 1-methylpent-2-enyl, 4-methylpent-1-enyl, 3-methylpent-1-enyl, 2-methylpent-1-enyl, 1-methylpent-1-enyl, 3-ethylbut-3-enyl, 2-ethylbut-3-enyl 1-ethylbut-3-enyl, 3-ethylbut-2-enyl, 2-ethylbut-2-enyl, 1-ethylbut-2-enyl, 3-ethylbut-1-enyl, 2-ethylbut-1-enyl, 1-ethylbut-1-enyl, 2-propylprop-2-enyl, 1-propylprop-2-enyl, 2-isopropylprop-2-enyl, 1-isopropylprop-2-enyl, 2-propylprop-1-enyl, 1-propylprop-1-enyl, 2-isopropylprop-1-enyl, 1-isopropylprop-1-enyl, 3,3-dimethylprop-1-enyl, 1-(1,1-dimethylethyl)ethenyl, buta-1,3-dienyl, penta-1,4-dienyl or hexa-1,5-dienyl.

[0101] The term "C2-C6-alkynyl" denotes a straight-chain or branched monovalent hydrocarbon radical containing one triple bond and containing 2, 3, 4, 5 or 6 carbon atoms, in particular 2, 3 or 4 carbon atoms ("C2-C4-alkynyl"). The C2-C6-alkynyl group is, for example, ethynyl, prop-1-ynyl, prop-2-ynyl (or "propargyl"), but-1-ynyl, but-2-ynyl, but-3-ynyl, pent-1-ynyl, pent-2-ynyl, pent-3-ynyl, pent-4-ynyl, hex-1-ynyl, hex-2-ynyl, hex-3-ynyl, hex-4-ynyl, hex-5-ynyl, 1-methylprop-2-ynyl, 2-methylbut-3-ynyl, 1-methylbut-3-ynyl, 1-methylbut-2-ynyl, 3-methylbut-1-ynyl, 1-ethylprop-2-ynyl, 3-methylpent-4-ynyl, 2-methylpent-4-ynyl, 1-methylpent-4-ynyl, 1-methylpent-3-ynyl, 1-methylpent-3-ynyl, 4-methylpent-2-ynyl, 1-methylpent-2-ynyl, 4-methylpent-1-ynyl, 3-methylpent-1-ynyl, 2-ethylbut-3-ynyl, 1-ethylbut-3-ynyl, 1-ethylbut-2-ynyl, 1-propylprop-2-ynyl, 1-isopropylprop-2-ynyl, 2,2-dimethylbut-3-ynyl, 1,1-dimethylbut-3-ynyl, 1,1-dimethylbut-2-ynyl or 3,3-dimethylbut-1-ynyl group.

[0102] The term "C3-C6-cycloalkyl" means a saturated monovalent monocyclic hydrocarbon ring containing 3, 4, 5 or 6 carbon atoms. The C3-C6-cycloalkyl group is, for example, a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group. In particular, the group has 3, 4 or 5 carbon atoms ("C3-C5-cycloalkyl"), including, for example, a cyclopropyl, cyclobutyl or cyclopentyl group. In particular, the group has 3 or 4 carbon atoms ("C3-C4-cycloalkyl"), including, for example, a cyclopropyl or cyclobutyl group.

[0103] The term "C4-C6-cycloalkenyl" means a monocyclic hydrocarbon ring containing 4, 5 or 6 carbon atoms and one double bond. In particular, the ring contains 5 or 6 carbon atoms ("C5-C6-cycloalkenyl"). The C4-C6-cycloalkenyl group is, for example, a monocyclic hydrocarbon ring, such as a cyclobutenyl, cyclopentenyl, cyclohexenyl or cycloheptenyl group.

[0104] The term "C3-C6-cycloalkyloxy" means a saturated monovalent radical of the formula (C3-C6-cycloalkyl)-O-, where the term "C3-C6-cycloalkyl" is as defined above, for example a cyclopropyloxy, cyclobutyloxy, cyclopentyloxy or cyclohexyloxy group.

[0105] The term "4- to 7-membered heterocycloalkyl" means a monocyclic, saturated heterocycle having a total of 4, 5, 6, or 7 ring atoms, containing one or two identical or different ring heteroatoms from the series N, O, and S.

[0106] The heterocycloalkyl group can be, but is not limited to, a four-membered ring such as, for example, azetidinyl, oxetanyl, or thietanyl; or a five-membered ring such as, for example, tetrahydrofuranyl, 1,3-dioxolanyl, thiolanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, 1,1-dioxidethiolanyl, 1,2-oxazolidinyl, 1,3-oxazolidinyl, or 1,3-thiazolidinyl; or a six-membered ring such as, for example, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, 1,3-dioxanyl, 1,4-dioxanyl, or 1,2-oxazinanyl; or a seven-membered ring such as, for example, azepanyl, 1,4-diazepanyl, or 1,4-oxazepanyl.

[0107] The term "5- to 7-membered heterocycloalkenyl" means a monocyclic, unsaturated, non-aromatic heterocyclic ring having a total of 5, 6, or 7 ring atoms, containing one or two double bonds and one or two identical or different ring heteroatoms from the series N, O, and S.

[0108] The heterocycloalkenyl group is, for example, 4H-pyranyl, 2H-pyranyl, 2,5-dihydro-1H-pyrrolyl, [1,3]dioxolyl, 4H-[1,3,4]thiadiazinyl, 2,5-dihydrofuranyl, 2,3-dihydrofuranyl, 2,5-dihydrothiophenyl, 2,3-dihydrothiophenyl, 4,5-dihydrooxazolyl or 4H-[1,4]thiazinyl.

[0109] The term "(4- to 7-membered heterocycloalkyl)oxy" means a monocyclic saturated heterocycloalkyl of the formula (4- to 7-membered heterocycloalkyl)-O, where the term "4- to 7-membered heterocycloalkyl" is as defined above.

[0110] The term "nitrogen-containing 4- to 7-membered heterocycloalkyl group" means a monocyclic, saturated heterocycle having a total of 4, 5, 6, or 7 ring atoms, including one ring nitrogen atom and optionally one additional ring heteroatom from the series N, O, and S.

[0111] The nitrogen-containing 4- to 7-membered heterocycloalkyl group may be, but is not limited to, a 4-membered ring such as azetidinyl; or a 5-membered ring such as pyrrolidinyl, imidazolidinyl, pyrazolidinyl, 1,2-oxazolidinyl, 1,3-oxazolidinyl, or 1,3-thiazolidinyl; or a 6-membered ring such as piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, or 1,2-oxazinanyl; or a 7-membered ring such as azepanyl, 1,4-diazepanyl, or 1,4-oxazepanyl.

[0112] The term "heteroaryl" means a monovalent monocyclic or bicyclic aromatic ring having 5, 6, 8, 9, or 10 ring atoms (a "5- to 10-membered heteroaryl" group), containing at least one ring heteroatom and optionally containing 1, 2, or 3 additional ring heteroatoms from the series N, O, and / or S, bonded via ring carbon atoms.

[0113] The heteroaryl group can be, for example, a 5-membered heteroaryl group such as thienyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, or tetrazolyl; or a 6-membered heteroaryl group such as, for example, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, or triazinyl; or a 9-membered heteroaryl group such as, for example, benzofuranyl, benzothienyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, benzothiazolyl, benzotriazolyl, thiazolopyridinyl, indazolyl, indolyl, isoindolyl, indolizinyl, or purinyl; or a 10-membered heteroaryl group such as, for example, quinolinyl, quinazolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, or pteridinyl.

[0114] In general, unless otherwise specified, a heteroaryl or heteroarylene group includes all possible isomeric forms thereof, such as tautomers and positional isomers with respect to the point of attachment to the rest of the molecule. Thus, in some illustrative, non-limiting examples, the term pyridinyl includes pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl; or the term thienyl includes thien-2-yl and thien-3-yl.

[0115] The term "C1-C6" as used herein, for example in the definition of "C1-C6-alkyl", "C1-C6-haloalkyl", "C1-C6-hydroxyalkyl", "C1-C6-alkoxy" or "C1-C6-haloalkoxy", refers to an alkyl group having a finite number of carbon atoms from 1 to 6, i.e., 1, 2, 3, 4, 5 or 6 carbon atoms.

[0116] Furthermore, as used herein, the term "C3-C8" refers to a cycloalkyl group having a finite number of carbon atoms, from 3 to 6, i.e., 3, 4, 5 or 6, for example, with respect to the definition of "C3-C6-cycloalkyl".

[0117] When a range of values ​​is given, said range includes each value and sub-range within said range.

[0118] for example: "C1-C6" means C1, C2, C3, C4, C5, C6, C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, C2-C6 , including C2-C5, C2-C4, C2-C3, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6; "C2-C6" encompasses C2, C3, C4, C5, C6, C2-C6, C2-C5, C2-C4, C2-C3, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6; "C3-C6" encompasses C3, C4, C5, C6, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6;

[0119] As used herein, the term "leaving group" refers to an atom or group of atoms that displaces a bonding electron as a stable species in a chemical reaction. In particular, such leaving groups are selected from the group including halide, especially fluoride, chloride, bromide or iodide, (methylsulfonyl)oxy, [(trifluoromethyl)sulfonyl]oxy, [(nonafluorobutylsulfonyl)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.

[0120] Definition of DGK inhibitors of formula (II) The terms described herein in connection with the DGK inhibitors of formula (II) have the following meanings: The term "substituted" means that one or more hydrogen atoms on the specified atom or group are replaced with one selected from the specified group, provided that the normal valence of the specified atom under the existing circumstances is not exceeded. Combinations of substituents and / or variables are permissible.

[0121] The term "optionally substituted" means that the number of substituents may be equal to or different from zero. Unless otherwise specified, an optionally substituted group can be substituted with as many optional substituents as can be accommodated by replacing hydrogen atoms on available carbon or nitrogen atoms with non-hydrogen substituents. Generally, if present, the number of optional substituents can be 1, 2, 3 or 4, particularly 1, 2 or 3.

[0122] When the radical in the compound of the present invention is substituted, said radical can be mono- or polysubstituted by substituent unless otherwise specified.Within the scope of the present invention, the meanings of all repeating radicals are independent of each other.The radical of the compound of the present invention can be substituted by 1, 2 or 3 identical or different substituents, particularly 1 substituent.

[0123] As used herein, an oxo substituent represents an oxygen atom that is attached to a carbon or sulfur atom via a double bond.

[0124] When a composite substituent is composed of two or more moieties, such as (C-C-alkoxy)-(C-C-alkyl), a given moiety can be attached to any suitable position on the composite substituent, e.g., a C-C-alkoxy moiety can be attached to any suitable carbon atom on the C-C-alkyl moiety of the (C-C-alkoxy)-(C-C-alkyl) group. The first or last hyphen on such a composite substituent indicates the point of attachment of the composite substituent to the rest of the molecule. For example, when a ring containing carbon atoms and optionally containing one or more heteroatoms, such as nitrogen, oxygen, or sulfur atoms, is substituted with a substituent, the substituent can be attached at any suitable position on the ring and be attached to a suitable carbon atom and / or heteroatom.

[0125] The term "comprising" as used herein includes "consisting of." When any item is referred to as "mentioned herein," it means that it may be mentioned anywhere in the text.

[0126] The terms mentioned herein have the following meanings: The term "halogen atom" means a fluorine, chlorine, bromine or iodine atom, in particular a fluorine, chlorine or bromine atom.

[0127] The term "C1-C6-alkyl" means a straight-chain or branched, saturated, monovalent hydrocarbon radical having 1, 2, 3, 4, 5 or 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neo-pentyl, 1,1-dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2,3-dimethylbutyl, 1,2-dimethylbutyl or 1,3-dimethylbutyl group, or an isomer thereof. In particular, the groups have 1, 2, 3 or 4 carbon atoms ("C1-C4-alkyl"), including, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl or tert-butyl groups, more particularly, have 1, 2 or 3 carbon atoms ("C1-C3-alkyl"), including, for example, methyl, ethyl, n-propyl or isopropyl groups, and even more particularly, have 1 or 2 carbon atoms ("C1-C2-alkyl"), including, for example, methyl or ethyl groups.

[0128] The term "C1-C4-hydroxyalkyl" means a linear or branched saturated monovalent hydrocarbon radical, wherein the term "C1-C4-alkyl" is defined above and in which one or two hydrogen atoms have been replaced by a hydroxy group, and includes, for example, a hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1,2-dihydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-hydroxypropyl, 1-hydroxypropan-2-yl, 2-hydroxypropan-2-yl, 2,3-dihydroxypropyl, 1,3-dihydroxypropan-2-yl, 3-hydroxy-2-methyl-propyl, 2-hydroxy-2-methyl-propyl, 1-hydroxy-2-methyl-propyl, 1-hydroxybutyl, 2-hydroxybutyl, 3-hydroxybutyl, 4-hydroxybutyl group, or an isomer thereof.

[0129] The term "C1-C6-haloalkyl" means a linear or branched, saturated, monovalent hydrocarbon radical, in which the term "C1-C6-alkyl" is as defined above, and in which one or more hydrogen atoms, identical or different, are replaced by halogen atoms. In particular, said halogen atoms are fluorine atoms. Said C1-C6-haloalkyl radicals are, 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.

[0130] The term "C1-C6-alkoxy" means a linear or branched, saturated, monovalent radical of the formula (C1-C6-alkyl)-O-, where the term "C1-C6-alkyl" is as defined above, such as a methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, tert-butoxy, pentyloxy, isopentyloxy or n-hexyloxy radical, or an isomer thereof.

[0131] The term "C1-C6-haloalkoxy" means a linear or branched, saturated, monovalent C1-C6-alkoxy group as defined above, in which one or more hydrogen atoms are replaced by halogen atoms, whether identical or different. In particular, said halogen atoms are fluorine atoms. Said C1-C6-haloalkoxy groups are, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy or pentafluoroethoxy.

[0132] The term "C3-C4-alkenyl" means a straight-chain or branched monovalent hydrocarbon radical containing one or two double bonds and having three or four carbon atoms. The alkenyl radical is, for example, a prop-2-en-1-yl (or "allyl"), prop-1-en-1-yl, but-3-enyl, but-2-enyl or but-1-enyl radical.

[0133] 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 radical is, for example, a prop-1-ynyl, prop-2-ynyl (or "propargyl"), but-1-ynyl, but-2-ynyl or but-3-ynyl radical.

[0134] 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"). Said C3-C7-cycloalkyl group is, for example, a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl group.

[0135] “Bicyclic C6-C 11 The term "-cycloalkyl" includes spirocycloalkyl, fused C-C 10 -cycloalkyl or bridged C7-C 10 means a cycloalkyl group: The term "spirocycloalkyl" refers to a bicyclic, saturated, monovalent C-C 11means a hydrocarbon group in which two rings share one common ring carbon atom, wherein the bicyclic hydrocarbon group contains 5, 6, 7, 8, 9, 10, or 11 carbon atoms, and the spirocycloalkyl group can be attached to the rest of the molecule through any one of the carbon atoms except the spiro carbon atom, such as 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.

[0136] "Fused C6-C 10 The term "-cycloalkyl" means a bicyclic, saturated, monovalent hydrocarbon group in which two rings share two adjacent ring atoms, for example, bicyclo[4.2.0]octyl, octahydropentalenyl, or decalinyl.

[0137] “Cross-linked C7-C 10 The term "-cycloalkyl" means a bicyclic, saturated, monovalent hydrocarbon group in which the two rings share two common ring atoms that are not adjacent, for example, bicyclo[2.2.1]heptyl (also known as norbornyl).

[0138] “Bicyclic C5-C 11 The term "-cycloalkyl" includes spirocycloalkyl, fused C-C 10 -cycloalkyl or bridged C5-C 10 means a cycloalkyl group: The term "spirocycloalkyl" refers to a bicyclic, saturated, monovalent C-C 11means a hydrocarbon group in which two rings share one common ring carbon atom, wherein the bicyclic hydrocarbon group contains 5, 6, 7, 8, 9, 10, or 11 carbon atoms, and the spirocycloalkyl group can be attached to the rest of the molecule through any one of the carbon atoms except the spiro carbon atom, such as 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.

[0139] "Fused C5-C 10 The term "-cycloalkyl" means a bicyclic, saturated, monovalent hydrocarbon group in which two rings share two adjacent ring atoms, for example, bicyclo[4.2.0]octyl, octahydropentalenyl, or decalinyl.

[0140] The term "bridged C5-C7-cycloalkyl" means a bicyclic, saturated, monovalent hydrocarbon group in which two rings share two common ring atoms that are not adjacent, such as, for example, bicyclo[1.1.1]pentyl or bicyclo[2.2.1]heptyl (also known as norbornyl).

[0141] The term "monocyclic 4- to 7-membered heterocycloalkyl" means a monocyclic, saturated heterocycle having a total of 4, 5, 6, or 7 ring atoms, which contains one or two identical or different ring heteroatoms from the series N, O, and S.

[0142] The monocyclic heterocycloalkyl group can be, but is not limited to, a four-membered ring such as, for example, azetidinyl, oxetanyl, or thietanyl; or a five-membered ring such as, for example, tetrahydrofuranyl, 1,3-dioxolanyl, thiolanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, 1,1-dioxidethiolanyl, 1,2-oxazolidinyl, 1,3-oxazolidinyl, or 1,3-thiazolidinyl; or a six-membered ring such as, for example, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, 1,3-dioxanyl, 1,4-dioxanyl, or 1,2-oxazinanyl; or a seven-membered ring such as, for example, azepanyl, 1,4-diazepanyl, or 1,4-oxazepanyl.

[0143] The term "monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group" means a monocyclic, saturated heterocycle having a total of 4, 5, 6, or 7 ring atoms, which includes one ring nitrogen atom and optionally contains one additional ring heteroatom from the series N, O, and S.

[0144] The monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group can be, but is not limited to, a 4-membered ring such as, for example, azetidinyl; or a 5-membered ring such as, for example, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, 1,2-oxazolidinyl, 1,3-oxazolidinyl, or 1,3-thiazolidinyl; or a 6-membered ring such as, for example, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, or 1,2-oxazinanyl; or a 7-membered ring such as, for example, azepanyl, 1,4-diazepanyl, or 1,4-oxazepanyl.

[0145] The term "optionally benzo-fused monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group" means a monocyclic, saturated heterocycle having a total of 4, 5, 6 or 7 ring atoms, including one ring nitrogen atom and optionally one further ring heteroatom from the N, O and S series, wherein two adjacent ring carbon atoms are optionally shared by an optionally fused benzene ring; such a group is one of the monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl groups mentioned above, such as pyrrolidinyl, piperidinyl, etc., or a benzo-fused 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.

[0146] The term "bicyclic 6-11 membered heterocycloalkyl" means a 6-11 membered heterospirocycloalkyl, a 6-10 membered fused heterocycloalkyl, or a 7-10 membered bridged heterocycloalkyl group as defined below: The term "6-11 membered heterospirocycloalkyl" means a bicyclic, saturated heterocycle having a total of 6, 7, 8, 9, 10 or 11 ring atoms, where the two rings share one common ring carbon atom, and "heterospirocycloalkyl" contains one or two identical or different ring heteroatoms from the series: N, O, S; said heterospirocycloalkyl group can be attached to the rest of the molecule through any one of the carbon atoms excluding the spiro carbon atom or, if present, through the nitrogen atom.

[0147] Examples of the heterospirocycloalkyl group include azaspiro[2.3]hexyl, azaspiro[3.3]heptyl, oxazaspiro[3.3]heptyl, thiazaspiro[3.3]heptyl, oxaspiro[3.3]heptyl, oxazaspiro[5.3]nonyl, oxazaspiro[4.3]octyl, azaspiro[4.5]decyl, oxazaspiro[5.5]undecyl, dia ... It is one of the further homologous skeletons such as spiro[3.3]heptyl, thiazaspiro[3.3]heptyl, thiazaspiro[4.3]octyl, azaspiro[5.5]undecyl, or 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]-.

[0148] The term "6-10 membered fused heterocycloalkyl" means a bicyclic, saturated heterocycle having a total of 6, 7, 8, 9, or 10 ring atoms, where two rings share two adjacent ring atoms, and "fused heterocycloalkyl" contains one or two identical or different ring heteroatoms from the series: N, O, S; said fused heterocycloalkyl group can be attached to the remainder of the molecule through any one of the carbon atoms or, if present, the nitrogen atom.

[0149] Said fused heterocycloalkyl group is for example azabicyclo[3.3.0]octyl, azabicyclo[4.3.0]nonyl, diazabicyclo[4.3.0]nonyl, oxazabicyclo[4.3.0]nonyl, thiazabicyclo[4.3.0]nonyl or azabicyclo[4.4.0]decyl.

[0150] The term "7-10 membered bridged heterocycloalkyl" means a bicyclic, saturated heterocycle having a total of 7, 8, 9, or 10 ring atoms, where the two rings share two common ring atoms that are not adjacent, and "bridged heterocycloalkyl" contains one or two identical or different ring heteroatoms from the series: N, O, S; said bridged heterocycloalkyl group can be attached to the rest of the molecule through any one of the carbon atoms or, if present, the nitrogen atom, excluding the spiro carbon atom.

[0151] Examples of the bridged heterocycloalkyl group include azabicyclo[2.2.1]heptyl, oxazabicyclo[2.2.1]heptyl, thiazabicyclo[2.2.1]heptyl, diazabicyclo[2.2.1]heptyl, azabicyclo[2.2.2]octyl, diazabicyclo[2.2.2]octyl, oxazabicyclo[2.2.2]octyl, thiazabicyclo[2.2.2]octyl, azabicyclo[3.2.1]octyl, diazabicyclo[3.2.1]octyl, oxazabicyclo[3.2.1]octyl, thiazabicyclo[3.2.1] octyl, azabicyclo[3.3.1]nonyl, diazabicyclo[3.3.1]nonyl, oxazabicyclo[3.3.1]nonyl, thiazabicyclo[3.3.1]nonyl, azabicyclo[4.2.1]nonyl, diazabicyclo[4.2.1]nonyl, oxazabicyclo[4.2.1]nonyl, thiazabicyclo[4.2.1]nonyl, azabicyclo[3.3.2]decyl, diazabicyclo[3.3.2]decyl, oxazabicyclo[3.3.2]decyl, thiazabicyclo[3.3.2]decyl or azabicyclo[4.2.2]decyl.

[0152] The term "bicyclic nitrogen-containing 6-11-membered heterocycloalkyl" means a 6-11-membered heterospirocycloalkyl, a 6-10-membered fused heterocycloalkyl or a 7-10-membered bridged heterocycloalkyl group as defined above, with the proviso that it contains one ring nitrogen atom and optionally one or two additional ring heteroatoms from the series N, O and S; said bicyclic nitrogen-containing 6-11-membered heterocycloalkyl group can be attached to the rest of the molecule through any one of the carbon atoms, except for the nitrogen atom or the spiro carbon atom.

[0153] The term "bicyclic 5-11 membered heterocycloalkyl" means a 5-11 membered heterospirocycloalkyl, a 5-11 membered fused heterocycloalkyl, or a 5-11 membered bridged heterocycloalkyl group as defined below: The term "5-11 membered heterospirocycloalkyl" means a bicyclic, saturated heterocycle having a total of 5, 6, 7, 8, 9, 10 or 11 ring atoms, where the two rings share one common ring carbon atom, and "heterospirocycloalkyl" contains one or two identical or different ring heteroatoms from the series: N, O, S; said heterospirocycloalkyl group can be attached to the rest of the molecule through any one of the carbon atoms, excluding the spiro carbon atom, or the nitrogen atom, if present.

[0154] Examples of the heterospirocycloalkyl group include azaspiro[2.2]pentyl, azaspiro[2.3]hexyl, azaspiro[3.3]heptyl, oxazaspiro[3.3]heptyl, thiazaspiro[3.3]heptyl, oxaspiro[3.3]heptyl, oxazaspiro[5.3]nonyl, oxazaspiro[4.3]octyl, azaspiro[4,5]decyl, oxazaspiro[5.5]unyl, and the like. decyl, diazaspiro[3.3]heptyl, thiazaspiro[3.3]heptyl, thiazaspiro[4.3]octyl, azaspiro[5.5]undecyl, or one of further homologous skeletons such as spiro[3.4]-, spiro[4.4]-, spiro[2.4]-, spiro[2.5]-, spiro[2.6]-, spiro[3.5]-, spiro[3.6]-, spiro[4.5]- and spiro[4.6]-.

[0155] The term "5- to 11-membered fused heterocycloalkyl" means a bicyclic, saturated heterocycle having a total of 5, 6, 7, 8, 9, or 10 ring atoms, where two rings share two adjacent ring atoms, and "fused heterocycloalkyl" contains one or two identical or different ring heteroatoms from the series: N, O, S; said fused heterocycloalkyl group can be attached to the remainder of the molecule through any one of the carbon atoms or, if present, the nitrogen atom.

[0156] The fused heterocycloalkyl group may be, for example, azabicyclo[3.1.0]hexyl, azabicyclo[3.3.0]octyl, azabicyclo[4.3.0]nonyl, diazabicyclo[4.3.0]nonyl, oxazabicyclo[4.3.0]nonyl, thiazabicyclo[4.3.0]nonyl or azabicyclo[4.4.0]decyl.

[0157] The term "5- to 11-membered bridged heterocycloalkyl" means a bicyclic, saturated heterocycle having a total of 5, 6, 7, 8, 9, or 10 ring atoms, where the two rings share two common ring atoms that are not adjacent, and "bridged heterocycloalkyl" contains one or two identical or different ring heteroatoms from the series: N, O, S; said bridged heterocycloalkyl group can be attached to the remainder of the molecule through any one of the carbon atoms excluding the spiro carbon atom or, if present, the nitrogen atom.

[0158] Examples of the bridged heterocycloalkyl group include azabicyclo[2.2.1]heptyl, oxazabicyclo[2.2.1]heptyl, thiazabicyclo[2.2.1]heptyl, diazabicyclo[2.2.1]heptyl, azabicyclo[2.2.2]octyl, diazabicyclo[2.2.2]octyl, oxazabicyclo[2.2.2]octyl, thiazabicyclo[2.2.2]octyl, azabicyclo[3.2.1]octyl, diazabicyclo[3.2.1]octyl, oxazabicyclo[3.2.1]octyl, thiazabicyclo[3.2.1] octyl, azabicyclo[3.3.1]nonyl, diazabicyclo[3.3.1]nonyl, oxazabicyclo[3.3.1]nonyl, thiazabicyclo[3.3.1]nonyl, azabicyclo[4.2.1]nonyl, diazabicyclo[4.2.1]nonyl, oxazabicyclo[4.2.1]nonyl, thiazabicyclo[4.2.1]nonyl, azabicyclo[3.3.2]decyl, diazabicyclo[3.3.2]decyl, oxazabicyclo[3.3.2]decyl, thiazabicyclo[3.3.2]decyl or azabicyclo[4.2.2]decyl.

[0159] The term "bicyclic nitrogen-containing 5-11 membered heterocycloalkyl" means a 5-11 membered heterospirocycloalkyl, a 5-11 membered fused heterocycloalkyl or a 5-11 membered bridged heterocycloalkyl group as defined above, with the proviso that it contains one ring nitrogen atom and optionally one or two additional ring heteroatoms from the N, O and S series; said bicyclic nitrogen-containing 5-11 membered heterocycloalkyl group can be attached to the remainder of the molecule via the nitrogen atom or any one of the carbon atoms excluding the spiro carbon atom.

[0160] The term "heteroaryl" means a monovalent monocyclic or bicyclic aromatic ring having 5, 6, 8, 9 or 10 ring atoms (a "5-10 membered heteroaryl" group), containing at least one ring heteroatom and optionally containing 1, 2 or 3 additional ring heteroatoms from the series: N, O and / or S, bonded via a ring carbon atom or, where valency allows, via a nitrogen atom, for example, in pyrrol-1-yl.

[0161] The heteroaryl group can be, for example, a 5-membered heteroaryl group such as thienyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, or tetrazolyl; or a 6-membered heteroaryl group such as, for example, pyridinyl (also referred to herein as pyridyl), pyridazinyl, pyrimidinyl, pyrazinyl, or triazinyl; or a 9-membered heteroaryl group such as, for example, benzofuranyl, benzothienyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, benzothiazolyl, benzotriazolyl, thiazolopyridinyl, indazolyl, indolyl, isoindolyl, indolizinyl, or purinyl; or a 10-membered heteroaryl group such as, for example, quinolinyl, quinazolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, or pteridinyl.

[0162] In general, unless otherwise specified, a heteroaryl or heteroarylene group includes all possible isomeric forms thereof, such as tautomers and positional isomers with respect to the point of attachment to the rest of the molecule. Thus, in some illustrative, non-limiting examples, the term pyridinyl includes pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl; or the term thienyl includes thien-2-yl and thien-3-yl.

[0163] The term "C1-C6" as used herein means an alkyl group having a finite number of carbon atoms from 1 to 6, i.e., 1, 2, 3, 4, 5 or 6 carbon atoms, for example in the definition of "C1-C6-alkyl", "C1-C6-haloalkyl", "C1-C6-hydroxyalkyl", "C1-C6-alkoxy" or "C1-C6-haloalkoxy".

[0164] Furthermore, as used herein, the term "C3-C7" as used herein, for example in the definition "C3-C7-cycloalkyl", refers to a cycloalkyl group having a finite number of carbon atoms from 3 to 7, i.e., 3, 4, 5, 6 or 7 carbon atoms.

[0165] When a range of values ​​is given, said range includes each value and sub-range within said range.

[0166] for example: "C1-C6" means C1, C2, C3, C4, C5, C6, C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, C2-C6 , including C2-C5, C2-C4, C2-C3, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6; "C2-C6" encompasses C2, C3, C4, C5, C6, C2-C6, C2-C5, C2-C4, C2-C3, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6; "C3-C6" includes C3, C4, C5, C6, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6.

[0167] As used herein, the term "leaving group" refers to an atom or group of atoms that displaces a bonding electron to form a stable species in a chemical reaction. In particular, such leaving groups are selected from the group consisting of halogen atoms, particularly fluorine, chlorine, bromine, or iodine atoms (substituted as halides, particularly fluoride, chloride, bromide, or iodide); (methylsulfonyl)oxy, [(trifluoromethyl)sulfonyl]oxy, [(nonafluorobutyl)sulfonyl]oxy, (phenylsulfonyl)oxy, [(4-methylphenyl)sulfonyl]oxy, [(4-bromophenyl)sulfonyl]oxy, [(4-nitrophenyl)sulfonyl]oxy, [(2-nitrophenyl)sulfonyl]oxy, [(4-isopropylphenyl)sulfonyl]oxy, [(2,4,6-triisopropylphenyl)sulfonyl]oxy, [(2,4,6-trimethylphenyl)sulfonyl]oxy, [(4-tert-butylphenyl)sulfonyl]oxy, and [(4-methoxyphenyl)sulfonyl]oxy.

[0168] As used herein, the term "dipolar aprotic solvent" refers to a solvent selected from acetone, acetonitrile, propionitrile, dimethyl sulfoxide, diethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N,N-diethylformamide, N,N-diethylacetamide, 1-methyl-2-pyrrolidinone, 1-ethyl-2-pyrrolidinone, 1-methyl-2-piperidinone, and 1-ethyl-2-piperidinone, or a mixture thereof. In particular, the dipolar aprotic solvent is acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, or 1-methyl-2-pyrrolidinone.

[0169] As used herein, the term "room temperature" means a temperature in the range of 15°C to 25°C.

[0170] Further definition of DGK inhibitors As used herein, the term "one or more", e.g., in the definition of substituents of DGK inhibitors of the general formula of the invention, is understood to mean "1, 2, 3, 4 or 5, in particular 1, 2, 3 or 4, more in particular 1, 2 or 3, even more in particular 1 or 2".

[0171] The definition of each DGK inhibitor of formula (I) or (II) also includes all suitable isotopic variants of each DGK inhibitor of formula (I) or (II).Therefore, "isotopic variant" is defined as at least one atom having the same atomic number but replaced by an atom having an atomic mass different from the atomic mass usually or predominantly found in nature.Isotopes that can be incorporated into the DGK inhibitor of formula (I) or (II) include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine and iodine, for example, 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, 129 I and 131 Specific isotopic variants of the DGK inhibitors of formula (I) or (II), such as 3 H or 14 Those incorporating one or more radioactive isotopes, such as C, are useful for drug and / or substrate tissue distribution studies. Tritiated and carbon-14, i.e. 14C isotopes are particularly preferred because of their ease of preparation and detectability.In addition, substitution with isotopes such as deuterium can provide certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements, and therefore may be preferred in some circumstances.The isotopic variant of the DGK inhibitor of formula (I) or (II) can generally be prepared by conventional procedures known to those skilled in the art, for example, by exemplary method or by the preparation described in the following examples using suitable isotopic variations of suitable reagents.

[0172] When the plural of the terms compounds, salts, polymorphs, hydrates, solvates, etc. is used herein, this is taken to mean a single compound, salt, polymorph, isomer, hydrate, solvate, etc.

[0173] The DGK inhibitors of formula (I) and (II) may contain one or more asymmetric centers depending on the position and nature of the various desired substituents. The asymmetric carbon atoms may be in the (R) or (S) configuration, resulting in a racemic mixture in the case of a single asymmetric center, and a diastereomeric mixture in the case of multiple asymmetric centers. In certain instances, asymmetry may also exist due to restricted rotation around a given bond, for example, the central bond adjacent to the two substituted aromatic rings of a particular compound.

[0174] Substituents on the ring may also be present in either cis or trans form, and all such configurations (including enantiomers and diastereomers) are intended to be included within the definition of each DGK inhibitor.

[0175] Preferred DGK inhibitors of formula (I) and (II) are those that produce more desirable biological activity. Separate, pure or partially purified isomers and stereoisomers or racemic or diastereomeric mixtures of DGK inhibitors of formula (I) and (II) are also included within the scope of the present invention. Purification and separation of such materials can be achieved by standard techniques known in the art.

