[1,2,4]Triazolo[1,5-C]quinazolin-5-amine

Abstract

The present invention relates to [1,2,4]triazolo[1,5-c]quinazolin-5-amine compounds of general formula (I): TIFF2022544952001142.tif74169 (in the formula, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 as defined herein), methods for preparing said compounds, intermediate compounds useful in preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds, either as the sole agent or in combination with other active ingredients, for the manufacture of a pharmaceutical composition for the treatment or prevention of disease, particularly cancer or conditions involving a dysregulated immune response or other disorders associated with abnormal AHR signaling.

Description

[Technical Field]

[0001] The present invention covers [1,2,4]triazolo[1,5-c]quinazolin-5-amine compounds of the general formula (I) as described and defined herein, processes for preparing said compounds, intermediate compounds useful in preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds, either as the sole agent or in combination with other active ingredients, for the manufacture of pharmaceutical compositions for the treatment or prevention of diseases, particularly cancer or conditions involving a dysregulated immune response. [Background technology]

[0002] The aromatic hydrocarbon receptor (AHR) is a ligand-activated transcription factor belonging to the basic helix-loop-helix / Per-Arnt-Sim (bHLH / PAS) family and is located in the cytosol. Upon ligand binding, AHR translocates to the nucleus, where it heterodimerizes with ARNT (AHR nuclear transporter), where it interacts with and regulates the transcription of dioxin-responsive elements (DREs) of AHR-responsive genes. AHR is best known for binding to environmental toxins and inducing metabolic machinery, such as cytochrome P450 enzymes (e.g., CYP1A1, CYP1A2, and CYP1B1) required for their elimination (Reyes et al., Science, 1992, 256(5060):1193-5). Activation of AHR by xenobiotics has demonstrated its role in numerous cellular processes, including embryogenesis, tumorigenesis, and inflammation.

[0003] AHR is expressed in many cells of the immune system, including dendritic cells (DCs), macrophages, T cells, and NK cells, and plays an important role in immunoregulation (Nguyen et al., Front Immunol, 2014, 5:551). Classic exogenous AHR ligands, TCDD and 3-methylcholanthrene, are known to induce profound immunosuppression, promote carcinogenesis, and induce tumor growth (Gramatzki et al., Oncogene, 2009, 28(28):2593-605; Bui et al., Oncogene, 2009, 28(41):3642-51; Esser et al., Trends Immunol, 2009, 30:447-454). In the context of immunosuppression, AHR activation promotes regulatory T cell generation, directly and indirectly inhibits Th1 and Th17 differentiation, and reduces DC activation and maturation (Wang et al., Clin Exp Immunol, 2014, 177(2):521-30; Mezrich et al., J Immunol, 2010, 185(6):3190-8; Wei et al., Lab Invest, 2014, 94(5):528-35; Nguyen et al., PNAS, 2010, 107(46):19961-6). AHR activation regulates innate immune responses, and constitutive AHR expression has been shown to negatively regulate type I interferon responses to viral infection (Yamada et al., Nat Immunol, 2016). Furthermore, mice with constitutively active AHR spontaneously develop tumors (Andersson et al., PNAS, 2002, 99(15):9990-5).

[0004] In addition to xenobiotics, the AHR can also bind metabolites of tryptophan degradation. Tryptophan metabolites, such as kynurenine and kynurenic acid, are endogenous AHR ligands that activate the AHR under physiological conditions (DiNatale et al., Toxicol Sci, 2010, 115(1):89-97; Mezrich et al., J Immunol, 2010, 185(6):3190-8; Opitz et al., Nature, 2011, 478(7368):197-203). Other endogenous ligands are known to bind to the AHR, but their physiological roles are currently unknown (Nguyen & Bradfield, Chem Res Toxicol, 2008, 21(1):102-116).

[0005] The immunosuppressive properties of kynurenine and tryptophan degradation have been well documented and are involved in cancer-associated immunosuppression. The enzymes indoleamine-2,3-dioxygenase 1 and 2 (IDO1 / IDO2) and tryptophan-2,3-dioxygenase 2 (TDO2) catalyze the first, rate-limiting step in tryptophan metabolism. Because IDO1 / 2-mediated degradation of tryptophan in tumors and tumor-draining lymph nodes reduces antitumor immune responses, inhibition of IDO can suppress tumorigenesis in animal models (Uyttenhove et al., Nat Med, 2003, 9(10):1269-74; Liu et al., Blood, 2005, 115(17):3520-30; Muller et al., Nat Med, 11(3):312-9; Metz, Cancer Res, 2007, 67(15):7082-7).

[0006] TDO2 is also strongly expressed in cancers, potentially leading to the production of the immunosuppressive kynurenine. In gliomas, AHR activation by kynurenine, downstream of TDO-mediated tryptophan degradation, enhances tumor growth by inhibiting antitumor immune responses and directly promoting tumor cell survival and motility (Opitz et al., Nature, 2011, 478(7368):197-203). Thus, AHR ligands produced by tumor cells promote tumor growth by acting in both autocrine and paracrine ways on tumor cells and lymphocytes, respectively.

[0007] The present invention encompasses [1,2,4]triazolo[1,5-c]quinazolin-5-amine compounds of general formula (I) that inhibit the AHR.

[0008] prior art WO 2010 / 059401 relates to compounds and compositions for increasing the number of CD34+ cells for transplantation. In particular, WO 2010 / 059401 relates to heterocyclic compounds that can, inter alia, downregulate AHR activity and / or expression.

[0009] WO 2012 / 015914 relates to compositions and methods for modulating AHR activity. In particular, WO 2012 / 015914 relates to, inter alia, heterocyclic compounds that modulate AHR activity for use in therapeutic compositions.

[0010] WO2007040565 relates to the use of [1,2,4]triazolo[1,5-c]pyrimidin-5-amine derivatives as adenosine receptor antagonists.

[0011] US Pat. No. 6,358,964 relates to [1,2,4]triazolo[1,5-c]quinazolin-5-amine derivatives useful as potent modulators of the adenosine A3 receptor.

[0012] However, the prior art does not describe the [1,2,4]triazolo[1,5-c]quinazolin-5-amine compounds of general formula (I) of the present invention as described and defined herein.

[0013] It has now been found that the compounds of the invention have surprising and advantageous properties, which form the basis of the present invention.

[0014] In particular, the compounds of the present invention have surprisingly been found to effectively inhibit AHR, data of which are presented in the Biological Experimental Section, and therefore are useful in treating cancer or other conditions in which exogenous and endogenous AHR ligands induce a dysregulated immune response, uncontrolled cell growth, proliferation and / or survival of tumor cells, cancer-associated immunosuppression, inappropriate cellular immune responses, or inappropriate cellular inflammatory responses, or diseases involving uncontrolled cell growth, proliferation and / or survival of tumor cells, cancer-associated immunosuppression, inappropriate cellular immune responses, or inappropriate cellular inflammatory responses (particularly uncontrolled cell growth, proliferation and / or survival of tumor cells, cancer-associated immunosuppression, inappropriate cellular immune responses, or inappropriate cellular inflammatory responses). The present invention may be used to treat or prevent diseases in which AHR is mediated (e.g., cancer-associated immunosuppression, inappropriate cellular immune response, or inappropriate cellular inflammatory response), such as liquid and solid tumors, and / or metastases thereof, e.g., head and neck tumors (including brain tumors and brain metastases), thoracic tumors (including non-small cell and small cell lung tumors), gastrointestinal tumors (including colon, colorectal, and pancreatic tumors), liver tumors, endocrine tumors, breast and other gynecological tumors, urinary tumors (including kidney, bladder, and prostate tumors), skin tumors, and sarcomas, and / or metastases thereof. [Prior art documents] [Patent documents]

[0015] [Patent Document 1] International Publication No. 2010 / 059401 Brochure [Patent Document 2] International Publication No. 2012 / 015914 Brochure [Patent Document 3] International Publication No. 2007040565 Brochure [Patent Document 4] U.S. Patent No. 6,358,964 [Non-patent literature]

[0016] [Non-Patent Document 1] Reyes et al., Science, 1992, 256(5060):1193-5 [Non-patent document 2] Nguyen et al., Front Immunol, 2014, 5:551 [Non-patent document 3] Gramatzki et al., Oncogene, 2009, 28(28):2593-605 [Non-patent document 4] Bui et al., Oncogene, 2009, 28(41):3642-51; [Non-Patent Document 5] Esser et al., Trends Immunol, 2009, 30:447~454 [Non-patent document 6] Wang et al., Clin Exp Immunol, 2014, 177(2):521-30 [Non-Patent Document 7] Mezrich et al., J Immunol, 2010, 185(6):3190-8 [Non-patent document 8] Wei et al., Lab Invest, 2014, 94(5):528-35 [Non-Patent Document 9] Nguyen et al., PNAS, 2010, 107(46):19961-6 [Non-Patent Document 10] Yamada et al., NatImmunol, 2016 [Non-Patent Document 11] Andersson et al., PNAS, 2002, 99(15):9990-5 [Non-Patent Document 12] DiNatale et al., Toxicol Sci, 2010, 115(1):89-97 [Non-Patent Document 13] Opitz et al., Nature, 2011, 478(7368):197-203 [Non-Patent Document 14] Nguyen & Bradfield, Chem Res Toxicol, 2008, 21(1):102~116 [Non-Patent Document 15] Uyttenhove et al., Nat Med, 2003, 9(10):1269-74 [Non-Patent Document 16] Liu et al., Blood, 2005, 115(17):3520-30 [Non-Patent Document 17] Muller et al., Nat Med, 11(3):312-9 [Non-Patent Document 18] Metz, Cancer Res, 2007, 67(15):7082-7 Summary of the Invention

[0017] According to a first aspect, the present invention provides compounds of general formula (I): [ka] (In the formula, R 1 teeth, Independently of each other, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C1-C4-hydroxyalkyl, C1-C4-alkoxy-C1-C4-alkyl-, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl-, C3-C6-cycloalkyl-O-, 4- to 6-membered heterocycloalkyl, -NR 9 R 10 , R 9 R 10 N-C1-C4-alkyl-, C1-C3-alkyl-S(O) m - or C1-C3-alkyl-SO(NH)-, optionally substituted 1-3 times; represents phenyl or heteroaryl; R 2represents hydrogen, C1-C4-alkyl, C1-C4-haloalkyl or C3-C6-cycloalkyl; R 3 represents hydrogen, C1-C6-alkyl, phenyl or phenyl-C1-C3-alkyl, The C1-C6 alkyl groups are each independently selected from hydroxy, halogen, C1-C4 alkoxy, -S(O) n -C1-C4-alkyl, phenyl-C1-C3-alkoxy or -NR 9 R 10 optionally substituted one or more times with the phenyl groups are optionally substituted one or more times, independently of one another, by hydroxy, halogen, cyano, C1-C3-alkyl, C1-C3-haloalkyl, C1-C3-alkoxy or C1-C3-haloalkoxy, or R 2 and R 3 together with the carbon atoms to which they are attached form a 3- to 6-membered ring, and the ring is a (In the formula, R a represents a C1-C4 alkyl group); R 4 is hydroxy, C1-C4-alkoxy or -NR 11 R 12 represents, or R 2 and R 4 together, * -C2~C5-alkanediyl-X 1 - ** , * -C1~C2-alkanediyl-X 2 -C1~C3-alkanediyl- ** or * -C1~C2-alkanediyl-X 2 -C2~C3-alkanediyl-X 1 - ** and form a 5- to 9-membered ring, * is R 2 indicates the point of attachment of said group to **is R 4 indicates the point of attachment of said group to R 5 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl, 4- to 6-membered heterocycloalkyl, -CO2-C1-C4-alkyl, -CO-NR 9 R 10 or -NR 9 R 10 represents; R 6 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl or -NR 9 R 10 represents; R 7 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl or -NR 9 R 10 represents; R 8 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl, 1-R 15 -C3~C6-cycloalkyl, -CO2-C1~C4-alkyl, -CO-NR 9 R 10 , -NR 9 R 10 , C1-C4-hydroxyalkyl, C1-C4-alkoxy-C1-C4-alkyl-, C1-C4-alkyl-S-, C1-C4-alkyl-S-C1-C4-alkyl-, -S(=O)R', -S(=O)2R', -S(=O)2NH2, -S(=O)2NHR', -S(=O)2N(R')R'', -S(=O)(=NH)R', 4- to 6-membered heterocycloalkyl or -OR 16 represents; R 9 and R 10are the same or different and independently represent hydrogen, C1-C3-alkyl or tert-butoxycarbonyl, or Together with the nitrogen atom to which they are attached, they form a 4- to 6-membered nitrogen-containing heterocyclic ring, which ring is not affected by O, S, NH, NR a (In the formula, R a represents C1-C4-alkyl or C1-C4-alkoxycarbonyl); R 11 and R 12 are the same or different and independently represent hydrogen, C1-C4-alkyl, C2-C4-hydroxyalkyl, C1-C4-alkoxy-C2-C4-alkyl-, R 9 R 10 N—C2-C4-alkyl-, C3-C6-cycloalkyl, 4- to 7-membered heterocycloalkyl, wherein the 4- to 7-membered heterocycloalkyl groups are each independently hydroxy, oxo, halogen, C1-C4-alkyl, C1-C4-alkoxy or —NR 9 R 10 , optionally substituted once or twice with, or Together with the nitrogen atom to which they are attached, they form a 4- to 6-membered nitrogen-containing heterocyclic ring, which ring is not affected by O, S, NH, NR a (In the formula, R a represents C1-C4-alkyl or C1-C4-alkoxycarbonyl), and are independently hydroxy, halogen, C1-C4-alkyl, C1-C4-alkoxy or -NR 9 R 10 , optionally substituted once or twice with, or Together with the nitrogen atom to which they are attached, independently of one another, they represent hydroxy, halogen, C1-C4-alkyl, C1-C4-alkoxy or -NR 9 R 10 forming a heterospirocycloalkyl group which is optionally substituted once or twice by Together with the nitrogen atom to which they are attached, independently of one another, they represent hydroxy, halogen, C1-C4-alkyl, C1-C4-alkoxy or -NR 9 R 10 forming a bridged heterocycloalkyl group which is optionally substituted once or twice; R 13 represents hydrogen, C1-C4-alkyl, benzyl, 4-methoxybenzyl or tert-butoxycarbonyl; R 14 represents hydrogen, C1-C4-alkyl, benzyl or 4-methoxybenzyl; R 15 represents C1-C3-alkyl or C1-C3-haloalkyl; R 16 represents C2-C6-hydroxyalkyl, C1-C4-alkoxy-C2-C6-alkyl- or C3-C6-cycloalkyl; R' and R'' independently of one another represent C1-C6-alkyl, C1-C6-haloalkyl or C3-C6-cycloalkyl; X 1 is O, S(O) m or NR 13 represents; X 2 is O, S(O) m or NR 14 represents; m represents 0, 1 or 2; n represents 0, 1 or 2), It encompasses their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as their physiologically acceptable salts and solvates of these salts, and mixtures thereof.

[0018] Additionally, the present invention encompasses their use in combination with other anti-cancer medications such as immunotherapeutics, targeted anti-cancer agents or chemotherapy.

[0019] definition The term "substituted" means that one or more hydrogen atoms on the specified atom or group are replaced with one selected from the indicated group, provided that the normal valence of the specified atom in the circumstances present is not exceeded. Combinations of substituents and / or variables are permissible.

[0020] The term "optionally substituted" means that the number of substituents can be equal to or different from 0. Unless otherwise specified, an optionally substituted group can be substituted with as many optional substituents as can be accommodated by replacing a hydrogen atom on any available carbon atom with a non-hydrogen substituent. Generally, if present, the number of optional substituents can be 1, 2, or 3.

[0021] The term "comprising" as used herein includes "consisting of."

[0022] In the text, when any item is referred to as "mentioned in this specification", it means that it can be mentioned anywhere in the text.

[0023] Terms referred to in this document have the following meanings: The term "halogen" means a fluorine, chlorine, bromine or iodine atom, in particular a fluorine, chlorine or bromine atom.

[0024] The term "C1-C6-alkyl" means a linear or branched saturated monovalent hydrocarbon radical having 1, 2, 3, 4, 5 or 6 carbon atoms, such as a methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neo-pentyl, 1,1-dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2,3-dimethylbutyl, 1,2-dimethylbutyl or 1,3-dimethylbutyl group, or an isomer thereof. In particular, the radicals have 1, 2, 3 or 4 carbon atoms ("C1-C4-alkyl"), such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl or tert-butyl radicals, and more in particular have 1, 2 or 3 carbon atoms ("C1-C3-alkyl"), such as methyl, ethyl, n-propyl or isopropyl radicals.

[0025] The term "C1-C6-haloalkyl" means a linear or branched saturated monovalent hydrocarbon radical in which the term "C1-C6-alkyl" is defined as above and in which one or more hydrogen atoms are replaced by identical or different halogen atoms. In particular, the halogen atoms are fluorine atoms. The C1-C6-haloalkyl radical is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3,3,3-trifluoropropyl or 1,3-difluoropropan-2-yl.

[0026] The term "C1-C4-hydroxyalkyl" is as defined above for the term "C1-C4-alkyl" and means a linear or branched saturated monovalent hydrocarbon radical in which one or two hydrogen atoms have been replaced by a hydroxy group, such as a hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1,2-dihydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-hydroxypropyl, 1-hydroxypropan-2-yl, 2-hydroxypropan-2-yl, 2,3-dihydroxypropyl, 1,3-dihydroxypropan-2-yl, 3-hydroxy-2-methyl-propyl, 2-hydroxy-2-methyl-propyl or 1-hydroxy-2-methyl-propyl group.

[0027] The term "C1-C4-alkoxy" denotes a linear or branched saturated monovalent radical of the formula (C1-C4-alkyl)-O-, which means methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy or tert-butoxy.

[0028] The term "C1-C4-haloalkoxy" means a linear or branched saturated monovalent C1-C4-alkoxy group as defined above, in which one or more hydrogen atoms are replaced by identical or different halogen atoms. In particular, said halogen atoms are fluorine atoms. C1-C4-haloalkoxy groups are, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy or pentafluoroethoxy.

[0029] The term "C1-C5-alkanediyl" means a divalent saturated aliphatic group deemed to be derived from a C1-C5-alkane by removing a hydrogen atom from each of the two terminal carbon atoms of the chain, e.g., methylene, ethylene, propylene, trimethylene, tetramethylene, or pentamethylene.

[0030] The term "C3-C6-cycloalkyl" means a saturated monovalent monocyclic hydrocarbon ring ("C3-C6-cycloalkyl") containing 3, 4, 5 or 6 carbon atoms. The C3-C6-cycloalkyl group is a monocyclic hydrocarbon ring, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0031] The term "4- to 7-membered heterocycloalkyl" refers to -NR b -, -O-, -S-, -SO-, -SO2-, -SO2-NR b -, -SO(=NR b )-(wherein, R b means a hydrogen atom or a C1-C3-alkyl group), said heterocycloalkyl group can be attached to the rest of the molecule via any one of the carbon atoms or, if present, the nitrogen atom.