[0176] Optical isomers can be obtained by resolving racemic mixtures according to conventional methods, for example, by forming diastereomeric salts or covalent diastereomers with optically active acids or bases. Examples of suitable acids are tartaric acid, diacetyltartaric acid, ditoluoyltartaric acid, and camphorsulfonic acid. Mixtures of diastereoisomers can be separated into their individual diastereomers based on their physical and / or chemical differences by methods known in the art, such as chromatography or fractional crystallization. The optically active base or acid is then liberated from the separated diastereomeric salts. Different methods for separating optical isomers involve the use of chiral chromatography (e.g., chiral HPLC columns) with or without conventional derivatization, optimally selected to maximize the separation of the enantiomers. Suitable chiral HPLC columns are manufactured by Daicel, including Chiracel OD and Chiracel OJ, all of which are routinely selectable. Enzymatic separation, with or without derivatization, is also useful. The optically active compounds of this invention can also be obtained by chiral syntheses utilizing optically active starting materials.

[0177] To define different types of isomers, reference is made to IUPAC Rules Section E (Pure Appl Chem 45, 11-30, 1976).

[0178] The definition of DGK inhibitors described in accordance with the present invention includes, but is not limited to, all possible stereoisomers of the DGK inhibitors of formula (I) and (II), either as a single stereoisomer or as any mixture of said stereoisomers in any ratio, for example, R- or S-isomers, or E- or Z-isomers. The isolation of a single stereoisomer of the DGK inhibitors of formula (I) or (II), for example, a single enantiomer or a single diastereomer, can be achieved by any suitable state-of-the-art method, such as chromatography, in particular chiral chromatography.

[0179] Additionally, some of the DGK inhibitors of formula (I) and (II) can exist as "tautomers." For example, the DGK inhibitors of the present invention can contain a pyridone moiety and can exist as a pyridone, as a hydroxypyridine, or as any amount of the two tautomers, i.e., [ka] It can exist as a mixture of

[0180] This definition of DGK inhibitor includes, but is not limited to, all possible tautomers of the DGK inhibitors of formula (I) and (II), either as single tautomers or as any mixture of said tautomers, in any ratio.

[0181] Additionally, the DGK inhibitors of formula (I) and (II) can exist as "N-oxides," which are defined as compounds of the present invention in which at least one nitrogen is oxidized. The combinations of the present invention include, but are not limited to, all such possible N-oxides of the DGK inhibitors of formula (I) and (II).

[0182] This definition of DGK inhibitor also relates to useful forms of the DGK inhibitors of formula (I) and (II) disclosed herein, such as metabolites, hydrates, solvates, prodrugs, salts, particularly pharmaceutically acceptable salts, and coprecipitates.

[0183] The DGK inhibitors of formula (I) and (II) can exist as "hydrates" or "solvates", where the compounds described herein contain polar solvents, particularly water, methanol or ethanol, as structural elements of the crystalline lattice of the compounds. The amount of polar solvent, particularly water, can be stoichiometric or non-stoichiometric. In the case of stoichiometric solvates, for example, in the case of hydrates, hemi-, (semi-), mono-, sesqui-, di-, tri-, tetra-, penta-, etc. solvates or hydrates are possible. The DGK inhibitors of formula (I) and (II) include all such hydrates or solvates.

[0184] Furthermore, the DGK inhibitors of formula (I) and (II) can exist in free form, for example as a free base, or as a free acid, or as a zwitterion, or in the form of a salt, which can be any salt, either organic or inorganic, particularly any pharmaceutically acceptable organic or inorganic addition salt conventionally used in pharmacy.

[0185] The DGK inhibitors of formula (I) and (II) include all possible salts of the DGK inhibitors of formula (I) and (II), either as a single salt or as any mixture of said salts in any ratio.

[0186] The term "pharmaceutically acceptable salts" of the DGK inhibitors of formula (I) and (II) refers to relatively non-toxic inorganic or organic acid addition salts of the compounds of the present invention. See, for example, S.M. Berge et al., "Pharmaceutical Salts," J.Pharm.Sci. 1977, 66, 1-19. Pharmaceutically acceptable salts include salts obtained by reacting the main compound, which functions as a base, with an inorganic or organic acid to form salts, such as salts of hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid, camphorsulfonic acid, oxalic acid, maleic acid, succinic acid, and citric acid. Pharmaceutically acceptable salts also include salts obtained by reacting the main compound, which functions as an acid, with a suitable base to form, for example, sodium, potassium, calcium, magnesium, ammonium, and chloride salts. Those skilled in the art will further recognize that acid addition salts of the claimed compounds can be prepared by reacting the compound with a suitable inorganic or organic acid via any of a number of known methods. Alternatively, alkali and alkaline earth metal salts of acidic compounds of the invention are prepared by reacting the compounds of the invention with the appropriate base via a variety of known methods.

[0187] Representative salts of the DGK inhibitors of formula (I) and (II) include the conventional non-toxic salts and the quaternary ammonium salts formed, for example, from inorganic or organic acids or bases by means well known in the art. For example, such acid addition salts include acetate, adipate, alginate, ascorbate, aspartate, benzoate, benzenesulfonate, bisulfite, butyrate, citrate, camphorate, camphorsulfonate, cinnamate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, fumarate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, chloride, iodide, 2-hydroxyethanesulfonate, itaconate, lactate, maleate, mandelate, 2-hydroxyethanesulfonate, nicotinate, nitrate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, sulfonate, sulfate, tartrate, thiocyanate, tosylate, and undecanoate salts.

[0188] Base salts include alkali metal salts such as potassium and sodium salts, alkaline earth metal salts such as calcium and magnesium salts, and ammonium salts with organic bases such as dicyclohexylamine and N-methyl-D-glucamine. Additionally, basic nitrogen-containing groups can be quaternized with agents such as lower alkyl halides such as methyl, ethyl, propyl, or butyl chlorides, bromides, and iodides; dialkyl sulfates such as dimethyl, diethyl, dibutyl sulfate, or diamyl sulfate; long-chain halides such as decyl, lauryl, myristyl, and stearyl chlorides, bromides, and iodides; and aralkyl halides such as benzyl and phenethyl bromides.

[0189] Furthermore, the DGK inhibitors of formula (I) and (II) include all possible crystalline forms or polymorphs of the DGK inhibitors of formula (I) and (II), either as a single polymorph or as a mixture of two or more polymorphs in any ratio.

[0190] When the radicals in the DGK inhibitors of formula (I) and (II) are substituted, they may be mono- or polysubstituted unless otherwise specified. In the DGK inhibitors of formula (I) and (II), all radicals that occur more than once are defined independently of each other. Substitution with one, two or three identical or different substituents is preferred.

[0191] Inhibitors of DGKalpha and DGKzeta Below, DGKalpha inhibitors and DGKzeta inhibitors that can be preferably used in the present invention according to any one of embodiment 1, embodiment 2, embodiment 3, embodiment 4, embodiment 5, embodiment 6, embodiment 7, embodiment 8 or embodiment 9 of the present invention are described. Hereinafter, the terms "DGKalpha inhibitors" and "DGKalpha inhibitors" are used interchangeably. Similarly, below, the terms "DGKzeta inhibitors" and "DGKzeta inhibitors" are used interchangeably.

[0192] Inhibitors of DGK have been previously disclosed as described above.

[0193] Two members of the DGK family, DGKalpha and DGKzeta, specifically regulate the pool of DAG produced as a second messenger after T cell receptor (TCR) stimulation, and therefore inhibitors of these two members are desirable.

[0194] Furthermore, as used herein, the term "DGK inhibitor" refers to a compound that inhibits one or more isoforms of DGK. A DGKalpha inhibitor may inhibit the DGKalpha isoform and be a selective DGKalpha inhibitor, or may inhibit other DGK isoforms, such as DGKzeta, in addition to its DGKalpha inhibitory activity. Similarly, a DGKzeta inhibitor may inhibit the DGKzeta isoform and be a selective DGKzeta inhibitor, or may inhibit other DGK isoforms, such as DGKalpha, in addition to its DGKzeta inhibitory activity. In the present invention, a DGKalpha inhibitor is preferably selective for DGKzeta, and a DGKzeta inhibitor is preferably selective for DGKalpha.

[0195] More preferably, inhibitors of DGKalpha are characterized by a selectivity of 20-fold or more with respect to DGKzeta, i.e., an IC of 10 or more for DGKalpha in, for example, the in vitro assay described in the experimental section. 50 20-fold higher IC against DGKzeta compared to the titer 50 and inhibitors of DGKzeta are characterized by a selectivity of 20-fold or more with respect to DGKalpha, i.e., an IC of 10 or more for DGKzeta in the in vitro assay described, for example, in the experimental section. 50 20-fold higher IC against DGKalpha compared to the titer 50 It is characterized by value.

[0196] More preferably, the inhibitor of DGKalpha is characterized by a selectivity of 20-fold or more with respect to DGKzeta, i.e., an IC of 20-fold or more for DGKalpha in the in vitro assay described, for example, in the experimental section. 50 Compared with the IC value, the IC for DGKzeta was 100-fold higher 50 and inhibitors of DGKzeta are characterized by a selectivity of 100-fold or more with respect to DGKalpha, i.e., an IC value of 100 or more for DGKzeta in the in vitro assay described, for example, in the experimental section.50 IC value of 100-fold higher against DGKalpha compared to 50 Characterized by value.

[0197] The compounds of general formula (I) used herein are typically DGKalpha inhibitors, and the compounds of general formula (II) used herein are typically DGKzeta inhibitors.As shown below, particularly preferred DGKalpha inhibitor A is characterized by a selectivity of more than 100 times compared to DGKzeta, and particularly preferred DGKzeta inhibitor A' is characterized by a selectivity of more than 100 times compared to DGKalpha.

[0198] DGKalpha inhibitors DGKalpha Inhibitor Embodiment A Below, DGKalpha inhibitors that can be preferably used in the present invention according to any one of embodiment 1, embodiment 2, embodiment 3, embodiment 4, embodiment 5, embodiment 6, embodiment 7, embodiment 8 or embodiment 9 of the present invention are described.

[0199] In some embodiments of the present invention, the inhibitor of DGKalpha has formula (I): [ka] [During the ceremony: R 1 are cyano, -C(=O)NH2, -C(=O)N(H)CH3, -C(=O)N(H)C2H5, -C(=O)N(CH3)2 and -C(=O)OR 15 represents a group selected from R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl; wherein the 5- to 10-membered heteroaryl group is bonded to the remainder of the molecule through a carbon atom of the 5- to 10-membered heteroaryl group. and wherein phenyl, naphthyl and 5- to 10-membered heteroaryl groups may be substituted one, two, three or four times, each substituent independently being a halogen atom or C-C-alkyl, C-C-cycloalkyl, C-C-hydroxyalkyl, C-C-haloalkyl, (C-C-alkoxy)-(C-C-alkyl)-, C-C-alkoxy, (C-C-alkoxy)-(C-C-alkoxy)-, C-C-haloalkoxy, C-C-cycloalkyloxy, phenoxy, -SR 14 , -S(=O)R 14 , -S(=O)2R 14 , -P(=O)(R 14 )2, cyano, hydroxy, -N(R 9 )(R 10 ), -C(=O)N(R 9 )(R 10 ), -C(=O)R 11 , -N(R 12 )C(=O)R 13 , -N(R 12 )S(=O)2R 14 , -N=S(=NH)(R 14 )2, -N=S(=O)(R 14 )2, 4-7 membered heterocycloalkyl, 5-7 membered heterocycloalkenyl, (4-7 membered heterocycloalkyl)oxy, phenyl, and 5- or 6-membered heteroaryl; or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are -(CH2)3-, -CH2-CH(OH)-CH2-, -(CH2)4-, -O-(CH2)2-, -(CH2)2-O-, -CH2-CH(CH3)-O-, -CH2-O-CH2-, -O-(CH2)3-, -(CH2)3-O-, -CH2-O-(CH2)2-, -(CH2)2-O-CH2-, -O-CH2-O-, -OC(CH3)2-O-, -O-(CH2)2-O-, -N(R 18 )-C(=O)-(C(R 18 )(R 19 )) m -, -N(R 18 )-C(=O)-(C(CH2)3)-, -N(R 18)-(C(R 18 )(R 19 )) m -, -N(R 18 )-C(=O)-O and -N(R 18 )-C(=O)-N(R 18 )-, wherein the 4- to 7-membered heterocycloalkyl group and the 5- to 7-membered heterocycloalkenyl group are attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group and the 5- to 7-membered heterocycloalkenyl group; and wherein the 4- to 7-membered heterocycloalkyl group, the 5- to 7-membered heterocycloalkenyl group and the (4- to 7-membered heterocycloalkyl)oxy group may be substituted one, two or three times, and each substituent independently represents a halogen atom or a C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl, -N(R 9 )(R 10 ) and oxo, and wherein the C1-C6-alkyl and C1-C6-alkoxy groups may be substituted by groups selected from C3-C4-cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl, wherein the 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group; and wherein the 4- to 7-membered heterocycloalkyl group may be substituted one, two or three times, and each substituent independently represents a halogen atom or C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl, -N(R 9 )(R 10 ) and oxo, and wherein the phenyl group may be substituted one or two times, each substituent independently being a halogen atom or C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl and -N(R 9 )(R 10 ) selected from the group selected from and wherein the C3-C4-cycloalkyl group may be substituted once or twice, and each substituent is independently selected from a halogen atom or a group selected from cyano and hydroxy, and wherein the C3-C6-cycloalkyl group may be substituted once or twice, and each substituent is independently selected from a halogen atom or a C1-C4-alkyl group; and wherein the phenyl, phenoxy and 5- or 6-membered heteroaryl groups may be substituted once or twice, each substituent independently being a halogen atom or C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl and -N(R 9 )(R 10 ) selected from the group selected from R 3 represents a hydrogen atom, a halogen atom, or C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C4-C6-cycloalkenyl, C1-C6-hydroxyalkyl, C1-C6-haloalkyl, (C1-C2-alkoxy)-(C1-C6-alkyl)-, C1-C6-alkoxy, (C1-C2-alkoxy)-(C1-C6-alkoxy)-, C1-C4-haloalkoxy, C3-C6-cycloalkyloxy, phenoxy, -SR 14 , -S(=O)R 14 , -S(=O)2R 14 , cyano, hydroxy, -N(R 9 )(R 10 ), -C(=O)N(R 9 )(R 10 ), -C(=O)R 11, -N(R 12 )C(=O)R 13 , -N(R 12 )S(=O)2R 14 , -N=S(=NH)(R 14 )2, -N=S(=O)(R 14 )2, -P(=O)(R 14 )2, represents a group selected from 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl, and 5- or 6-membered heteroaryl; wherein the 4- to 7-membered heterocycloalkyl group and the 5- to 7-membered heterocycloalkenyl group are attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group and the 5- to 7-membered heterocycloalkenyl group; and wherein the 4- to 7-membered heterocycloalkyl group, the 5- to 7-membered heterocycloalkenyl group and the (4- to 7-membered heterocycloalkyl)oxy group may be substituted one, two or three times, and each substituent independently represents a halogen atom or a C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl, -N(R 9 )(R 10 ) and oxo, and wherein the C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl and C1-C6-alkoxy groups are optionally substituted by groups selected from C3-C4-cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl, wherein the 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group; and wherein the 4- to 7-membered heterocycloalkyl group may be substituted one, two or three times, and each substituent independently represents a halogen atom or C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl, -N(R 9 )(R10 ) and oxo, and wherein the phenyl group may be substituted one or two times, each substituent independently being a halogen atom or C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl and -N(R 9 )(R 10 ) selected from the group selected from and wherein the C3-C4-cycloalkyl group may be substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from cyano and hydroxy, and wherein the C2-C6-alkenyl group may be substituted by a C1-C4-haloalkyl group, and wherein the C3-C6-cycloalkyl and C4-C6-cycloalkenyl groups may be substituted one or two times, each substituent being independently selected from a halogen atom or a group selected from C1-C4-alkyl and C1-C4-haloalkyl; and wherein the phenyl, phenoxy and 5- or 6-membered heteroaryl groups may be substituted once or twice, each substituent independently being a halogen atom or C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl and -N(R 9 )(R 10 ) selected from the group selected from R 4represents a hydrogen atom, a halogen atom, or C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C4-C6-cycloalkenyl, C1-C6-hydroxyalkyl, C1-C6-haloalkyl, (C1-C2-alkoxy)-(C1-C6-alkyl)-, C1-C6-alkoxy, (C1-C2-alkoxy)-(C1-C6-alkoxy)-, C1-C4-haloalkoxy, -O-(C1-C4-alkyl)-C(=O)OR 15 , -O-(C1-C4-alkyl)-C(=O)N(R 9 )(R 10 ), C3-C6-cycloalkyloxy, -S(=O)R 14 , -S(=O)2R 14 , cyano, nitro, hydroxy, -N(R 9 )(R 10 ), -N(R 16 )(R 17 ), -N(R 16 )(R 20 ), -C(=O)N(R 9 )(R 10 ), -C(=O)R 11 , -N(R 12 )C(=O)R 13 , -N(R 12 )S(=O)2R 14 , -N=S(=NH)(R 14 )2, -N=S(=O)(R 14 )2, -P(=O)(R 14 )2, represents a group selected from 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl, and 5- or 6-membered heteroaryl; wherein the 4- to 7-membered heterocycloalkyl group and the 5- to 7-membered heterocycloalkenyl group are attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group and the 5- to 7-membered heterocycloalkenyl group; and wherein the 4- to 7-membered heterocycloalkyl group, the 5- to 7-membered heterocycloalkenyl group and the (4- to 7-membered heterocycloalkyl)oxy group may be substituted one, two or three times, and each substituent independently represents a halogen atom or a C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl, -N(R 9 )(R 10 ) and oxo, and wherein the C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl and C1-C6-alkoxy groups may be substituted by groups selected from C3-C4-cycloalkyl and 4- to 7-membered heterocycloalkyl, wherein the 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group; and wherein the 4- to 7-membered heterocycloalkyl group may be substituted one, two or three times, and each substituent independently represents a halogen atom or C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl, -N(R 9 )(R 10 ) and oxo, and wherein the phenyl group may be substituted one or two times, each substituent independently being a halogen atom or C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl and -N(R 9 )(R 10 ) selected from the group selected from and wherein the C3-C4-cycloalkyl group may be substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from cyano and hydroxy, and wherein the C1-C6-alkoxy group may be substituted with an oxiran-2-yl group, and wherein the C3-C6-cycloalkyl and C4-C6-cycloalkenyl groups may be substituted one or two times, each substituent being independently selected from a halogen atom or a C1-C4-alkyl group; and wherein the phenyl and 5- or 6-membered heteroaryl groups may be substituted one or two times, each substituent independently being a halogen atom or C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl and -N(R 9 )(R 10 ) selected from the group selected from R 5 represents a hydrogen atom, a halogen atom, or C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C4-C6-cycloalkenyl, C1-C6-hydroxyalkyl, C1-C6-haloalkyl, (C1-C2-alkoxy)-(C1-C6-alkyl)-, C1-C6-alkoxy, (C1-C2-alkoxy)-(C2-C6-alkoxy)-, C1-C4-haloalkoxy, C3-C6-cycloalkyloxy, phenoxy, -SR 14 , -S(=O)R 14 , -S(=O)2R 14 , cyano, hydroxy, -N(R 9 )(R 10 ), -C(=O)N(R 9 )(R 10 ), -C(=O)R 11 , -N(R 12 )C(=O)R 13 , -N(R 12 )S(=O)2R 14 , -N=S(=NH)(R 14 )2, -N=S(=O)(R 14 )2, -P(=O)(R 14)2, represents a group selected from 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl, and 5- or 6-membered heteroaryl; wherein the 4- to 7-membered heterocycloalkyl group and the 5- to 7-membered heterocycloalkenyl group are attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group and the 5- to 7-membered heterocycloalkenyl group; and wherein the 4- to 7-membered heterocycloalkyl group, the 5- to 7-membered heterocycloalkenyl group and the (4- to 7-membered heterocycloalkyl)oxy group may be substituted one, two or three times, and each substituent independently represents a halogen atom or a C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl, -N(R 9 )(R 10 ) and oxo, and wherein the C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl and C1-C6-alkoxy groups are optionally substituted by groups selected from C3-C4-cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl, wherein the 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group; and wherein the 4- to 7-membered heterocycloalkyl group may be substituted one, two or three times, and each substituent independently represents a halogen atom or C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl, -N(R 9 )(R 10 ) and oxo, and wherein the phenyl group may be substituted one or two times, each substituent independently being a halogen atom or C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl and -N(R 9 )(R 10 ) selected from the group selected from and wherein the C3-C4-cycloalkyl group may be substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from cyano and hydroxy; and wherein the C3-C6-cycloalkyl and C4-C6-cycloalkenyl groups may be substituted one or two times, each substituent being independently selected from a halogen atom or a C1-C4-alkyl group; and wherein the phenyl, phenoxy and 5- or 6-membered heteroaryl groups may be substituted one or two times, each substituent independently being a halogen atom or C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl and -N(R 9 )(R 10 ) selected from the group selected from R 6 represents a hydrogen atom, a fluorine atom or a group selected from C1-C4-alkyl, C1-C4-hydroxyalkyl, C1-C4-alkoxy, hydroxy and oxo, R 7 represents a hydrogen atom, a halogen atom or a group selected from C1-C4-alkyl, C1-C4-alkoxy, hydroxy and cyano, R 8 represents a group selected from methyl and ethyl, R 9 and R 10each independently represent a hydrogen atom or a group selected from C-C-alkyl, C-C-hydroxyalkyl, N≡C—(C-C-alkyl)-, (C-C-alkoxy)-(C-C-alkyl)-, C-C-cycloalkyl and C-C-haloalkyl, or R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen-containing 4- to 7-membered heterocycloalkyl group; wherein the nitrogen-containing 4- to 7-membered heterocycloalkyl group may be substituted one, two or three times, each substituent being independently selected from a halogen atom or a group selected from C1-C4-alkyl, C3-C4-cycloalkyl, hydroxy and oxo; or two substituents bonded to the same carbon atom of the nitrogen-containing 4- to 7-membered heterocycloalkyl group, taken together with the carbon atom to which they are bonded, form a 4- to 7-membered heterocycloalkyl group; wherein the 4- to 7-membered heterocycloalkyl group may be substituted once or twice, and each substituent is independently selected from a halogen atom or a group selected from C-C-alkyl, C-C-cycloalkyl, C-C-haloalkyl, hydroxy and oxo; R 11 represents a hydrogen atom or a group selected from C1-C4-alkyl, C1-C4-hydroxyalkyl, C1-C4-haloalkyl, phenyl and 5- or 6-membered heteroaryl, wherein the phenyl group and the 5- or 6-membered heteroaryl group may be substituted once or twice, each substituent independently being a halogen atom or C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl and -N(R 9 )(R 10 ) selected from the group selected from R 12 represents a hydrogen atom or a C1-C4-alkyl group, R 13represents a hydrogen atom or a group selected from C1-C6-alkyl, phenyl and 5- or 6-membered heteroaryl, wherein the phenyl group and the 5- or 6-membered heteroaryl group may be substituted once or twice, each substituent independently being a halogen atom or C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl and -N(R 9 )(R 10 ) selected from the group selected from R 14 represents a group selected from C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, phenyl and 5- or 6-membered heteroaryl, wherein the phenyl group and the 5- or 6-membered heteroaryl group may be substituted once or twice, each substituent independently being a halogen atom or C-C-alkyl, C-C-haloalkyl, cyano, hydroxy, C-C-alkoxy, C-C-cycloalkyl and -N(R 9 )(R 10 ) selected from the group selected from R 15 represents a hydrogen atom or a C1-C4-alkyl group, R 16 represents a hydrogen atom or a group selected from C1-C4-alkyl, C3-C4-cycloalkyl and C2-C4-haloalkyl, R 17 represents a 4- to 7-membered heterocycloalkyl group, wherein the 4- to 7-membered heterocycloalkyl group may be substituted one, two or three times, each substituent being independently selected from a halogen atom or a group selected from C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-alkoxy, hydroxy and oxo, and wherein the 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group; R 18represents a hydrogen atom or a group selected from methyl and ethyl, R 19 represents a hydrogen atom or a group selected from methyl and ethyl, R 20 represents a (4- to 7-membered heterocycloalkyl)-(C1-C4-alkyl) group, wherein the (4- to 7-membered heterocycloalkyl) part of said group may be substituted one, two or three times, and each substituent is independently selected from a halogen atom or a group selected from C-C-alkyl, C-C-cycloalkyl, C-C-alkoxy, hydroxy and oxo; m represents an integer selected from 1, 2 and 3; and n represents an integer selected from 1, 2 and 3. or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0200] In a preferred embodiment, at least one inhibitor of DGKalpha is characterized by formula (I) with the limitations defined under this heading.

[0201] DGKalpha inhibitor embodiment B In some other embodiments of the present invention, the inhibitor of DGKalpha is represented by formula (I) above. [During the ceremony, R 1 represents a group selected from cyano, —C(═O)NH2, —C(═O)N(H)CH3 and —C(═O)N(CH3)2, R 2 represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl; wherein the 5- to 10-membered heteroaryl group is attached to the remainder of the molecule through a carbon atom of said 5- to 10-membered heteroaryl group; and where phenyl, naphthyl and 5- to 10-membered heteroaryl groups may be substituted one, two, three or four times, each substituent independently being a halogen atom or C-C-alkyl, C-C-cycloalkyl, C-C-haloalkyl, (C-C-alkoxy)-(C-C-alkyl)-, C-C-alkoxy, C-C-haloalkoxy, phenoxy, -S(=O)R 14 , -P(=O)(R 14 )2, cyano, hydroxy, -N(R 9 )(R 10 ), -C(=O)N(R 9 )(R 10 ), -C(=O)R 11 , -N(R 12 )C(=O)R 13 , -N(R 12 )S(=O)2R 14 , -N=S(=O)(R 14 ) selected from groups selected from 2, 4 to 7 membered heterocycloalkyl, phenyl and 5 or 6 membered heteroaryl; or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are -CH2-CH(OH)-CH2-, -CH2-CH(CH3)-O-, -OC(CH3)2-O-, -N(R 18 )-C(=O)-(C(R 18 )(R 19 )) m -, -N(R 18 )-C(=O)-(C(CH2)3)-, -N(R 18 )-(C(R 18 )(R 19 )) m -, -N(R 18 )-C(=O)-O- and -N(R 18 )-C(=O)-N(R 18 )-, wherein the 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group; and wherein the C1-C4-alkoxy group is optionally substituted with a group selected from 4- to 7-membered heterocycloalkyl and phenyl; wherein the 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group; and wherein the phenyl and 5- or 6-membered heteroaryl groups are optionally substituted one or two times, each substituent being independently selected from a halogen atom or a group selected from C1-C2-alkyl, C1-C2-haloalkyl and C1-C2-alkoxy; R 3 is a hydrogen atom, a halogen atom or C1-C6-alkyl, C2-C4-alkenyl, C3-C5-cycloalkyl, (C1-C2-alkoxy)-(C1-C4-alkyl)-, C1-C4-alkoxy, C1-C4-haloalkoxy, C3-C5-cycloalkyloxy, -S(=O)2R 14 , cyano, hydroxy, -N(R 9 )(R 10 ), -C(=O)N(R 9 )(R 10 ), -P(=O)(R 14 )2, 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, and phenyl; wherein the 4- to 7-membered heterocycloalkyl group and the 5- to 7-membered heterocycloalkenyl group are attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group and the 5- to 7-membered heterocycloalkenyl group; and wherein the C1-C6-alkyl and C1-C4-alkoxy groups may be substituted by groups selected from C3-C4-cycloalkyl and 4- to 7-membered heterocycloalkyl, wherein the 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group; and wherein the C3-C4-cycloalkyl group is optionally substituted once or twice by a cyano group, and wherein the C2-C4-alkenyl group may be substituted with a C1-C4-haloalkyl group, and wherein the C3-C5-cycloalkyl group is optionally substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from C1-C4-alkyl and C1-C4-haloalkyl, R 4 represents a hydrogen atom, a halogen atom, or C1-C6-alkyl, C1-C6-haloalkyl, C3-C5-cycloalkyl, (C1-C2-alkoxy)-(C1-C4-alkyl)-, C1-C4-alkoxy, (C1-C2-alkoxy)-(C1-C4-alkoxy)-, -O-(C1-C4-alkyl)-C(=O)OR 15 , -O-(C1-C4-alkyl)-C(=O)N(R 9 )(R 10 ), C3-C5-cycloalkyloxy, -S(=O)2R 14 , cyano, nitro, hydroxy, -N(R 9 )(R 10 ), -N(R 16 )(R 17 ), -N(R 16 )(R 20 ), -N=S(=NH)(R 14 )2, -N=S(=O)(R 14 )2, -P(=O)(R 14 )2, 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, and phenyl; wherein the 4- to 7-membered heterocycloalkyl group and the 5- to 7-membered heterocycloalkenyl group are attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group and the 5- to 7-membered heterocycloalkenyl group; and wherein the C1-C6-alkyl and C1-C4-alkoxy groups may be substituted by groups selected from C3-C4-cycloalkyl and 4- to 7-membered heterocycloalkyl, wherein the 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group; and wherein the C3-C4-cycloalkyl group may be substituted one or two times, and each substituent is independently selected from a halogen atom or a group selected from cyano and hydroxy, and wherein the C1-C4-alkoxy group may be substituted with an oxiran-2-yl group, and wherein said C3-C5-cycloalkyl may be substituted one or two times, each substituent being independently selected from a halogen atom or a C1-C4-alkyl group; R 5 is a hydrogen atom, a halogen atom, or C1-C5-alkyl, C3-C5-cycloalkyl, C1-C4-alkoxy, C3-C5-cycloalkyloxy, -S(=O)2R 14 , cyano, hydroxy, -N(R 9 )(R 10 ), 4- to 7-membered heterocycloalkyl, and (4- to 7-membered heterocycloalkyl)oxy; wherein the 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group; R 6 represents a hydrogen atom or a group selected from C1-C4-alkyl and C1-C4-hydroxyalkyl, R 7 represents a hydrogen atom, a halogen atom or a group selected from C1-C4-alkyl, C1-C4-alkoxy and hydroxy, R 8 represents a group selected from methyl and ethyl, R 9 and R 10each independently represent a hydrogen atom or a group selected from C-C-alkyl, C-C-hydroxyalkyl, N≡C—(C-C-alkyl)-, (C-C-alkoxy)-(C-C-alkyl)- and C-C-cycloalkyl, or R 9 and R 10 together with the nitrogen to which they are attached represent a nitrogen-containing 4- to 7-membered heterocycloalkyl group; wherein the nitrogen-containing 4- to 7-membered heterocycloalkyl group may be substituted one, two or three times, each substituent being independently selected from a halogen atom or a group selected from C1-C4-alkyl, hydroxy and oxo; or two substituents bonded to the same carbon atom of the nitrogen-containing 4- to 7-membered heterocycloalkyl group, taken together with the carbon atom to which they are bonded, form a 4- to 7-membered heterocycloalkyl group; wherein the 4-7-membered heterocycloalkyl group is optionally substituted once or twice with a C1-C4-alkyl group, R 11 represents a group selected from C1-C4-alkyl and C1-C4-haloalkyl, R 12 represents a hydrogen atom, R 13 represents a phenyl group, R 14 represents a group selected from C1-C4-alkyl and phenyl, R 15 represents a hydrogen atom or a C1-C4-alkyl group, R 16 represents a hydrogen atom or a C1-C4-alkyl group, R 17 represents a 4- to 7-membered heterocycloalkyl group, wherein the 4-7-membered heterocycloalkyl group is optionally substituted once or twice with a C1-C4-alkyl group, and wherein the 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group; R 18 represents a hydrogen atom or a methyl group, R 19 represents a hydrogen atom or a methyl group, R 20 represents a (4- to 7-membered heterocycloalkyl)-(C1-C4-alkyl) group, wherein the (4-7 membered heterocycloalkyl) part of said group may be substituted once or twice with a C1-C4-alkyl group, m represents an integer selected from 1 and 2; wherein the 4-7-membered heterocycloalkyl group is optionally substituted once or twice with a C1-C4-alkyl group, and n represents an integer selected from 1, 2 and 3. or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0202] In some preferred embodiments, inhibitors of DGKalpha are characterized by formula (I) with the limitations defined under this heading.

[0203] DGKalpha inhibitor embodiment C In some other embodiments of the present invention, the inhibitor of DGKalpha is a compound represented by formula (I) above, R 1 represents a group selected from cyano, —C(═O)NH2, —C(═O)N(H)CH3 and —C(═O)N(CH3)2, R 2are phenyl, 1-naphthyl, 2-naphthyl, 1H-pyrazol-3-yl, 1H-pyrazol-4-yl, 1H-pyrazol-5-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1H-1,2,3-triazol-4-yl, 2H-1,2,3-triazol-4-yl, 1,3-thiazol-2-yl, pyridin-3-yl, pyrazin-2-yl, 1H-indol-5-yl, 1-benzofuran-4-yl, 1-benzofuran-7-yl, 1H-indol-6-yl, benzothiophen-2-yl, 1,3-benzoxazol-2-yl, 1,3-benzoxazol-5-yl, 1,3-benzoxazol-6-yl, 1,3-benzo represents a group selected from oxazol-7-yl, 1H-indazol-5-yl, 1H-benzimidazol-2-yl, 1H-benzimidazol-4-yl, 1,3-benzothiazol-2-yl, 1,3-benzothiazol-4-yl, 1,3-benzothiazol-5-yl, 1,3-benzothiazol-6-yl, 1,3-benzothiazol-7-yl, 1H-pyrrolo[2,3-b]pyridin-3-yl, quinolin-2-yl, quinolin-4-yl, quinolin-6-yl, quinolin-7-yl, isoquinolin-5-yl, isoquinolin-7-yl, isoquinolin-8-yl, quinoxalin-2-yl, quinoxalin-5-yl and 1,3-thiazolo[5,4-b]pyridin-2-yl, wherein the group may be substituted one or two times and each substituent is independently a fluorine, chlorine or bromine atom, or methyl, propyl, isopropyl, tert-butyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, (propan-2-yl)oxy, methoxymethyl, 2-methoxyethyl, benzyloxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, phenoxy, (oxolan-2-yl)methoxy, (tetrahydrofuran-2-yl)methoxy, methanesulfonyl Nyl, dimethylphosphoryl, cyano, hydroxy, dimethylamino, oxetan-3-yl, 2-oxopyrrolidin-1-yl, 4-methyl-2-oxopiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl, morpholino-4-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 8-methyl-3-oxo-2,8-diazaspiro[4.5]decan-2-yl, carbamoyl, acetyl, trifluoroacetyl, benzamide, benzenesulfonamide, [dimethyl(oxide)-λ 6 -sulfanylidene]amino, phenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl and pyridin-3-yl; or two substituents of said phenyl group, when attached to adjacent ring atoms, are linked to each other in such a way that they combine to form a group selected from -CH2-CH(OH)-CH2-, -CH2-CH(CH3)-O-, -OC(CH3)2-O-, -NH-C(=O)-CH(CH3)-, -N(CH3)-C(=O)-C(CH3)2-, -NH-C(=O)-(C(CH2)3)-, -NH-CH2-C(CH3)2-, -N(CH3)-C(=O)-O- and -N(CH3)-C(=O)-N(CH3)-; R 3is a hydrogen atom, a fluorine atom, a chlorine atom, or a bromine atom, or methyl, sec-butyl, (oxetan-3-yl)methyl, 3,3,3-trifluoroprop-1-en-2-yl, cyclopropyl, (trifluoromethyl)cyclopropyl, cyclobutyl, 2,2-dimethylcyclobutyl, 3,3-difluorocyclobutyl, methoxymethyl, methoxy, ethoxy, propoxy, 2,2-difluoroethoxy, 2,2-difluoropropoxy, cyclopropylmethyl represents a group selected from the group consisting of methoxy, (1-cyanocyclopropyl)methoxy, cyclopropyloxy, cyclobutyloxy, methanesulfonyl, cyano, hydroxy, 4-hydroxy-2-oxo-pyrrolidin-1-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, carbamoyl, dimethylphosphoryl, oxetan-3-yl, 3,6-dihydro-2H-pyran-4-yl, (oxetan-3-yl)oxy and phenyl; R 4 is a hydrogen atom, a fluorine, a chlorine or a bromine atom, or methyl, sec-butyl, (oxetan-3-yl)methyl, trifluoromethyl, cyclopropyl, 3,3-difluorocyclobutyl, methoxymethyl, methoxy, propoxy, 2-methoxyethoxy, (1-hydroxycyclopropyl)methoxy, (1-cyanocyclopropyl)methoxy, (oxiran-2-yl)methoxy, carboxymethoxy, 2-tert-butoxy-2-oxo-ethoxy, 2-amino-2-oxo-ethoxy, cyclopropyloxy, cyclobutyloxy, methanesulfonyl, dimethylphosphoryl, cyano, nitro, hydroxy, (cyano Methyl)(methyl)amino, (2-hydroxyethyl)amino, (2-hydroxyethyl)(methyl)amino, (2-methoxyethyl)amino, (2-methoxyethyl)(methyl)amino, cyclopropylamino, (oxetan-3-yl)amino, methyl(oxetan-3-yl)amino, methyl(oxolan-3-yl)amino, 3-hydroxyazetidin-1-yl, 2-oxopyrrolidin-1-yl, morpholino, 1,1-dioxidethiomorpholin-4-yl, 4-hydroxy-2-oxo-pyrrolidin-1-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 2,2-dimethyl-2λ6 -diazathia-1,2-dien-1-yl, [dimethyl(oxide)-λ 6 -sulfanylidene]amino, methyl(tetrahydrofuran-3-yl)amino, tetrahydrofuran-3-ylmethoxy, (tetrahydrofuran-3-ylmethyl)amino, oxetan-3-yl, 3,6-dihydro-2H-pyran-4-yl, (oxetan-3-yl)oxy, (tetrahydrofuran-3-yl)oxy, (tetrahydro-2H-pyran-3-yl)oxy, (tetrahydro-2H-pyran-4-yl)oxy and phenyl, R 5 represents a hydrogen atom, a fluorine, chlorine or bromine atom or a group selected from methyl, cyclopropyl, methoxy, propoxy, cyclopropyloxy, methanesulfonyl, cyano, hydroxy, oxetan-3-yl and oxetan-3-yloxy, R 6 represents a hydrogen atom or a group selected from methyl and hydroxymethyl, R 7 represents a hydrogen atom or a fluorine atom or a group selected from methyl, ethyl, methoxy and hydroxy, R 8 represents a group selected from methyl and ethyl, and n represents an integer selected from 1, 2 and 3. or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0204] In some preferred embodiments, inhibitors of DGKalpha are characterized by formula (I) with the limitations defined under this heading.

[0205] DGKalpha inhibitor embodiment D In some other embodiments of the present invention, the inhibitor of DGKalpha is a compound selected from the following: ● 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(7-fluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(6-fluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(5-fluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(6-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(5-bromo-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(5-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(5-fluoro-1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(6-bromo-1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-(7-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzothiazol-2-yl)-4-fluoropiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-(4-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(5-chloro-1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(5-chloro[1,3]thiazolo[5,4-b]pyridin-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-{4-methyl-4-[6-(trifluoromethoxy)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-methyl-4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(5,6-difluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{4-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(5-tert-butyl-1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 4-{4-[5-(methanesulfonyl)-1,3-benzoxazol-2-yl]-4-methylpiperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 4-[4-(4-fluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-7-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-bromo-1-methyl-4-{4-methyl-4-[6-(trifluoromethoxy)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 7-bromo-4-[4-(5-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 7-bromo-1-methyl-2-oxo-4-{4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile; 7-bromo-4-[4-(5,6-difluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 7-bromo-4-[4-(6-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-7-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-bromo-1-methyl-4-{4-methyl-4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-(2-oxopyrrolidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile; 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-(2-oxopyrrolidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-2-oxo-4-{4-[4-(2,2,2-trifluoroethoxy)phenyl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-(4-{4-[(propan-2-yl)oxy]phenyl}piperidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(4-ethoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(4-cyclopropylphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-2-oxo-4-[4-(4-propoxyphenyl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{4-[4-(trifluoromethoxy)phenyl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, N-{4-[1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)piperidin-4-yl]phenyl}benzenesulfonamide; ● 4-[4-(3-cyclopropylphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-{4-[4-(dimethylamino)phenyl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{4-[4-(propan-2-yl)phenyl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[4-(benzyloxy)phenyl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, N-{4-[1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)piperidin-4-yl]phenyl}benzamide; 1-methyl-4-[4-(1-methyl-1H-indol-5-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(3-fluoro-5-methylphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(2-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-([1,1'-biphenyl]-4-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(4-chlorophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(3-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-2-oxo-4-[4-(4-phenoxyphenyl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-2-oxo-4-(4-phenylpiperidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-(4-methyl-4-phenylpiperidin-1-yl)-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{4-[4-(2-oxopyrrolidin-1-yl)phenyl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(2-fluorophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{4-[4-(trifluoromethyl)phenyl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(3-fluorophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-{4-[3-(morpholin-4-yl)phenyl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(3-cyano-2-methylphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[4-(methanesulfonyl)phenyl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[4-(4-methyl-2-oxopiperazin-1-yl)phenyl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzoxazol-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, N-{3-[1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)piperidin-4-yl]phenyl}benzenesulfonamide; 4-[4-(3-{[dimethyl(oxo)-λ6-sulfanylidene]amino}phenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-[4-(naphthalen-1-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzothiazol-4-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[1-methyl-3-(trifluoroacetyl)-1H-indol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1-benzofuran-7-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(isoquinolin-7-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzothiazol-7-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, N-{3-[1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)piperidin-4-yl]phenyl}benzamide; 4-[4-(isoquinolin-8-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(isoquinolin-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-2-oxo-4-[4-(quinoxalin-5-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[3-(methanesulfonyl)phenyl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-fluorophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-(2-methylphenyl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-(4-methylphenyl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(3,5-dichlorophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(3-bromophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(4-cyanophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[3-(difluoromethyl)phenyl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(4-bromophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-bromo-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 7-bromo-1-methyl-2-oxo-4-(4-phenylpiperidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1,7-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-7-phenyl-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3,7-dicarbonitrile, 7-cyclopropyl-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 7-(2,2-dimethyl-2λ 6 -diazathia-1,2-dien-1-yl)-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-7-(2-oxopyrrolidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-7-(oxetan-3-yl)-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 7-(methanesulfonyl)-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 7-{[dimethyl(oxo)-λ6-sulfanylidene]amino}-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 7-(3,6-dihydro-2H-pyran-4-yl)-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1-benzofuran-4-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-(4-{4-[(propan-2-yl)oxy]phenyl}piperidin-1-yl)-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-{4-methyl-4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-7-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(1,3-benzoxazol-2-yl)-4-ethylpiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-2-oxo-4-{4-[4-(trifluoromethoxy)phenyl]piperidin-1-yl}-1,2-dihydroquinoline-3-carboxamide; 4-[4-(5,6-difluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 7-bromo-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-[3-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, mixture of stereoisomers; ● 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, ● 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, ● 1-methyl-2-oxo-4-(4-phenylpiperidin-1-yl)-1,2-dihydroquinoline-3-carboxamide, 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-7-(oxetan-3-yl)-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-(2-oxopyrrolidin-1-yl)-1,2-dihydroquinoline-3-carboxamide; (rac)-1-methyl-2-oxo-4-{4-[4-(propan-2-yl)phenyl]azepan-1-yl}-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-2-oxo-4-{(4S)-4-[4-(propan-2-yl)phenyl]azepan-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{(4R)-4-[4-(propan-2-yl)phenyl]azepan-1-yl}-1,2-dihydroquinoline-3-carbonitrile, • (rac)-4-[4-(1,3-benzoxazol-2-yl)azepan-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-2-oxo-4-[4-{4-[(propan-2-yl)oxy]phenyl}azepan-1-yl]-1,2-dihydroquinoline-3-carbonitrile, • (rac)-4-[4-(4-methoxyphenyl)azepan-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 4-[(4R)-4-(4-methoxyphenyl)azepan-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[(4S)-4-(4-methoxyphenyl)azepan-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, • (rac)-4-[4-(1,3-benzoxazol-2-yl)azepan-1-yl]-7-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 4-[(4R)-4-(1,3-benzoxazol-2-yl)azepan-1-yl]-7-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[(4S)-4-(1,3-benzoxazol-2-yl)azepan-1-yl]-7-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, • (rac)-4-[4-(4-chlorophenyl)azepan-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[(4R)-4-(4-chlorophenyl)azepan-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[(4SR)-4-(4-chlorophenyl)azepan-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● (rac)-1-methyl-2-oxo-4-[4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carbonitrile, • (rac)-7-bromo-1-methyl-2-oxo-4-[4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carbonitrile; • (rac)-1-methyl-7-(oxetan-3-yl)-2-oxo-4-[4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carbonitrile; (rac)-1-methyl-7-(morpholin-4-yl)-2-oxo-4-[4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carbonitrile; (rac)-1-methyl-2-oxo-7-(2-oxopyrrolidin-1-yl)-4-[4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carbonitrile; ● (rac)-7-(1,1-dioxo-1λ 6 -thiomorpholin-4-yl)-1-methyl-2-oxo-4-[4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carbonitrile, ● (rac)-7-bromo-1-methyl-2-oxo-4-[4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carboxamide, ● 7-bromo-1-methyl-2-oxo-4-[(4S)-4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carboxamide, ● 7-bromo-1-methyl-2-oxo-4-[(4S)-4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carboxamide, ● 4-[4-ethyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-bromo-4-[4-ethyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 4-[4-(6-methoxypyridin-3-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-[4-(6-methylpyridin-3-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-[4-(pyridin-3-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-N,1-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-N,N,1-trimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-[4-(1-methyl-1H-benzimidazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-2-oxo-4-[4-(3-propyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(1-methyl-1H-pyrazol-5-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-2-oxo-4-[4-(pyrazin-2-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-hydroxy-4-[3-(trifluoromethyl)phenyl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 8-fluoro-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-8-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-8-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-8-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 8-bromo-4-[4-(6-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 8-bromo-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 8-bromo-4-[4-(5-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 8-bromo-4-[4-(5,6-difluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-8-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-8-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3,8-dicarbonitrile, ● 8-(methanesulfonyl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-6-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-6-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-1-methyl-2-oxo-4-{4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile; ● 6-bromo-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3,6-dicarbonitrile, ● 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3,6-dicarbonitrile, ● 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3,6-dicarbonitrile, 6-cyclopropyl-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 6-(methanesulfonyl)-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-6-(oxetan-3-yl)-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 6-(3,6-dihydro-2H-pyran-4-yl)-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-6-phenyl-1,2-dihydroquinoline-3-carbonitrile, 6-(methanesulfonyl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(6-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1,6-dimethyl-4-[4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(5-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1,6-dimethyl-2-oxo-4-{4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, ● 1,6-dimethyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1,6-dimethyl-4-[4-methyl-4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1,6-dimethyl-4-{4-methyl-4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 6-methoxy-1-methyl-4-[4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 6-methoxy-1-methyl-4-[4-methyl-4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 6-chloro-1-methyl-4-[4-methyl-4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 1,6-dimethyl-4-[4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 1,6-dimethyl-4-[4-methyl-4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 1,6-dimethyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 1,6-dimethyl-4-{4-methyl-4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 1,6-dimethyl-2-oxo-4-{4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(5-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(6-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 6-bromo-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(1,3-benzoxazol-2-yl)azepan-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzoxazol-2-yl)azepan-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-6-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3,6-dicarbonitrile, ● 6-cyano-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 6-(3,3-difluorocyclobutyl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-cyclopropyl-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 6-(butan-2-yl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 7-(methoxymethyl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 6-(methoxymethyl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 6-fluoro-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-6-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1,7-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1,7-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1,7-dimethyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1,7-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1,7-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzoxazol-2-yl)-4-ethylpiperidin-1-yl]-7-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-7-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 8-bromo-1,6-dimethyl-4-[4-methyl-4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-7-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-7-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 7-chloro-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 7-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-8-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 8-chloro-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 8-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 8-bromo-1-methyl-4-{4-methyl-4-[5-methyl-4-(trifluoromethyl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[(2S,4S)-2-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-7-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-7-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 7-fluoro-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 7-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 7-[(1-hydroxycyclopropyl)methoxy]-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-7-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[(oxetan-3-yl)oxy]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 6-hydroxy-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-7-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-(cyclopropyloxy)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-8-(oxetan-3-yl)-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 6-methoxy-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-(cyclobutyloxy)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 7-methoxy-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3,7-dicarbonitrile, 7-cyclopropyl-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 7-[(1-cyanocyclopropyl)methoxy]-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 7-(3,3-difluorocyclobutyl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-8-[(oxetan-3-yl)oxy]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(5,6-difluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 1,7-dimethyl-2-oxo-4-(4-phenylpiperidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, ● 7-methoxy-1-methyl-2-oxo-4-(4-phenylpiperidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-propoxy-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(6-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(5-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 8-methoxy-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-(oxetan-3-yl)-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 8-(cyclopropyloxy)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1,8-dimethyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 7-(cyclopropyloxy)-1-methyl-2-oxo-4-(4-phenylpiperidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[4-(2-methoxyethyl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 7-[(2S)-butan-2-yl]-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-6-[(oxetan-3-yl)oxy]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-[(1-cyanocyclopropyl)methoxy]-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 7-[(4R)-4-hydroxy-2-oxopyrrolidin-1-yl]-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-propoxy-1,2-dihydroquinoline-3-carbonitrile, ● 8-hydroxy-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 8-cyclopropyl-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-8-propoxy-1,2-dihydroquinoline-3-carbonitrile, 6-(cyclopropyloxy)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3,7-dicarbonitrile, ● 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-6-cyclopropyl-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-[(4R)-4-hydroxy-2-oxopyrrolidin-1-yl]-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 6-(cyclobutyloxy)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-6-propoxy-1,2-dihydroquinoline-3-carbonitrile, 6-[(4R)-4-hydroxy-2-oxopyrrolidin-1-yl]-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 7-bromo-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 7-(dimethylphosphoryl)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 4-{4-[5-(2-methoxyethyl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 4-{4-[6-(2-methoxyethyl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[(oxetan-3-yl)methyl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-6-[(oxetan-3-yl)methyl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[5-(oxetan-3-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1-methyl-2-oxo-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carbonitrile, ● 7-hydroxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(6-bromo-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[5-(2-methoxyethyl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-6-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-7-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 6-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-6-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-7-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 7-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-7-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 7-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-7-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1-methyl-2-oxo-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carboxamide; 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carboxamide; 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-8-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-8-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1,7-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 1,7-dimethyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 1,7-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1,7-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-{4-[4-(2-methoxyethyl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-{4-[6-(2-methoxyethyl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-(2-oxopyrrolidin-1-yl)-1,2-dihydroquinoline-3-carboxamide; ● 8-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(4,5-dimethyl-1,3-thiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-2-oxo-4-[4-(quinoxalin-2-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-[4-(1H-pyrazol-3-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(1-methyl-1H-pyrazol-4-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(3,4-dimethoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(3-chlorophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[(2S,4S)-2-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)-1-piperidyl]-2-oxo-quinoline-3-carbonitrile, ● 4-[4-(3-cyanophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 8-fluoro-1-methyl-2-oxo-4-[(4S)-4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[rac-(2R,3S)-2-methyl-3-phenylpyrrolidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)piperidin-4-yl]benzamide, ● 4-[4-hydroxy-4-(2-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-ethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(4-chlorophenyl)piperidin-1-yl]-1-ethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{4-[5-(2-oxopyrrolidin-1-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(4-acetylphenyl)-4-methylpiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(3-chlorophenyl)-4-methoxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 6-(dimethylphosphoryl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 6-(dimethylphosphoryl)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-(methanesulfonyl)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1-benzothiophen-2-yl)-4-hydroxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1-benzothiophen-2-yl)-4-methoxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1-benzothiophen-2-yl)-4-methylpiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(6-methoxynaphthalen-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 6-[1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)piperidin-4-yl]-2-methylquinoline-4-carbonitrile, ● 1-methyl-4-[4-(2-methyl-1,3-benzoxazol-5-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-(2-methyl-1,3-benzothiazol-5-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, (rac)-1-methyl-4-[4-(3-methyl-2-oxo-2,3-dihydro-1H-indol-5-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-{4-[3-(3-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[5-(3-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[5-(3-chlorophenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 4-{4-[5-(3-chlorophenyl)-1,3,4-oxadiazol-2-yl]-4-methylpiperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(3,3-dimethyl-2,3-dihydro-1H-indol-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-{4-[(2R)-2-methyl-2,3-dihydro-1-benzofuran-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-[4-(1,3,3-trimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(2-hydroxy-2,3-dihydro-1H-inden-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(2,2-dimethyl-2H-1,3-benzodioxol-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-2-oxo-4-[4-(2'-oxo-1',2'-dihydrospiro[cyclobutan-1,3'-indol]-5'-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile; ● 1-methyl-4-[4-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-[4-methyl-4-(4-methylquinolin-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-fluoro-1-methyl-1H-indol-6-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-{4-[1-(3-methylphenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[1-(2-methylphenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[1-(3-chlorophenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 4-{4-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-2-oxo-4-{4-[3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(2-methylquinolin-6-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[4-(3-methoxyphenyl)-1,3-thiazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 4-{4-[4-(2-methoxyphenyl)-1,3-thiazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-{4-[4-(4-methylphenyl)-1,3-thiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(1,3-dimethyl-1H-indazol-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 1-methyl-4-[4-(2-methyl-1,3-benzoxazol-6-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-(2-methyl-1,3-benzothiazol-6-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[3-(difluoromethyl)quinolin-7-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; (rac)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[(oxan-4-yl)oxy]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 7-(2-methoxyethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-{[oxiran-2-yl]methoxy}-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[(oxetan-3-yl)oxy]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 4-[4-(5-methoxy-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-(4-{5-[(oxolan-2-yl)methoxy]-1,3-benzoxazol-2-yl}piperidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-{4-[6-(oxetan-3-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)-4-fluoropiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1,3-benzoxazol-2-yl)-4-methoxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[5-(methoxymethyl)-1,3-benzoxazol-2-yl]-4-methylpiperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 4-{4-[6-(methoxymethyl)-1,3-benzoxazol-2-yl]-4-methylpiperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-fluoro-4-(5-methoxy-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(5-cyclopropyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 4-[4-(6-cyclopropyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 6-bromo-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 8-bromo-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[methyl(oxetan-3-yl)amino]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 7-[(2-hydroxyethyl)(methyl)amino]-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; (rac)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[methyl(oxolan-3-yl)amino]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 7-[(cyanomethyl)(methyl)amino]-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 6-methoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3,6-dicarbonitrile, 3-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-6-carboxamide; 6-ethoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-(2,2-difluoropropoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 6-(2,2-difluoroethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-(cyclopropylmethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 6-cyclobutyl-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 6-[2,2-dimethylcyclobutyl]-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-6-(3,3,3-trifluoroprop-1-en-2-yl)-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-6-[1-(trifluoromethyl)cyclopropyl]-1,2-dihydroquinoline-3-carbonitrile; 2-({3-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinolin-7-yl}oxy)acetamide; 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-{[oxan-3-yl]oxy}-2-oxo-1,2-dihydroquinoline-3-carbonitrile; (rac)-tert-butyl({3-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinolin-7-yl}oxy)acetate, ({3-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinolin-7-yl}oxy)acetic acid; (rac)-4-[4-fluoro-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-(tetrahydrofuran-3-yloxy)-1,2-dihydroquinoline-3-carbonitrile; 7-(cyclopropylamino)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 7-methoxy-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 6-bromo-4-[4-fluoro-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-nitro-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 6-bromo-7-hydroxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 6-bromo-7-hydroxy-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; (rac)-6-bromo-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carbonitrile; (rac)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[tetrahydrofuran-3-yloxy]-1,2-dihydroquinoline-3,6-dicarbonitrile; ● 7-hydroxy-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3,6-dicarbonitrile; (rac)-6-ethoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[tetrahydrofuran-3-yloxy]-1,2-dihydroquinoline-3-carbonitrile; ● 7-hydroxy-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; (rac)-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[tetrahydrofuran-3-yloxy]-1,2-dihydroquinoline-3-carbonitrile; (rac)-6-(2,2-difluoroethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[tetrahydrofuran-3-yloxy]-1,2-dihydroquinoline-3-carbonitrile; (rac)-4-[4-fluoro-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-6-methoxy-1-methyl-2-oxo-7-[tetrahydrofuran-3-yloxy]-1,2-dihydroquinoline-3-carbonitrile; (rac)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3,6-dicarbonitrile; (rac)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-6-(3,3,3-trifluoroprop-1-en-2-yl)-1,2-dihydroquinoline-3-carbonitrile; (rac)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-6-[1-(trifluoromethyl)cyclopropyl]-1,2-dihydroquinoline-3-carbonitrile; 6-bromo-1-methyl-2-oxo-4-(4-{5-[3-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl}piperidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile; 6-methoxy-1-methyl-4-{4-[3-(3-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 6-methoxy-1-methyl-2-oxo-4-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile; 6-methoxy-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 6-methoxy-1-methyl-2-oxo-4-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-1-methyl-2-oxo-4-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile; ● 6-bromo-1-methyl-2-oxo-4-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 6-bromo-1-methyl-4-{4-[5-(3-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 7-hydroxy-1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 6-bromo-7-hydroxy-1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile; (rac)-1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-7-{[oxan-3-yl]oxy}-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-N,1-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● N,1-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, ● 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-N,1-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-2-oxo-4-{4-[5-(2-oxopyrrolidin-1-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carboxamide; 4-[4-(3-chlorophenyl)-4-methoxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 6-(dimethylphosphoryl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 6-(dimethylphosphoryl)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; 6-(methanesulfonyl)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(1-benzothiophen-2-yl)-4-methoxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(1-benzothiophen-2-yl)-4-hydroxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-[4-(6-methoxynaphthalen-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-{4-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-{4-[3-(3-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-{4-[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-{4-[5-(3-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-{4-[5-(3-chlorophenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-{4-[5-(3-chlorophenyl)-1,3,4-oxadiazol-2-yl]-4-methylpiperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-{4-[2-methyl-2,3-dihydro-1-benzofuran-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(2-hydroxy-2,3-dihydro-1H-inden-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(2,2-dimethyl-2H-1,3-benzodioxol-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 1-methyl-2-oxo-4-[4-(2'-oxo-1',2'-dihydrospiro[cyclobutan-1,3'-indol]-5'-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-[4-methyl-4-(4-methylquinolin-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-[4-(4-fluoro-1-methyl-1H-indol-6-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-{4-[1-(3-methylphenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-{4-[1-(2-methylphenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-{4-[1-(3-chlorophenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-2-oxo-4-{4-[3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carboxamide; 4-{4-[4-(3-methoxyphenyl)-1,3-thiazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-{4-[4-(2-methoxyphenyl)-1,3-thiazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-{4-[4-(4-methylphenyl)-1,3-thiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[(oxan-4-yl)oxy]-2-oxo-1,2-dihydroquinoline-3-carboxamide; 7-(2-methoxyethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-{[oxiran-2-yl]methoxy}-2-oxo-1,2-dihydroquinoline-3-carboxamide; (rac)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide, (-)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide, (+)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[(oxetan-3-yl)oxy]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(5-methoxy-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-2-oxo-4-(4-{5-[(oxolan-2-yl)methoxy]-1,3-benzoxazol-2-yl}piperidin-1-yl)-1,2-dihydroquinoline-3-carboxamide; 4-[4-(1,3-benzoxazol-2-yl)-4-fluoropiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 4-[4-(1,3-benzoxazol-2-yl)-4-methoxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-{4-[5-(methoxymethyl)-1,3-benzoxazol-2-yl]-4-methylpiperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-{4-[6-(methoxymethyl)-1,3-benzoxazol-2-yl]-4-methylpiperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 6-bromo-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 8-bromo-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[methyl(oxetan-3-yl)amino]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 7-[(2-hydroxyethyl)(methyl)amino]-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-{methyl[(3R)-oxolan-3-yl]amino}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-{methyl[(3S)-oxolan-3-yl]amino}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 6-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3,6-dicarboxamide; ● 7-[(cyanomethyl)(methyl)amino]-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; 6-methoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; 6-ethoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; 6-(2,2-difluoropropoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; 6-(2,2-difluoroethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; 6-(cyclopropylmethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; 6-cyclobutyl-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-6-[1-(trifluoromethyl)cyclopropyl]-1,2-dihydroquinoline-3-carboxamide; 7-(2-amino-2-oxoethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; 4-[4-fluoro-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide; ● 1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-nitro-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 6-bromo-7-hydroxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 6-bromo-7-hydroxy-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; (rac)-6-bromo-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide, (rac)-6-cyano-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide; 6-cyano-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide; 6-cyano-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide; (rac)-6-(2,2-difluoroethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide; (rac)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-6-[1-(trifluoromethyl)cyclopropyl]-1,2-dihydroquinoline-3-carboxamide; 6-bromo-1-methyl-2-oxo-4-(4-{5-[3-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl}piperidin-1-yl)-1,2-dihydroquinoline-3-carboxamide; 6-methoxy-1-methyl-4-{4-[3-(3-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 6-methoxy-1-methyl-2-oxo-4-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carboxamide; 6-methoxy-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 6-bromo-1-methyl-2-oxo-4-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carboxamide; 6-bromo-1-methyl-2-oxo-4-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carboxamide; 6-bromo-1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 6-bromo-1-methyl-4-{4-[5-(3-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-7-{[(3R)-oxan-3-yl]oxy}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-7-{[(3S)-oxan-3-yl]oxy}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 6-bromo-7-hydroxy-1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide; 6-bromo-7-methoxy-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 6-bromo-7-hydroxy-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile; (rac)-6-bromo-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carbonitrile; (rac)-6-bromo-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide; (rac)-6-cyano-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide; 6-cyano-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide; 6-cyano-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide; (−)-6-bromo-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carbonitrile; (rac)-6-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide, 6-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide; 6-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide; 6-methoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carbonitrile; 6-methoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carbonitrile; 6-methoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide; (rac)-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide; 1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide; 1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide; ● 7-[(2-methoxyethyl)amino]-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 7-(3-hydroxyazetidin-1-yl)-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[(oxetan-3-yl)amino]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 7-[(2-hydroxyethyl)amino]-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 7-[(2-hydroxyethyl)(methyl)amino]-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile; ● 7-[(2-methoxyethyl)amino]-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; ● 7-(3-hydroxyazetidin-1-yl)-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; (rac)-1,6-dimethyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carbonitrile; 1,6-dimethyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carbonitrile; 1,6-dimethyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carbonitrile; 1,6-dimethyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide; 1,6-dimethyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide; ● 7-[(2-hydroxyethyl)amino]-1,6-dimethyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 7-bromo-1,6-dimethyl-4-{4-[1-(2-methylphenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 7-[(2-hydroxyethyl)amino]-1,6-dimethyl-4-{4-[1-(2-methylphenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile; 6-bromo-7-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; 6-cyano-7-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide; (rac)-6-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(oxolan-3-yl)methyl]amino}-1,2-dihydroquinoline-3-carboxamide; 6-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-({[(3R)-oxolan-3-yl]methyl}amino)-1,2-dihydroquinoline-3-carboxamide; 6-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-({[(3S)-oxolan-3-yl]methyl}amino)-1,2-dihydroquinoline-3-carboxamide; ● 6-chloro-7-methoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, ● 6-chloro-7-hydroxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, (rac)-6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carbonitrile; (rac)-6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide; 6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide; 6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide; (rac)-6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)methoxy]-1,2-dihydroquinoline-3-carbonitrile; (rac)-6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)methoxy]-1,2-dihydroquinoline-3-carboxamide; 6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]methoxy}-1,2-dihydroquinoline-3-carboxamide; 6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3S)-oxolan-3-yl]methoxy}-1,2-dihydroquinoline-3-carboxamide; (rac)-6-bromo-1-methyl-2-oxo-7-[(oxolan-3-yl)oxy]-4-{4-[2-(pyridin-3-yl)-2H-1,2,3-triazol-4-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile; (rac)-6-bromo-1-methyl-4-{4-[1-(2-methylphenyl)-1H-1,2,3-triazol-4-yl]piperidin-1-yl}-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carbonitrile; (rac)-1,6-dimethyl-4-{4-[1-(2-methylphenyl)-1H-1,2,3-triazol-4-yl]piperidin-1-yl}-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carbonitrile; 7-bromo-1,6-dimethyl-4-{4-[1-(2-methylphenyl)-1H-pyrazol-4-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, and (rac)-1,6-dimethyl-4-{4-[1-(2-methylphenyl)-1H-pyrazol-4-yl]piperidin-1-yl}-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carbonitrile; or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0206] In some preferred embodiments, the inhibitor of DGKalpha is a compound from this list.

[0207] DGKalpha inhibitor A In a preferred embodiment of the present invention, the inhibitor of DGKalpha is 6-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0208] In another preferred embodiment of the invention, the inhibitor of DGKalpha is 6-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide.

[0209] In another preferred embodiment of the present invention, the inhibitor of DGKalpha has the structure: [ka] or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0210] In another preferred embodiment of the present invention, the inhibitor of DGKalpha has the structure [ka] It is a DGKalpha inhibitor A.

[0211] The synthesis of DGKalpha inhibitor A is described in International Patent Application PCT / EP2020 / 083198, published as WO2021 / 105117A1, as Example 298. International Patent Application PCT / EP2020 / 083198 also discloses methods for preparing other compounds of formula (I) described herein.

[0212] DGKzeta inhibitors DGKzeta Inhibitor Embodiment A Below, DGKzeta inhibitors that can be preferably used in the present invention according to any one of embodiment 1, embodiment 2, embodiment 3, embodiment 4, embodiment 5, embodiment 6, embodiment 7, embodiment 8, and embodiment 9 of the present invention are described.