[0032] The heterocycloalkyl group may be, but is not limited to, a 4-membered ring such as, for example, azetidinyl, oxetanyl, or thietanyl; or, for example, tetrahydrofuranyl, 1,3-dioxolanyl, thiolanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, 1,1-dioxidothiolanyl, 1,2-oxazolidinyl, 1,3-oxazolidinyl, or 1,3-thiazolidinyl, tetrahydrothiophene 1 -oxide, 1,2-thiazolidine 1-oxide, 1,3-thiazolidine 1-oxide, tetrahydrothiophene 1,1-dioxide, 1,2-thiazolidine 1,1-dioxide, 1,3-thiazolidine 1,1-dioxide, 1,2,5-thiadiazolidine 1,1-dioxide, 1,2,4-thiadiazolidine 1,1-dioxide, 1,2,3-thiadiazolidine 1,1-dioxide, tetrahydro-1H-1λ 4 -Thiophen-1-imine 1-oxide, 1λ 4 ,2-thiazolidine-1-imine 1-oxide or 1λ 4,3-thiazolidine-1-imine 1-oxide; or for example, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, 1,3-dioxanyl, 1,4-dioxanyl or 1,2-oxazinanyl, tetrahydro-2H-thiopyran 1-oxide, 1,2-thiazinane 1-oxide, 1,3-thiazinane 1-oxide, thiomorpholinyl, Pholine 1-oxide, tetrahydro-2H-thiopyran 1,1-dioxide, 1,2-thiazinane 1,1-dioxide, 1,3-thiazinane 1,1-dioxide, thiomorpholine 1,1-dioxide, 1,2,6-thiadiazinan 1,1-dioxide, 1,2,5-thiadiazinan 1,1-dioxide, 1,2,4-thiadiazinan 1,1-dioxide, 1,2,3-thiadiazinan 1,1-dioxide, hexahydro-1λ 4 -Thiopyran-1-imine 1-oxide, 1λ 4 ,2-thiazinane-1-imine 1-oxide, 1λ 4 ,3-thiazinane-1-imine 1-oxide or 1λ 4 -thiomorpholin-1-imine 1-oxide, or for example azepanyl, 1,4-diazepanyl, 1,4-oxazepanyl, 1,4-thiazepanyl or 1-imino-1λ 6 , 4-thiazepane-1-oxide and the like.

[0033] The term "heterospirocycloalkyl" means a bicyclic saturated heterocycle having a total of 6, 7, 8, 9, 10, or 11 ring atoms, containing one or two ring heteroatoms of the same or different series: N, O, S, and the two rings share one common ring carbon atom; a 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.

[0034] 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, diazaspiro[4,5]decyl, diazaspiro[4,5]un ... azaspiro[3.3]heptyl, thiazaspiro[3.3]heptyl, thiazaspiro[4.3]octyl, azaspiro[5.5]undecyl, or one of further homologous scaffolds 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]-.

[0035] The term "bridged heterocycloalkyl" means a bicyclic saturated heterocycle having a total of 7, 8, 9, or 10 ring atoms, containing one or two ring heteroatoms of the same or different series: N, O, S, where the two rings share two common ring atoms that are not adjacent; 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.

[0036] 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.

[0037] The term "heteroaryl" means a monovalent monocyclic, bicyclic, or tricyclic aromatic ring having 5, 6, 8, 9, 10, 11, 12, 13, or 14 ring atoms (a "5- to 14-membered heteroaryl" group), particularly 5, 6, 9, or 10 ring atoms, containing at least one ring heteroatom and optionally one, two, or three further ring heteroatoms of the series: N, O, and / or S, and bonded via a ring carbon atom or optionally a ring nitrogen atom (where permitted by valence).

[0038] Heteroaryl groups include 5-membered heteroaryl groups (such as thienyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, or tetrazolyl); or 6-membered heteroaryl groups (such as pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, or triazinyl); or tricyclic heteroaryl groups (such as carbazolyl, acridinyl, or furanyl). or a 9-membered heteroaryl group (such as benzofuranyl, benzothienyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, benzothiazolyl, benzotriazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, or purinyl); or a 10-membered heteroaryl group (such as quinolinyl, quinazolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, or pteridinyl).

[0039] The term "monocyclic heteroaryl" means a monovalent aromatic ring having 5 or 6 ring atoms (a "5- to 6-membered heteroaryl" group) containing at least one ring heteroatom and optionally one or two additional ring heteroatoms of the series: N, O and / or S, and bonded via a ring carbon atom or optionally a ring nitrogen atom (where permitted by valence).

[0040] 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.

[0041] In general, unless otherwise specified, a heteroaryl or heteroarylene group includes all its possible isomeric forms, such as tautomers and positional isomers, with respect to the point of attachment to the rest of the molecule. Thus, for some illustrative, non-limiting examples, the term pyridinyl includes pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl; or the term thienyl includes thien-2-yl and thien-3-yl.

[0042] When the plural of a word such as compounds, salts, polymorphs, hydrates, solvates, etc. is used herein, this is also taken to mean a single compound, salt, polymorph, isomer, hydrate, solvate, etc.

[0043] By "stable compound" or "stable structure" is meant a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.

[0044] The compounds of the present invention may contain one or more asymmetric centers, depending on the position and nature of various desired substituents.One or more asymmetric carbon atoms may be present in (R) or (S) configuration, which may result in a racemic mixture in the case of a single asymmetric center, or a diastereomeric mixture in the case of multiple asymmetric centers.In certain cases, asymmetry may exist due to restricted rotation around a given bond, for example, the central bond connecting two substituted aromatic rings of a specified compound.

[0045] Additionally, it is possible for the compounds of the present invention to exist as tautomers. For example, any compound containing a [1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one moiety can exist as the keto tautomer or the enol tautomer, or even as a mixture of any amount of the two tautomers: [ka]

[0046] The present invention includes all possible tautomers of the compounds of the present invention as single tautomers or any mixture of said tautomers in any ratio.

[0047] Preferred compounds are those that exhibit the more desirable biological activity. Also included within the scope of the present invention are separated, pure or partially purified isomers and stereoisomers, or racemic or diastereomeric mixtures, of the compounds of the present invention. Purification and separation of such materials can be accomplished by standard techniques known in the art.

[0048] Preferred isomers are those that result in the more desirable biological activity. These separated, pure or partially purified isomers or racemic mixtures of the compounds of the present invention are also within the scope of the present invention. Purification and separation of such materials can be accomplished by standard techniques known in the art.

[0049] Optical isomers can be obtained by conventional resolution of racemic mixtures, for example, by the formation of diastereomeric salts or covalent diastereomers with optically active acids or bases. Examples of suitable acids include tartaric acid, diacetyltartaric acid, ditoluoyltartaric acid, and camphorsulfonic acid. Diastereoisomeric mixtures can be separated into individual diastereomers based on their physical and / or chemical differences by methods known in the art, for example, chromatography or fractional crystallization. The optically active base or acid is then liberated from the separated diastereomeric salts. Another method for separating optical isomers involves the use of chiral chromatography (e.g., an HPLC column using a chiral phase), with or without conventional derivatization, which may be selected to maximize the separation of the enantiomers. Suitable HPLC columns using chiral phases are commercially available, for example, those manufactured by Daicel, among others, such as Chiracel OD and Chiracel OJ, all of which are routinely selectable. Enzymatic separations, with or without derivatization, are also useful. The optically active compounds of this invention can also be obtained by chiral syntheses utilizing optically active starting materials.

[0050] To distinguish different types of isomers from one another, reference is made to IUPAC Rules Section E (Pure Appl Chem 45, 11-30, 1976).

[0051] The present invention includes all possible stereoisomers of the compounds of the present invention, either as single stereoisomers or as any mixture of said stereoisomers in any ratio, e.g., (R)- or (S)-isomers. Isolation of a single stereoisomer of a compound of the present invention, e.g., a single enantiomer or a single diastereomer, is achieved by any suitable prior art method, e.g., chromatography, in particular chiral chromatography.

[0052] Additionally, compounds of the present invention can exist as N-oxides, which are defined in that at least one nitrogen in a compound of the present invention is oxidized, and the present invention includes all such possible N-oxides.

[0053] The present invention also encompasses useful forms of the compounds of the present invention, such as metabolites, hydrates, solvates, prodrugs, salts, particularly pharmaceutically acceptable salts, and / or coprecipitates.

[0054] The compounds of the present invention can exist as hydrates or solvates, and for example, the compounds of the present invention contain polar solvents, particularly water, methanol, or ethanol, as structural elements of the crystal lattice of the compounds. The amount of polar solvent, particularly water, can be stoichiometric or non-stoichiometric. In the case of stoichiometric solvates, for example, hydrates, hemi-, (semi-), mono-, sesqui-, di-, tri-, tetra-, penta-isosolvates, or hydrates are possible. The present invention includes all such hydrates or solvates.

[0055] Furthermore, the compounds of the present invention can exist in free form, for example as a free base or free acid or zwitterion, or in salt form, which can be any salt, either organic or inorganic addition salt, particularly any pharmaceutically acceptable organic or inorganic addition salt customarily used in pharmacy or used, for example, to isolate or purify the compounds of the present invention.

[0056] The term "pharmaceutically acceptable salt" refers to an inorganic or organic acid addition salt of a compound of the present invention. See, for example, S. M. Berge et al., "Pharmaceutical Salts," J. Pharm. Sci. 1977, 66, 1-19.

[0057] Suitable pharmaceutically acceptable salts of the compounds of the present invention include, for example, acid addition salts of compounds of the present invention that are sufficiently basic and have a nitrogen atom in the chain or in the ring, for example, acid addition salts with inorganic or "mineral acids" such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfamic acid, bisulfuric acid, phosphoric acid or nitric acid, or organic acids such as formic acid, acetic acid, acetoacetic acid, pyruvic acid, trifluoroacetic acid, propionic acid, butyric acid, hexanoic acid, heptanoic acid, undecanoic acid, lauric acid, benzoic acid, salicylic acid, 2-(4-hydroxybenzoyl)-benzoic acid, camphoric acid, cinnamic acid, cyclopentanepropionic acid, digluconic acid, 3-hydroxy-2-naphthoic acid, nicotinic acid , pamoic acid, pectinic acid, 3-phenylpropionic acid, pivalic acid, 2-hydroxyethanesulfonic acid, itaconic acid, trifluoromethanesulfonic acid, dodecylsulfuric acid, ethanesulfonic acid, benzenesulfonic acid, para-toluenesulfonic acid, methanesulfonic acid, 2-naphthalenesulfonic acid, naphthalenedisulfonic acid, camphorsulfonic acid, citric acid, tartaric acid, stearic acid, lactic acid, oxalic acid, malonic acid, succinic acid, malic acid, adipic acid, alginic acid, maleic acid, fumaric acid, D-gluconic acid, mandelic acid, ascorbic acid, glucoheptanoic acid, glycerophosphate, aspartic acid, sulfosalicylic acid or thiocyanic acid.

[0058] Further suitable pharmaceutically acceptable salts of the compounds of the present invention that are sufficiently acidic include alkali metal salts, such as sodium or potassium salts, alkaline earth metal salts, such as calcium, magnesium or strontium salts, or aluminum or zinc salts, or ammonia or organic primary, secondary or tertiary amines having 1 to 20 carbon atoms, such as ethylamine, diethylamine, triethylamine, ethyldiisopropylamine, monoethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, dimethylaminoethanol, diethylaminoethanol, tris(hydroxymethyl)aminomethane, procaine, dibenzylamine, N-methylmorpholine, , arginine, lysine, 1,2-ethylenediamine, N-methylpiperidine, N-methyl-glucamine, N,N-dimethyl-glucamine, N-ethyl-glucamine, 1,6-hexanediamine, glucosamine, sarcosine, serinol, 2-amino-1,3-propanediol, 3-amino-1,2-propanediol, 4-amino-1,2,3-butanetriol, or a salt with a quaternary ammonium ion having 1 to 20 carbon atoms, such as tetramethylammonium, tetraethylammonium, tetra(n-propyl)ammonium, tetra(n-butyl)ammonium, N-benzyl-N,N,N-trimethylammonium, choline or benzalkonium.

[0059] Those skilled in the art will further recognize that acid addition salts of the claimed compounds can be prepared by reacting the compounds with the appropriate inorganic or organic acid via any of several 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.

[0060] The present invention includes all possible salts of the compounds of the present invention, either as a single salt or as any mixture of said salts in any ratio.

[0061] When compounds are referred to herein, particularly in the experimental section, for the synthesis of intermediates and examples of the present invention as salt forms with the corresponding bases or acids, the exact stoichiometry of said salt forms obtained by each preparation and / or purification step is in most cases unknown.

[0062] Unless otherwise specified, for example, "hydrochloride", "trifluoroacetate", "sodium salt" or "xHCl", "xCF3COOH", "xNa + A suffix to a chemical name or structural formula for a salt, such as "," denotes the salt form, and does not specify the stoichiometry of the salt form.

[0063] This also applies if synthetic intermediates or example compounds or salts thereof are obtained by the preparation and / or purification process as solvates, such as hydrates of unknown stoichiometric composition (if defined).

[0064] Furthermore, the present invention includes all possible crystalline forms or polymorphs of the compounds of the present invention, either as a single polymorph or as a mixture of two or more polymorphs in any ratio.

[0065] Furthermore, the present invention also includes prodrugs of the compounds according to the present invention. The term "prodrug" as used herein refers to a compound that may itself be biologically active or inactive, but that is converted (e.g., metabolically or hydrolytically) into a compound according to the present invention during its residence in the body.

[0066] The present invention further includes all possible crystalline forms and polymorphic forms of the compounds of the present invention, whether they exist as a single polymorphic form or as a mixture of several polymorphs in all concentrations.

[0067] The compounds are commercially available or can be prepared according to procedures available in the public domain, as will be appreciated by those skilled in the art. Specific examples are described in the experimental section.

[0068] According to a second embodiment of the first aspect, the present invention provides a method for manufacturing a semiconductor device comprising: R 1 but, Independently of each other, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl-, C3-C6-cycloalkyl-O-, 4- to 6-membered heterocycloalkyl, -NR 9 R 10 or R 9 R 10 optionally substituted 1 to 3 times with N-C1-C4-alkyl, represents phenyl or heteroaryl; R 2 represents hydrogen, C1-C4-alkyl, C1-C4-haloalkyl or C3-C6-cycloalkyl; R 3 represents hydrogen, C1-C6-alkyl, phenyl or phenyl-C1-C3-alkyl, The C1-C6 alkyl groups are each independently selected from hydroxy, halogen, C1-C4 alkoxy, -S(O) n -C1-C4-alkyl, phenyl-C1-C3-alkoxy or -NR 9 R 10 optionally substituted one or more times with the phenyl groups are optionally substituted one or more times, independently of one another, by hydroxy, halogen, cyano, C1-C3-alkyl, C1-C3-haloalkyl, C1-C3-alkoxy or C1-C3-haloalkoxy, or R 2 and R 3 These, together with the carbon atoms to which they are attached, form a 3- to 6-membered ring, and the ring is O, S, NH, NR a (In the formula, R a represents a C1-C4 alkyl group); R 4 is hydroxy, C1-C4-alkoxy or -NR 11 R 12 represents, or R2 and R 4 Together, * -C2~C5-alkanediyl-X 1 - ** , * -C1~C2-alkanediyl-X 2 -C1~C3-alkanediyl- ** or * -C1~C2-alkanediyl-X 2 -C2~C3-alkanediyl-X 1 - ** and form a 5- to 9-membered ring, * R 2 indicates the point of attachment of said group to ** R 4 indicates the point of attachment of said group to R 5 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl or -NR 9 R 10 represents; R 6 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl or -NR 9 R 10 represents; R 7 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl or -NR 9 R 10 represents; R 8 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl or -NR 9 R 10 represents; R 9 and R 10are the same or different and independently represent hydrogen, C1-C3-alkyl or tert-butoxycarbonyl, or Together with the nitrogen atom to which they are attached, they form a 4- to 6-membered nitrogen-containing heterocyclic ring, and the ring is not O, S, NH, NR a (In the formula, R a represents a C1-C4-alkyl group); R 11 and R 12 are the same or different and independently represent hydrogen, C1-C4-alkyl or C3-C6-cycloalkyl, said C1-C4-alkyl groups being optionally substituted with hydroxy; R 13 represents hydrogen, C1-C4-alkyl, benzyl, 4-methoxybenzyl or tert-butoxycarbonyl; R 14 represents hydrogen, C1-C4-alkyl, benzyl or 4-methoxybenzyl; X 1 but O or NR 13 represents; X 2 but O or NR 14 represents; n represents 0, 1 or 2; It encompasses the compounds of the above general formula (I), their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0069] According to a third embodiment of the first aspect, the present invention provides a method for manufacturing a semiconductor device comprising: R 1 but, independently of each other, halogen, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl-, C3-C6-cycloalkyl-O-, 4- to 6-membered heterocycloalkyl or -NR 9 R10 , which was occasionally replaced once or twice, represents phenyl or monocyclic heteroaryl; R 2 represents hydrogen or C1-C4-alkyl; R 3 represents hydrogen, C1-C4-alkyl, phenyl or phenyl-methyl, The C1-C4 alkyl group is hydroxy, methoxy, -S(O) n -methyl, phenyl-methoxy or -NR 9 R 10 , optionally substituted once with the phenyl group is optionally substituted once with hydroxy, or R 2 and R 3 together with the carbon atom to which they are attached form a 3- to 6-membered ring, said ring optionally containing one oxygen atom; R 4 is hydroxy, methoxy or -NR 11 R 12 represents, or R 2 and R 4 Together, [ka] (In the formula, * indicates the point of attachment of said group to the NH group in formula (I). represents a group selected from: R 5 represents hydrogen, halogen, C1-C4-alkyl, methoxy, trifluoromethyl or cyclopropyl; R 6 represents hydrogen, halogen or methyl; R 7 represents hydrogen, halogen, methyl or methoxy; R 8 represents hydrogen, halogen or methyl; R 9 and R 10are the same or different and independently represent hydrogen, methyl or tert-butoxycarbonyl; R 11 and R 12 are the same or different and independently represent hydrogen, C1-C3-alkyl or C3-C4-cycloalkyl, said C1-C3-alkyl groups being optionally substituted with hydroxy; R 13 represents hydrogen or methyl; X 3 represents CH2 or NH; n represents 0 or 2; It encompasses the compounds of the above general formula (I), their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0070] According to a fourth embodiment of the first aspect, the present invention provides compounds of general formula (Ia): [ka] (In the formula, R 1 teeth, Independently of each other, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl-, C3-C6-cycloalkyl-O-, 4- to 6-membered heterocycloalkyl, -NR 9 R 10 or R 9 R 10 optionally substituted 1 to 3 times with N-C1-C4-alkyl, represents phenyl or heteroaryl; R 5 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl or -NR 9 R10 represents; R 6 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl or -NR 9 R 10 represents; R 7 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl or -NR 9 R 10 represents; R 8 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl or -NR 9 R 10 represents; R 9 and R 10 are the same or different and independently represent hydrogen, C1-C3-alkyl or tert-butoxycarbonyl, or Together with the nitrogen atom to which they are attached, they form a 4- to 6-membered nitrogen-containing heterocyclic ring, which ring is not affected by O, S, NH, NR a (In the formula, R a represents a C1-C4-alkyl group); R 14 represents hydrogen, C1-C4-alkyl, benzyl or 4-methoxybenzyl; X 3 is CH2 or NR 14 ), It encompasses their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as their physiologically acceptable salts and solvates of these salts, and mixtures thereof.