[0213] In some embodiments of the present invention, the inhibitor of DGKzeta has the formula (II): [ka] [During the ceremony: R 1 represents a phenyl or 6-membered heteroaryl group which may be substituted one, two or three times, each substituent being independently a halogen atom or hydroxy, cyano, nitro, C-C-alkyl, (phenyl)-(C-C-alkyl)-, C-C-haloalkyl, C-C-alkoxy, (phenyl)-(C-C-alkoxy)-, C-C-haloalkoxy, -N(R) 5 (R 6 ) selected from the group selected from wherein the phenyl group in the (phenyl)-(C1-C3-alkyl)- and (phenyl)-(C1-C3-alkoxy) groups may be substituted once or twice, and each substituent is independently selected from a halogen atom or a group selected from cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy, or two substituents attached to adjacent carbon atoms of said phenyl or 6-membered heteroaryl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -(CH2)2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O-, -O-CF2-O-, -O-CH2-CF2-O-, and -O-CF2-CF2-O-; or R 1 represents a 5-membered heteroaryl group which may be substituted one or two times, each substituent being independently selected from a halogen atom or a group selected from cyano, C1-C3-alkyl, and C1-C3-alkoxy; R 2 The base: [ka] represents where "*" means R 2 indicates the point of attachment to the nitrogen atom to which it is attached; R 3 represents a group selected from methyl and -NH; R4 represents a phenyl or 6-membered heteroaryl group which may be substituted one, two or three times, each substituent being independently a halogen atom or cyano, nitro, C-C-alkyl, (phenyl)-(C-C-alkyl)-, (5- or 6-membered heteroaryl)-(C-C-alkyl)-, (C-C-cycloalkyl)-(C-C-alkyl)-, ((R 9 )O)-(C1-C6-alkyl)-, C1-C6-haloalkyl, C3-C7-cycloalkyl, -OR 9 , -N(R 10 )(R 11 ), ((R 10 )(R 11 )N)-(C1-C3-alkyl)-, -C(=O)-N(R 12 )(R 13 ), -S(=O) n -R 14 , -C(=O)R 14 , -C(=O)-OR 17 and a 5- or 6-membered heteroaryl group, which may itself be substituted with one or two substituents selected from a halogen atom and a methyl group; or two substituents attached to adjacent carbon atoms of said phenyl or 6-membered heteroaryl group together form a divalent group selected from -(CH2)3-, -(CH2)4-, -(CH2)2-O-, -(CH2)3-O-, -CH2-O-CH2-, -(CH2)2-O-CH2-, -O-CH2-O-, -O-CH2-CH2-O-, -O-CF2-O-, -O-CH2-CF2-O-, and -O-CF2-CF2-O-; R 5 and R 6 are each independently a hydrogen atom or a group selected from C-C-alkyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl and (phenyl)-(C-C-alkyl)-, or R 5 and R 6together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one, two or three times, wherein each substituent is independently selected from a halogen atom or a group selected from oxo, hydroxy, C-C-alkyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl and C-C-alkoxy; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a group selected from -C(=O)-NH2 and -S(=O)2-NH2; R 9 is a hydrogen atom or C1-C6-alkyl, (5- or 6-membered heteroaryl)-(C1-C3-alkyl)-, (phenyl)-(C1-C3-alkyl)-, C1-C6-haloalkyl, C2-C4-hydroxyalkyl, (C1-C3-alkoxy)-C2-C3-alkyl-, ((C1-C3-alkyl)-C(=O)-O)-C2-C3-alkyl-, -C(R 18 )(R 19 )-C(=O)-OR 17 , -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ), -C(=O)-N(R 20 )(R 21 ), phenyl and 5- or 6-membered heteroaryl groups, wherein the phenyl group in the (phenyl)-(C1-C3-alkyl) group and the phenyl group itself, the 5- or 6-membered heteroaryl group in the (5- or 6-membered heteroaryl)-(C1-C3-alkyl) group, and the 5- or 6-membered heteroaryl group itself may be substituted once or twice, each substituent being independently selected from a halogen atom or a group selected from cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy; R 10 and R 11are each independently a hydrogen atom or a C1-C4-alkyl, C1-C4-haloalkyl, C2-C4-hydroxyalkyl, (C1-C3-alkoxy)-C2-C3-alkyl-, ((R 22 )(R 23 )N)—C2-C3-alkyl, (C3-C7-cycloalkyl)-(C1-C3-alkyl)-, (C1-C4-alkyl)-C(═O)—, C3-C7-cycloalkyl, (C3-C7-cycloalkyl)-C(═O)—, (phenyl)-(C1-C3-alkyl)-, (phenyl)-(C1-C3-alkyl)-C(═O)—, (phenyl)-(C1-C3-alkyl)-OC(═O)—, phenyl and a 5- or 6-membered heteroaryl group, wherein C3-C7-cycloalkyl, and C3-C7-cycloalkyl in the (C3-C7-cycloalkyl)-(C1-C3-alkyl)- and (C3-C7-cycloalkyl)-C(=O) groups, may be substituted one or two times, each substituent being independently selected from a fluorine atom or a group selected from cyano, C1-C2-alkyl and C1-C2-haloalkyl, and wherein said phenyl and said 5- or 6-membered heteroaryl groups, and the phenyl groups in said (phenyl)-(C-C)-(alkyl)-, (phenyl)-(C-C)-C(=O)- and (phenyl)-(C-C)-OC(=O)- groups, are optionally substituted one or two times, each substituent being independently selected from a halogen atom or a group selected from cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy; or R 10 and R 11together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group which may be substituted one, two or three times, or a bicyclic nitrogen-containing 5- to 11-membered heterocycloalkyl group, each substituent independently being a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, -N(R 22 )(R 23 ), and monocyclic 4- to 7-membered heterocycloalkyl groups; R 12 and R 13 are each independently a hydrogen atom or a group selected from C-C-alkyl, C-C-haloalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-C-alkyl-, (C-C-haloalkoxy)-C-C-alkyl-, (phenoxy)-C-C-alkyl-, C-C-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl may be substituted one, two or three times, each substituent being 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; and wherein the phenyl group in said (phenoxy)-C2-C3-alkyl group and said (phenyl)-(C1-C3-alkyl) group may be substituted once or twice, each substituent being independently selected from a halogen atom or a group selected from cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy, or R 12 and R 13together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted one, two or three times, wherein each substituent is independently selected from a halogen atom or a group selected from cyano, oxo, hydroxy, C-C-alkyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl and C-C-alkoxy; R 14 represents a group selected from C1-C4-alkyl, C1-C4-haloalkyl and phenyl, wherein the phenyl group may be 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; R 17 represents a C1-C4-alkyl group; R 18 and R 19 each independently represents a hydrogen atom or a C1-C4-alkyl group; R 20 is a hydrogen atom or a C1-C6-alkyl, C3-C4-alkenyl, C3-C4-alkynyl, C1-C3-alkoxy, C3-C7-cycloalkyl, bicyclic C5-C 11 -represents a group selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 5- to 11-membered heterocycloalkyl, phenyl, naphthyl, and 5- to 10-membered heteroaryl; wherein the C1-C6-alkyl group may be substituted one, two or three times, and each substituent is independently a halogen atom, or a hydroxy, cyano, C1-C3-alkoxy, -N(R 22 )(R 23 ), C3-C7-cycloalkyl, bicyclic C5-C 11- selected from groups selected from cycloalkyl, adamantyl, monocyclic 4-7 membered heterocycloalkyl, bicyclic 5-11 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl, wherein said phenyl and 5-10 membered heteroaryl substituents are themselves optionally substituted one or two times, each substituent being independently selected from a halogen atom or a group selected from cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino, and trifluoromethoxy; and wherein C3-C7-cycloalkyl, bicyclic C5-C 11 -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl and bicyclic 5- to 11-membered heterocycloalkyl may be substituted one, two or three times, each substituent being independently selected from a halogen atom or a group selected from cyano, oxo, hydroxy, C-C-alkyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl and C-C-alkoxy; and wherein the phenyl, naphthyl and 5- to 10-membered heteroaryl groups may be substituted one, two or three times, each substituent independently being a halogen atom or cyano, C-C-alkyl, C-C-haloalkyl, C-C-alkoxy, C-C-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 ) selected from the group selected from R 21 represents a hydrogen atom or a C1-C4-alkyl group, or 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 may be benzo-fused and which may be substituted one, two or three times, in which each substituent is independently a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-haloalkyl, (phenyl)-(C-C-alkyl)-, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-haloalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 ) selected from the group selected from; R 22 and R 23 each independently represent a hydrogen atom or a group selected from C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 24 and R 25 each independently represent a hydrogen atom or a C1-C4-alkyl group, and n represents an integer of 0, 1, or 2. or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0214] DGKzeta inhibitor embodiment B In some embodiments of the present invention, the inhibitor of DGKzeta is represented by the formula (II) above. [During the ceremony, R 1 represents a phenyl or pyridinyl group which may be substituted one, two or three times, each substituent independently being a fluorine atom, a chlorine atom and a bromine atom, or a hydroxy, cyano, C-C-alkyl, C-C-fluoroalkyl, C-C-alkoxy, (phenyl)-(C-C-alkoxy)-, C-C-fluoroalkoxy and -N(R 5 )(R 6 ) selected from the group selected from or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O- and -O-CF2-O-; or R 1 represents a pyrazolyl group optionally substituted with one methyl group; R 2 The base: [ka] represents where "*" means R 2 indicates the point of attachment to the nitrogen atom to which it is attached; R 3 represents a group selected from methyl and -NH; R 4 represents a phenyl or pyridinyl group which may be substituted one, two or three times, each substituent independently being a halogen atom or cyano, C1-C3-alkyl, ((R 9 )O)—(C1-C3-alkyl)-, C1-C3-fluoroalkyl, —OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R 12 )(R 13 ), S(=O) n -R 14 and -C(=O)-OR 17 selected from the group selected from or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form a divalent group selected from -(CH2)3-, -O-CH2-O-, and -O-CF2-O-; R 5 and R 6 each independently represents a hydrogen atom or a C1-C2-alkyl group, or R 5 and R 6together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group which may be substituted one or two times, each substituent being independently selected from a fluorine atom or a group selected from hydroxy and C1-C2-alkyl; R 7 represents hydrogen or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; R 9 is a hydrogen atom or C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, C2-hydroxyalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(R 18 )(R 19 )-C(=O)-OR 17 , -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R 21 ), -C(=O)-N(R 20 )(R 21 ) and phenyl, wherein the phenyl groups within said benzyl groups and said phenyl groups themselves may be substituted one or two times, each substituent independently being a group selected from fluorine and chlorine atoms, or cyano and methyl; R 10 and R 11 are each independently a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, (C-C-cycloalkyl)-(C-C-alkyl)-, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-cycloalkyl-(C=O)-, (phenyl)-(C-C-alkyl)-, (phenyl)-(C-C-alkyl)-C(=O)- and (phenyl)-(C-C-alkyl)-OC(=O)-, wherein C3-C7-cycloalkyl, and C3-C5-cycloalkyl in the (C3-C5-cycloalkyl)-(C1-C2-alkyl)-, and C3-C7-cycloalkyl in the C3-C7-cycloalkyl-(C=O)- group, may be substituted once or twice, and each substituent is independently selected from a fluorine atom or a group selected from cyano, C1-C2-alkyl and C1-C2-fluoroalkyl, and wherein the phenyl group in said (phenyl)-(C1-C2-alkyl)-, (phenyl)-(C1-C2-alkyl)-C(=O)- and (phenyl)-(C1-C2-alkyl)-OC(=O)- groups may be substituted one or two times, each substituent being independently selected from a fluorine atom, a chlorine atom and a methyl group; or R 10 and R 11 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted once or twice, wherein each substituent is independently selected from a fluorine atom or a group selected from cyano, oxo, C-C-alkyl, C-C-fluoroalkyl and (C-C-alkyl)-C(=O)-; R 12 and R 13 are each independently a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-C-alkyl-, (C-C-fluoroalkoxy)-C-C-alkyl-, (phenoxy)-C-C-alkyl-, C-C-cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C-C-alkyl)-, wherein C3-C7-cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl may be substituted one or two times, each substituent being independently selected from a fluorine atom or a group selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; and wherein the phenyl group in said (phenoxy)-C2-C3-alkyl group and said (phenyl)-(C1-C2-alkyl) group may be substituted once or twice, each substituent being independently selected from fluorine and chlorine atoms or a group selected from methyl, trifluoromethyl and methoxy, or R 12 and R 13 together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, optionally substituted once or twice, wherein each substituent is independently selected from a halogen atom or a group selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 14 represents a group selected from methyl and trifluoromethyl; R 17 represents a C1-C2-alkyl group; R 18 and R 19 each independently represents a hydrogen atom or a methyl group; R 20 represents a hydrogen atom or a group selected from optionally substituted C1-C3-alkyl, unsubstituted C4-C6-alkyl, prop-2-ynyl, methoxy, C3-C6-cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl and 5- to 10-membered heteroaryl, wherein the C1-C3-alkyl group may be substituted one, two or three times, and each substituent independently represents a halogen atom or 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, wherein the phenyl and 5- to 10-membered heteroaryl substituents may be substituted once or twice, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a methyl group; and wherein the C3-C6-cycloalkyl, adamantyl and monocyclic 4- to 7-membered heterocycloalkyl groups are optionally substituted one, two or three times, each substituent being independently selected from a fluorine atom or a group selected from oxo, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; and wherein the phenyl and 5- to 10-membered heteroaryl groups may be substituted one, two or three times, each substituent independently being a fluorine atom and a chlorine atom, or cyano, C-C-alkyl, C-C-fluoroalkyl, C-C-alkoxy, C-C-fluoroalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 ) selected from the group selected from R 21 represents a hydrogen atom or a C1-C2-alkyl group, or 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 may be benzo-fused and which may be substituted one, two or three times, in which each substituent is independently a halogen atom or cyano, oxo, hydroxy, C-C-alkyl, C-C-fluoroalkyl, benzyl, (C-C-alkyl)-C(=O)-, C-C-cycloalkyl, C-C-alkoxy, C-C-fluoroalkoxy, -N(R 22 )(R 23 ) and -C(=O)-N(R 24 )(R 25 ) selected from the group selected from; R 22 and R 23 each independently represents a group selected from a hydrogen atom, C1-C2-alkyl and (C1-C2-alkyl)-C(=O)-; R 24 and R 25 each independently represent a hydrogen atom or a C1-C2-alkyl group, and n represents the integer 2. or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0215] DGKzeta inhibitor embodiment C In some embodiments of the present invention, the inhibitor of DGKzeta is represented by the formula (II) above. [During the ceremony, R 1 The base: [ka] represents where "**" means R 1 indicates the point of attachment to the nitrogen atom to which it is attached; R 2 The base: [ka] represents where "*" means R 2 indicates the point of attachment to the nitrogen atom to which it is attached; R 3 represents a group selected from methyl and -NH; R 4 The base: [ka] represents where "#" is R 4 indicates the point of attachment to the carbonyl group; R 7 represents a hydrogen atom or a C1-C2-alkyl group; R 8 represents a -C(=O)-NH group; R 9 is a hydrogen atom or C1-C2-alkyl, benzyl, C1-C2-fluoroalkyl, (C1-C2-alkoxy)-C2-alkyl-, ((C1-C2-alkyl)-C(=O)-O)-C2-alkyl-, -C(R 18 )(R 19 )-C(=O)-N(R 20 )(R21 ), -C(=O)-N(R 20 )(R 21 ) and phenyl, wherein the phenyl groups within said benzyl groups and said phenyl groups themselves may be substituted one or two times, each substituent being independently selected from a group selected from fluorine and chlorine atoms, or cyano and methyl; R 10 and R 11 each independently represent a hydrogen atom or a group selected from C1-C2-alkyl, C3-C7-cycloalkyl and (benzyl)-OC(=O)-, wherein C3-C7-cycloalkyl may be substituted one or two times, each substituent being independently selected from a fluorine atom or a group selected from methyl and trifluoromethyl, and wherein the phenyl group in said (benzyl)-OC(=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; or R 10 and R 11 together with the nitrogen atom to which they are attached, represent an optionally monocyclic, nitrogen-containing, 4- to 7-membered heterocycloalkyl group, which may be substituted one or two times, and each substituent is independently selected from a fluorine atom or a group selected from cyano, methyl, and trifluoromethyl; R 12 and R 13 are each independently a hydrogen atom or a group selected from C-C-alkyl, C-C-fluoroalkyl, C-C-hydroxyalkyl, (C-C-alkoxy)-C-alkyl-, (C-C-fluoroalkoxy)-C-alkyl-, (phenoxy)-C-alkyl-, C-C-cycloalkyl and (phenyl)-(C-C-alkyl)-, wherein the phenyl group in said (phenoxy)-C2-alkyl group and said (phenyl)-(C1-C2-alkyl) group may be substituted one or two times, and each substituent is independently selected from fluorine and chlorine atoms or a group selected from methyl, trifluoromethyl and methoxy; R 17 represents a C1-C2-alkyl group; R 18 and R 19 each independently represents a hydrogen atom or a methyl group; R 20 represents a group selected from benzyl and phenyl, wherein the phenyl group and the phenyl group within the benzyl group may be substituted one or two times, and each substituent is independently selected from a fluorine atom, a chlorine atom, and a methyl group; R 21 represents a hydrogen atom or a methyl group, Y 1 represents -C(H)=, -C(F)=, -C(Cl)=, -C(CN)= or -N=; Y 2 represents -C(H)= or -N=; Y 3 is -C(R 27 )= or -N=, However, Y 2 If represents -N=, then Y 3 is -C(R 27 ) = and Y 3 If represents -N=, then Y 2 represents -C(H)=; R 26 represents a fluorine, chlorine or bromine atom or a group selected from methyl, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy, and R 27 is a halogen atom or C1-C2-alkyl, C1-C2-fluoroalkyl, -OR 9 , -N(R 10 )(R 11 ), -C(=O)-N(R12 )(R 13 ) and -C(=O)-OR 17 represents] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0216] DGKzeta inhibitor embodiment D In some embodiments of the invention, the inhibitor of DGKzeta is a compound selected from the following: ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-methoxy-2-methyl-anilino)propanamide, ● rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-4-(dimethylamino)anilino]propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-isopropoxy-anilino)propanamide, ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2,4,6-trifluoroanilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2-bromo-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(6-methylpyridine-3-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(2-fluorobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-cyano-anilino)propanamide, rac-2-(N-[4-amino-5-[4-chloro-3-(trifluoromethyl)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2-chloro-4-fluoro-anilino)propanamide, ● rac-2-(N-[4-amino-5-(3-cyanobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, ● rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-3-chloro-4-(dimethylamino)anilino]propanamide, rac-2-(N-[4-amino-5-(6-methoxypyridine-3-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-4-[4-amino-2-(N-[2-amino-1-methyl-2-oxo-ethyl]-4-fluoro-anilino)thiazole-5-carbonyl]-N-methyl-benzamide; rac-2-(N-[4-amino-5-(3-fluorobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3-chloro-4-methoxy-anilino)propanamide, rac-2-(N-[4-amino-5-(4-fluorobenzoyl)thiazol-2-yl]-4-methoxy-anilino)propanamide, ● rac-2-(N-[4-amino-5-(4-methylsulfonylbenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-imidazol-1-ylbenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, ● rac-2-(N-[4-amino-5-(4-cyano-3-fluoro-benzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-cyano-3-fluoro-benzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-(4-cyano-3-fluoro-benzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-(4-cyano-2-fluoro-benzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(2-fluoro-4-methoxy-benzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-4-(trifluoromethoxy)anilino]propanamide, rac-2-(N-[4-amino-5-(3,4-difluorobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(3,4-dichlorobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, ● rac-2-[N-[4-amino-5-(4-fluorobenzoyl)thiazol-2-yl]-4-(trifluoromethoxy)anilino]propanamide, (R)-2-[N-[4-amino-5-(4-fluorobenzoyl)thiazol-2-yl]-4-(trifluoromethoxy)anilino]propanamide; (S)-2-[N-[4-amino-5-(4-fluorobenzoyl)thiazol-2-yl]-4-(trifluoromethoxy)anilino]propanamide; rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-4-(trifluoromethyl)anilino]propanamide, rac-2-(N-[4-amino-5-[6-(trifluoromethyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-[6-(trifluoromethyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-[6-(trifluoromethyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-chloro-2-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(indan-5-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3,4-difluoro-anilino)propanamide, ● rac-2-(N-[4-amino-5-(4-cyanobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-cyanobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-(4-cyanobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide; ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-chloro-anilino)propanamide, ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3,4-dichloro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-chloro-3-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-fluorobenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-fluorobenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide; ● (S)-2-(N-[4-amino-5-(4-fluorobenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide; ● rac-ethyl 2-[4-[4-amino-2-(N-[2-amino-1-methyl-2-oxo-ethyl]-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]-2-methyl-propanoate, rac-2-(N-[4-amino-5-[4-(trifluoromethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-[4-(trifluoromethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-[4-(trifluoromethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; ● rac-2-(N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide; ● (S)-2-(N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-(trifluoromethyl)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, ● rac-2-[N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-(trifluoromethyl)anilino]propanamide, (R)-2-[N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-(trifluoromethyl)anilino]propanamide; ● (S)-2-[N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-(trifluoromethyl)anilino]propanamide; rac-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; (R)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; 2-(N-[4-amino-5-[4-[2-amino-1-methyl-2-oxo-ethoxy]benzoyl]thiazol-2-yl]anilino)propanamide (mixture of stereoisomers); (2R)-(N-[4-amino-5-[4-[2-amino-(1R)-methyl-2-oxo-ethoxy]benzoyl]thiazol-2-yl]anilino)propanamide, (2R)-(N-[4-amino-5-[4-[2-amino-(1S)-methyl-2-oxo-ethoxy]benzoyl]thiazol-2-yl]anilino)propanamide, (2S)-(N-[4-amino-5-[4-[2-amino-(1R)-methyl-2-oxo-ethoxy]benzoyl]thiazol-2-yl]anilino)propanamide, (2S)-(N-[4-amino-5-[4-[2-amino-(1S)-methyl-2-oxo-ethoxy]benzoyl]thiazol-2-yl]anilino)propanamide, rac-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-2-fluoro-anilino)propanamide; (R)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-2-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-2-fluoro-anilino)propanamide; ● rac-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-anilino)propanamide, (R)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-anilino)propanamide; ● (S)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide; (R)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide; (R)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide; rac-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide; ● rac-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide; rac-2-(N-[4-amino-5-(6-methoxypyridine-3-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(6-methoxypyridine-3-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-(6-methoxypyridine-3-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[6-(trifluoromethyl)pyridine-3-carbonyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-[6-(trifluoromethyl)pyridine-3-carbonyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-[6-(trifluoromethyl)pyridine-3-carbonyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide; ● rac-2-(N-[5-[4-(difluoromethoxy)benzoyl]-4-methyl-thiazol-2-yl]-4-fluoro-anilino)propanamide, ● rac-2-(N-[5-[4-(difluoromethoxy)benzoyl]-4-methyl-thiazol-2-yl]-3,4-difluoro-anilino)propanamide, ● (R)-2-(N-[5-[4-(difluoromethoxy)benzoyl]-4-methyl-thiazol-2-yl]-3,4-difluoro-anilino)propanamide; ● (S)-2-(N-[5-[4-(difluoromethoxy)benzoyl]-4-methyl-thiazol-2-yl]-3,4-difluoro-anilino)propanamide; rac-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-chloro-anilino)propanamide, (R)-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-chloro-anilino)propanamide; (S)-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-chloro-anilino)propanamide; ● rac-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide, ● (R)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide, ● (S)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide; ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-fluoro-anilino)propanamide, (R)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-fluoro-anilino)propanamide; (S)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-fluoro-anilino)propanamide; ● rac-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide; ● (S)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, ● rac-2-(N-[4-amino-5-(4-methylbenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-methylbenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide; ● (S)-2-(N-[4-amino-5-(4-methylbenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-fluorobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2,4-difluoro-anilino)propanamide, ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-methoxy-anilino)propanamide, ● rac-2-[(4-amino-5-benzoyl-1,3-thiazol-2-yl)(phenyl)amino]butanamide, ● rac-2-[(4-amino-5-benzoyl-1,3-thiazol-2-yl)(4-fluorophenyl)amino]butanamide, 2-(N-[4-amino-5-[4-(2-amino-1-methyl-2-oxo-ethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide (mixture of stereoisomers), rac-2-{[4-amino-5-(4-methoxybenzoyl)-1,3-thiazol-2-yl](4-fluorophenyl)amino}butanamide; ● 2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-fluoro-anilino)acetamide, ● 2-(N-[4-amino-5-(4-methylbenzoyl)thiazol-2-yl]-4-fluoro-anilino)acetamide, ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-methyl-anilino)propanamide, (R)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-methyl-anilino)propanamide; ● (S)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-methyl-anilino)propanamide, ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3-fluoro-anilino)propanamide, (R)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3-fluoro-anilino)propanamide; (S)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3-fluoro-anilino)propanamide; ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2-fluoro-anilino)propanamide, (R)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2-fluoro-anilino)propanamide; (S)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2-fluoro-anilino)propanamide; ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3-methyl-anilino)propanamide, (R)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3-methyl-anilino)propanamide; ● (S)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3-methyl-anilino)propanamide, ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2-methyl-anilino)propanamide, (R)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2-methyl-anilino)propanamide; ● (S)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2-methyl-anilino)propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(1-methylpyrazol-4-yl)amino]propanamide, (R)-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(1-methylpyrazol-4-yl)amino]propanamide; (S)-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(1-methylpyrazol-4-yl)amino]propanamide; rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(3-pyridyl)amino]propanamide, (R)-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(3-pyridyl)amino]propanamide, (S)-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(3-pyridyl)amino]propanamide, ● rac-2-(N-[4-amino-5-(4-bromobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, ● rac-ethyl 2-[4-[4-amino-2-(4-fluoro-N-[2-amino-1-methyl-2-oxo-ethyl]anilino)thiazole-5-carbonyl]phenoxy]acetate; ● (R)-ethyl 2-[4-[4-amino-2-(4-fluoro-N-[2-amino-1-methyl-2-oxo-ethyl]anilino)thiazole-5-carbonyl]phenoxy]acetate, ● (S)-ethyl 2-[4-[4-amino-2-(4-fluoro-N-[2-amino-1-methyl-2-oxo-ethyl]anilino)thiazole-5-carbonyl]phenoxy]acetate; rac-2-(N-[4-amino-5-[4-[2-(isopropylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(m-tolylmethylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(o-tolylmethylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[(3-chlorophenyl)methylamino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(4-methylpiperazin-1-yl)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(3-methylanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-(2-morpholino-2-oxo-ethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-oxo-2-[2-(1-piperidyl)ethylamino]ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(4-benzyl-1-piperidyl)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(2-methoxyethylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(4-cyanoanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-[methyl(prop-2-ynyl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-[(2-methoxyphenyl)methylamino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-[(3-methoxyphenyl)methylamino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-[(2-fluorophenyl)methylamino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-[(4-fluorophenyl)methylamino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(1H-benzimidazol-2-ylmethylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-oxo-2-(2,2,2-trifluoroethylamino)ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-[methyl(2-pyridyl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-[methyl-(1-methyl-4-piperidyl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(methoxyamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-[(5-methylisoxazol-3-yl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(ethylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(4-methylanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(cyclohexylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, • rac-3-[[2-[4-[4-amino-2-(N-[2-amino-1-methyl-2-oxo-ethyl]-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]acetyl]amino]benzamide; rac-2-(N-[4-amino-5-[4-[2-oxo-2-(6-quinolylamino)ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; • rac-4-[[2-[4-[4-amino-2-(N-[2-amino-1-methyl-2-oxo-ethyl]-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]acetyl]amino]benzamide; (2S)-1-[2-[4-[4-amino-2-(N-[2-amino-(1RS)-methyl-2-oxo-ethyl]-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]acetyl]pyrrolidine-2-carboxamide (mixture of two diastereomers), rac-2-(N-[4-amino-5-[4-[2-[ethyl(methyl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-[(3-methylisoxazol-5-yl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-[3-(dimethylamino)propyl-methyl-amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[5-[4-[2-(4-acetylpiperazin-1-yl)-2-oxo-ethoxy]benzoyl]-4-amino-thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-oxo-2-(3-pyridylmethylamino)ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; 2-(N-[4-amino-5-[4-[2-(2,3-dihydroxypropylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide (mixture of stereoisomers); rac-2-(N-[4-amino-5-[4-[2-(4-methoxyanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-[benzyl(methyl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(4-chloroanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-[(2-chlorophenyl)methylamino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-[(4-chlorophenyl)methylamino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(4-fluoroanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(azepan-1-yl)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[(4-methoxyphenyl)methylamino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; 2-(N-[4-amino-5-[4-[2-oxo-2-(1-phenylethylamino)ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide (mixture of stereoisomers); rac-2-(N-[4-amino-5-[4-[2-oxo-2-(p-tolylmethylamino)ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[methyl(2-phenylethyl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; 2-(N-[4-amino-5-[4-[2-(3-methyl-1-piperidyl)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide (mixture of stereoisomers); rac-2-(N-[4-amino-5-[4-[2-(4-methyl-1-piperidyl)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[5-[4-[2-(4-acetamidoanilino)-2-oxo-ethoxy]benzoyl]-4-amino-thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-oxo-2-(1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(cyclopentylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(3,4-dihydro-1H-isoquinolin-2-yl)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-(2-isoindolin-2-yl-2-oxo-ethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[2-furylmethyl(methyl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[4-(dimethylamino)-1-piperidyl]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-[methyl(3-pyridylmethyl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(N,2-dimethylanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(N,4-dimethylanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(N,3-dimethylanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[4-[2-(2,2-dimethylpropylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; ● 2-(N-[5-[4-[2-(1-adamantylamino)-2-oxo-ethoxy]benzoyl]-4-amino-thiazol-2-yl]-4-fluoro-anilino)propanamide (single stereoisomer); ● 2-(N-[5-[4-[2-(1-adamantylmethylamino)-2-oxo-ethoxy]benzoyl]-4-amino-thiazol-2-yl]-4-fluoro-anilino)propanamide (single stereoisomer); ● 2-(N-[5-[4-[2-[2-(1-adamantyl)ethylamino]-2-oxo-ethoxy]benzoyl]-4-amino-thiazol-2-yl]-4-fluoro-anilino)propanamide (single stereoisomer); • 2-(N-[4-amino-5-[4-[2-(4-chloroanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide (single stereoisomer); ● 4-[[2-[4-[4-amino-2-(4-fluoro-N-[2-amino-1-methyl-2-oxo-ethyl]anilino)thiazole-5-carbonyl]phenoxy]acetyl]amino]benzamide (single stereoisomer); 2-(N-[4-amino-5-[4-[2-((2RS),3-dihydroxypropylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide (mixture of two diastereomers), • 2-(N-[4-amino-5-[4-[2-oxo-2-[2-(1-piperidyl)ethylamino]ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide (single stereoisomer); ● 2-(N-[4-amino-5-[4-(2-amino-2-oxo-ethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide (single stereoisomer); (R)-2-(N-[4-amino-5-[4-[2-(methylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-[4-[2-(methylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; (R)-2-(N-[4-amino-5-[4-[2-(isopropylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-[4-[2-(isopropylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]-N-isopropyl-2-methyl-propanamide; rac-2-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]-2-methyl-propanamide; ● rac-2-(N-(5-benzoyl-4-methyl-thiazol-2-yl)-4-fluoro-anilino)propanamide, ● rac-2-(N-[4-amino-5-(4-hydroxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, ● rac-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(difluoromethyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3-chloro-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3-chloro-4-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3-chloro-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3-chloro-4-fluoro-anilino)propanamide, ● (R)- 2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3-chloro-4-fluoro-anilino)propanamide, ● (S)- 2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3-chloro-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide; (R)-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide; (S)-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide; (R)-2-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide; rac-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide; ● rac-benzyl N-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-3,4-difluoro-anilino)thiazole-5-carbonyl]phenyl]carbamate, ● (R)-benzyl N-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-3,4-difluoro-anilino)thiazole-5-carbonyl]phenyl]carbamate, ● (S)-benzyl N-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-3,4-difluoro-anilino)thiazole-5-carbonyl]phenyl]carbamate, ● rac-2-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]ethyl acetate; ● rac-benzyl N-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenyl]carbamate, ● (R)-benzyl N-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenyl]carbamate, ● (S)-benzyl N-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenyl]carbamate, ● rac-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide; ● (S)-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, ● rac-2-(N-[4-amino-5-(4-iodobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(6-methoxypyridine-3-carbonyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(6-methoxypyridine-3-carbonyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-(6-methoxypyridine-3-carbonyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide; ● rac-2-(N-[4-amino-5-(4-phenoxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-methoxy-anilino)propanamide, (R)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-methoxy-anilino)propanamide; ● (S)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-methoxy-anilino)propanamide, ● rac-2-(N-[4-amino-5-(4-nitrobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, ● rac-2-(4-fluoro-N-[5-(4-methoxybenzoyl)-4-methyl-thiazol-2-yl]anilino)propanamide, (R)-2-(4-fluoro-N-[5-(4-methoxybenzoyl)-4-methyl-thiazol-2-yl]anilino)propanamide; ● (S)-2-(4-fluoro-N-[5-(4-methoxybenzoyl)-4-methyl-thiazol-2-yl]anilino)propanamide, rac-4-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenyl]cyclopropanecarboxamide; rac-2-(N-[4-amino-5-(4-morpholinobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-(pyrazol-1-ylmethyl)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, ● rac-2-(N-[4-amino-5-[4-(dimethylamino)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-pyrrolidin-1-ylbenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-benzyloxy-anilino)propanamide, (R)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-benzyloxy-anilino)propanamide; (S)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-benzyloxy-anilino)propanamide; ● rac-2-(N-[4-amino-5-[3-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(pyridine-3-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(pyridine-3-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-(pyridine-3-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide; ● rac-2-(N-[5-(4-acetamidobenzoyl)-4-amino-thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(2-chloropyridine-4-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(2-methylpyridine-4-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(2-methylpyridine-4-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-(2-methylpyridine-4-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[2-(difluoromethyl)pyridine-4-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(4-pyridyl)amino]propanamide, rac-2-(N-[4-amino-5-(2-methoxypyridine-4-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3-fluoro-4-methoxy-anilino)propanamide, ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-cyano-3-fluoro-anilino)propanamide, ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-bromo-anilino)propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-3-chloro-4-(difluoromethoxy)anilino]propanamide, ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-ethoxy-anilino)propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(1,3-benzodioxol-5-yl)amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(2,2-difluoro-1,3-benzodioxol-5-yl)amino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-4-(difluoromethoxy)-3-fluoro-anilino]propanamide, ● rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-benzyloxy-anilino)propanamide, ● rac-2-[N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3-chloro-4-(difluoromethoxy)anilino]propanamide, ● rac-2-[N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-3-chloro-4-(difluoromethoxy)anilino]propanamide; ● rac-2-[N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-3-chloro-4-(difluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3-chloro-4-(difluoromethoxy)anilino]propanamide; rac-2-[N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-3-chloro-4-(difluoromethoxy)anilino]propanamide; rac-2-[N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-(difluoromethoxy)-3-fluoro-anilino]propanamide; rac-2-[N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-4-(difluoromethoxy)-3-fluoro-anilino]propanamide; - rac-2-[N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-(difluoromethoxy)-3-fluoro-anilino]propanamide; rac-2-[N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-(difluoromethoxy)-3-fluoro-anilino]propanamide; rac-2-[N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-4-(difluoromethoxy)-3-fluoro-anilino]propanamide; rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-3-chloro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-(2,2-difluoro-1,3-benzodioxol-5-yl)amino]propanamide; rac-2-[[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-(2,2-difluoro-1,3-benzodioxol-5-yl)amino]propanamide; rac-2-[[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-(2,2-difluoro-1,3-benzodioxol-5-yl)amino]propanamide; rac-2-[[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-(2,2-difluoro-1,3-benzodioxol-5-yl)amino]propanamide; rac-2-[[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-(2,2-difluoro-1,3-benzodioxol-5-yl)amino]propanamide; rac-2-[N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3-fluoro-4-(trifluoromethoxy)anilino]propanamide; rac-2-[N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-3-fluoro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-3-fluoro-4-(trifluoromethoxy)anilino]propanamide; rac-2-[N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3-fluoro-4-(trifluoromethoxy)anilino]propanamide; rac-2-[N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-3-fluoro-4-(trifluoromethoxy)anilino]propanamide; rac-2-[N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3-chloro-4-(trifluoromethoxy)anilino]propanamide; ● rac-2-[N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-3-chloro-4-(trifluoromethoxy)anilino]propanamide, ● rac-2-[N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-3-chloro-4-(trifluoromethoxy)anilino]propanamide; rac-2-[N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3-chloro-4-(trifluoromethoxy)anilino]propanamide; rac-2-[N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-3-chloro-4-(trifluoromethoxy)anilino]propanamide; rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(6-methoxy-3-pyridyl)amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-[6-(trifluoromethoxy)-3-pyridyl]amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-[6-(difluoromethoxy)-3-pyridyl]amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-[6-(trifluoromethyl)-3-pyridyl]amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-[6-(difluoromethyl)-3-pyridyl]amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(6-chloro-3-pyridyl)amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(6-fluoro-3-pyridyl)amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(6-methyl-3-pyridyl)amino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-4-fluoro-3-(trifluoromethoxy)anilino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-4-chloro-3-(trifluoromethoxy)anilino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-3-(difluoromethoxy)-4-fluoro-anilino]propanamide; rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-4-chloro-3-(difluoromethoxy)anilino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-2-fluoro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-2-chloro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-4-(difluoromethoxy)-2-fluoro-anilino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-2-chloro-4-(difluoromethoxy)anilino]propanamide, ● rac-2-[N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-(difluoromethyl)anilino]propanamide, ● rac-2-[N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-4-(difluoromethyl)anilino]propanamide, - rac-2-[N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-(difluoromethyl)anilino]propanamide; rac-2-[N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-(difluoromethyl)anilino]propanamide, rac-2-[N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-4-(difluoromethyl)anilino]propanamide; - rac-2-[[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-[6-(trifluoromethoxy)-3-pyridyl]amino]propanamide; rac-2-[[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-[6-(trifluoromethoxy)-3-pyridyl]amino]propanamide; rac-2-[[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-[6-(trifluoromethoxy)-3-pyridyl]amino]propanamide; rac-2-[[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-[6-(trifluoromethoxy)-3-pyridyl]amino]propanamide; ● rac-2-[[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-[6-(difluoromethoxy)-3-pyridyl]amino]propanamide, - rac-2-[[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-[6-(difluoromethoxy)-3-pyridyl]amino]propanamide; - rac-2-[[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-[6-(difluoromethoxy)-3-pyridyl]amino]propanamide; rac-2-[[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-[6-(difluoromethoxy)-3-pyridyl]amino]propanamide; ● rac-benzyl N-[5-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-2-pyridyl]carbamate, ● rac-ethyl 4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]benzoate, ● rac-ethyl 4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-chloro-3-fluoro-anilino)thiazole-5-carbonyl]benzoate, ● rac-ethyl 2-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]-2-methyl-propanoate, rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-N-cyclohexyl-benzamide; rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-N-isopropyl-benzamide; rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-N-benzyl-benzamide; ● 4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-N-[(2S)-2-hydroxypropyl]benzamide (mixture of stereoisomers); rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-N-(2-methoxyethyl)benzamide; 4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-N-[(2R)-2-hydroxypropyl]benzamide (mixture of stereoisomers); rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-N-cyclopropyl-benzamide; rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-N-cyclopentyl-benzamide; rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-chloro-3-fluoro-anilino)thiazole-5-carbonyl]-N-(2-phenoxyethyl)benzamide; rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-chloro-3-fluoro-anilino)thiazole-5-carbonyl]-N-[2-(trifluoromethoxy)ethyl]benzamide; rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-chloro-3-fluoro-anilino)thiazole-5-carbonyl]-N-[2-(difluoromethoxy)ethyl]benzamide; rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-chloro-3-fluoro-anilino)thiazole-5-carbonyl]-N-(2-tert-butoxyethyl)benzamide; rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-chloro-3-fluoro-anilino)thiazole-5-carbonyl]-N-(2-methoxyethyl)benzamide; rac-2-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]-N-[(4-chlorophenyl)methyl]-2-methyl-propanamide; rac-2-(N-[4-amino-5-(6-bromopyridine-3-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-[4-(trifluoromethyl)-1-piperidyl]pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(4-methyl-1-piperidyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-[4-(oxetan-3-yl)-1-piperidyl]pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[6-(dimethylamino)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(4,4-dimethyl-1-piperidyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[6-(3-azabicyclo[3.2.1]octan-3-yl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(3,5-dimethyl-1-piperidyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[6-(3-azabicyclo[3.1.0]hexan-3-yl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(1-piperidyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; rac-2-(N-[4-amino-5-[6-(4,4-difluoro-1-piperidyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(4-cyano-4-methyl-1-piperidyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; (R)-2-(N-[4-amino-5-[6-(4-cyano-4-methyl-1-piperidyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; (S)-2-(N-[4-amino-5-[6-(4-cyano-4-methyl-1-piperidyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide; ● 2-(N-[4-amino-5-(4-hydroxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide (single enantiomer), ● (R)-2-(N-[4-amino-5-(4-hydroxybenzoyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, ● (S)-2-(N-[4-amino-5-(4-hydroxybenzoyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, ● 2-(N-[4-amino-5-(4-hydroxybenzoyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide (enantiomer 1); ● 2-(N-[4-amino-5-(4-hydroxybenzoyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide (enantiomer 2), ● 2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-hydroxy-anilino)propanamide (single enantiomer), and rac-2-(N-[4-amino-5-[4-(2-hydroxyethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0217] In some preferred embodiments, the inhibitor of DGKzeta is a compound according to this list.

[0218] DGKzeta inhibitor A' In a preferred embodiment of the present invention, the inhibitor of DGKzeta is (R)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0219] In another preferred embodiment of the present invention, the inhibitor of DGKzeta is (R)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0220] In another preferred embodiment of the present invention, the inhibitor of DGKzeta is (R)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide.

[0221] In another preferred embodiment of the present invention, the inhibitor of DGKzeta has the structure: [ka] or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0222] In another preferred embodiment of the present invention, the inhibitor of DGKzeta has the structure: [ka] or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0223] In another preferred embodiment of the present invention, the DGKzeta inhibitor has the structure: [ka] DGKzeta inhibitor A'.

[0224] The synthesis of DGKzeta inhibitor A' is described in International Patent Application PCT / EP2021 / 060167, Example 62.2. International Patent Application PCT / EP2021 / 060167 also discloses methods for preparing other compounds of formula (II) described herein.

[0225] Embodiment Combination Embodiments Aspect 1 According to a first aspect, the present invention provides a combination comprising one or more inhibitors of DGKalpha and one or more inhibitors of DGKzeta.

[0226] In another embodiment, the present invention provides a combination comprising one inhibitor of DGKalpha and one inhibitor of DGKzeta.

[0227] In another embodiment, the present invention provides a combination comprising one DGKalpha inhibitor compound of general formula (I) as described herein and one DGKzeta inhibitor compound of general formula (II) as described herein, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0228] In another embodiment, the present invention provides a combination comprising one DGKalpha inhibitor compound of general formula (I) as described herein and one DGKzeta inhibitor compound of general formula (II) as described herein.

[0229] In another embodiment, the present invention provides a combination comprising DGKalpha inhibitor A and DGKzeta inhibitor A' described herein, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0230] In another embodiment, the present invention provides a combination comprising a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein.

[0231] In another embodiment, the present invention provides a combination comprising a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 20:1 to 1:20.

[0232] In another embodiment, the present invention provides a combination comprising a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 12:1 to 1:12.

[0233] In another embodiment, the present invention provides a combination comprising a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 12:1 to 8:1.

[0234] In another embodiment, the present invention provides a combination comprising a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 10:1 to 1:1.

[0235] In another embodiment, the present invention provides a combination comprising a DGKalpha inhibitor A and a DGKzeta inhibitor A' described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is about 10:1.

[0236] In another embodiment, the present invention provides a combination comprising a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 4:1 to 2:1.

[0237] In another embodiment, the present invention provides a combination comprising a DGKalpha inhibitor A and a DGKzeta inhibitor A' described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is about 3:1.

[0238] In another embodiment, the present invention provides a combination comprising a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 2:1 to 1:2.

[0239] In another embodiment, the present invention provides a combination comprising a DGKalpha inhibitor A and a DGKzeta inhibitor A' described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is about 1:1.

[0240] In another embodiment, the present invention provides a combination comprising a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 1:2 to 1:4.

[0241] In another embodiment, the present invention provides a combination comprising a DGKalpha inhibitor A and a DGKzeta inhibitor A' described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is about 1:3.

[0242] In another embodiment, the present invention provides a combination comprising a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 1:8 to 1:12.

[0243] In another embodiment, the present invention provides a combination comprising a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 1:1 to 1:10.

[0244] In another embodiment, the present invention provides a combination comprising a DGKalpha inhibitor A and a DGKzeta inhibitor A' described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is about 1:10.

[0245] In another embodiment, the present invention provides a combination consisting of one or more inhibitors of DGKalpha and one or more inhibitors of DGKzeta.

[0246] In another embodiment, the present invention provides a combination consisting of one inhibitor of DGKalpha and one inhibitor of DGKzeta.

[0247] In another embodiment, the present invention provides a combination consisting of one DGKalpha inhibitor compound of general formula (I) as described herein and one DGKzeta inhibitor compound of general formula (II) as described herein, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0248] In another embodiment, the present invention provides a combination consisting of one DGKalpha inhibitor compound of general formula (I) as described herein and one DGKzeta inhibitor compound of general formula (II) as described herein.

[0249] In a preferred embodiment, the present invention provides a combination consisting of DGKalpha inhibitor A and DGKzeta inhibitor A' described herein, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0250] In another preferred embodiment, the present invention provides a combination consisting of DGKalpha inhibitor A and DGKzeta inhibitor A', or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof, as described herein.

[0251] In another preferred embodiment, the present invention provides a combination consisting of a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein.

[0252] In another embodiment, the present invention provides a combination consisting of a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 20:1 to 1:20.

[0253] In another embodiment, the present invention provides a combination consisting of a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 12:1 to 1:12.

[0254] In another embodiment, the present invention provides a combination consisting of a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 12:1 to 8:1.

[0255] In another embodiment, the present invention provides a combination consisting of a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 10:1 to 1:1.

[0256] In another embodiment, the present invention provides a combination consisting of a DGKalpha inhibitor A and a DGKzeta inhibitor A' described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is about 10:1.

[0257] In another embodiment, the present invention provides a combination consisting of a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 4:1 to 2:1.

[0258] In another embodiment, the present invention provides a combination consisting of a DGKalpha inhibitor A and a DGKzeta inhibitor A' described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is about 3:1.

[0259] In another embodiment, the present invention provides a combination consisting of a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 2:1 to 1:2.

[0260] In another embodiment, the present invention provides a combination consisting of a DGKalpha inhibitor A and a DGKzeta inhibitor A' described herein, wherein the dosage ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is about 1:1.

[0261] In another embodiment, the present invention provides a combination consisting of a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 1:2 to 1:4.

[0262] In another embodiment, the present invention provides a combination consisting of a DGKalpha inhibitor A and a DGKzeta inhibitor A' described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is about 1:3.

[0263] In another embodiment, the present invention provides a combination consisting of a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 1:8 to 1:12.

[0264] In another embodiment, the present invention provides a combination consisting of a DGKalpha inhibitor A and a DGKzeta inhibitor A' as described herein, wherein the dose ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 1:1 to 1:10.

[0265] In another embodiment, the present invention provides a combination consisting of a DGKalpha inhibitor A and a DGKzeta inhibitor A' described herein, wherein the dosage ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is about 1:10.

[0266] In another preferred embodiment, the combination of the present invention comprises DGKalpha inhibitor A and DGKzeta inhibitor A', or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0267] In another preferred embodiment, the combination of the present invention consists of DGKalpha inhibitor A and DGKzeta inhibitor A', or stereoisomers, tautomers, N-oxides, hydrates, solvates, or salts thereof, or mixtures thereof.

[0268] In another preferred embodiment, the combination of the present invention comprises a DGKalpha inhibitor A and a DGKzeta inhibitor A'.

[0269] In another preferred embodiment, the combination of the present invention consists of a DGKalpha inhibitor A and a DGKzeta inhibitor A'.

[0270] In another preferred embodiment, the combination of the present invention comprises 6-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide and (R)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0271] In another preferred embodiment, the combination of the present invention consists of 6-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide and (R)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

[0272] In another preferred embodiment, the combination of the invention comprises 6-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide and (R)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide.

[0273] In another preferred embodiment, the combination of the invention consists of 6-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide and (R)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide.

[0274] The combinations of the present invention can be administered by oral, intravenous, topical, local installations, intraperitoneal or intranasal routes.

[0275] Inhibitors of DGKalpha can be administered orally, intravenously, topically, locally, intraperitoneally or via the intranasal route.

[0276] Inhibitors of DGKzeta can be administered orally, intravenously, topically, locally, intraperitoneally or via the nasal route.

[0277] The inhibitor of DGKalpha may be in the form of a ready-to-use pharmaceutical formulation to be administered simultaneously, concurrently, separately or sequentially with the inhibitor of DGKzeta and optionally component C, as further described below. The inhibitor of DGKalpha and the inhibitor of DGKzeta and optionally component C may be administered independently of each other by oral, intravenous, topical, local, intraperitoneal or nasal routes.

[0278] A combination comprising one or more inhibitors of DGKalpha and one or more inhibitors of DGKzeta as described and defined herein is also referred to as a "combination of the invention".

[0279] The surprising behavior of the combination of the present invention has been demonstrated using DGK inhibitors (DGKalpha inhibitor A and DGKzeta inhibitor A') as specifically disclosed in the Examples section herein.

[0280] Kit embodiments Aspect 2 According to a second aspect, the present invention provides a method for producing a method for manufacturing a semiconductor device comprising: one DGKalpha inhibitor compound of general formula (I) as described herein, more particularly DGKalpha inhibitor A, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof; One DGKzeta inhibitor compound of general formula (II) as described herein, more specifically DGKzeta inhibitor A', or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof. A kit comprising:

[0281] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof; DGKzeta inhibitor A', or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof A kit comprising:

[0282] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof; DGKzeta inhibitor A', or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof A kit comprising:

[0283] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, DGKzeta inhibitor A' A kit comprising:

[0284] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, DGKzeta inhibitor A' The present invention provides a kit comprising the above-mentioned compounds, wherein the dosage ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 20:1 to 1:20.

[0285] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, DGKzeta inhibitor A' The present invention provides a kit comprising the above-mentioned compounds, wherein the dosage ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 12:1 to 1:12.

[0286] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, DGKzeta inhibitor A' The present invention provides a kit comprising the above-mentioned compounds, wherein the dosage ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 12:1 to 8:1.

[0287] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, DGKzeta inhibitor A' The present invention provides a kit comprising the above-mentioned compounds, wherein the dosage ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 10:1 to 1:1.

[0288] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, DGKzeta inhibitor A', wherein the dosage ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is about 10:1.

[0289] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, DGKzeta inhibitor A' The present invention provides a kit comprising the above-mentioned compounds, wherein the dosage ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 4:1 to 2:1.

[0290] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, DGKzeta inhibitor A' wherein the dosage ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is about 3:1.

[0291] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, DGKzeta inhibitor A' The present invention provides a kit comprising the above-mentioned compounds, wherein the dosage ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 2:1 to 1:2.

[0292] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, DGKzeta inhibitor A' wherein the dosage ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is about 1:1.

[0293] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, DGKzeta inhibitor A' The present invention provides a kit comprising the above-mentioned compounds, wherein the dosage ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 1:2 to 1:4.

[0294] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, DGKzeta inhibitor A' wherein the dosage ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is about 1:3.

[0295] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, DGKzeta inhibitor A' The present invention provides a kit comprising the above-mentioned compounds, wherein the dosage ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 1:8 to 1:12.

[0296] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, DGKzeta inhibitor A' The present invention provides a kit comprising the above-mentioned compounds, wherein the dosage ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is within the range of 1:1 to 1:10.

[0297] In another preferred embodiment, the present invention provides: DGKalpha inhibitor A, DGKzeta inhibitor A' wherein the dosage ratio (mg or mg / kg of DGKalpha inhibitor A:mg or mg / kg of DGKzeta inhibitor A') is about 1:10.

[0298] In the kit, optionally, one or both of the DGKalpha inhibitor compound and the DGKzeta inhibitor compound in any of the above combinations are in the form of a pharmaceutical composition that can be administered simultaneously, in parallel, separately, or sequentially.The DGKalpha inhibitor compound and the DGKzeta inhibitor compound can be administered orally, intravenously, topically, locally, intraperitoneally, or intranasally, independently of each other.Preferably, the DGKalpha inhibitor compound and the DGKzeta inhibitor compound are both administered orally, or the DGKalpha inhibitor compound is administered orally and the DGKzeta inhibitor compound is administered intravenously, or vice versa.

[0299] In another embodiment, the present invention provides: one DGKalpha inhibitor compound of general formula (I) as described herein, more particularly DGKalpha inhibitor A, or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof; one DGKzeta inhibitor compound of general formula (II) as described herein, more particularly DGKzeta inhibitor A', or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof, and optionally Component C: One or more, preferably one, additional agent(s), and / or CAR-T cells A kit comprising: In any of the above combinations, optionally, a kit is provided in which the one DGKalpha inhibitor compound, the one DGKzeta inhibitor compound, and any or all of the component C are in the form of a pharmaceutical composition that can be administered simultaneously, in parallel, separately, or sequentially. The one DGKalpha inhibitor compound, the one DGKzeta inhibitor compound, and optionally component C can be administered orally, intravenously, topically, locally, intraperitoneally, or intranasally, independently of each other.

[0300] In another embodiment, the present invention provides: DGKalpha inhibitor A, or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof; DGKzeta inhibitor A', or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof, and optionally Component C: One or more, preferably one, additional agents and / or CAR-T cells A kit comprising: In any of the above combinations, optionally, a kit is provided in which any or all of the DGKalpha inhibitor A, or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof, the DGKzeta inhibitor A', or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, and component C are in the form of a pharmaceutical composition that can be administered simultaneously, in parallel, separately, or sequentially. The DGKalpha inhibitor A, or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof, the DGKzeta inhibitor A', or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, and optionally component C can be administered orally, intravenously, topically, locally, intraperitoneally, or intranasally, independently of one another.

[0301] In another embodiment, the present invention provides: DGKalpha inhibitor A, DGKzeta inhibitor A', and optionally, Component C: One or more, preferably one, additional agents and / or CAR-T cells A kit comprising: In any of the above combinations, optionally, a kit is provided in which any or all of the DGKalpha inhibitor A, the DGKzeta inhibitor A', and the component C are in the form of a pharmaceutical composition that can be administered simultaneously, in parallel, separately, or sequentially. The DGKalpha inhibitor A, the DGKzeta inhibitor A', and optionally the component C can be administered orally, intravenously, topically, locally, intraperitoneally, or intranasally, independently of each other.

[0302] In another embodiment, the present invention provides a kit wherein the one DGKalpha inhibitor compound, the one DGKzeta inhibitor compound, and optionally component C are each in the form of a pharmaceutical composition, and the one DGKalpha inhibitor compound is administered before the one DGKzeta inhibitor compound, and optionally the one DGKalpha inhibitor compound is administered before component C.

[0303] In another embodiment, the present invention provides a kit, wherein the one DGKalpha inhibitor compound and the one DGKzeta inhibitor compound are in the form of two or more pharmaceutical compositions, and the one DGKalpha inhibitor compound is administered before the one DGKzeta inhibitor compound.

[0304] In another embodiment, the present invention provides a kit wherein the one DGKalpha inhibitor compound and the one DGKzeta inhibitor compound are in the form of two or more pharmaceutical compositions, and the one DGKzeta inhibitor compound is administered before the one DGKalpha inhibitor compound.

[0305] The term "component C" refers to the active compound itself, as well as its pharmaceutically acceptable salts, solvates, hydrates, or stereoisomers, and any additional components containing at least one drug, including any pharmaceutical composition containing such an active compound or its pharmaceutically acceptable salts, solvates, hydrates, or stereoisomers, and / or chimeric antigen receptor T cells (CAR-T cells), such as axicabtagen-ciloleucel or tisagenlecleucel. CAR-T cell activity can be suppressed by the tumor microenvironment (TME). Knockout of DGK by techniques such as Crispr has been shown to enhance CAR-T cell activity in the suppressive TME (IY Jung et al., Mol. Cells 2018, 41(8), 717-723). As used herein, the term "CAR-T cells" includes chimeric antigen receptor natural killer T cells (CAR-NKT cells) and chimeric antigen receptor natural killer cells (CAR-NK cells).

[0306] A list of said agents of Component C is further provided below. Preferably, the chimeric antigen receptor T cells (CAR-T cells) of Component C are Axicabtagen-Ciloleucel or Tisagenlecleucel.

[0307] The DGK inhibitor combination of the present invention can be administered as a single agent or in combination with one or more additional agents C, where the resulting combination of the DGK inhibitor and component C does not cause unacceptable adverse effects. For example, the DGK inhibitor combination of the present invention, e.g., a combination of one inhibitor of DGKalpha and one inhibitor of DGKzeta, can be combined with component C, i.e., one or more additional agents, such as known antiangiogenic agents, antihyperproliferative agents, anti-inflammatory agents, analgesics, immunomodulators, diuretics, antiarrhythmic agents, antihypercholesterolemic agents, antidyslipidemic agents, antidiabetic agents, or antiviral agents, as well as mixtures and combinations thereof.

[0308] The optional drug that can be added as component C to the DGK inhibitor combination of the present invention, e.g., a combination of one inhibitor of DGKalpha and one inhibitor of DGKzeta, can be one or more drugs, and can be, for example, 131I-chTNT, abarelix, abiraterone, aclarubicin, adalimumab, adotrastuzumab emtansine, afatinib, aflibercept, aldesleukin, alectinib, alemtuzumab, alendronate, alitretinoin, altretamine, amifostine, aminoglutethimide, hexylaminolevulinic acid, benzodiazepine, benzocaine, benzophenone, benzocaine ... nate, amrubicin, amsacrine, anastrozole, ancestim, anetholedithiole, anetumab ravtansine, angiotensin II, antithrombin III, aprepitant, arcitumomab, aruglavin, arsenic trioxide, asparaginase, axitinib, azacitidine, basiliximab, belotecan, bendamustine, besilesomab, belinostat, bevacizumab, bexarotene, bicalutamide, bisantrene, bleomycin, blinatumomab, bortezomib, buserelin, bosutinib, brentuximab vedotin, busulfan, cabazitaxel, cabozantinib, calcitonin, calcium folinate, calcium levofolinate, capecitabine, capromab, carbamazepine Carboplatin, carboquin, carfilzomib, carmofur, carmustine, catumaxomab, celecoxib, cermoleukin, ceritinib, cetuximab, chlorambucil, chlormadinone, chlormethine, cidofovir, cinacalcet, cisplatin, cladribine, clodronate, clofarabine, cobimetinib, copanlisib, crisantaspase, crizotinib, cyclophosphamide, cyproterone, cytarabine, dacarbazine, dactinomycin, daratumumab, darbepoetin alfa, dabrafenib, dasatinib, daunorubicin, decitabine, degarelix, denileukin Diftitox, denosumab, depreotide, deslorelin, dianhydrogalactitol, dexrazoxane, dibrospidium chloride, dianhydrogalactitol, diclofenac, dinutuximab, docetaxel, dolasetron, doxifluridine, doxorubicin, doxorubicin + estrone, dronabinol, eculizumab, edrecolomab,Elliptinium acetate, elotuzumab, eltrombopag, endostatin, enocitabine, enzalutamide, epirubicin, epithiostanol, epoetin alfa, epoetin beta, epoetin zeta, eptaplatin, eribulin, erlotinib, esomeprazole, estradiol, estramustine, ethinyl estradiol, etoposide, everolimus, exemestane, fadrozole, fentanyl, filgrastim, fluoxymesterone, floxuridine, fludarabine, fluorouracil, flutamide, folinic acid Acid, formestane, fosaprepitant, fotemustine, fulvestrant, gadobutrol, gadoteridol, gadoterate meglumine, gadovertamide, gadoxetic acid, gallium nitrate, ganirelix, gefitinib, gemcitabine, gemtuzumab, glucarpidase, glutoxime, GM-CSF, goserelin, granisetron, granulocyte colony-stimulating factor, histamine dihydrochloride, histrelin, hydroxycarbamide, I-125 seed, lansoprazole, ibandronate, ibritumomab tiuxetan, ibrutinib, idarubicin, ifos Famid, imatinib, imiquimod, improsulfan, indisetron, incadronic acid, ingenol mebutate, interferon alpha, interferon beta, interferon gamma, iobitridol, iobengan (123I), iomeprol, irinotecan, itraconazole, ixabepilone, ixazomib, lanreotide, lansoprazole, lapatinib, iasocoline, lenalidomide, lenvatinib, lenograstim, lentinan, letrozole, leuprorelin, levamisole, levonorgestrel, levothyroxine sodium, rizulide, lobaplatin, lomustine, lonidamine, masoprocol, medroxyprogesterone, megastrol, melarsoprol, melphalan, mepitiostane, mercaptopurine, mesna, methadone, methotrexate, methoxsalen, methyl aminolevulinate, methylprednisolone, methyltestosterone, metyrosine, mifamurtide, miltefosine, miriplatin, mitobronitol, mitoguazone, mitolactol, mitomycin, mitotane, mitoxantrone, mogamulizumab, molgramostim, mopidamol,Morphine hydrochloride, morphine sulfate, nabilone, nabiximols, nafarelin, naloxone + pentazocine, naltrexone, nartograstim, necitumumab, nedaplatin, nelarabine, neridronic acid, netupitant / palonosetron, pentetreotide, nilotinib, nilutamide, nimorazole, nimotuzumab, nimustine, nintedanib, nitracrine, nivolumab, obinutuzumab, octreotide, ofatumumab, olaparib, olaratumab, omacetaxine mepesuxinate, omeprazole, ondancetro oprelvekin, orgotein, olilotimod, osimertinib, oxaliplatin, oxycodone, oxymetholone, ozogamicin, p53 gene therapy, paclitaxel, palbociclib, palifermin, palladium-103 seed, palonosetron, pamidronate, panitumumab, panobinostat, pantoprazole, pazopanib, pegaspargase, pegepoetin beta (methoxy PEG-epoetin beta), pegfilgrastim, peginterferon alfa-2b, pemetrexed, pentazocine , pentostatin, peplomycin, perflubutan, perfosfamide, pertuzumab, picibanil, pilocarpine, pirarubicin, pixantrone, plerixafor, plicamycin, poliglusum, 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, risedronate, etidronate rhenium 186, rituximab, rolapitant, romidepsin, romiplostim, romurtide, rucaparib, samarium (153Sm) lexidronam, sargramostim, satumomab, secretin, siltuximab, sipuleucel-T, sizofiran, sobuzoxane, sodium glycididazole, sonidegib, sorafenib, stanozolol, streptozocin,Sunitinib, talaporfin, talimogine 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, thyrotropin alfa, thioguanine, tocilizumab, topotecan, toremifene, tositumomab, trabectedin, trametinib, tramadol, trastuzumab Emtansine, treosulfan, tretinoin, trifluridine + tipiracil, trilostane, triptorelin, trametinib, trofosfamide, thrombopoietin, tryptophan, ubenimex, varatinib, valrubicin, vandetanib, vapreotide, vemurafenib, vinblastine, vincristine, vindesine, vinflunine, vinorelbine, vismodegib, vorinostat, vorozole, yttrium-90 glass microspheres, zinostatin, zinostatin stimalamer, zoledronic acid, and zorubicin.

[0309] In general, the use of an agent as component C in combination with a combination of inhibitors of DGK according to the invention, for exa...

Claims

1. A combination comprising one or more inhibitors of DGKalpha and one or more inhibitors of DGKzeta.

2. 2. The combination of claim 1, comprising one inhibitor of DGKalpha and one inhibitor of DGKzeta.