[0071] According to a fifth embodiment of the first aspect, the present invention provides compounds of general formula (Ib): [ka] (In the formula, R 1 represent, independently of one another, phenyl, pyridinyl, pyridazinyl, furanyl, oxazolyl, pyrazolyl or oxadiazolyl, optionally substituted once or twice by fluoro, chloro, C1-C4-alkyl, methoxy, trifluoromethyl, trifluoromethoxy, cyclopropyl, oxanyl or -N(CH3)2; R 5 , R 6 , R 7 , R 8 represent, independently of one another, hydrogen, fluoro, chloro, bromo, methyl, methoxy, trifluoromethyl or cyclopropyl), It encompasses their polymorphs, tautomers, N-oxides, hydrates and solvates, as well as their physiologically acceptable salts and solvates of these salts, and mixtures thereof.

[0072] According to a sixth embodiment of the first aspect, the present invention provides compounds of general formula (I): [ka] (In the formula, R 1 teeth, Independently of each other, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C1-C4-hydroxyalkyl, C1-C4-alkoxy-C1-C4-alkyl-, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl-, C3-C6-cycloalkyl-O-, 4- to 6-membered heterocycloalkyl, -NR 9 R 10 , R 9 R 10 N-C1-C4-alkyl-, C1-C3-alkyl-S(O) m- or C1-C3-alkyl-SO(NH)-, optionally substituted 1-3 times; represents phenyl or heteroaryl; R 2 represents hydrogen, C1-C4-alkyl, C1-C4-haloalkyl or C3-C6-cycloalkyl; R 3 represents hydrogen, C1-C6-alkyl, phenyl or phenyl-C1-C3-alkyl, The C1-C6 alkyl groups are each independently selected from hydroxy, halogen, C1-C4 alkoxy, -S(O) n -C1-C4-alkyl, phenyl-C1-C3-alkoxy or -NR 9 R 10 optionally substituted one or more times with the phenyl groups are optionally substituted one or more times, independently of one another, by hydroxy, halogen, cyano, C1-C3-alkyl, C1-C3-haloalkyl, C1-C3-alkoxy or C1-C3-haloalkoxy, or R 2 and R 3 together with the carbon atoms to which they are attached form a 3- to 6-membered ring, and the ring is a (In the formula, R a represents a C1-C4 alkyl group); R 4 is hydroxy, C1-C4-alkoxy or -NR 11 R 12 represents, or R 2 and R 4 together, * -C2~C5-alkanediyl-X 1 - ** , * -C1~C2-alkanediyl-X 2 -C1~C3-alkanediyl- ** or * -C1~C2-alkanediyl-X 2 -C2~C3-alkanediyl-X 1- ** and form a 5- to 9-membered ring, * is R 2 indicates the point of attachment of said group to ** is R 4 indicates the point of attachment of said group to R 5 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl, 4- to 6-membered heterocycloalkyl, -CO2-C1-C4-alkyl, -CO-NR 9 R 10 or -NR 9 R 10 represents; R 6 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl or -NR 9 R 10 represents; R 7 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl or -NR 9 R 10 represents; R 8 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl, 1-R 15 -C3~C6-cycloalkyl, -CO2-C1~C4-alkyl, -CO-NR 9 R 10 or -NR 9 R 10 represents; R 9 and R 10 are the same or different and independently represent hydrogen, C1-C3-alkyl or tert-butoxycarbonyl, or Together with the nitrogen atom to which they are attached, they form a 4- to 6-membered nitrogen-containing heterocyclic ring, which ring is not affected by O, S, NH, NR a (In the formula, R a represents a C1-C4-alkyl group); R 11 and R 12 are the same or different and independently represent hydrogen, C1-C4-alkyl or C3-C6-cycloalkyl, said C1-C4-alkyl groups being optionally substituted with hydroxy; R 13 represents hydrogen, C1-C4-alkyl, benzyl, 4-methoxybenzyl or tert-butoxycarbonyl; R 14 represents hydrogen, C1-C4-alkyl, benzyl or 4-methoxybenzyl; R 15 represents C1-C3-alkyl or C1-C3-haloalkyl; X 1 is O or NR 13 represents; X 2 is O or NR 14 represents; m represents 0, 1 or 2; n represents 0, 1 or 2), It encompasses their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as their physiologically acceptable salts and solvates of these salts, and mixtures thereof.

[0073] According to a second aspect, the present invention provides a method for preparing a compound of general formula (I) as defined above, comprising reacting an intermediate compound of general formula (V): [ka] (In the formula, R 1 , R 5 , R 6 , R 7 and R 8 is as defined above) with a compound of general formula (VII): [ka] (In the formula, R 2 , R 3 and R 4 is as defined above) thereby producing a compound of general formula (I): [ka] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 is as defined above) The present invention covers a method including the step of obtaining

[0074] The present invention covers methods for preparing the compounds of the present invention of general formula (I), comprising the steps described in the experimental section herein.

[0075] According to a third aspect, the present invention covers intermediate compounds useful in the preparation of compounds of general formula (I) above.

[0076] In particular, the present invention relates to an intermediate compound of general formula (V) [ka] (In the formula, R 1 , R 5 , R 6 , R 7 and R 8 is as defined above) Covers:

[0077] According to a fourth aspect, the present invention covers the use of said intermediate compounds for preparing compounds of general formula (I) as defined above.

[0078] In particular, the present invention relates to an intermediate compound of general formula (V) for preparing a compound of general formula (I) as defined above: [ka] (In the formula, R 1 , R 5 , R 6 , R 7 and R 8 is as defined above) Covers the use of

[0079] The present invention encompasses the intermediate compounds disclosed in the Examples section of the text below.

[0080] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 1 but, Independently of each other, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C1-C4-hydroxyalkyl, C1-C4-alkoxy-C1-C4-alkyl-, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl-, C3-C6-cycloalkyl-O-, 4- to 6-membered heterocycloalkyl, -NR 9 R 10 , R 9 R 10 N-C1-C4-alkyl-, C1-C3-alkyl-S(O) m - or C1-C3-alkyl-SO(NH)-, optionally substituted 1-3 times; represents phenyl or heteroaryl, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0081] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 1 but, Independently of each other, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl-, C3-C6-cycloalkyl-O-, 4- to 6-membered heterocycloalkyl, -NR 9 R 10 or R 9 R 10 optionally substituted 1 to 3 times with N-C1-C4-alkyl, represents phenyl or heteroaryl, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0082] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 1 but, Independently of each other, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl-, C3-C6-cycloalkyl-O-, 4- to 6-membered heterocycloalkyl, -NR 9 R 10 or R 9 R 10 optionally substituted 1 to 3 times with N-C1-C4-alkyl, represents phenyl or monocyclic heteroaryl, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0083] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 1 but, independently of each other, halogen, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl-, C3-C6-cycloalkyl-O-, 4- to 6-membered heterocycloalkyl or -NR 9 R 10 , possibly substituted once or twice with represents phenyl or monocyclic heteroaryl, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0084] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 1 but, independently of each other, halogen, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl-, C3-C6-cycloalkyl-O-, 5- to 6-membered heterocycloalkyl or -NR 9 R 10 , possibly substituted once or twice with represents phenyl or monocyclic heteroaryl, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0085] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 1represent, independently of one another, phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, furanyl, thiophenyl, pyrrolyl, 1,2-thiazolyl, oxazolyl, triazolyl, imidazolyl, oxazolyl, pyrazolyl, oxadiazolyl or imidazopyridinyl, optionally substituted once or twice by fluoro, chloro, bromo, cyano, C1-C4-alkyl, methoxy, trifluoromethyl, difluoromethoxy, trifluoromethoxy, cyclopropyl, cyclobutyl, cyclopropylmethyl, oxanyl or -N(CH3)2, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0086] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 1 represent, independently of one another, phenyl, pyridinyl, pyridazinyl, furanyl, oxazolyl, pyrazolyl or oxadiazolyl, optionally substituted once or twice by fluoro, chloro, C1-C4-alkyl, methoxy, trifluoromethyl, trifluoromethoxy, cyclopropyl, oxanyl or -N(CH3)2, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0087] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 2 represents hydrogen, C1-C4-alkyl, C1-C4-haloalkyl or C3-C6-cycloalkyl, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0088] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 2 represents hydrogen or C1-C4-alkyl, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0089] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 3 represents hydrogen, C1-C6-alkyl, phenyl or phenyl-C1-C3-alkyl, The C1-C6 alkyl groups are each independently selected from hydroxy, halogen, C1-C4 alkoxy, -S(O) n -C1-C4-alkyl, phenyl-C1-C3-alkoxy or -NR 9 R 10 optionally substituted one or more times with the phenyl groups are optionally substituted one or more times, independently of one another, by hydroxy, halogen, cyano, C1-C3-alkyl, C1-C3-haloalkyl, C1-C3-alkoxy or C1-C3-haloalkoxy, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0090] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 3represents hydrogen, C1-C4-alkyl, phenyl or phenyl-methyl, The C1-C4 alkyl group is hydroxy, methoxy, -S(O) n -methyl, phenyl-methoxy or -NR 9 R 10 , optionally substituted once with the phenyl group is optionally substituted once with hydroxy; It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0091] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 2 and R 3 These, together with the carbon atoms to which they are attached, form a 3- to 6-membered ring, and the ring is O, S, NH, NR a (In the formula, R a represents a C1-C4 alkyl group), It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0092] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 2 and R 3 together with the carbon atom to which they are attached form a 3- to 6-membered ring, said ring optionally containing one oxygen atom; It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0093] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 4 is hydroxy, C1-C4-alkoxy or -NR 11 R 12 Represents, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0094] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 4 is hydroxy, methoxy or -NR 11 R 12 Represents, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0095] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 2 and R 4 Together, * -C2~C5-alkanediyl-X 1 - ** , * -C1~C2-alkanediyl-X 2 -C1~C3-alkanediyl- ** or * -C1~C2-alkanediyl-X 2 -C2~C3-alkanediyl-X 1 - ** and form a 5- to 9-membered ring, * R 2 indicates the point of attachment of said group to ** R 4 indicates the point of attachment of said group to It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0096] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 2 and R 4 Together, [ka] (In the formula, * indicates the point of attachment of said group to the NH group in formula (I). represents a group selected from It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0097] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 5 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl, 4- to 6-membered heterocycloalkyl, -CO2-C1-C4-alkyl, -CO-NR 9 R 10 or -NR 9 R 10 Represents, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0098] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 5is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl or -NR 9 R 10 Represents, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0099] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 5 represents hydrogen, halogen, C1-C4-alkyl, methoxy, trifluoromethyl or cyclopropyl, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0100] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 6 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl or -NR 9 R 10 Represents, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0101] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 6 represents hydrogen, halogen or methyl; It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0102] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 7 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl or -NR 9 R 10 Represents, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0103] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 7 represents hydrogen, halogen, methyl or methoxy; It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0104] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 8 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl, 1-R 15 -C3~C6-cycloalkyl, -CO2-C1~C4-alkyl, -CO-NR 9 R 10 , -NR 9 R 10, C1-C4-hydroxyalkyl, C1-C4-alkoxy-C1-C4-alkyl-, C1-C4-alkyl-S-, C1-C4-alkyl-S-C1-C4-alkyl-, -S(=O)R', -S(=O)2R', -S(=O)2NH2, -S(=O)2NHR', -S(=O)2N(R')R'', -S(=O)(=NH)R', 4- to 6-membered heterocycloalkyl or -OR 16 Represents, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0105] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 8 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl, 1-R 15 -C3~C6-cycloalkyl, -CO2-C1~C4-alkyl, -CO-NR 9 R 10 or -NR 9 R 10 Represents, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0106] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 8 is hydrogen, halogen, cyano, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C6-cycloalkyl or -NR 9 R 10 Represents, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0107] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 8 represents hydrogen, halogen or methyl; It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0108] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 5 , R 6 , R 7 , R 8 represent, independently of one another, hydrogen, fluoro, chloro, bromo, methyl, methoxy, trifluoromethyl or cyclopropyl, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0109] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 9 and R 10 are the same or different and independently represent hydrogen, C1-C3-alkyl or tert-butoxycarbonyl, or Together with the nitrogen atom to which they are attached, they form a 4- to 6-membered nitrogen-containing heterocyclic ring, and the ring is not O, S, NH, NR a (In the formula, R a represents C1-C4-alkyl or C1-C4-alkoxycarbonyl), It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0110] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 9 and R 10 are the same or different and independently represent hydrogen, C1-C3-alkyl or tert-butoxycarbonyl, or Together with the nitrogen atom to which they are attached, they form a 4- to 6-membered nitrogen-containing heterocyclic ring, and the ring is not O, S, NH, NR a (In the formula, R a represents a C1-C4 alkyl group), It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0111] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 9 and R 10 are the same or different and independently represent hydrogen, methyl or tert-butoxycarbonyl, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0112] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 11 and R 12are the same or different and independently represent hydrogen, C1-C4-alkyl, C2-C4-hydroxyalkyl, C1-C4-alkoxy-C2-C4-alkyl-, R 9 R 10 N—C2-C4-alkyl-, C3-C6-cycloalkyl, 4- to 7-membered heterocycloalkyl, wherein the 4- to 7-membered heterocycloalkyl groups are each independently hydroxy, oxo, halogen, C1-C4-alkyl, C1-C4-alkoxy, or —NR 9 R 10 , optionally substituted once or twice with, or Together with the nitrogen atom to which they are attached, they form a 4- to 6-membered nitrogen-containing heterocyclic ring, and the ring is not O, S, NH, NR a (In the formula, R a represents C1-C4-alkyl or C1-C4-alkoxycarbonyl), and are independently hydroxy, halogen, C1-C4-alkyl, C1-C4-alkoxy or -NR 9 R 10 , optionally substituted once or twice with, or Together with the nitrogen atom to which they are attached, independently of one another, they represent hydroxy, halogen, C1-C4-alkyl, C1-C4-alkoxy or -NR 9 R 10 forming a heterospirocycloalkyl group which is optionally substituted once or twice by Together with the nitrogen atom to which they are attached, independently of one another, they represent hydroxy, halogen, C1-C4-alkyl, C1-C4-alkoxy or -NR 9 R 10 forming a bridged heterocycloalkyl group which is optionally substituted once or twice with It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0113] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 11 and R 12 are the same or different and independently represent hydrogen, C1-C4-alkyl or C3-C6-cycloalkyl, said C1-C4-alkyl groups being optionally substituted by hydroxy, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0114] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 11 and R 12 are the same or different and independently represent hydrogen, C1-C3-alkyl or C3-C4-cycloalkyl, said C1-C3-alkyl groups being optionally substituted by hydroxy, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0115] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 13 represents hydrogen, C1-C4-alkyl, benzyl, 4-methoxybenzyl or tert-butoxycarbonyl, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0116] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 13 represents hydrogen or methyl; It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0117] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 14 represents hydrogen, C1-C4-alkyl, benzyl or 4-methoxybenzyl, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0118] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 15 represents C1-C3-alkyl or C1-C3-haloalkyl, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0119] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 15 represents methyl or trifluoromethyl, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0120] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R 16 represents C2-C6-hydroxyalkyl, C1-C4-alkoxy-C2-C6-alkyl- or C3-C6-cycloalkyl, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0121] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: R' and R'' independently of one another represent C1-C6-alkyl, C1-C6-haloalkyl or C3-C6-cycloalkyl, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0122] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: X 1 But O, S(O) m or NR 13 Represents, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0123] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: X 1 but O or NR 13 Represents, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0124] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: X 2 But O, S(O) mor NR 14 Represents, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0125] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: X 2 but O or NR 14 Represents, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0126] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: X 3 but CH2 or NR 14 Represents, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0127] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: X 3 represents CH2 or NH, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0128] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: m represents 0, 1 or 2; It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0129] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: m represents 0 or 2; It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0130] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: m represents 2, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0131] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: n represents 0, 1 or 2; It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0132] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: n represents 0 or 2; It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0133] In a further embodiment of the first aspect, the present invention provides a method for producing a composition comprising: n represents 2, It encompasses the compounds of formula (I) above, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

[0134] In certain further embodiments of the first aspect, the invention covers combinations of two or more of the above embodiments under the heading "Further embodiments of the first aspect of the invention".

[0135] The present invention covers any subcombination within any embodiment or aspect of the invention of intermediate compounds of general formula (V) above.

[0136] The compound of general formula (I) of the present invention can be converted into any salt described herein, preferably a pharmaceutically acceptable salt, by any method known to those skilled in the art.Similarly, any salt of the compound of general formula (I) of the present invention can be converted into a free compound by any method known to those skilled in the art.

[0137] The compounds of the present invention of general formula (I) can be prepared according to the following scheme 1. The scheme and procedures described below show synthetic routes to the compounds of general formula (I) of the present invention, but are not intended to be limiting. It will be apparent to those skilled in the art that the order of the transformations illustrated in scheme 1 can be modified in various ways. Therefore, the order of the transformations illustrated in this scheme is not intended to be limiting. Furthermore, before and / or after the illustrated transformations, the substituent R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 or R 8These modifications can be, for example, the introduction of protecting groups, cleavage of protecting groups, reduction or oxidation of functional groups, halogenation, metallation, metal-catalyzed coupling reactions, substitutions, or other reactions known to those skilled in the art. These transformations include those that introduce functional groups that allow further interconversion of substituents. Suitable protecting groups and their introduction and cleavage are well known to those skilled in the art. Specific examples are described in the following paragraphs.

[0138] Scheme 1 shows a route for preparing compounds of general formula (I). [ka] Scheme 1: Route for preparing compounds of general formula (I) 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 has the meaning given for general formula (I) above, and R a represents C1-C6-alkyl or C3-C6-alkenyl, R b is hydrogen or -C(O)OR a represents the

[0139] Scheme 2 describes an alternative route for preparing compounds of formula (I). [ka] Scheme 2: Route for preparing compounds of general formula (I) 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and n has the meaning given for general formula (I) above).

[0140] Scheme 3 describes an alternative route for preparing intermediate (IV). [ka] Scheme 3: Route for the preparation of compounds of general formula (IV) 1 , R 5 , R 6 , R 7 and R 8 has the meaning given for general formula (I) above).

[0141] Scheme 4 describes an alternative route for preparing compounds of formula (I). [ka] Scheme 4: Route for preparing compounds of general formula (I) 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 has the meaning given for general formula (I) above).

[0142] Scheme 5 describes an alternative route for preparing compounds of formula (I). [ka] Scheme 5: Route for preparing compounds of general formula (I) 1 , R 2 , R 3 , R 5 , R 6 , R 7 and R 8 has the meaning given for general formula (I) above, and R 4 is the —NR 11 R 12 where R represents hydrogen, C1-C6-alkyl or C3-C6-alkenyl).

[0143] Scheme 6 describes alternative routes for preparing intermediates (IV) and (IX), respectively. [ka] Scheme 6: Route for the preparation of compounds of general formula (IV) 1 , R 5 , R 6 , R 7 and R 8 has the meaning given for general formula (I) above, and X represents oxygen or sulfur).

[0144] Scheme 7 describes alternative routes for preparing intermediates (IV) and (IX), respectively. [ka] Scheme 7: Route for the preparation of compounds of general formula (IV) 1 , R 5 , R 6 , R 7 and R 8 has the meaning given for general formula (I) above, X represents oxygen or sulfur, and Y represents chloro or bromo).

[0145] Scheme 8 describes an alternative route for preparing intermediate (IV). [ka] Scheme 8: Route for the preparation of compounds of general formula (IV) 1 , R 5 , R 6 , R 7 and R 8 has the meaning given for general formula (I) above).