3. General formula (I): 【Chemistry 1】 [During the ceremony, R １ is cyano, -C(=O)NH ２ , -C(=O)N(H)CH ３ , -C(=O)N(H)C ２ H ５ , -C(=O)N(CH ３ ) ２ and —C(═O)OR １５ represents R ２ represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl; wherein the 5- to 10-membered heteroaryl group is attached to the remainder of the molecule through a carbon atom of said 5- to 10-membered heteroaryl group; and wherein the phenyl, naphthyl and 5- to 10-membered heteroaryl groups may be substituted 1, 2, 3 or 4 times, and each substituent is independently a halogen atom or a C １ -C ６ -Alkyl, C ３ -C ６ -cycloalkyl, C １ -C ６ -hydroxyalkyl, C １ -C ６ -haloalkyl, (C １ -C ２ -alkoxy)-(C １ -C ６ -alkyl)-, C １ -C ６ -alkoxy, (C １ -C ２ -alkoxy)-(C １ -C ６ -alkoxy)-, C １ -C ６ -haloalkoxy, C ３ -C ６ -cycloalkyloxy, phenoxy, -SR １４ , -S(=O)R １４ , -S(=O) ２ R １４ , -P(=O)(R １４ ) ２ , cyano, hydroxy, -N(R ９ ) (R １０ ), -C(=O)N(R ９ ) (R １０ ), -C(=O)R １１ , -N(R １２ ) C(=O)R １３ , -N(R １２ ) S(=O) ２ R １４ , -N=S(=NH)(R １４ ) ２ , -N=S(=O)(R １４ ) ２ , 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl, and 5- or 6-membered heteroaryl; Or, two substituents of the phenyl group, when they are attached to adjacent ring atoms, can be joined to form —(CH ２ ) ３ -, -CH ２ -CH(OH)-CH ２ -, -(CH ２ ) ４ -, -O-(CH ２ ) ２ -, -(CH ２ ) ２ —O—, —CH ２ -CH(CH ３ ) —O—, —CH ２ -O-CH ２ -, -O-(CH ２ ) ３ -, -(CH ２ ) ３ —O—, —CH ２ -O-(CH ２ ) ２ -, -(CH ２ ) ２ -O-CH ２ --, --O-CH ２ -O-, -OC(CH ３ ) ２ -O-, -O-(CH ２ ) ２ -O-, -N(R １８ )-C(=O)-(C(R １８ ) (R １９ )) ｍ -, -N(R １８ )-C(=O)-(C(CH ２ ) ３ ) -, -N(R １８ )-(C(R １８ ) (R １９ )) ｍ -, -N(R １８ )—C(═O)—O— and —N(R １８ )-C(=O)-N(R １８ )-, wherein said 4- to 7-membered heterocycloalkyl group and said 5- to 7-membered heterocycloalkenyl group are attached to the remainder of the molecule through a carbon atom of said 4- to 7-membered heterocycloalkyl group and said 5- to 7-membered heterocycloalkenyl group; and wherein the 4- to 7-membered heterocycloalkyl group, the 5- to 7-membered heterocycloalkenyl group, and the (4- to 7-membered heterocycloalkyl)oxy group may be substituted one, two, or three times, and each substituent is independently a halogen atom, or １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl, -N(R ９ ) (R １０ ) and oxo; and Here, the C １ -C ６ -Alkyl and C １ -C ６ -alkoxy group is C ３ -C ４ - optionally substituted with a group selected from cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl; wherein said 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of said 4- to 7-membered heterocycloalkyl group; and wherein the 4- to 7-membered heterocycloalkyl group may be substituted one, two or three times, and each substituent is independently a halogen atom or a C １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl, -N(R ９ ) (R １０ ) and oxo; and wherein the phenyl group may be substituted one or two times, and each substituent is independently a halogen atom or a C １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl and -N(R ９ ) (R １０ ) selected from the group selected from and Here, C ３ -C ４ - the cycloalkyl group may be substituted one or two times, each substituent being independently selected from a halogen atom or a group selected from cyano and hydroxy; and Here, the C ３ -C ６ -cycloalkyl groups may be substituted one or two times, each substituent independently being a halogen atom or a C １ -C ４ - alkyl groups, and wherein the phenyl, phenoxy and 5- or 6-membered heteroaryl groups may be substituted one or two times, each substituent independently being a halogen atom or a C １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl and -N(R ９ ) (R １０ ) selected from the group selected from R ３ is a hydrogen atom, a halogen atom, or C １ -C ６ -Alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl, C ３ -C ６ -cycloalkyl, C ４ -C ６ -cycloalkenyl, C １ -C ６ -hydroxyalkyl, C １ -C ６ -haloalkyl, (C １ -C ２ -alkoxy)-(C １ -C ６ -alkyl)-, C １ -C ６ -alkoxy, (C １ -C ２ -alkoxy)-(C １ -C ６ -alkoxy)-, C １ -C ４ -haloalkoxy, C ３ -C ６ -cycloalkyloxy, phenoxy, -SR １４ , -S(=O)R １４ , -S(=O) ２ R １４ , cyano, hydroxy, -N(R ９ ) (R １０ ), -C(=O)N(R ９ ) (R １０ ), -C(=O)R １１ , -N(R １２ ) C(=O)R １３ , -N(R １２ ) S(=O) ２ R １４ , -N=S(=NH)(R １４ ) ２ , -N=S(=O)(R １４ ) ２ , -P(=O)(R １４ ) ２ represents a group selected from 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl, and 5- or 6-membered heteroaryl; wherein said 4- to 7-membered heterocycloalkyl group and said 5- to 7-membered heterocycloalkenyl group are linked to the remainder of the molecule through a carbon atom of said 4- to 7-membered heterocycloalkyl group and said 5- to 7-membered heterocycloalkenyl group; and wherein the 4- to 7-membered heterocycloalkyl group, the 5- to 7-membered heterocycloalkenyl group, and the (4- to 7-membered heterocycloalkyl)oxy group may be substituted one, two, or three times, and each substituent is independently a halogen atom, or １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl, -N(R ９ ) (R １０ ) and oxo; and Here, the C １ -C ６ -Alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl and C １ -C ６ -alkoxy group is C ３ -C ４ - optionally substituted with a group selected from cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl; wherein said 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of said 4- to 7-membered heterocycloalkyl group; and wherein the 4- to 7-membered heterocycloalkyl group may be substituted one, two or three times, and each substituent is independently a halogen atom or a C １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl, -N(R ９ ) (R １０ ) and oxo; and wherein the phenyl group may be substituted one or two times, and each substituent is independently a halogen atom or a C １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl and -N(R ９ ) (R １０ ) selected from the group selected from and Here, C ３ -C ４ - the cycloalkyl group may be substituted one or two times, each substituent being independently selected from a halogen atom or a group selected from cyano and hydroxy; and Here, the C ２ -C ６ -Alkenyl group is C １ -C ４ -optionally substituted with a haloalkyl group, and Here, the C ３ -C ６ -cycloalkyl and C ４ -C ６ -cycloalkenyl groups may be substituted one or two times, each substituent independently being a halogen atom or a C １ -C ４ -Alkyl and C １ -C ４ -haloalkyl, and wherein the phenyl, phenoxy and 5- or 6-membered heteroaryl groups may be substituted one or two times, each substituent independently being a halogen atom or a C １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl and -N(R ９ ) (R １０ ) selected from the group selected from R ４ is a hydrogen atom or a halogen atom, or C １ -C ６ -Alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl, C ３ -C ６ -cycloalkyl, C ４ -C ６ -cycloalkenyl, C １ -C ６ -hydroxyalkyl, C １ -C ６ -haloalkyl, (C １ -C ２ -alkoxy)-(C １ -C ６ -alkyl)-, C １ -C ６ -alkoxy, (C １ -C ２ -alkoxy)-(C １ -C ６ -alkoxy)-, C １ -C ４ -haloalkoxy, -O-(C １ -C ４ -alkyl)-C(=O)OR １５ , —O—(C １ -C ４ -alkyl)-C(=O)n(R ９ ) (R １０ ), C ３ -C ６ -cycloalkyloxy, -S(=O)R １４ , -S(=O) ２ R １４ , cyano, nitro, hydroxy, -N(R ９ ) (R １０ ), -N(R １６ ) (R １７ ), -N(R １６ ) (R ２０ ), -C(=O)N(R ９ ) (R １０ ), -C(=O)R １１ , -N(R １２ ) C(=O)R １３ , -N(R １２ ) S(=O) ２ R １４ , -N=S(=NH)(R １４ ) ２ , -N=S(=O)(R １４ ) ２ , -P(=O)(R １４ ) ２ represents a group selected from 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl, and 5- or 6-membered heteroaryl; wherein said 4- to 7-membered heterocycloalkyl group and said 5- to 7-membered heterocycloalkenyl group are attached to the remainder of the molecule through a carbon atom of said 4- to 7-membered heterocycloalkyl group and said 5- to 7-membered heterocycloalkenyl group; and wherein the 4- to 7-membered heterocycloalkyl group, the 5- to 7-membered heterocycloalkenyl group, and the (4- to 7-membered heterocycloalkyl)oxy group may be substituted one, two, or three times, and each substituent is independently a halogen atom, or １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl, -N(R ９ ) (R １０ ) and oxo; and Here, the C １ -C ６ -Alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl and C １ -C ６ -alkoxy group is C ３ -C ４ - optionally substituted with a group selected from cycloalkyl and 4- to 7-membered heterocycloalkyl; wherein said 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of said 4- to 7-membered heterocycloalkyl group; and wherein the 4- to 7-membered heterocycloalkyl group may be substituted one, two or three times, and each substituent is independently a halogen atom or a C １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl, -N(R ９ ) (R １０ ) and oxo; and wherein the phenyl group may be substituted one or two times, and each substituent is independently a halogen atom or a C １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl and -N(R ９ ) (R １０ ) selected from the group selected from and Here, C ３ -C ４ - the cycloalkyl group may be substituted one or two times, each substituent being independently selected from a halogen atom or a group selected from cyano and hydroxy; and Here, the C １ -C ６ -alkoxy groups may be substituted with oxiran-2-yl groups, and Here, the C ３ -C ６ -cycloalkyl and C ４ -C ６ -cycloalkenyl groups may be substituted one or two times, each substituent independently being a halogen atom or a C １ -C ４ - alkyl groups, and wherein the phenyl and 5- or 6-membered heteroaryl groups may be substituted one or two times, each substituent independently being a halogen atom or a C １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl and -N(R ９ ) (R １０ ) selected from the group selected from R ５ is a hydrogen atom or a halogen atom, or C １ -C ６ -Alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl, C ３ -C ６ -cycloalkyl, C ４ -C ６ -cycloalkenyl, C １ -C ６ -hydroxyalkyl, C １ -C ６ -haloalkyl, (C １ -C ２ -alkoxy)-(C １ -C ６ -alkyl)-, C １ -C ６ -alkoxy, (C １ -C ２ -alkoxy)-(C ２ -C ６ -alkoxy)-, C １ -C ４ -haloalkoxy, C ３ -C ６ -cycloalkyloxy, phenoxy, -SR １４ , -S(=O)R １４ , -S(=O) ２ R １４ , cyano, hydroxy, -N(R ９ ) (R １０ ), -C(=O)N(R ９ ) (R １０ ), -C(=O)R １１ , -N(R １２ ) C(=O)R １３ , -N(R １２ ) S(=O) ２ R １４ , -N=S(=NH)(R １４ ) ２ , -N=S(=O)(R １４ ) ２ , -P(=O)(R １４ ) ２ represents a group selected from 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, phenyl, and 5- or 6-membered heteroaryl; wherein said 4- to 7-membered heterocycloalkyl group and said 5- to 7-membered heterocycloalkenyl group are attached to the remainder of the molecule through a carbon atom of said 4- to 7-membered heterocycloalkyl group and said 5- to 7-membered heterocycloalkenyl group; and wherein the 4- to 7-membered heterocycloalkyl group, the 5- to 7-membered heterocycloalkenyl group, and the (4- to 7-membered heterocycloalkyl)oxy group may be substituted one, two, or three times, and each substituent is independently a halogen atom, or １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl, -N(R ９ ) (R １０ ) and oxo; and Here, the C １ -C ６ -Alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl and C １ -C ６ -alkoxy group is C ３ -C ４ - optionally substituted with a group selected from cycloalkyl, phenyl and 4- to 7-membered heterocycloalkyl; wherein said 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of said 4- to 7-membered heterocycloalkyl group; and wherein the 4- to 7-membered heterocycloalkyl group may be substituted one, two or three times, and each substituent is independently a halogen atom or a C １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl, -N(R ９ ) (R １０ ) and oxo; and wherein the phenyl group may be substituted one or two times, and each substituent is independently a halogen atom or a C １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl and -N(R ９ ) (R １０ ) selected from the group selected from and Here, C ３ -C ４ - the cycloalkyl group may be substituted one or two times, each substituent being independently selected from a halogen atom or a group selected from cyano and hydroxy; and Here, the C ３ -C ６ -cycloalkyl and C ４ -C ６ -cycloalkenyl groups may be substituted one or two times, each substituent independently being a halogen atom or a C １ -C ４ - alkyl groups, and wherein the phenyl, phenoxy and 5- or 6-membered heteroaryl groups may be substituted one or two times, each substituent independently being a halogen atom or a C １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl and -N(R ９ ) (R １０ ) selected from the group selected from R ６ is a hydrogen atom, a fluorine atom, or C １ -C ４ -Alkyl, C １ -C ４ -hydroxyalkyl, C １ -C ４ represents a group selected from alkoxy, hydroxy and oxo, R ７ is a hydrogen atom or a halogen atom, or C １ -C ４ -Alkyl, C １ -C ４ represents a group selected from alkoxy, hydroxy and cyano, R ８ represents a group selected from methyl and ethyl, R ９ and R １０ are each independently a hydrogen atom or C １ -C ４ -Alkyl, C ２ -C ４ -hydroxyalkyl, N≡C—(C １ -C ４ -alkyl)-, (C １ -C ４ -alkoxy)-(C ２ -C ４ -alkyl)-, C ３ -C ４ -cycloalkyl and C ２ -C ４ -haloalkyl, or R ９ and R １０ together with the nitrogen to which they are attached represent a nitrogen-containing 4- to 7-membered heterocycloalkyl group; wherein the nitrogen-containing 4- to 7-membered heterocycloalkyl group may be substituted one, two or three times, and each substituent is independently a halogen atom or a C １ -C ４ -Alkyl, C ３ -C ４ - selected from the group selected from cycloalkyl, hydroxy and oxo, or two substituents attached to the same carbon atom of said nitrogen-containing 4- to 7-membered heterocycloalkyl group, taken together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group; wherein the 4- to 7-membered heterocycloalkyl group may be substituted one or two times, and each substituent is independently a halogen atom or a C １ -C ４ -Alkyl, C ３ -C ４ -cycloalkyl, C １ -C ４ - selected from the group selected from haloalkyl, hydroxy and oxo, R １１ is a hydrogen atom or C １ -C ４ -Alkyl, C １ -C ４ -hydroxyalkyl, C １ -C ４ represents a group selected from haloalkyl, phenyl and 5- or 6-membered heteroaryl, wherein the phenyl and 5- or 6-membered heteroaryl groups may be substituted one or two times, and each substituent independently represents a halogen atom or a C １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl and -N(R ９ ) (R １０ ) selected from the group selected from R １２ is a hydrogen atom or C １ -C ４ represents an alkyl group, R １３ is a hydrogen atom or C １ -C ６ represents a group selected from alkyl, phenyl and 5- or 6-membered heteroaryl, wherein the phenyl and 5- or 6-membered heteroaryl groups may be substituted one or two times, and each substituent is independently a halogen atom or a C １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl and -N(R ９ ) (R １０ ) selected from the group selected from R １４ is C １ -C ６ -Alkyl, C １ -C ６ -haloalkyl, C ３ -C ６ represents a group selected from cycloalkyl, phenyl and 5- or 6-membered heteroaryl, wherein the phenyl and 5- or 6-membered heteroaryl groups may be substituted one or two times, and each substituent is independently a halogen atom or a C １ -C ２ -Alkyl, C １ -C ２ -haloalkyl, cyano, hydroxy, C １ -C ２ -alkoxy, C ３ -C ４ -cycloalkyl and -N(R ９ ) (R １０ ) selected from the group selected from R １５ is a hydrogen atom or C １ -C ４ represents an alkyl group, R １６ is a hydrogen atom or C １ -C ４ -Alkyl, C ３ -C ４ -cycloalkyl and C ２ -C ４ -haloalkyl, R １７ represents a 4- to 7-membered heterocycloalkyl group; wherein the 4- to 7-membered heterocycloalkyl group may be substituted one, two or three times, and each substituent is independently a halogen atom or a C １ -C ４ -Alkyl, C ３ -C ４ -cycloalkyl, C １ -C ４ - selected from the group selected from alkoxy, hydroxy and oxo, and wherein the 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group; R １８ represents a hydrogen atom or a group selected from methyl and ethyl, R １９ represents a hydrogen atom or a group selected from methyl and ethyl, R ２０ is (4- to 7-membered heterocycloalkyl)-(C １ -C ４ -alkyl) group, wherein the (4-7 membered heterocycloalkyl) portion of said group may be substituted one, two or three times, and each substituent is independently a halogen atom, or １ -C ４ -Alkyl, C ３ -C ４ -cycloalkyl, C １ -C ４ - selected from the group selected from alkoxy, hydroxy and oxo, m represents an integer selected from 1, 2 and 3; and n represents an integer selected from 1, 2 and 3. or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof; and General formula (II): 【Chemistry 2】 [During the ceremony, R １ represents a phenyl or 6-membered heteroaryl group which may be substituted one, two or three times, each substituent independently being a halogen atom, or hydroxy, cyano, nitro, C １ -C ６ -alkyl, (phenyl)-(C １ -C ３ -alkyl)-, C １ -C ６ -haloalkyl, C １ -C ６ -alkoxy, (phenyl)-(C １ -C ３ -alkoxy)-, C １ -C ６ -haloalkoxy, -N(R) ５ (R ６ ) selected from the group selected from Here, the (phenyl)-(C １ -C ３ -alkyl)- and (phenyl)-(C １ -C ３ the phenyl group in the (-alkoxy) group may be substituted one or two times, each substituent being independently selected from a halogen atom or a group selected from cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy; or two substituents attached to adjacent carbon atoms of said phenyl or 6-membered heteroaryl group together represent -(CH ２ ) ３ -, -(CH ２ ) ４ -, -(CH ２ ) ２ -O-, -(CH ２ ) ３ —O—, —CH ２ -O-CH ２ -, -(CH ２ ) ２ -O-CH ２ --, --O-CH ２ —O—, —O—CH ２ -CH ２ —O—, —O—CF ２ —O—, —O—CH ２ -CF ２ —O—, and —O—CF ２ -CF ２ -O-, or R １ represents a 5-membered heteroaryl group which may be substituted one or two times, each substituent independently being a halogen atom, or cyano, C １ -C ３ -alkyl, and C １ -C ３ -alkoxy; R ２ is the group: 【Transformation 3】 represents Here, "*" means R ２ indicates the point of attachment to the nitrogen atom to which is attached; R ３ is methyl and -NH ２ represents a group selected from R ４ represents a phenyl or 6-membered heteroaryl group which may be substituted one, two or three times, each substituent independently being a halogen atom, or cyano, nitro, C １ -C ６ -alkyl, (phenyl)-(C １ -C ３ -alkyl)-, (5- or 6-membered heteroaryl)-(C １ -C ３ -alkyl)-, (C ３ -C ７ -cycloalkyl)-(C １ -C ３ -alkyl)-, ((R ９ ) O) -(C １ -C ６ -alkyl)-, C １ -C ６ -haloalkyl, C ３ -C ７ -cycloalkyl, -OR ９ , -N(R １０ ) (R １１ ), ((R １０ ) (R １１ )N)-(C １ -C ３ -alkyl)-, -C(=O)-N(R １２ ) (R １３ ), -S(=O) ｎ -R １４ , -C(=O)R １４ , -C(=O)-OR １７ and a 5- or 6-membered heteroaryl group which may itself be substituted with one or two substituents selected from a halogen atom and a methyl group; or two substituents attached to adjacent carbon atoms of said phenyl or 6-membered heteroaryl group together represent -(CH ２ ) ３ -, -(CH ２ ) ４ -, -(CH ２ ) ２ -O-, -(CH ２ ) ３ —O—, —CH ２ -O-CH ２ -, -(CH ２ ) ２ -O-CH ２ --, --O-CH ２ —O—, —O—CH ２ -CH ２ —O—, —O—CF ２ —O—, —O—CH ２ -CF ２ —O—, and —O—CF ２ -CF ２ -O-, R ５ and R ６ are each independently a hydrogen atom or C １ -C ４ - alkyl, (C １ -C ４ -alkyl)-C(=O)-, C ３ -C ４ -cycloalkyl and (phenyl)-(C １ -C ３ -alkyl)-, or R ５ and R ６ together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group which may be substituted one, two or three times, and each substituent is independently a halogen atom, or an oxo, hydroxy, C １ -C ４ - alkyl, (C １ -C ４ -alkyl)-C(=O)-, C ３ -C ４ -cycloalkyl and C １ -C ４ -alkoxy; R ７ is a hydrogen atom or C １ -C ２ represents an alkyl group; R ８ is -C(=O)-NH ２ and -S(=O) ２ -NH ２ represents a group selected from R ９ is a hydrogen atom or C １ -C ６ -alkyl, (5- or 6-membered heteroaryl)-(C １ -C ３ -alkyl)-, (phenyl)-(C １ -C ３ -alkyl)-, C １ -C ６ -haloalkyl, C ２ -C ４ -hydroxyalkyl, (C １ -C ３ -alkoxy)-C ２ -C ３ -alkyl-, ((C １ -C ３ -alkyl)-C(═O)-O)-C ２ -C ３ -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 ), a group selected from phenyl and 5- or 6-membered heteroaryl groups, Here, the (phenyl)-(C １ -C ３ -alkyl) groups and the phenyl group itself, １ -C ３ -alkyl) groups, as well as the 5- or 6-membered heteroaryl groups themselves, may be substituted one or two times, each substituent being independently selected from a halogen atom or a group selected from cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino, and trifluoromethoxy; R １０ and R １１ are each independently a hydrogen atom or C １ -C ４ -Alkyl, C １ -C ４ -haloalkyl, C ２ -C ４ -hydroxyalkyl, (C １ -C ３ -alkoxy)-C ２ -C ３ -alkyl-, ((R ２２ ) (R ２３ ) N) -C ２ -C ３ - alkyl, (C ３ -C ７ -cycloalkyl)-(C １ -C ３ -alkyl)-, (C １ -C ４ -alkyl)-C(=O)-, C ３ -C ７ -cycloalkyl, (C ３ -C ７ -cycloalkyl)-C(=O)-, (phenyl)-(C １ -C ３ -alkyl)-, (phenyl)-(C １ -C ３ -alkyl)-C(=O)-, (phenyl)-(C １ -C ３ -alkyl)-O-C(=O)-, phenyl and a 5- or 6-membered heteroaryl group; Here, C ３ -C ７ -cycloalkyl, and the above (C ３ -C ７ -cycloalkyl)-(C １ -C ３ -alkyl)- and (C ３ -C ７ C in the -cycloalkyl)-C(=O) group ３ -C ７ -cycloalkyl may be substituted one or two times, each substituent independently being a fluorine atom or cyano, C １ -C ２ -Alkyl and C １ -C ２ -haloalkyl, and wherein said phenyl and said 5- or 6-membered heteroaryl groups, and said (phenyl)-(C １ -C ３ )-(alkyl)-, (phenyl)-(C １ -C ３ )-C(=O)- and (phenyl)-(C １ -C ３ the phenyl group in the —O—C(═O)— group may be substituted one or two times, each substituent being independently selected from a halogen atom or a group selected from cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino, and trifluoromethoxy; or R １０ and R １１ together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group or a bicyclic nitrogen-containing 5- to 11-membered heterocycloalkyl group which may be substituted one, two or three times, and each substituent is independently a halogen atom, or cyano, oxo, hydroxy, C １ -C ４ -Alkyl, C １ -C ４ -haloalkyl, (C １ -C ４ -alkyl)-C(=O)-, C ３ -C ７ -cycloalkyl, C １ -C ４ -alkoxy, -N(R ２２ ) (R ２３ ), and monocyclic 4- to 7-membered heterocycloalkyl groups; R １２ and R １３ are each independently a hydrogen atom or C １ -C ４ -Alkyl, C １ -C ４ -haloalkyl, C １ -C ４ -hydroxyalkyl, (C １ -C ４ -alkoxy)-C ２ -C ３ -alkyl-, (C １ -C ４ -haloalkoxy)-C ２ -C ３ -Alkyl-, (phenoxy)-C ２ -C ３ -Alkyl-, C ３ -C ７ -cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C １ -C ３ -alkyl)-, Here, C ３ -C ７ -Cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl may be substituted one, two or three times, each substituent independently being a halogen atom or a cyano, oxo, hydroxy, C １ -C ４ - alkyl, (C １ -C ４ -alkyl)-C(=O)-, C ３ -C ４ -cycloalkyl and C １ -C ４ -alkoxy, and wherein said (phenoxy)-C ２ -C ３ -alkyl group and the (phenyl)-(C １ -C ３ the phenyl group within the (-alkyl) group may be substituted one or two times, each substituent being independently selected from a halogen atom or a group selected from cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino and trifluoromethoxy; or R １２ and R １３ together with the nitrogen atom to which they are attached, represent a monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group which may be substituted one, two or three times, and each substituent is independently a halogen atom, or cyano, oxo, hydroxy, C １ -C ４ - alkyl, (C １ -C ４ -alkyl)-C(=O)-, C ３ -C ４ -cycloalkyl and C １ -C ４ -alkoxy; R １４ is C １ -C ４ -Alkyl, C １ -C ４ represents a group selected from haloalkyl and phenyl, wherein the phenyl group may be 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; R １７ is C １ -C ４ represents an alkyl group; R １８ and R １９ are each independently a hydrogen atom or C １ -C ４ represents an alkyl group; R ２０ is a hydrogen atom or C １ -C ６ -Alkyl, C ３ -C ４ -alkenyl, C ３ -C ４ -alkynyl, C １ -C ３ -alkoxy, C ３ -C ７ -cycloalkyl, bicyclic C ５ -C １１ -represents a group selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 5- to 11-membered heterocycloalkyl, phenyl, naphthyl, and 5- to 10-membered heteroaryl; Here, the C １ -C ６ The alkyl group may be substituted one, two or three times, each substituent independently being a halogen atom or a hydroxy, cyano, C １ -C ３ -alkoxy, -N(R ２２ ) (R ２３ ), C ３ -C ７ -cycloalkyl, bicyclic C ５ -C １１ - selected from groups selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, bicyclic 5- to 11-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein said phenyl and 5- to 10-membered heteroaryl substituents may themselves be substituted once or twice, each substituent being independently selected from a halogen atom or a group selected from cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, dimethylamino, and trifluoromethoxy; and where C ３ -C ７ -cycloalkyl, bicyclic C ５ -C １１ -cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl and bicyclic 5- to 11-membered heterocycloalkyl may be substituted one, two or three times, each substituent independently being a halogen atom or cyano, oxo, hydroxy, C １ -C ４ - alkyl, (C １ -C ４ -alkyl)-C(=O)-, C ３ -C ４ -cycloalkyl and C １ -C ４ -alkoxy, and wherein said phenyl, naphthyl and 5- to 10-membered heteroaryl groups may be substituted one, two or three times, each substituent independently being a halogen atom, or cyano, C １ -C ４ -Alkyl, C １ -C ４ -haloalkyl, C １ -C ４ -alkoxy, C １ -C ４ -haloalkoxy, -N(R ２２ ) (R ２３ ) and —C(═O)—N(R ２４ ) (R ２５ ) selected from the group selected from R ２１ is a hydrogen atom or C １ -C ４ represents an alkyl group, or R ２０ and R ２１ together with the nitrogen atom to which they are attached, represent an optionally benzo-fused, monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group which may be substituted one, two or three times, and each substituent is independently a halogen atom, or cyano, oxo, hydroxy, C １ -C ４ -Alkyl, C １ -C ４ -haloalkyl, (phenyl)-(C １ -C ３ -alkyl)-, (C １ -C ４ -alkyl)-C(=O)-, C ３ -C ４ -cycloalkyl, C １ -C ４ -alkoxy, C １ -C ３ -haloalkoxy, -N(R ２２ ) (R ２３ ) and —C(═O)—N(R ２４ ) (R ２５ ) selected from the group selected from R ２２ and R ２３ are each independently a hydrogen atom or C １ -C ２ -Alkyl and (C １ -C ２ -C(═O)—; R ２４ and R ２５ are each independently a hydrogen atom or C １ -C ４ represents an alkyl group, and n represents an integer of 0, 1, or 2. or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

3. The combination according to claim 1 or 2, comprising:

4. General formula (I) [wherein R １ is cyano, -C(=O)NH ２ , -C(=O)N(H)CH ３ and -C(=O)N(CH ３ ) ２ represents a group selected from R ２ represents a group selected from phenyl, naphthyl and 5- to 10-membered heteroaryl; wherein the 5- to 10-membered heteroaryl group is attached to the remainder of the molecule through a carbon atom of said 5- to 10-membered heteroaryl group; and wherein the phenyl, naphthyl and 5- to 10-membered heteroaryl groups may be substituted 1, 2, 3 or 4 times, and each substituent is independently a halogen atom or a C １ -C ６ -Alkyl, C ３ -C ５ -cycloalkyl, C １ -C ４ -haloalkyl, (C １ -C ２ -alkoxy)-(C １ -C ２ -alkyl)-, C １ -C ４ -alkoxy, C １ -C ４ -haloalkoxy, phenoxy, -S(=O) ２ R １４ , -P(=O)(R １４ ) ２ , cyano, hydroxy, -N(R ９ ) (R １０ ), -C(=O)N(R ９ ) (R １０ ), -C(=O)R １１ , -N(R １２ ) C(=O)R １３ , -N(R １２ ) S(=O) ２ R １４ , -N=S(=O)(R １４ ) ２ , 4- to 7-membered heterocycloalkyl, phenyl, and 5- or 6-membered heteroaryl; or two substituents of said phenyl group, when they are attached to adjacent ring atoms, are -CH ２ -CH(OH)-CH ２ -, -CH ２ -CH(CH ３ )-O-, -OC(CH ３ ) ２ -O-, -N(R １８ )-C(=O)-(C(R １８ ) (R １９ )) ｍ -, -N(R １８ )-C(=O)-(C(CH ２ ) ３ ) -, -N(R １８ )-(C(R １８ ) (R １９ )) ｍ -, -N(R １８ )—C(═O)—O— and —N(R １８ )-C(=O)-N(R １８ )—, wherein said 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of said 4- to 7-membered heterocycloalkyl group; and Here, the C １ -C ４ the alkoxy group may be substituted with a group selected from 4- to 7-membered heterocycloalkyl and phenyl; wherein said 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of said 4- to 7-membered heterocycloalkyl group; and wherein the phenyl and 5- or 6-membered heteroaryl groups may be substituted one or two times, each substituent independently being a halogen atom or a C １ -C ２ -Alkyl, C １ -C ２ -haloalkyl and C １ -C ２ -alkoxy, R ３ is a hydrogen atom or a halogen atom, or C １ -C ６ -Alkyl, C ２ -C ４ -alkenyl, C ３ -C ５ -cycloalkyl, (C １ -C ２ -alkoxy)-(C １ -C ４ -alkyl)-, C １ -C ４ -alkoxy, C １ -C ４ -haloalkoxy, C ３ -C ５ -cycloalkyloxy, -S(=O) ２ R １４ , cyano, hydroxy, -N(R ９ ) (R １０ ), -C(=O)N(R ９ ) (R １０ ), -P(=O)(R １４ ) ２ represents a group selected from 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, and phenyl; wherein said 4- to 7-membered heterocycloalkyl group and said 5- to 7-membered heterocycloalkenyl group are attached to the remainder of the molecule through a carbon atom of said 4- to 7-membered heterocycloalkyl group and said 5- to 7-membered heterocycloalkenyl group; and Here, the C １ -C ６ -Alkyl and C １ -C ４ -alkoxy group is C ３ -C ４ - optionally substituted with a group selected from cycloalkyl and 4- to 7-membered heterocycloalkyl; wherein said 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of said 4- to 7-membered heterocycloalkyl group; and Here, C ３ -C ４ the cycloalkyl group may be substituted once or twice with a cyano group, and Here, the C ２ -C ４ -Alkenyl group is C １ -C ４ -optionally substituted with a haloalkyl group, and Here, the C ３ -C ５ -cycloalkyl groups may be substituted one or two times, each substituent independently being a halogen atom or a C １ -C ４ -Alkyl and C １ -C ４ -haloalkyl, R ４ is a hydrogen atom or a halogen atom, or C １ -C ６ -Alkyl, C １ -C ６ -haloalkyl, C ３ -C ５ -cycloalkyl, (C １ -C ２ -alkoxy)-(C １ -C ４ -alkyl)-, C １ -C ４ -alkoxy, (C １ -C ２ -alkoxy)-(C １ -C ４ -alkoxy)-, -O-(C １ -C ４ -alkyl)-C(=O)OR １５ , —O—(C １ -C ４ -alkyl)-C(=O)N(R ９ ) (R １０ ), C ３ -C ５ -cycloalkyloxy, -S(=O) ２ R １４ , cyano, nitro, hydroxy, -N(R ９ ) (R １０ ), -N(R １６ ) (R １７ ), -N(R １６ ) (R ２０ ), -N=S(=NH)(R １４ ) ２ , -N=S(=O)(R １４ ) ２ , -P(=O)(R １４ ) ２ represents a group selected from 4- to 7-membered heterocycloalkyl, 5- to 7-membered heterocycloalkenyl, (4- to 7-membered heterocycloalkyl)oxy, and phenyl; wherein said 4- to 7-membered heterocycloalkyl group and said 5- to 7-membered heterocycloalkenyl group are attached to the remainder of the molecule through a carbon atom of said 4- to 7-membered heterocycloalkyl group and said 5- to 7-membered heterocycloalkenyl group; and Here, the C １ -C ６ -Alkyl and C １ -C ４ -alkoxy group is C ３ -C ４ - optionally substituted with a group selected from cycloalkyl and 4- to 7-membered heterocycloalkyl; wherein said 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of said 4- to 7-membered heterocycloalkyl group; and Here, C ３ -C ４ - the cycloalkyl group may be substituted one or two times, each substituent being independently selected from a halogen atom or a group selected from cyano and hydroxy; and Here, the C １ -C ４ -alkoxy groups may be substituted with oxiran-2-yl groups, and Here, the C ３ -C ５ -cycloalkyl may be substituted one or two times, each substituent independently being a halogen atom or a C １ -C ４ - alkyl groups, R ５ is a hydrogen atom or a halogen atom, or C １ -C ５ -Alkyl, C ３ -C ５ -cycloalkyl, C １ -C ４ -alkoxy, C ３ -C ５ -cycloalkyloxy, -S(=O) ２ R １４ , cyano, hydroxy, -N(R ９ ) (R １０ ), 4- to 7-membered heterocycloalkyl, and (4- to 7-membered heterocycloalkyl)oxy; wherein said 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of said 4- to 7-membered heterocycloalkyl group; R ６ is a hydrogen atom or C １ -C ４ -Alkyl and C １ -C ４ -hydroxyalkyl, R ７ is a hydrogen atom or a halogen atom, or C １ -C ４ -Alkyl, C １ -C ４ represents a group selected from alkoxy and hydroxy, R ８ represents a group selected from methyl and ethyl, R ９ and R １０ are each independently a hydrogen atom or C １ -C ４ -Alkyl, C ２ -C ４ -hydroxyalkyl, N≡C—(C １ -C ４ -alkyl)-, (C １ -C ４ -alkoxy)-(C ２ -C ４ -alkyl)- and C ３ -C ４ -cycloalkyl, or R ９ and R １０ together with the nitrogen to which they are attached represent a nitrogen-containing 4- to 7-membered heterocycloalkyl group; wherein the nitrogen-containing 4- to 7-membered heterocycloalkyl group may be substituted one, two or three times, and each substituent is independently a halogen atom or a C １ -C ４ - selected from the group selected from alkyl, hydroxy and oxo, or two substituents attached to the same carbon atom of said nitrogen-containing 4- to 7-membered heterocycloalkyl group, taken together with the carbon atom to which they are attached, represent a 4- to 7-membered heterocycloalkyl group; Here, the 4- to 7-membered heterocycloalkyl group is C １ -C ４ - optionally substituted once or twice with alkyl groups, R １１ is C １ -C ４ -Alkyl and C １ -C ４ -haloalkyl, R １２ represents a hydrogen atom, R １３ represents a phenyl group, R １４ is C １ -C ４ represents a group selected from alkyl and phenyl, R １５ is a hydrogen atom or C １ -C ４ represents an alkyl group, R １６ is a hydrogen atom or C １ -C ４ represents an alkyl group, R １７ represents a 4- to 7-membered heterocycloalkyl group; Here, the 4- to 7-membered heterocycloalkyl group is C １ -C ４ - optionally substituted once or twice with alkyl groups, and wherein the 4- to 7-membered heterocycloalkyl group is attached to the remainder of the molecule through a carbon atom of the 4- to 7-membered heterocycloalkyl group; R １８ represents a hydrogen atom or a methyl group, R １９ represents a hydrogen atom or a methyl group, R ２０ is (4- to 7-membered heterocycloalkyl)-(C １ -C ４ -alkyl) group, wherein the (4- to 7-membered heterocycloalkyl) portion of the group is C １ -C ４ - optionally substituted once or twice with alkyl groups, m represents an integer selected from 1 and 2; Here, the 4- to 7-membered heterocycloalkyl group is C １ -C ４ - optionally substituted once or twice with alkyl groups, and n represents an integer selected from 1, 2 and 3. or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof; and General formula (II) [wherein R １ represents a phenyl or pyridinyl group which may be substituted one, two or three times, each substituent independently being a fluorine atom, a chlorine atom, a bromine atom, or a hydroxyl, cyano, C １ -C ４ -Alkyl, C １ -C ２ -fluoroalkyl, C １ -C ２ -alkoxy, (phenyl)-(C １ -C ２ -alkoxy)-, C １ -C ２ -fluoroalkoxy and -N(R ５ ) (R ６ ) selected from the group selected from or two substituents attached to adjacent carbon atoms of said phenyl or pyridinyl group together form -(CH ２ ) ３ --, --O-CH ２ —O— and —O—CF ２ -O-, or R １ represents a pyrazolyl group optionally substituted with one methyl group; R ２ is the group: 【Chemistry 4】 represents Here, "*" means R ２ indicates the point of attachment to the nitrogen atom to which is attached; R ３ is methyl and -NH ２ represents a group selected from R ４ represents a phenyl or pyridinyl group which may be substituted one, two or three times, each substituent independently being a halogen atom, or cyano, C １ -C ３ - alkyl, ((R ９ ) O) -(C １ -C ３ -alkyl)-, C １ -C ３ -fluoroalkyl, -OR ９ , -N(R １０ ) (R １１ ), -C(=O)-N(R １２ ) (R １３ ), S(=O) ｎ -R １４ and —C(═O)—OR １７ selected from the group selected from or two substituents attached to adjacent carbon atoms of the phenyl or pyridinyl group together form —(CH ２ ) ３ --, --O-CH ２ —O— and —O—CF ２ -O-; R ５ and R ６ are each independently a hydrogen atom or C １ -C ２ represents an alkyl group, or R ５ and R ６ together with the nitrogen atom to which they are attached represent an optionally mono- or di-substituted monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, each substituent independently being a fluorine atom or a hydroxyl and C １ -C ２ - selected from the group selected from alkyl; R ７ is hydrogen or C １ -C ２ represents an alkyl group; R ８ is -C(=O)-NH ２ represents a group; R ９ is a hydrogen atom or C １ -C ２ -Alkyl, benzyl, C １ -C ２ -fluoroalkyl, C ２ -hydroxyalkyl, (C １ -C ２ -alkoxy)-C ２ -alkyl-, ((C １ -C ２ -alkyl)-C(═O)-O)-C ２ -alkyl-, -C(R １８ ) (R １９ )-C(=O)-OR １７ , -C(R １８ ) (R １９ )-C(=O)-N(R ２０ ) (R ２１ ), -C(=O)-N(R ２０ ) (R ２１ ) and phenyl, wherein the phenyl groups within said benzyl groups and said phenyl groups themselves may be substituted one or two times, each substituent being independently selected from a group selected from fluorine and chlorine atoms, or cyano and methyl; R １０ and R １１ are each independently a hydrogen atom or C １ -C ２ -Alkyl, C １ -C ２ -fluoroalkyl, (C ３ -C ５ -cycloalkyl)-(C １ -C ２ -alkyl)-, (C １ -C ２ -alkyl)-C(=O)-, C ３ -C ７ -cycloalkyl, C ３ -C ７ -cycloalkyl-(C═O)-, (phenyl)-(C １ -C ２ -alkyl)-, (phenyl)-(C １ -C ２ -alkyl)-C(═O)- and (phenyl)-(C １ -C ２ -alkyl)-O-C(=O)-, Here, C ３ -C ７ -cycloalkyl, and the above (C ３ -C ５ -cycloalkyl)-(C １ -C ２ -alkyl)- in C ３ -C ５ -cycloalkyl, and C ３ -C ７ C in the -cycloalkyl-(C═O)- group ３ -C ７ -cycloalkyl may be substituted one or two times, each substituent independently being a fluorine atom or cyano, C １ -C ２ -Alkyl and C １ -C ２ -fluoroalkyl, and wherein said (phenyl)-(C １ -C ２ -alkyl)-, (phenyl)-(C １ -C ２ -alkyl)-C(═O)- and (phenyl)-(C １ -C ２ the phenyl group in the (-alkyl)-O-C(=O)- group may be substituted one or two times, each substituent being independently selected from a fluorine atom, a chlorine atom and a methyl group; or R １０ and R １１ together with the nitrogen atom to which they are attached, represent an optionally mono- or di-substituted monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, each substituent independently being a fluorine atom, or a cyano, oxo, C １ -C ２ -Alkyl, C １ -C ２ -fluoroalkyl and (C １ -C ２ -C(═O)—; R １２ and R １３ are each independently a hydrogen atom or C １ -C ４ -Alkyl, C １ -C ４ -fluoroalkyl, C １ -C ４ -hydroxyalkyl, (C １ -C ４ -alkoxy)-C ２ -C ３ -alkyl-, (C １ -C ２ -fluoroalkoxy)-C ２ -C ３ -Alkyl-, (phenoxy)-C ２ -C ３ -Alkyl-, C ３ -C ７ -cycloalkyl, monocyclic 4- to 7-membered heterocycloalkyl and (phenyl)-(C １ -C ２ -alkyl)-, Here, C ３ -C ７ -cycloalkyl and monocyclic 4- to 7-membered heterocycloalkyl may be substituted one or two times, each substituent independently being a fluorine atom, or oxo, C １ -C ２ -Alkyl and (C １ -C ２ -alkyl)-C(═O)—, and wherein said (phenoxy)-C ２ -C ３ -alkyl group and the (phenyl)-(C １ -C ２ -alkyl) groups, each of which is independently selected from fluorine and chlorine atoms or a group selected from methyl, trifluoromethyl and methoxy; or R １２ and R １３ together with the nitrogen atom to which they are attached, represent an optionally mono- or di-substituted monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, each substituent independently being a halogen atom, or oxo, C １ -C ２ -Alkyl and (C １ -C ２ -C(═O)—; R １４ represents a group selected from methyl and trifluoromethyl; R １７ is C １ -C ２ represents an alkyl group; R １８ and R １９ each independently represents a hydrogen atom or a methyl group; R ２０ represents a hydrogen atom or an optionally substituted C １ -C ３ - alkyl, unsubstituted C ４ -C ６ -alkyl, prop-2-ynyl, methoxy, C ３ -C ６ -represents a group selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, Here, the C １ -C ３ The alkyl group may be substituted one, two or three times, each substituent independently being a halogen atom or a hydroxy, cyano, C １ -C ３ -alkoxy, -N(R ２２ ) (R ２３ ), C ３ -C ６ - selected from groups selected from cycloalkyl, adamantyl, monocyclic 4- to 7-membered heterocycloalkyl, phenyl, and 5- to 10-membered heteroaryl, wherein said phenyl and 5- to 10-membered heteroaryl substituents may themselves be substituted once or twice, each substituent being independently selected from fluorine atoms, chlorine atoms, and methyl groups; and wherein said C ３ -C ６ -cycloalkyl, adamantyl and monocyclic 4- to 7-membered heterocycloalkyl groups may be substituted one, two or three times, each substituent independently being a fluorine atom or an oxo, C １ -C ２ -Alkyl and (C １ -C ２ -alkyl)-C(═O)—, and wherein said phenyl and 5- to 10-membered heteroaryl groups may be substituted one, two or three times, each substituent independently being a fluorine atom, a chlorine atom, or a cyano, C １ -C ２ -Alkyl, C １ -C ２ -fluoroalkyl, C １ -C ２ -alkoxy, C １ -C ２ -fluoroalkoxy, -N(R ２２ ) (R ２３ ) and —C(═O)—N(R ２４ ) (R ２５ ) selected from the group selected from R ２１ is a hydrogen atom or C １ -C ２ represents an alkyl group, or R ２０ and R ２１ together with the nitrogen atom to which they are attached, represent an optionally benzofused, monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group which may be substituted one, two or three times, and each substituent is independently a halogen atom, or cyano, oxo, hydroxy, C １ -C ２ -Alkyl, C １ -C ２ -fluoroalkyl, benzyl, (C １ -C ２ -alkyl)-C(=O)-, C ３ -C ４ -cycloalkyl, C １ -C ２ -alkoxy, C １ -C ２ -fluoroalkoxy, -N(R ２２ ) (R ２３ ) and —C(═O)—N(R ２４ ) (R ２５ ) selected from the group selected from R ２２ and R ２３ are each independently a hydrogen atom or C １ -C ２ -Alkyl and (C １ -C ２ -C(═O)—; R ２４ and R ２５ are each independently a hydrogen atom or C １ -C ２ represents an alkyl group, and n represents the integer 2. or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