[0146] Scheme 9 describes an alternative route for preparing compounds of formula (I). [ka] Scheme 9: Route for preparing compounds of general formula (I) 1 , R 2 , R 3 , R4 , R 5 , R 6 , R 7 and R 8 has the meaning given for general formula (I) above, and R represents C1-C6-alkyl).

[0147] The compounds of general formula (I) of the present invention exhibit an unexpectedly beneficial pharmacological spectrum of action. Surprisingly, the compounds of the present invention have been found to effectively inhibit AHR, which allows them to be used in the treatment or prevention of diseases in humans and animals, preferably cancer or conditions involving a dysregulated immune response or other disorders associated with abnormal AHR signaling.

[0148] Disorders and conditions particularly suitable for treatment with the AHR inhibitors of the present invention include liquid and solid tumors, such as cancers of the breast, respiratory tract, brain, reproductive organs, gastrointestinal tract, urinary tract, eye, liver, skin, head and neck, thyroid, and parathyroid, as well as distant metastases thereof. These disorders also include lymphomas, sarcomas, and leukemias.

[0149] Examples of breast cancer include, but are not limited to, triple-negative breast cancer, invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, and lobular carcinoma in situ.

[0150] Examples of cancers of the respiratory tract include, but are not limited to, small-cell and non-small-cell lung carcinoma, as well as bronchial adenoma and pleuropulmonary blastoma.

[0151] Examples of brain cancers include, but are not limited to, brain stem and hypothalamic glioma, cerebellar and cerebral astrocytoma, glioblastoma, medulloblastoma, ependymoma, as well as neuroectodermal and pineal tumor.

[0152] Tumors of the male reproductive organs include, but are not limited to, prostate and testicular cancer.

[0153] Tumors of the female reproductive organs include, but are not limited to, endometrial, cervical, ovarian, vaginal, and vulvar cancer, as well as sarcoma of the uterus.

[0154] Examples of ovarian cancer include, but are not limited to, serous tumor, endometrioid tumor, mucinous cystadenocarcinoma, granulosa cell tumor, Sertoli-Leydig cell tumor, and androgenic cell tumor.

[0155] Examples of cervical cancer include, but are not limited to, squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, small cell carcinoma, neuroendocrine tumors, hyaline cell carcinoma, and choriocarcinoma.

[0156] Tumors of the digestive tract include, but are not limited to, anal, colon, colorectal, esophageal, gallbladder, gastric, pancreatic, rectal, small-intestine, and salivary gland cancer.

[0157] Examples of esophageal cancer include, but are not limited to, esophageal carcinoma and adenocarcinoma, as well as squamous cell carcinoma, leiomyosarcoma, malignant melanoma, rhabdomyosarcoma, and lymphoma.

[0158] Examples of gastric cancer include, but are not limited to, intestinal-type and diffuse gastric adenocarcinoma.

[0159] Examples of pancreatic cancer include, but are not limited to, pancreatic ductal adenocarcinoma, adenosquamous carcinoma, and pancreatic endocrine tumors.

[0160] Tumors of the urinary tract include, but are not limited to bladder, penile, kidney, renal pelvis, ureter, urethral, ​​and human papillary renal cancer.

[0161] Examples of kidney cancer include, but are not limited to, renal cell carcinoma, urothelial cell carcinoma, juxtaglomerular cell tumor (nephroma), angiomyolipoma, renal oncocytoma, Bellini duct carcinoma, clear cell sarcoma of the kidney, mesoblastic nephroma, and Wilms' tumor.

[0162] Examples of bladder cancer include, but are not limited to, transitional cell carcinoma, squamous cell carcinoma, adenocarcinoma, sarcoma, and small cell carcinoma.

[0163] Eye cancers include, but are not limited to, intraocular melanoma and retinoblastoma.

[0164] Examples of liver cancer include, but are not limited to, hepatocellular carcinoma (liver cell carcinoma with or without fibrolamellar transformation), cholangiocarcinoma (intrahepatic cholangiocarcinoma), and mixed hepatocellular-cholangiocarcinoma.

[0165] Skin cancers include, but are not limited to, squamous cell carcinoma, Kaposi's sarcoma, malignant melanoma, Merkel cell skin cancer, and non-melanoma skin cancer.

[0166] Head and neck cancers include, but are not limited to, squamous cell carcinoma of the head and neck, laryngeal, hypopharyngeal, nasopharyngeal, oropharyngeal cancer, salivary gland cancer, lip and oral cavity cancer, and squamous cell.

[0167] Lymphomas include, but are not limited to AIDS-related lymphoma, non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, Burkitt lymphoma, Hodgkin's disease, and lymphoma of the central nervous system.

[0168] Sarcomas include, but are not limited to, sarcoma of the soft tissue, osteosarcoma, malignant fibrous histiocytoma, lymphosarcoma, and rhabdomyosarcoma.

[0169] Leukemias include, but are not limited to acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, and hairy cell leukemia.

[0170] The terms "treating" or "treatment" as used throughout this document are used conventionally and refer to the management or care of a subject for the purpose of combating, alleviating, reducing, ameliorating or ameliorating the condition of a disease or disorder, e.g., cancer.

[0171] The compounds of the present invention can be used in particular for the treatment and prevention, ie prophylaxis, of tumor growth and metastasis, especially of solid tumors of all indications and stages, with or without prior treatment of tumor growth.

[0172] Generally, the use of chemotherapeutic and / or anti-cancer agents in combination with the compounds or pharmaceutical compositions of the present invention includes: provide superior efficacy in reducing tumor growth or even eliminating tumors compared to administration of either agent alone; resulting in the administration of smaller doses of chemotherapeutic agents being administered; To provide chemotherapy treatments that are well tolerated by patients with fewer adverse pharmacological complications than those observed with single agent chemotherapy and certain other combination therapies; providing treatment for a wide range of different cancer types in mammals, particularly humans; providing a high response rate among treated patients, Providing longer survival times among treated patients compared to standard chemotherapy treatments, resulting in a longer time to tumor progression, and / or Providing efficacy and tolerability results at least as good as those of the drugs used alone, compared with known antagonistic effects of other cancer drug combinations It is useful.

[0173] Furthermore, the compounds of general formula (I) of the present invention can also be used in combination with radiotherapy and / or surgical intervention.

[0174] In a further embodiment of the present invention, the compounds of general formula (I) of the present invention can be used to sensitize cells to radiation, i.e., treating cells with a compound of the present invention prior to radiotherapy of the cells makes the cells more susceptible to DNA damage and cell death than if the cells had not been treated with a compound of the present invention. In one aspect, cells are treated with at least one compound of general formula (I) of the present invention.

[0175] Thus, the present invention also provides a method of killing cells, in which the cells are administered one or more compounds of the present invention in combination with conventional radiation therapy.

[0176] The present invention also provides a method for making cells more susceptible to cell death, wherein the cells are treated with one or more compounds of the present invention's general formula (I) prior to treatment of the cells to cause or induce cell death. In one embodiment, the cells are treated with at least one compound or at least one method, or a combination thereof, after treatment with one or more compounds of the present invention's general formula (I) to cause DNA damage in order to inhibit normal cell function or kill the cells.

[0177] In another embodiment of the present invention, cells are killed by treating with at least one DNA damaging agent, i.e., cells are treated with one or more compounds of general formula (I) of the present invention to sensitize the cells to cell death, and then cells are treated with at least one DNA damaging agent to kill the cells.DNA damaging agents useful in the present invention include, but are not limited to, chemotherapeutic agents (e.g., cisplatin), ionizing radiation (X-rays, ultraviolet radiation), carcinogens and mutagens.

[0178] In other embodiments, cells are killed by being treated with at least one method to cause or induce DNA damage.Such methods include but are not limited to: activating the cell signaling pathway that causes DNA damage when the pathway is activated; inhibiting the cell signaling pathway that causes DNA damage when the pathway is inhibited; and inducing biochemical changes in cells, where the changes cause DNA damage.Non-limiting examples include inhibiting the DNA repair pathway of cells, thereby preventing DNA damage repair, and causing the abnormal accumulation of DNA damage in cells.

[0179] In one embodiment of the present invention, the compound of general formula (I) of the present invention is administered to cells before radiation or other induction of DNA damage in cells. In another embodiment of the present invention, the compound of general formula (I) of the present invention is administered to cells simultaneously with radiation or other induction of DNA damage in cells. In yet another embodiment of the present invention, the compound of general formula (I) of the present invention is administered to cells immediately after radiation or other induction of DNA damage in cells.

[0180] In another embodiment, the cell is in vitro. In another embodiment, the cell is in vivo.