4. The combination of claim 1, 2 or 3, comprising:

5. General formula (I) [Here, R １ is cyano, -C(=O)NH ２ , -C(=O)N(H)CH ３ and -C(=O)N(CH ３ ) ２ represents a group selected from R ２ is phenyl, 1-naphthyl, 2-naphthyl, 1H-pyrazol-3-yl, 1H-pyrazol-4-yl, 1H-pyrazol-5-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1H-1,2,3-triazol-4-yl, 2H-1,2,3-triazol-4-yl, 1,3-thiazol-2-yl, pyridin-3-yl, pyrazin-2-yl, 1H-indol-5-yl, 1-benzofuran-4-yl, 1-benzofuran-7-yl, 1H-indol-6-yl, benzothiophen-2-yl, 1,3-benzoxazol-2-yl, 1,3-benzoxazol-5-yl, 1,3-benzoxazol-6-yl, 1,3-benzo represents a group selected from oxazol-7-yl, 1H-indazol-5-yl, 1H-benzimidazol-2-yl, 1H-benzimidazol-4-yl, 1,3-benzothiazol-2-yl, 1,3-benzothiazol-4-yl, 1,3-benzothiazol-5-yl, 1,3-benzothiazol-6-yl, 1,3-benzothiazol-7-yl, 1H-pyrrolo[2,3-b]pyridin-3-yl, quinolin-2-yl, quinolin-4-yl, quinolin-6-yl, quinolin-7-yl, isoquinolin-5-yl, isoquinolin-7-yl, isoquinolin-8-yl, quinoxalin-2-yl, quinoxalin-5-yl and 1,3-thiazolo[5,4-b]pyridin-2-yl, wherein the group may be substituted one or two times, and each substituent independently represents a fluorine, chlorine, or bromine atom, or a methyl, propyl, isopropyl, tert-butyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, propoxy, (propan-2-yl)oxy, methoxymethyl, 2-methoxyethyl, benzyloxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, phenoxy, (oxolan-2-yl)methoxy, (tetrahydrofuran-2-yl)methoxy, methanesulfonyl, phenyl, dimethylphosphoryl, cyano, hydroxy, dimethylamino, oxetan-3-yl, 2-oxopyrrolidin-1-yl, 4-methyl-2-oxopiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl, morpholino-4-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 8-methyl-3-oxo-2,8-diazaspiro[4.5]decan-2-yl, carbamoyl, acetyl, trifluoroacetyl, benzamide, benzenesulfonamide, [dimethyl(oxide)-λ ６ -sulfanylidene]amino, phenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl and pyridin-3-yl; or Two substituents of the phenyl group, when attached to adjacent ring atoms, can be joined to form a -CH ２ -CH(OH)-CH ２ -, -CH ２ -CH(CH ３ )-O-, -OC(CH ３ ) ２ -O-, -NH-C(=O)-CH(CH ３ ) -, -N(CH ３ )-C(=O)-C(CH ３ ) ２ -, -NH-C(=O)-(C(CH ２ ) ３ )-, -NH-CH ２ -C(CH ３ ) ２ -, -N(CH ３ )—C(═O)—O— and —N(CH ３ )-C(=O)-N(CH ３ )—, R ３ represents a hydrogen atom, or a fluorine, chlorine or bromine atom, or methyl, sec-butyl, (oxetan-3-yl)methyl, 3,3,3-trifluoroprop-1-en-2-yl, cyclopropyl, (trifluoromethyl)cyclopropyl, cyclobutyl, 2,2-dimethylcyclobutyl, 3,3-difluorocyclobutyl, methoxymethyl, methoxy, ethoxy, propoxy, 2,2-difluoroethoxy, 2,2-difluoropropoxy, cyclopropyl represents a group selected from pyrmethoxy, (1-cyanocyclopropyl)methoxy, cyclopropyloxy, cyclobutyloxy, methanesulfonyl, cyano, hydroxy, 4-hydroxy-2-oxo-pyrrolidin-1-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, carbamoyl, dimethylphosphoryl, oxetan-3-yl, 3,6-dihydro-2H-pyran-4-yl, (oxetan-3-yl)oxy and phenyl, R ４ is a hydrogen atom, or a fluorine, chlorine or bromine atom, or methyl, sec-butyl, (oxetan-3-yl)methyl, trifluoromethyl, cyclopropyl, 3,3-difluorocyclobutyl, methoxymethyl, methoxy, propoxy, 2-methoxyethoxy, (1-hydroxycyclopropyl)methoxy, (1-cyanocyclopropyl)methoxy, (oxiran-2-yl)methoxy, carboxymethoxy, 2-tert-butoxy-2-oxo-ethoxy, 2-amino-2-oxo-ethoxy, cyclopropyloxy, cyclobutyloxy, methanesulfonyl, dimethylphosphoryl, cyano, nitro, hydroxy, (cyano) ananomethyl)(methyl)amino, (2-hydroxyethyl)amino, (2-hydroxyethyl)(methyl)amino, (2-methoxyethyl)amino, (2-methoxyethyl)(methyl)amino, cyclopropylamino, (oxetan-3-yl)amino, methyl(oxetan-3-yl)amino, methyl(oxolan-3-yl)amino, 3-hydroxyazetidin-1-yl, 2-oxopyrrolidin-1-yl, morpholino, 1,1-dioxidethiomorpholin-4-yl, 4-hydroxy-2-oxo-pyrrolidin-1-yl, 7-oxo-2-oxa-6-azaspiro[3.4]octan-6-yl, 2,2-dimethyl-2λ ６ -diazathia-1,2-dien-1-yl, [dimethyl(oxide)-λ ６ -sulfanylidene]amino, methyl(tetrahydrofuran-3-yl)amino, tetrahydrofuran-3-ylmethoxy, (tetrahydrofuran-3-ylmethyl)amino, oxetan-3-yl, 3,6-dihydro-2H-pyran-4-yl, (oxetan-3-yl)oxy, (tetrahydrofuran-3-yl)oxy, (tetrahydro-2H-pyran-3-yl)oxy, (tetrahydro-2H-pyran-4-yl)oxy and phenyl; R ５ represents a hydrogen atom, or a fluorine, chlorine or bromine atom, or a group selected from methyl, cyclopropyl, methoxy, propoxy, cyclopropyloxy, methanesulfonyl, cyano, hydroxy, oxetan-3-yl and oxetan-3-yloxy, R ６ represents a hydrogen atom or a group selected from methyl and hydroxymethyl, R ７ represents a hydrogen atom or a fluorine atom or a group selected from methyl, ethyl, methoxy and hydroxy, R ８ represents a group selected from methyl and ethyl, and n represents an integer selected from 1, 2 and 3. or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof; and General formula (II) [Here, R １ is the group: 【Transformation 5】 represents Here, "**" is R １ indicates the point of attachment to the nitrogen atom to which is attached; R ２ is the group: 【Transformation 6】 represents Here, "*" means R ２ indicates the point of attachment to the nitrogen atom to which is attached; R ３ is methyl and -NH ２ represents a group selected from R ４ is the group: 【Transformation 7】 represents Here, "#" means R ４ indicates the point of attachment to the carbonyl group to which it is attached; R ７ is a hydrogen atom or C １ -C ２ represents an alkyl group; R ８ is -C(=O)-NH ２ represents a group; R ９ is a hydrogen atom or C １ -C ２ -Alkyl, benzyl, C １ -C ２ -fluoroalkyl, (C １ -C ２ -alkoxy)-C ２ -alkyl-, ((C １ -C ２ -alkyl)-C(═O)-O)-C ２ -alkyl-, -C(R １８ ) (R １９ )-C(=O)-N(R ２０ ) (R ２１ ), -C(=O)-N(R ２０ ) (R ２１ ) and phenyl, wherein the phenyl groups within said benzyl groups and said phenyl groups themselves may be substituted one or two times, each substituent being independently selected from fluorine and chlorine atoms, or a group selected from cyano and methyl; R １０ and R １１ are each independently a hydrogen atom or C １ -C ２ -Alkyl, C ３ -C ７ represents a group selected from -cycloalkyl and (benzyl)-O-C(=O)-, Here, C ３ -C ７ -cycloalkyl may be substituted one or two times, each substituent being independently selected from a fluorine atom or a group selected from methyl and trifluoromethyl; and wherein the phenyl group in said (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 a methyl group; or R １０ and R １１ together with the nitrogen atom to which they are attached represent an optionally monocyclic nitrogen-containing 4- to 7-membered heterocycloalkyl group, which may be substituted one or two times, and each substituent is independently selected from a fluorine atom or a group selected from cyano, methyl and trifluoromethyl; R １２ and R １３ are each independently a hydrogen atom or C １ -C ４ -Alkyl, C １ -C ２ -fluoroalkyl, C １ -C ２ -hydroxyalkyl, (C １ -C ４ -alkoxy)-C ２ -alkyl-, (C １ -C ２ -fluoroalkoxy)-C ２ -Alkyl-, (phenoxy)-C ２ -Alkyl-, C ３ -C ７ -cycloalkyl and (phenyl)-(C １ -C ２ -alkyl)-, Here, the (phenoxy)-C ２ -alkyl group and the (phenyl)-(C １ -C ２ -alkyl) groups, each of which is independently selected from fluorine and chlorine atoms or a group selected from methyl, trifluoromethyl and methoxy; R １７ is C １ -C ２ represents an alkyl group; R １８ and R １９ each independently represents a hydrogen atom or a methyl group; R ２０ represents a group selected from benzyl and phenyl, wherein the phenyl group and the phenyl group within the benzyl group may be substituted one or two times, each substituent being independently selected from a fluorine atom, a chlorine atom, and a methyl group; R ２１ represents a hydrogen atom or a methyl group, Y １ represents -C(H)=, -C(F)=, -C(Cl)=, -C(CN)=, or -N=; Y ２ represents -C(H)= or -N=; Y ３ is -C(R ２７ )= or -N=, However, Y ２ When represents -N=, Y ３ is -C(R ２７ )=, and Y ３ When represents -N=, Y ２ represents -C(H)=; R ２６ represents a fluorine, chlorine or bromine atom or a group selected from methyl, difluoromethyl, trifluoromethyl, methoxy, benzyloxy, difluoromethoxy and trifluoromethoxy, and R ２７ is a halogen atom or C １ -C ２ -Alkyl, C １ -C ２ -fluoroalkyl, -OR ９ , -N(R １０ ) (R １１ ), -C(=O)-N(R １２ ) (R １３ ) and —C(═O)—OR １７ represents a group selected from the group or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof. The combination according to any one of claims 1 to 4, comprising:

6. The following groups: 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(7-fluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(6-fluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(5-fluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(6-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(5-bromo-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(5-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(5-fluoro-1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(6-bromo-1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(7-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzothiazol-2-yl)-4-fluoropiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(4-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(5-chloro-1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(5-chloro[1,3]thiazolo[5,4-b]pyridin-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-methyl-4-[6-(trifluoromethoxy)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-methyl-4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(5,6-difluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{4-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(5-tert-butyl-1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[5-(methanesulfonyl)-1,3-benzoxazol-2-yl]-4-methylpiperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-fluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-7-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-bromo-1-methyl-4-{4-methyl-4-[6-(trifluoromethoxy)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-bromo-4-[4-(5-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-bromo-1-methyl-2-oxo-4-{4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 7-bromo-4-[4-(5,6-difluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-bromo-4-[4-(6-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-7-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-bromo-1-methyl-4-{4-methyl-4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-(2-oxopyrrolidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-(2-oxopyrrolidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{4-[4-(2,2,2-trifluoroethoxy)phenyl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-(4-{4-[(propan-2-yl)oxy]phenyl}piperidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-ethoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-cyclopropylphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-[4-(4-propoxyphenyl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{4-[4-(trifluoromethoxy)phenyl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, N-{4-[1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)piperidin-4-yl]phenyl}benzenesulfonamide, 4-[4-(3-cyclopropylphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[4-(dimethylamino)phenyl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{4-[4-(propan-2-yl)phenyl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[4-(benzyloxy)phenyl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, N-{4-[1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)piperidin-4-yl]phenyl}benzamide, 1-methyl-4-[4-(1-methyl-1H-indol-5-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(3-fluoro-5-methylphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(2-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-([1,1′-biphenyl]-4-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-chlorophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(3-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-[4-(4-phenoxyphenyl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-(4-phenylpiperidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-(4-methyl-4-phenylpiperidin-1-yl)-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{4-[4-(2-oxopyrrolidin-1-yl)phenyl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(2-fluorophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{4-[4-(trifluoromethyl)phenyl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(3-fluorophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[3-(morpholin-4-yl)phenyl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(3-cyano-2-methylphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[4-(methanesulfonyl)phenyl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[4-(4-methyl-2-oxopiperazin-1-yl)phenyl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, N-{3-[1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)piperidin-4-yl]phenyl}benzenesulfonamide, 4-[4-(3-{[dimethyl(oxo)-λ6-sulfanylidene]amino}phenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(naphthalen-1-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzothiazol-4-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[1-methyl-3-(trifluoroacetyl)-1H-indol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1-benzofuran-7-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(isoquinolin-7-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzothiazol-7-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, N-{3-[1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)piperidin-4-yl]phenyl}benzamide, 4-[4-(isoquinolin-8-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(isoquinolin-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-[4-(quinoxalin-5-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[3-(methanesulfonyl)phenyl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-fluorophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(2-methylphenyl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(4-methylphenyl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(3,5-dichlorophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(3-bromophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-cyanophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[3-(difluoromethyl)phenyl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-bromophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-bromo-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-bromo-1-methyl-2-oxo-4-(4-phenylpiperidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1,7-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-7-phenyl-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3,7-dicarbonitrile, 7-cyclopropyl-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-(2,2-dimethyl-2λ ６ -diazathia-1,2-dien-1-yl)-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-7-(2-oxopyrrolidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-7-(oxetan-3-yl)-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-(methanesulfonyl)-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-{[dimethyl(oxo)-λ6-sulfanylidene]amino}-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-(3,6-dihydro-2H-pyran-4-yl)-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1-benzofuran-4-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-(4-{4-[(propan-2-yl)oxy]phenyl}piperidin-1-yl)-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-{4-methyl-4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-7-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)-4-ethylpiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-2-oxo-4-{4-[4-(trifluoromethoxy)phenyl]piperidin-1-yl}-1,2-dihydroquinoline-3-carboxamide, 4-[4-(5,6-difluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 7-bromo-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[3-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, mixture of stereoisomers, 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-2-oxo-4-(4-phenylpiperidin-1-yl)-1,2-dihydroquinoline-3-carboxamide, 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-7-(oxetan-3-yl)-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-(2-oxopyrrolidin-1-yl)-1,2-dihydroquinoline-3-carboxamide, (rac)-1-methyl-2-oxo-4-{4-[4-(propan-2-yl)phenyl]azepan-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{(4S)-4-[4-(propan-2-yl)phenyl]azepan-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{(4R)-4-[4-(propan-2-yl)phenyl]azepan-1-yl}-1,2-dihydroquinoline-3-carbonitrile, (rac)-4-[4-(1,3-benzoxazol-2-yl)azepan-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-[4-{4-[(propan-2-yl)oxy]phenyl}azepan-1-yl]-1,2-dihydroquinoline-3-carbonitrile, (rac)-4-[4-(4-methoxyphenyl)azepan-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[(4R)-4-(4-methoxyphenyl)azepan-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[(4S)-4-(4-methoxyphenyl)azepan-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, (rac)-4-[4-(1,3-benzoxazol-2-yl)azepan-1-yl]-7-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[(4R)-4-(1,3-benzoxazol-2-yl)azepan-1-yl]-7-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[(4S)-4-(1,3-benzoxazol-2-yl)azepan-1-yl]-7-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, (rac)-4-[4-(4-chlorophenyl)azepan-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[(4R)-4-(4-chlorophenyl)azepan-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[(4SR)-4-(4-chlorophenyl)azepan-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, (rac)-1-methyl-2-oxo-4-[4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carbonitrile, (rac)-7-bromo-1-methyl-2-oxo-4-[4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carbonitrile, (rac)-1-methyl-7-(oxetan-3-yl)-2-oxo-4-[4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carbonitrile, (rac)-1-methyl-7-(morpholin-4-yl)-2-oxo-4-[4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carbonitrile, (rac)-1-methyl-2-oxo-7-(2-oxopyrrolidin-1-yl)-4-[4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carbonitrile, (rac)-7-(1,1-dioxo-1λ ６ -thiomorpholin-4-yl)-1-methyl-2-oxo-4-[4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carbonitrile, (rac)-7-bromo-1-methyl-2-oxo-4-[4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carboxamide, 7-bromo-1-methyl-2-oxo-4-[(4S)-4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carboxamide, 7-bromo-1-methyl-2-oxo-4-[(4S)-4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carboxamide, 4-[4-ethyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-bromo-4-[4-ethyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(6-methoxypyridin-3-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(6-methylpyridin-3-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-[4-(pyridin-3-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-N,1-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-N,N,1-trimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-[4-(1-methyl-1H-benzimidazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-[4-(3-propyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(1-methyl-1H-pyrazol-5-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-[4-(pyrazin-2-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-hydroxy-4-[3-(trifluoromethyl)phenyl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 8-fluoro-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-8-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-8-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-8-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 8-bromo-4-[4-(6-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 8-bromo-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 8-bromo-4-[4-(5-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 8-bromo-4-[4-(5,6-difluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-8-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-8-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3,8-dicarbonitrile, 8-(methanesulfonyl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-6-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-6-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-1-methyl-2-oxo-4-{4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3,6-dicarbonitrile, 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3,6-dicarbonitrile, 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3,6-dicarbonitrile, 6-cyclopropyl-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-(methanesulfonyl)-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-6-(oxetan-3-yl)-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-(3,6-dihydro-2H-pyran-4-yl)-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-6-phenyl-1,2-dihydroquinoline-3-carbonitrile, 6-(methanesulfonyl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(6-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1,6-dimethyl-4-[4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(5-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1,6-dimethyl-2-oxo-4-{4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 1,6-dimethyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1,6-dimethyl-4-[4-methyl-4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1,6-dimethyl-4-{4-methyl-4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-methoxy-1-methyl-4-[4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-methoxy-1-methyl-4-[4-methyl-4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-chloro-1-methyl-4-[4-methyl-4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1,6-dimethyl-4-[4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1,6-dimethyl-4-[4-methyl-4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1,6-dimethyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1,6-dimethyl-4-{4-methyl-4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1,6-dimethyl-2-oxo-4-{4-[5-(propan-2-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carboxamide, 4-[4-(5-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(6-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-bromo-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)azepan-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)azepan-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-6-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3,6-dicarbonitrile, 6-cyano-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-(3,3-difluorocyclobutyl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-cyclopropyl-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-(butan-2-yl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-(methoxymethyl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-(methoxymethyl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1,6-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-fluoro-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-6-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1,7-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1,7-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1,7-dimethyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1,7-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1,7-dimethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)-4-ethylpiperidin-1-yl]-7-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-7-bromo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 8-bromo-1,6-dimethyl-4-[4-methyl-4-(6-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-7-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-7-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-chloro-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-8-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 8-chloro-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 8-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 8-bromo-1-methyl-4-{4-methyl-4-[5-methyl-4-(trifluoromethyl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[(2S,4S)-2-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-7-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-7-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-fluoro-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-[(1-hydroxycyclopropyl)methoxy]-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-7-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[(oxetan-3-yl)oxy]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-hydroxy-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-7-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-(cyclopropyloxy)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-8-(oxetan-3-yl)-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-methoxy-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-(cyclobutyloxy)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-methoxy-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3,7-dicarbonitrile, 7-cyclopropyl-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-[(1-cyanocyclopropyl)methoxy]-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-(3,3-difluorocyclobutyl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-8-[(oxetan-3-yl)oxy]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(5,6-difluoro-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1,7-dimethyl-2-oxo-4-(4-phenylpiperidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, 7-methoxy-1-methyl-2-oxo-4-(4-phenylpiperidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-propoxy-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(6-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(5-chloro-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 8-methoxy-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-(oxetan-3-yl)-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 8-(cyclopropyloxy)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1,8-dimethyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-(cyclopropyloxy)-1-methyl-2-oxo-4-(4-phenylpiperidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[4-(2-methoxyethyl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-[(2S)-butan-2-yl]-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-6-[(oxetan-3-yl)oxy]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-[(1-cyanocyclopropyl)methoxy]-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-[(4R)-4-hydroxy-2-oxopyrrolidin-1-yl]-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-propoxy-1,2-dihydroquinoline-3-carbonitrile, 8-hydroxy-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 8-cyclopropyl-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-8-propoxy-1,2-dihydroquinoline-3-carbonitrile, 6-(cyclopropyloxy)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3,7-dicarbonitrile, 4-[4-(1,3-benzothiazol-2-yl)piperidin-1-yl]-6-cyclopropyl-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-[(4R)-4-hydroxy-2-oxopyrrolidin-1-yl]-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-(cyclobutyloxy)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-6-propoxy-1,2-dihydroquinoline-3-carbonitrile, 6-[(4R)-4-hydroxy-2-oxopyrrolidin-1-yl]-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 7-bromo-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-(dimethylphosphoryl)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[5-(2-methoxyethyl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[6-(2-methoxyethyl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[(oxetan-3-yl)methyl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-6-[(oxetan-3-yl)methyl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[5-(oxetan-3-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1-methyl-2-oxo-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carbonitrile, 7-hydroxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(6-bromo-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[5-(2-methoxyethyl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-6-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-7-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-6-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-7-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 7-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-7-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 7-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-7-fluoro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1-methyl-2-oxo-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-8-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-8-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-1,7-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1,7-dimethyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1,7-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1,7-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-{4-[4-(2-methoxyethyl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-{4-[6-(2-methoxyethyl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-(2-oxopyrrolidin-1-yl)-1,2-dihydroquinoline-3-carboxamide, 8-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(4,5-dimethyl-1,3-thiazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-[4-(quinoxalin-2-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-[4-(1H-pyrazol-3-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(1-methyl-1H-pyrazol-4-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(3,4-dimethoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(3-chlorophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[(2S,4S)-2-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)-1-piperidyl]-2-oxo-quinoline-3-carbonitrile, 4-[4-(3-cyanophenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 8-fluoro-1-methyl-2-oxo-4-[(4S)-4-phenylazepan-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[rac-(2R,3S)-2-methyl-3-phenylpyrrolidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)piperidin-4-yl]benzamide, 4-[4-hydroxy-4-(2-methoxyphenyl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-1-ethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-chlorophenyl)piperidin-1-yl]-1-ethyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{4-[5-(2-oxopyrrolidin-1-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-acetylphenyl)-4-methylpiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(3-chlorophenyl)-4-methoxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-(dimethylphosphoryl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-(dimethylphosphoryl)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-(methanesulfonyl)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1-benzothiophen-2-yl)-4-hydroxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1-benzothiophen-2-yl)-4-methoxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1-benzothiophen-2-yl)-4-methylpiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(6-methoxynaphthalen-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-[1-(3-cyano-1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)piperidin-4-yl]-2-methylquinoline-4-carbonitrile, 1-methyl-4-[4-(2-methyl-1,3-benzoxazol-5-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(2-methyl-1,3-benzothiazol-5-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, (rac)-1-methyl-4-[4-(3-methyl-2-oxo-2,3-dihydro-1H-indol-5-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[3-(3-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[5-(3-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[5-(3-chlorophenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[5-(3-chlorophenyl)-1,3,4-oxadiazol-2-yl]-4-methylpiperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(3,3-dimethyl-2,3-dihydro-1H-indol-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[(2R)-2-methyl-2,3-dihydro-1-benzofuran-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-[4-(1,3,3-trimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(2-hydroxy-2,3-dihydro-1H-inden-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(2,2-dimethyl-2H-1,3-benzodioxol-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-[4-(2'-oxo-1',2'-dihydrospiro[cyclobutane-1,3'-indol]-5'-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-methyl-4-(4-methylquinolin-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(4-fluoro-1-methyl-1H-indol-6-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[1-(3-methylphenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[1-(2-methylphenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[1-(3-chlorophenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-{4-[3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(2-methylquinolin-6-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[4-(3-methoxyphenyl)-1,3-thiazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[4-(2-methoxyphenyl)-1,3-thiazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[4-(4-methylphenyl)-1,3-thiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-dimethyl-1H-indazol-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(2-methyl-1,3-benzoxazol-6-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(2-methyl-1,3-benzothiazol-6-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[3-(difluoromethyl)quinolin-7-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, (rac)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[(oxan-4-yl)oxy]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-(2-methoxyethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-{[oxiran-2-yl]methoxy}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[(oxetan-3-yl)oxy]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(5-methoxy-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-2-oxo-4-(4-{5-[(oxolan-2-yl)methoxy]-1,3-benzoxazol-2-yl}piperidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-{4-[6-(oxetan-3-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)-4-fluoropiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)-4-methoxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[5-(methoxymethyl)-1,3-benzoxazol-2-yl]-4-methylpiperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-{4-[6-(methoxymethyl)-1,3-benzoxazol-2-yl]-4-methylpiperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-fluoro-4-(5-methoxy-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(5-cyclopropyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(6-cyclopropyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 8-bromo-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[methyl(oxetan-3-yl)amino]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-[(2-hydroxyethyl)(methyl)amino]-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, (rac)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[methyl(oxolan-3-yl)amino]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-[(cyanomethyl)(methyl)amino]-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-methoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3,6-dicarbonitrile, 3-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-6-carboxamide, 6-ethoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-(2,2-difluoropropoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-(2,2-difluoroethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-(cyclopropylmethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-cyclobutyl-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-[2,2-dimethylcyclobutyl]-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-6-(3,3,3-trifluoroprop-1-en-2-yl)-1,2-dihydroquinoline-3-carbonitrile, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-6-[1-(trifluoromethyl)cyclopropyl]-1,2-dihydroquinoline-3-carbonitrile, 2-({3-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinolin-7-yl}oxy)acetamide, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-{[oxan-3-yl]oxy}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, (rac)-tert-butyl({3-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinolin-7-yl}oxy)acetate, ({3-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinolin-7-yl}oxy)acetic acid, (rac)-4-[4-fluoro-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-(tetrahydrofuran-3-yloxy)-1,2-dihydroquinoline-3-carbonitrile, 7-(cyclopropylamino)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-methoxy-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-4-[4-fluoro-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-methoxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-nitro-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-7-hydroxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-7-hydroxy-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, (rac)-6-bromo-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carbonitrile, (rac)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[tetrahydrofuran-3-yloxy]-1,2-dihydroquinoline-3,6-dicarbonitrile, 7-hydroxy-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3,6-dicarbonitrile, (rac)-6-ethoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[tetrahydrofuran-3-yloxy]-1,2-dihydroquinoline-3-carbonitrile, 7-hydroxy-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, (rac)-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[tetrahydrofuran-3-yloxy]-1,2-dihydroquinoline-3-carbonitrile, (rac)-6-(2,2-difluoroethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[tetrahydrofuran-3-yloxy]-1,2-dihydroquinoline-3-carbonitrile, (rac)-4-[4-fluoro-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-6-methoxy-1-methyl-2-oxo-7-[tetrahydrofuran-3-yloxy]-1,2-dihydroquinoline-3-carbonitrile, (rac)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3,6-dicarbonitrile, (rac)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-6-(3,3,3-trifluoroprop-1-en-2-yl)-1,2-dihydroquinoline-3-carbonitrile, (rac)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-6-[1-(trifluoromethyl)cyclopropyl]-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-1-methyl-2-oxo-4-(4-{5-[3-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl}piperidin-1-yl)-1,2-dihydroquinoline-3-carbonitrile, 6-methoxy-1-methyl-4-{4-[3-(3-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-methoxy-1-methyl-2-oxo-4-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 6-methoxy-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-methoxy-1-methyl-2-oxo-4-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-1-methyl-2-oxo-4-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-1-methyl-2-oxo-4-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-1-methyl-4-{4-[5-(3-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-hydroxy-1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-7-hydroxy-1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, (rac)-1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-7-{[oxan-3-yl]oxy}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 4-[4-(1,3-benzoxazol-2-yl)piperidin-1-yl]-N,1-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, N,1-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)-4-methylpiperidin-1-yl]-N,1-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-2-oxo-4-{4-[5-(2-oxopyrrolidin-1-yl)-1,3-benzoxazol-2-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carboxamide, 4-[4-(3-chlorophenyl)-4-methoxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-(dimethylphosphoryl)-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-(dimethylphosphoryl)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-(methanesulfonyl)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1-benzothiophen-2-yl)-4-methoxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1-benzothiophen-2-yl)-4-hydroxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(6-methoxynaphthalen-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-{4-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-{4-[3-(3-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-{4-[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-{4-[5-(3-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-{4-[5-(3-chlorophenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-{4-[5-(3-chlorophenyl)-1,3,4-oxadiazol-2-yl]-4-methylpiperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-{4-[2-methyl-2,3-dihydro-1-benzofuran-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(2-hydroxy-2,3-dihydro-1H-inden-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(2,2-dimethyl-2H-1,3-benzodioxol-5-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-2-oxo-4-[4-(2'-oxo-1',2'-dihydrospiro[cyclobutane-1,3'-indol]-5'-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-[4-methyl-4-(4-methylquinolin-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(4-fluoro-1-methyl-1H-indol-6-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-{4-[1-(3-methylphenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-{4-[1-(2-methylphenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-{4-[1-(3-chlorophenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-2-oxo-4-{4-[3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carboxamide, 4-{4-[4-(3-methoxyphenyl)-1,3-thiazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-{4-[4-(2-methoxyphenyl)-1,3-thiazol-2-yl]piperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-{4-[4-(4-methylphenyl)-1,3-thiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[(oxan-4-yl)oxy]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 7-(2-methoxyethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-{[oxiran-2-yl]methoxy}-2-oxo-1,2-dihydroquinoline-3-carboxamide, (rac)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide, (-)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide, (+)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[(oxetan-3-yl)oxy]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(5-methoxy-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-2-oxo-4-(4-{5-[(oxolan-2-yl)methoxy]-1,3-benzoxazol-2-yl}piperidin-1-yl)-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)-4-fluoropiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-(1,3-benzoxazol-2-yl)-4-methoxypiperidin-1-yl]-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-{4-[5-(methoxymethyl)-1,3-benzoxazol-2-yl]-4-methylpiperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-{4-[6-(methoxymethyl)-1,3-benzoxazol-2-yl]-4-methylpiperidin-1-yl}-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-bromo-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 8-bromo-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[methyl(oxetan-3-yl)amino]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 7-[(2-hydroxyethyl)(methyl)amino]-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-{methyl[(3R)-oxolan-3-yl]amino}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-{methyl[(3S)-oxolan-3-yl]amino}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3,6-dicarboxamide, 7-[(cyanomethyl)(methyl)amino]-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-methoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-ethoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-(2,2-difluoropropoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-(2,2-difluoroethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-(cyclopropylmethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-cyclobutyl-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-6-[1-(trifluoromethyl)cyclopropyl]-1,2-dihydroquinoline-3-carboxamide, 7-(2-amino-2-oxoethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4-[4-fluoro-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide, 1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-nitro-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-bromo-7-hydroxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-bromo-7-hydroxy-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, (rac)-6-bromo-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide, (rac)-6-cyano-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide, 6-cyano-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide, 6-cyano-1-methyl-4-[4-methyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide, (rac)-6-(2,2-difluoroethoxy)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide, (rac)-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-6-[1-(trifluoromethyl)cyclopropyl]-1,2-dihydroquinoline-3-carboxamide, 6-bromo-1-methyl-2-oxo-4-(4-{5-[3-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl}piperidin-1-yl)-1,2-dihydroquinoline-3-carboxamide, 6-methoxy-1-methyl-4-{4-[3-(3-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-methoxy-1-methyl-2-oxo-4-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carboxamide, 6-methoxy-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-bromo-1-methyl-2-oxo-4-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carboxamide, 6-bromo-1-methyl-2-oxo-4-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)piperidin-1-yl]-1,2-dihydroquinoline-3-carboxamide, 6-bromo-1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-bromo-1-methyl-4-{4-[5-(3-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-7-{[(3R)-oxan-3-yl]oxy}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-7-{[(3S)-oxan-3-yl]oxy}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-bromo-7-hydroxy-1-methyl-4-{4-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-bromo-7-methoxy-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-7-hydroxy-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, (rac)-6-bromo-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carbonitrile, (rac)-6-bromo-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide, (rac)-6-cyano-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide, 6-cyano-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide, 6-cyano-1-methyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide, (-)-6-bromo-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carbonitrile, (rac)-6-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide, 6-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide, 6-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide, 6-methoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carbonitrile, 6-methoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carbonitrile, 6-methoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide, (rac)-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide, 1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide, 1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide, 7-[(2-methoxyethyl)amino]-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-(3-hydroxyazetidin-1-yl)-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-[(oxetan-3-yl)amino]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-[(2-hydroxyethyl)amino]-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-[(2-hydroxyethyl)(methyl)amino]-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-[(2-methoxyethyl)amino]-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 7-(3-hydroxyazetidin-1-yl)-1,6-dimethyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, (rac)-1,6-dimethyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carbonitrile, 1,6-dimethyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carbonitrile, 1,6-dimethyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carbonitrile, 1,6-dimethyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide, 1,6-dimethyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide, 7-[(2-hydroxyethyl)amino]-1,6-dimethyl-4-{4-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-bromo-1,6-dimethyl-4-{4-[1-(2-methylphenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 7-[(2-hydroxyethyl)amino]-1,6-dimethyl-4-{4-[1-(2-methylphenyl)-1H-pyrazol-3-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-bromo-7-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, 6-cyano-7-fluoro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carboxamide, (rac)-6-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(oxolan-3-yl)methyl]amino}-1,2-dihydroquinoline-3-carboxamide, 6-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-({[(3R)-oxolan-3-yl]methyl}amino)-1,2-dihydroquinoline-3-carboxamide, 6-cyano-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-({[(3S)-oxolan-3-yl]methyl}amino)-1,2-dihydroquinoline-3-carboxamide, 6-chloro-7-methoxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, 6-chloro-7-hydroxy-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-1,2-dihydroquinoline-3-carbonitrile, (rac)-6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carbonitrile, (rac)-6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carboxamide, 6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide, 6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3S)-oxolan-3-yl]oxy}-1,2-dihydroquinoline-3-carboxamide, (rac)-6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)methoxy]-1,2-dihydroquinoline-3-carbonitrile, (rac)-6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-[(oxolan-3-yl)methoxy]-1,2-dihydroquinoline-3-carboxamide, 6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3R)-oxolan-3-yl]methoxy}-1,2-dihydroquinoline-3-carboxamide, 6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-2-oxo-7-{[(3S)-oxolan-3-yl]methoxy}-1,2-dihydroquinoline-3-carboxamide, (rac)-6-bromo-1-methyl-2-oxo-7-[(oxolan-3-yl)oxy]-4-{4-[2-(pyridin-3-yl)-2H-1,2,3-triazol-4-yl]piperidin-1-yl}-1,2-dihydroquinoline-3-carbonitrile, (rac)-6-bromo-1-methyl-4-{4-[1-(2-methylphenyl)-1H-1,2,3-triazol-4-yl]piperidin-1-yl}-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carbonitrile, (rac)-1,6-dimethyl-4-{4-[1-(2-methylphenyl)-1H-1,2,3-triazol-4-yl]piperidin-1-yl}-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carbonitrile, 7-bromo-1,6-dimethyl-4-{4-[1-(2-methylphenyl)-1H-pyrazol-4-yl]piperidin-1-yl}-2-oxo-1,2-dihydroquinoline-3-carbonitrile, and (rac)-1,6-dimethyl-4-{4-[1-(2-methylphenyl)-1H-pyrazol-4-yl]piperidin-1-yl}-2-oxo-7-[(oxolan-3-yl)oxy]-1,2-dihydroquinoline-3-carbonitrile or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof, of the general formula (I) selected from: and The following groups: rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-methoxy-2-methyl-anilino)propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-4-(dimethylamino)anilino]propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-isopropoxy-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2,4,6-trifluoroanilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2-bromo-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(6-methylpyridine-3-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(2-fluorobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-cyano-anilino)propanamide, rac-2-(N-[4-amino-5-[4-chloro-3-(trifluoromethyl)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2-chloro-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(3-cyanobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-3-chloro-4-(dimethylamino)anilino]propanamide, rac-2-(N-[4-amino-5-(6-methoxypyridine-3-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-4-[4-amino-2-(N-[2-amino-1-methyl-2-oxo-ethyl]-4-fluoro-anilino)thiazole-5-carbonyl]-N-methyl-benzamide, rac-2-(N-[4-amino-5-(3-fluorobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3-chloro-4-methoxy-anilino)propanamide, rac-2-(N-[4-amino-5-(4-fluorobenzoyl)thiazol-2-yl]-4-methoxy-anilino)propanamide, rac-2-(N-[4-amino-5-(4-methylsulfonylbenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-imidazol-1-ylbenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-cyano-3-fluoro-benzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-cyano-3-fluoro-benzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(4-cyano-3-fluoro-benzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-cyano-2-fluoro-benzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(2-fluoro-4-methoxy-benzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-4-(trifluoromethoxy)anilino]propanamide, rac-2-(N-[4-amino-5-(3,4-difluorobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(3,4-dichlorobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-[N-[4-amino-5-(4-fluorobenzoyl)thiazol-2-yl]-4-(trifluoromethoxy)anilino]propanamide, (R)-2-[N-[4-amino-5-(4-fluorobenzoyl)thiazol-2-yl]-4-(trifluoromethoxy)anilino]propanamide, (S)-2-[N-[4-amino-5-(4-fluorobenzoyl)thiazol-2-yl]-4-(trifluoromethoxy)anilino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-4-(trifluoromethyl)anilino]propanamide, rac-2-(N-[4-amino-5-[6-(trifluoromethyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-[6-(trifluoromethyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-[6-(trifluoromethyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-chloro-2-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(indan-5-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3,4-difluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-cyanobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-cyanobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(4-cyanobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-chloro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3,4-dichloro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-chloro-3-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-fluorobenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-fluorobenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide, (S)-2-(N-[4-amino-5-(4-fluorobenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-ethyl 2-[4-[4-amino-2-(N-[2-amino-1-methyl-2-oxo-ethyl]-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]-2-methyl-propanoate, rac-2-(N-[4-amino-5-[4-(trifluoromethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-[4-(trifluoromethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-[4-(trifluoromethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide, (S)-2-(N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-(trifluoromethyl)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-[N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-(trifluoromethyl)anilino]propanamide, (R)-2-[N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-(trifluoromethyl)anilino]propanamide, (S)-2-[N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-(trifluoromethyl)anilino]propanamide, rac-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, 2-(N-[4-amino-5-[4-[2-amino-1-methyl-2-oxo-ethoxy]benzoyl]thiazol-2-yl]anilino)propanamide (mixture of stereoisomers), (2R)-(N-[4-amino-5-[4-[2-amino-(1R)-methyl-2-oxo-ethoxy]benzoyl]thiazol-2-yl]anilino)propanamide, (2R)-(N-[4-amino-5-[4-[2-amino-(1S)-methyl-2-oxo-ethoxy]benzoyl]thiazol-2-yl]anilino)propanamide, (2S)-(N-[4-amino-5-[4-[2-amino-(1R)-methyl-2-oxo-ethoxy]benzoyl]thiazol-2-yl]anilino)propanamide, (2S)-(N-[4-amino-5-[4-[2-amino-(1S)-methyl-2-oxo-ethoxy]benzoyl]thiazol-2-yl]anilino)propanamide, rac-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-2-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-2-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-2-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-anilino)propanamide, (R)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-anilino)propanamide, (S)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(6-methoxypyridine-3-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(6-methoxypyridine-3-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(6-methoxypyridine-3-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(trifluoromethyl)pyridine-3-carbonyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-[6-(trifluoromethyl)pyridine-3-carbonyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-[6-(trifluoromethyl)pyridine-3-carbonyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide, rac-2-(N-[5-[4-(difluoromethoxy)benzoyl]-4-methyl-thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[5-[4-(difluoromethoxy)benzoyl]-4-methyl-thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (R)-2-(N-[5-[4-(difluoromethoxy)benzoyl]-4-methyl-thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (S)-2-(N-[5-[4-(difluoromethoxy)benzoyl]-4-methyl-thiazol-2-yl]-3,4-difluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-chloro-anilino)propanamide, (R)-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-chloro-anilino)propanamide, (S)-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-chloro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide, (S)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-chloro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-fluoro-anilino)propanamide, (R)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-fluoro-anilino)propanamide, (S)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-methylbenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-methylbenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(4-methylbenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-fluorobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2,4-difluoro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-methoxy-anilino)propanamide, rac-2-[(4-amino-5-benzoyl-1,3-thiazol-2-yl)(phenyl)amino]butanamide, rac-2-[(4-amino-5-benzoyl-1,3-thiazol-2-yl)(4-fluorophenyl)amino]butanamide, 2-(N-[4-amino-5-[4-(2-amino-1-methyl-2-oxo-ethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide (mixture of stereoisomers), rac-2-{[4-amino-5-(4-methoxybenzoyl)-1,3-thiazol-2-yl](4-fluorophenyl)amino}butanamide, 2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-fluoro-anilino)acetamide, 2-(N-[4-amino-5-(4-methylbenzoyl)thiazol-2-yl]-4-fluoro-anilino)acetamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-methyl-anilino)propanamide, (R)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-methyl-anilino)propanamide, (S)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-methyl-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3-fluoro-anilino)propanamide, (R)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3-fluoro-anilino)propanamide, (S)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3-fluoro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2-fluoro-anilino)propanamide, (R)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2-fluoro-anilino)propanamide, (S)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2-fluoro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3-methyl-anilino)propanamide, (R)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3-methyl-anilino)propanamide, (S)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3-methyl-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2-methyl-anilino)propanamide, (R)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2-methyl-anilino)propanamide, (S)-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-2-methyl-anilino)propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(1-methylpyrazol-4-yl)amino]propanamide, (R)-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(1-methylpyrazol-4-yl)amino]propanamide, (S)-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(1-methylpyrazol-4-yl)amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(3-pyridyl)amino]propanamide, (R)-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(3-pyridyl)amino]propanamide, (S)-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(3-pyridyl)amino]propanamide, rac-2-(N-[4-amino-5-(4-bromobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-ethyl 2-[4-[4-amino-2-(4-fluoro-N-[2-amino-1-methyl-2-oxo-ethyl]anilino)thiazole-5-carbonyl]phenoxy]acetate, (R)-ethyl 2-[4-[4-amino-2-(4-fluoro-N-[2-amino-1-methyl-2-oxo-ethyl]anilino)thiazole-5-carbonyl]phenoxy]acetate, (S)-ethyl 2-[4-[4-amino-2-(4-fluoro-N-[2-amino-1-methyl-2-oxo-ethyl]anilino)thiazole-5-carbonyl]phenoxy]acetate, rac-2-(N-[4-amino-5-[4-[2-(isopropylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(m-tolylmethylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(o-tolylmethylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[(3-chlorophenyl)methylamino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(4-methylpiperazin-1-yl)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(3-methylanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-(2-morpholino-2-oxo-ethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-oxo-2-[2-(1-piperidyl)ethylamino]ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(4-benzyl-1-piperidyl)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(2-methoxyethylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(4-cyanoanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[methyl(prop-2-ynyl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[(2-methoxyphenyl)methylamino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[(3-methoxyphenyl)methylamino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[(2-fluorophenyl)methylamino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[(4-fluorophenyl)methylamino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(1H-benzimidazol-2-ylmethylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-oxo-2-(2,2,2-trifluoroethylamino)ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[methyl(2-pyridyl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[methyl-(1-methyl-4-piperidyl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(methoxyamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[(5-methylisoxazol-3-yl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(ethylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(4-methylanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(cyclohexylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-3-[[2-[4-[4-amino-2-(N-[2-amino-1-methyl-2-oxo-ethyl]-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]acetyl]amino]benzamide, rac-2-(N-[4-amino-5-[4-[2-oxo-2-(6-quinolylamino)ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-4-[[2-[4-[4-amino-2-(N-[2-amino-1-methyl-2-oxo-ethyl]-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]acetyl]amino]benzamide, (2S)-1-[2-[4-[4-amino-2-(N-[2-amino-(1RS)-methyl-2-oxo-ethyl]-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]acetyl]pyrrolidine-2-carboxamide (mixture of two diastereomers), rac-2-(N-[4-amino-5-[4-[2-[ethyl(methyl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[(3-methylisoxazol-5-yl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[3-(dimethylamino)propyl-methyl-amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[5-[4-[2-(4-acetylpiperazin-1-yl)-2-oxo-ethoxy]benzoyl]-4-amino-thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-oxo-2-(3-pyridylmethylamino)ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, 2-(N-[4-amino-5-[4-[2-(2,3-dihydroxypropylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide (mixture of stereoisomers), rac-2-(N-[4-amino-5-[4-[2-(4-methoxyanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[benzyl(methyl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(4-chloroanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[(2-chlorophenyl)methylamino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[(4-chlorophenyl)methylamino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(4-fluoroanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(azepan-1-yl)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[(4-methoxyphenyl)methylamino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, 2-(N-[4-amino-5-[4-[2-oxo-2-(1-phenylethylamino)ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide (mixture of stereoisomers), rac-2-(N-[4-amino-5-[4-[2-oxo-2-(p-tolylmethylamino)ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[methyl(2-phenylethyl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, 2-(N-[4-amino-5-[4-[2-(3-methyl-1-piperidyl)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide (mixture of stereoisomers), rac-2-(N-[4-amino-5-[4-[2-(4-methyl-1-piperidyl)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[5-[4-[2-(4-acetamidoanilino)-2-oxo-ethoxy]benzoyl]-4-amino-thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-oxo-2-(1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(cyclopentylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(3,4-dihydro-1H-isoquinolin-2-yl)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-(2-isoindolin-2-yl-2-oxo-ethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[2-furylmethyl(methyl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[4-(dimethylamino)-1-piperidyl]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-[methyl(3-pyridylmethyl)amino]-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(N,2-dimethylanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(N,4-dimethylanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(N,3-dimethylanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-[2-(2,2-dimethylpropylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, 2-(N-[5-[4-[2-(1-adamantylamino)-2-oxo-ethoxy]benzoyl]-4-amino-thiazol-2-yl]-4-fluoro-anilino)propanamide (single stereoisomer), 2-(N-[5-[4-[2-(1-adamantylmethylamino)-2-oxo-ethoxy]benzoyl]-4-amino-thiazol-2-yl]-4-fluoro-anilino)propanamide (single stereoisomer), 2-(N-[5-[4-[2-[2-(1-adamantyl)ethylamino]-2-oxo-ethoxy]benzoyl]-4-amino-thiazol-2-yl]-4-fluoro-anilino)propanamide (single stereoisomer), 2-(N-[4-amino-5-[4-[2-(4-chloroanilino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide (single stereoisomer), 4-[[2-[4-[4-amino-2-(4-fluoro-N-[2-amino-1-methyl-2-oxo-ethyl]anilino)thiazole-5-carbonyl]phenoxy]acetyl]amino]benzamide (single stereoisomer), 2-(N-[4-amino-5-[4-[2-((2RS),3-dihydroxypropylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide (mixture of two diastereomers), 2-(N-[4-amino-5-[4-[2-oxo-2-[2-(1-piperidyl)ethylamino]ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide (single stereoisomer), 2-(N-[4-amino-5-[4-(2-amino-2-oxo-ethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide (single stereoisomer), (R)-2-(N-[4-amino-5-[4-[2-(methylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-[4-[2-(methylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-[4-[2-(isopropylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-[4-[2-(isopropylamino)-2-oxo-ethoxy]benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]-N-isopropyl-2-methyl-propanamide, rac-2-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]-2-methyl-propanamide, rac-2-(N-(5-benzoyl-4-methyl-thiazol-2-yl)-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-hydroxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(difluoromethyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3-chloro-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3-chloro-4-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3-chloro-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3-chloro-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3-chloro-4-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3-chloro-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (R)-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (S)-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-3,4-difluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, rac-benzyl N-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-3,4-difluoro-anilino)thiazole-5-carbonyl]phenyl]carbamate, (R)-benzyl N-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-3,4-difluoro-anilino)thiazole-5-carbonyl]phenyl]carbamate, (S)-benzyl N-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-3,4-difluoro-anilino)thiazole-5-carbonyl]phenyl]carbamate, rac-2-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]ethyl acetate, rac-benzyl N-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenyl]carbamate, (R)-benzyl N-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenyl]carbamate, (S)-benzyl N-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenyl]carbamate, rac-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(4-benzyloxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-iodobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(6-methoxypyridine-3-carbonyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(6-methoxypyridine-3-carbonyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(6-methoxypyridine-3-carbonyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-phenoxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-methoxy-anilino)propanamide, (R)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-methoxy-anilino)propanamide, (S)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-methoxy-anilino)propanamide, rac-2-(N-[4-amino-5-(4-nitrobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(4-fluoro-N-[5-(4-methoxybenzoyl)-4-methyl-thiazol-2-yl]anilino)propanamide, (R)-2-(4-fluoro-N-[5-(4-methoxybenzoyl)-4-methyl-thiazol-2-yl]anilino)propanamide, (S)-2-(4-fluoro-N-[5-(4-methoxybenzoyl)-4-methyl-thiazol-2-yl]anilino)propanamide, rac-4-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenyl]cyclopropanecarboxamide, rac-2-(N-[4-amino-5-(4-morpholinobenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-(pyrazol-1-ylmethyl)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-(dimethylamino)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(4-pyrrolidin-1-ylbenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-benzyloxy-anilino)propanamide, (R)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-benzyloxy-anilino)propanamide, (S)-2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-benzyloxy-anilino)propanamide, rac-2-(N-[4-amino-5-[3-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(pyridine-3-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(pyridine-3-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(pyridine-3-carbonyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, rac-2-(N-[5-(4-acetamidobenzoyl)-4-amino-thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(2-chloropyridine-4-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-(2-methylpyridine-4-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-(2-methylpyridine-4-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(2-methylpyridine-4-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[2-(difluoromethyl)pyridine-4-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(4-pyridyl)amino]propanamide, rac-2-(N-[4-amino-5-(2-methoxypyridine-4-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-3-fluoro-4-methoxy-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-cyano-3-fluoro-anilino)propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-bromo-anilino)propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-3-chloro-4-(difluoromethoxy)anilino]propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-ethoxy-anilino)propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(1,3-benzodioxol-5-yl)amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(2,2-difluoro-1,3-benzodioxol-5-yl)amino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-4-(difluoromethoxy)-3-fluoro-anilino]propanamide, rac-2-(N-(4-amino-5-benzoyl-thiazol-2-yl)-4-benzyloxy-anilino)propanamide, rac-2-[N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3-chloro-4-(difluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-3-chloro-4-(difluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-3-chloro-4-(difluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3-chloro-4-(difluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-3-chloro-4-(difluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-(difluoromethoxy)-3-fluoro-anilino]propanamide, rac-2-[N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-4-(difluoromethoxy)-3-fluoro-anilino]propanamide, rac-2-[N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-(difluoromethoxy)-3-fluoro-anilino]propanamide, rac-2-[N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-(difluoromethoxy)-3-fluoro-anilino]propanamide, rac-2-[N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-4-(difluoromethoxy)-3-fluoro-anilino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-3-chloro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-(2,2-difluoro-1,3-benzodioxol-5-yl)amino]propanamide, rac-2-[[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-(2,2-difluoro-1,3-benzodioxol-5-yl)amino]propanamide, rac-2-[[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-(2,2-difluoro-1,3-benzodioxol-5-yl)amino]propanamide, rac-2-[[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-(2,2-difluoro-1,3-benzodioxol-5-yl)amino]propanamide, rac-2-[[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-(2,2-difluoro-1,3-benzodioxol-5-yl)amino]propanamide, rac-2-[N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3-fluoro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-3-fluoro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-3-fluoro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3-fluoro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-3-fluoro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-3-chloro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-3-chloro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-3-chloro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-3-chloro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-3-chloro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(6-methoxy-3-pyridyl)amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-[6-(trifluoromethoxy)-3-pyridyl]amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-[6-(difluoromethoxy)-3-pyridyl]amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-[6-(trifluoromethyl)-3-pyridyl]amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-[6-(difluoromethyl)-3-pyridyl]amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(6-chloro-3-pyridyl)amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(6-fluoro-3-pyridyl)amino]propanamide, rac-2-[(4-amino-5-benzoyl-thiazol-2-yl)-(6-methyl-3-pyridyl)amino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-4-fluoro-3-(trifluoromethoxy)anilino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-4-chloro-3-(trifluoromethoxy)anilino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-3-(difluoromethoxy)-4-fluoro-anilino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-4-chloro-3-(difluoromethoxy)anilino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-2-fluoro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-2-chloro-4-(trifluoromethoxy)anilino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-4-(difluoromethoxy)-2-fluoro-anilino]propanamide, rac-2-[N-(4-amino-5-benzoyl-thiazol-2-yl)-2-chloro-4-(difluoromethoxy)anilino]propanamide, rac-2-[N-[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-4-(difluoromethyl)anilino]propanamide, rac-2-[N-[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-4-(difluoromethyl)anilino]propanamide, rac-2-[N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-(difluoromethyl)anilino]propanamide, rac-2-[N-[4-amino-5-(pyridine-4-carbonyl)thiazol-2-yl]-4-(difluoromethyl)anilino]propanamide, rac-2-[N-[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-4-(difluoromethyl)anilino]propanamide, rac-2-[[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-[6-(trifluoromethoxy)-3-pyridyl]amino]propanamide, rac-2-[[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-[6-(trifluoromethoxy)-3-pyridyl]amino]propanamide, rac-2-[[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-[6-(trifluoromethoxy)-3-pyridyl]amino]propanamide, rac-2-[[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-[6-(trifluoromethoxy)-3-pyridyl]amino]propanamide, rac-2-[[4-amino-5-(4-methoxybenzoyl)thiazol-2-yl]-[6-(difluoromethoxy)-3-pyridyl]amino]propanamide, rac-2-[[4-amino-5-(4-chlorobenzoyl)thiazol-2-yl]-[6-(difluoromethoxy)-3-pyridyl]amino]propanamide, rac-2-[[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-[6-(difluoromethoxy)-3-pyridyl]amino]propanamide, rac-2-[[4-amino-5-[6-(difluoromethoxy)pyridine-3-carbonyl]thiazol-2-yl]-[6-(difluoromethoxy)-3-pyridyl]amino]propanamide, rac-benzyl N-[5-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-2-pyridyl]carbamate, rac-ethyl 4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]benzoate, rac-ethyl 4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-chloro-3-fluoro-anilino)thiazole-5-carbonyl]benzoate, rac-ethyl 2-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]-2-methyl-propanoate, rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-N-cyclohexyl-benzamide, rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-N-isopropyl-benzamide, rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-N-benzyl-benzamide, 4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-N-[(2S)-2-hydroxypropyl]benzamide (mixture of stereoisomers), rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-N-(2-methoxyethyl)benzamide, 4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-N-[(2R)-2-hydroxypropyl]benzamide (mixture of stereoisomers), rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-N-cyclopropyl-benzamide, rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]-N-cyclopentyl-benzamide, rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-chloro-3-fluoro-anilino)thiazole-5-carbonyl]-N-(2-phenoxyethyl)benzamide, rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-chloro-3-fluoro-anilino)thiazole-5-carbonyl]-N-[2-(trifluoromethoxy)ethyl]benzamide, rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-chloro-3-fluoro-anilino)thiazole-5-carbonyl]-N-[2-(difluoromethoxy)ethyl]benzamide, rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-chloro-3-fluoro-anilino)thiazole-5-carbonyl]-N-(2-tert-butoxyethyl)benzamide, rac-4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-chloro-3-fluoro-anilino)thiazole-5-carbonyl]-N-(2-methoxyethyl)benzamide, rac-2-[4-[4-amino-2-(N-(2-amino-1-methyl-2-oxo-ethyl)-4-fluoro-anilino)thiazole-5-carbonyl]phenoxy]-N-[(4-chlorophenyl)methyl]-2-methyl-propanamide, rac-2-(N-[4-amino-5-(6-bromopyridine-3-carbonyl)thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-[4-(trifluoromethyl)-1-piperidyl]pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(4-methyl-1-piperidyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-[4-(oxetan-3-yl)-1-piperidyl]pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(dimethylamino)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(4,4-dimethyl-1-piperidyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(3-azabicyclo[3.2.1]octan-3-yl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(3,5-dimethyl-1-piperidyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(3-azabicyclo[3.1.0]hexan-3-yl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(1-piperidyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(4,4-difluoro-1-piperidyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, rac-2-(N-[4-amino-5-[6-(4-cyano-4-methyl-1-piperidyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, (R)-2-(N-[4-amino-5-[6-(4-cyano-4-methyl-1-piperidyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-[6-(4-cyano-4-methyl-1-piperidyl)pyridine-3-carbonyl]thiazol-2-yl]-4-fluoro-anilino)propanamide, 2-(N-[4-amino-5-(4-hydroxybenzoyl)thiazol-2-yl]-4-fluoro-anilino)propanamide (single enantiomer), (R)-2-(N-[4-amino-5-(4-hydroxybenzoyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, (S)-2-(N-[4-amino-5-(4-hydroxybenzoyl)thiazol-2-yl]-3,4-difluoro-anilino)propanamide, 2-(N-[4-amino-5-(4-hydroxybenzoyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide (enantiomer 1), 2-(N-[4-amino-5-(4-hydroxybenzoyl)thiazol-2-yl]-4-chloro-3-fluoro-anilino)propanamide (enantiomer 2), 2-(N-[4-amino-5-[4-(difluoromethoxy)benzoyl]thiazol-2-yl]-4-hydroxy-anilino)propanamide (single enantiomer), and rac-2-(N-[4-amino-5-[4-(2-hydroxyethoxy)benzoyl]thiazol-2-yl]-4-fluoro-anilino)propanamide or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof, of the general formula (II) selected from The combination according to any one of claims 1 to 5, comprising:

7. The DGKalpha inhibitor compound has the formula: 【Transformation 8】 or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof; and The DGKzeta inhibitor compound has the formula: 【Chemistry 9】 or a stereoisomer, tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

8. The DGKalpha inhibitor compound has the formula: 【Chemistry 10】 is a compound of and The DGKzeta inhibitor compound has the formula: 【Chemistry 11】 8. The combination according to any one of claims 1 to 7, wherein the compound is

9. 9. A combination according to any one of claims 1 to 8 for use in the treatment or prevention of a condition with a dysregulated immune response, in particular cancer, or another disorder associated with viral infection or aberrant DGKalpha and / or DGKzeta signalling in a mammal.

10. The combination for use according to claim 9, wherein the mammal is a human.

11. A method for treating or preventing a patient's disease, preferably a condition with a dysregulated immune response, in particular cancer, or another disorder associated with viral infection or aberrant DGKalpha and / or DGKzeta signaling in a mammal, said method comprising administering a combination according to any one of claims 1 to 8.

12. 12. The method of claim 11, wherein the mammal is a human.

13. Use of a combination according to any one of claims 1 to 8 for the preparation of a medicament for the treatment or prevention of a condition with a dysregulated immune response in a mammal, in particular cancer, or another disorder associated with viral infection or aberrant DGKalpha and / or DGKzeta signalling.

14. 14. The use according to claim 13, wherein the mammal is a human.

15. below - a DGKalpha inhibitor compound according to any one of claims 3 to 8; A DGKzeta inhibitor compound according to any one of claims 3 to 8. Includes a kit.

16. 16. The kit of claim 15, wherein the DGKalpha inhibitor compound and / or the DGKzeta inhibitor compound are in the form of pharmaceutical compositions ready for use for administration, optionally simultaneously, in parallel, separately or sequentially.

17. 16. The kit of claim 15, wherein each of the DGKalpha inhibitor compound and the DGKzeta inhibitor compound is in the form of a pharmaceutical composition, and the DGKalpha inhibitor compound is administered before the DGKzeta inhibitor compound.

18. A pharmaceutical composition comprising a combination according to any one of claims 1 to 8 together with one or more pharmaceutically acceptable excipients.

19. 19. The pharmaceutical composition of claim 18, wherein the DGKalpha inhibitor compound and the DGKzeta inhibitor compound are present in a combination drug.

20. 20. The pharmaceutical composition of claim 19, wherein the DGKalpha inhibitor compound and the DGKzeta inhibitor compound are present in separate formulations.

21. An inhibitor of DGKalpha for use in a method for the treatment or prevention of a disease, preferably a condition with a dysregulated immune response, in particular cancer, or a viral infection or another disorder associated with abnormal DGKalpha and / or DGKzeta signaling, characterized in that the method comprises administering at least one inhibitor of DGKzeta.

22. An inhibitor of DGKzeta for use in a method for the treatment or prevention of a disease, preferably a condition with a dysregulated immune response, in particular cancer, or a viral infection or another disorder associated with abnormal DGKalpha and / or DGKzeta signaling, characterized in that the method comprises administering at least one inhibitor of DGKalpha.

23. 23. An inhibitor of DGK according to any of claims 21 or 22 for use in a method for the treatment or prevention of a disease, preferably a condition with a dysregulated immune response, in particular cancer, or another disorder associated with a viral infection or aberrant DGKalpha and / or DGKzeta signaling, a. The inhibitor of DGKalpha is as defined in any one of claims 3 to 8, and / or b) An inhibitor of DGK, wherein the inhibitor of DGK zeta is as defined in any one of claims 3 to 8.

24. 24. An inhibitor of DGK for use in a method for the treatment or prevention of a disease, preferably a condition with a dysregulated immune response, in particular cancer, or another disorder associated with a viral infection or aberrant DGKalpha and / or DGKzeta signaling, according to any of claims 21 to 23, a. the inhibitor of DGKalpha is DGKalpha inhibitor A, or a tautomer, N-oxide, hydrate, solvate, or salt thereof, or a mixture thereof; and / or b. An inhibitor of DGK, wherein the inhibitor of DGK zeta is DGK zeta inhibitor A', or a stereoisomer, tautomer, N-oxide, hydrate, solvate or salt thereof, or a mixture thereof.

25. 25. An inhibitor of DGK for use in a method for the treatment or prevention of a disease, preferably a condition with a dysregulated immune response, in particular cancer, or another disorder associated with a viral infection or aberrant DGKalpha and / or DGKzeta signaling, according to any of claims 21 to 24, a. The DGKalpha inhibitor is DGKalpha inhibitor A, and / or b. An inhibitor of DGK, wherein the inhibitor of DGK zeta is DGK zeta inhibitor A'.

26. 26. An inhibitor of DGK for use in a method for the treatment or prevention of a disease, preferably a condition with a dysregulated immune response, in particular cancer, or another disorder associated with viral infection or aberrant DGKalpha and / or DGKzeta signaling, according to any one of claims 21 to 25, wherein the disease is cancer.

27. 27. The inhibitor of DGK for use in a method of treating cancer according to claim 26, wherein the cancer is selected from the group of non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), head and neck squamous cell carcinoma (HNSCC), melanoma, non-melanoma skin cancer, gastric cancer, renal cell carcinoma, microsatellite instability-high (MSI-high) colorectal cancer, or gastroesophageal junction adenocarcinoma.

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