[0181] The compounds of the present invention can be administered as the sole pharmaceutical agent or in combination with one or more other pharmaceutically active ingredients, provided that the combination does not result in unacceptable adverse effects. The present invention also encompasses such pharmaceutical combinations. For example, the compounds of the present invention can be combined with the following: I-chTNT, abarelix, abemaciclib, abiraterone, acalabrutinib, aclarubicin, adalimumab, ado-trastuzumab emtansine, afatinib, aflibercept, aldesleukin, alectinib, alemtuzumab, alendronate, alitretinoin, altretamine, amifostine, aminoglutethimide, hexylaminolevulinic acid, amrubicin, amsacrine, or anastrozole. , ancestim, anetholedithiolthione, anethumab·ravtansine, angiotensin II, antithrombin III, apalutamide, aprepitant, arcitumomab, aruglavin, arsenic trioxide, asparaginase, atezolizumab, avelumab, axicabtagene·ciloleucel, axitinib, azacitidine, basiliximab, belotecan, bendamustine, besilesomab, belinostat, bevacizumab, bexarotene, bicalutamide, bisantrene, bleomycin, blinatum Mab, bortezomib, bosutinib, buserelin, brentuximab vedotin, brigatinib, busulfan, cabazitaxel, cabozantinib, calcitonin, calcium folinate, calcium levofolinate, capecitabine, capromab, carbamazepine, carboplatin, carboquone, carfilzomib, carmofur, carmustine, catumaxomab, celecoxib, celmoleukin, ceritinib, cetuximab, chlorambucil, chlormadinone, chlormethine, cidofovir, cinacal Ceto, cisplatin, cladribine, clodronate, clofarabine, cobimetinib, copanlisib, crisantaspase, crizotinib, cyclophosphamide, cyproterone, cytarabine, dacarbazine, dactinomycin, daratumumab, darbepoetin alfa, dabrafenib, dasatinib, daunorubicin, decitabine, degarelix, denileukin diftitox, denosumab, depreotide, deslorelin, dianhydrogalactitol, dexrazoxane, dibrospidium chloride,Dianhydrogalactitol, diclofenac, dinutuximab, docetaxel, dolasetron, doxifluridine, doxorubicin, doxorubicin + estrone, dronabinol, durvalumab, eculizumab, edrecolomab, elliptinium acetate, elotuzumab, eltrombopag, enasidenib, endostatin, enocitabine, enzalutamide, epirubicin, epithiostanol, epoetin alfa, epoetin beta, epoetin zeta, eptaplatin, eribulin, erlotinib, esomeprazole estradiol, estramustine, ethinyl estradiol, etoposide, everolimus, exemestane, fadrozole, fentanyl, filgrastim, fluoxymesterone, floxuridine, fludarabine, fluorouracil, flutamide, folinic acid, formestane, fosaprepitant, fotemustine, fulvestrant, gadobutrol, gadoteridol, gadoterate meglumine, gadoversetamide, gadoxetic acid, gallium nitrate, ganirelix, gefitinib, gemcitabine, gemtuzumab Mab, glucarpidase, glutoxim, GM-CSF, goserelin, granisetron, granulocyte colony-stimulating factor, histamine dihydrochloride, histrelin, hydroxycarbamide, I-125 seed, lansoprazole, ibandronate, ibritumomab tiuxetan, ibrutinib, idarubicin, ifosfamide, imatinib, imiquimod, improsulfan, indisetron, incadronic acid, ingenol mebutate, inotuzumab ozogamicin, interferon alpha, interferon Interferon beta, interferon gamma, iobitridol, iobenguane (123I), iomeprol, ipilimumab, irinotecan, itraconazole, ixabepilone, ixazomib, lanreotide, lansoprazole, lapatinib, IASOcholine, lenalidomide, lenvatinib, lenograstim, lentinan, letrozole, leuprorelin, levamisole, levonorgestrel, levothyroxine sodium, lisuride, lobaplatin, lomustine, lonidamine, lutetium Lu 177 dotatate, masoprocol, medroxyprogesterone, megestrol, melarsoprol, melphalan,Mepitiostane, mercaptopurine, mesna, methadone, methotrexate, methoxsalen, methyl aminolevulinate, methylprednisolone, methyltestosterone, metyrosine, midostaurin, mifamurtide, miltefosine, miriplatin, mitobronitol, mitoguazone, mitolactol, mitomycin, mitotane, mitoxantrone, mogamulizumab, molgramostim, mopidamol, morphine hydrochloride, morphine sulfate, mvasi, nabilone, nabiximols, nafarelin, naloxone + pentazocine, naltrexone, nartog rastim, necitumumab, nedaplatin, nelarabine, neratinib, neridronic acid, netupitant / palonosetron, nivolumab pentetreotide, nilotinib, nilutamide, nimorazole, nimotuzumab, nimustine, nintedanib, niraparib, nitracrine, nivolumab, obinutuzumab, octreotide, ofatumumab, olaparib, olaratumab, omacetaxine / mepesuccinate, omeprazole, ondansetron, oprelvekin, orgotein, orilotim od), osimertinib, oxaliplatin, oxycodone, oxymetholone, ozogamicin, p53 gene therapy, paclitaxel, palbociclib, palifermin, palladium-103 seed, palonosetron, pamidronate, panitumumab, panobinostat, pantoprazole, pazopanib, pegaspargase, PEG-epoetin beta (methoxy PEG-epoetin beta), pembrolizumab, pegfilgrastim, peg interferon alfa-2b, pembrolizumab, pemetrexed, pentazocine, pentostatin, pep romycin, perflubutane, 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,Lalchitreki, Sed, ramosetron, ramucirumab, ranimustine, rasburicase, razoxane, refametinib, regorafenib, ribociclib, risedronate, etidronate rhenium-186, rituximab, rolapitant, romidepsin, romiplostim, romurtide, rucaparib, samarium (153Sm) lexidronam, sargramostim, sarilumab, satumomab, secretin, siltuximab, sipuleucel-T, sizofiran, sob Zoxan, glycididazole sodium, sonidegib, sorafenib, stanozolol, streptozocin, sunitinib, talaporfin, talimogene laherparepvec, tamibarotene, tamoxifen, tapentadol, tasonermin, teceleukin, technetium (99mTc) nofetumomab merpentane, 99mTc-HYNIC-[Tyr3]-octreotide, tegafur, tegafur + gimeracil + oteracil, temozolomide Porfin, temozolomide, temsirolimus, teniposide, testosterone, tetrofosmin, thalidomide, thiotepa, thymalfasin, thyrotropin alfa, thioguanine, tisagenlecleucel, tocilizumab, topotecan, toremifene, tositumomab, trabectedin, trametinib, tramadol, trastuzumab, trastuzumab emtansine, treosulfan, tretinoin, trifluridine + tipiracil, trilo Stan, triptorelin, trametinib, trophosfamide, thrombopoietin, tryptophan, ubenimex, baratinib, valrubicin, vandetanib, vapreotide, vemurafenib, vinblastine, vincristine, vindesine, vinflunine, vinorelbine, vismodegib, vorinostat, vorozole, yttrium-90 glass microspheres, zinostatin, zinostatin stimalamer, zoledronic acid, zorubicin.

[0182] The compounds of the present invention can be further combined with other agents that target the immune system, such as immune checkpoint inhibitors. Compositions containing PD-1 / -L1 axis antagonists and AHR antagonists, as well as methods for using them, are provided herein. Data presented herein demonstrate that the combination of AHR inhibition and PD-1 / -L1 axis blockade reduces tumor cell proliferation to a greater extent than either of the two is additive. PD-1, along with its ligands PD-L1 and PD-L2, functions as a negative regulator of T cell activation. AHR suppresses immune cell function while increasing cancer cell proliferation and motility. PD-L1 is overexpressed in many cancers, and overexpression of PD-1 is often concomitant with tumor-infiltrating T cells. This results in attenuated T cell activation and evasion of immune surveillance, contributing to impaired anti-tumor immune responses. (Keir ME et al. (2008) Annu. Rev. Immunol. 26:677). Simultaneous targeting of both the PD-1 / -L1 axis and AHR enhances antitumor immune responses and unexpectedly reduces tumor growth. In some experiments, the resulting effects are greater than the predicted or calculated additive effects of the individual components administered separately. Thus, compositions containing a PD-1 / -L1 axis antagonist and an AHR antagonist are surprisingly effective in enhancing immune responses and treating cancer.

[0183] Additionally, the compounds of the present invention can also be used as therapeutic agents for a variety of other disorders in which AHR is involved, such as cardiovascular and pulmonary diseases.

[0184] The compounds according to the invention are therefore particularly suitable for the treatment and / or prevention of cardiovascular, inflammatory and fibrotic disorders and renal disorders, in particular acute and chronic renal insufficiency and acute and chronic renal failure.

[0185] The compounds according to the invention can therefore be used in medicines for the treatment and / or prevention of cardiovascular, inflammatory and fibrotic disorders, renal disorders, in particular acute and chronic renal insufficiency, and acute and chronic renal failure.

[0186] For purposes of the present invention, the term renal insufficiency refers to both acute and chronic signs of renal insufficiency, which may be diagnostically characterized by, for example, abnormally low creatinine and / or water excretion and / or abnormally elevated blood levels of urea, nitrogen, potassium and / or creatinine, altered activity of renal enzymes, e.g., glutamyl synthetase, altered urine osmolality or volume, elevated microalbuminuria, macroalbuminuria, lesions on the glomeruli and arterioles, tubular dilation, hyperphosphatemia and / or the need for dialysis, as well as underlying or associated renal disorders, such as diabetic and non-diabetic nephropathy, hypertensive nephropathy, ischemic nephropathy, renal hypoperfusion, intradialytic hypotension, obstructive uropathy, renal stenosis, glomerulopathy, glomerulonephritis (e.g., primary glomerulonephritis, etc.); minimal change glomerulonephritis (lipoid nephrosis); membranous glomerulonephritis; focal segmental glomerulosclerosis (FSGS); membranous Proliferative glomerulonephritis; crescentic glomerulonephritis; mesangial proliferative glomerulonephritis (IgA nephritis, Berger's disease); post-infectious glomerulonephritis; secondary glomerulonephritis: diabetes mellitus, lupus erythematosus, amyloidosis, Goodpasture's syndrome, Wegener's granulomatosis, Henoch-Schönlein purpura, microscopic polyangiitis, acute glomerulonephritis, pyelonephritis (e.g., as a result of urolithiasis, benign prostatic hyperplasia, diabetes mellitus, malformations, analgesic abuse, Crohn's disease) , glomerulosclerosis, renal arteriolar necrosis (arteriolonecrose), tubulointerstitial disease, nephropathic disorders such as primary and congenital or acquired nephropathy, Alport syndrome, nephritis, immunological nephropathy such as renal transplant rejection and immune complex-induced nephropathy, toxicant-induced nephropathy, contrast agent-induced nephropathy, diabetic and non-diabetic nephropathy, renal cysts, nephrosclerosis, hypertensive nephrosclerosis and nephrotic syndrome. The present invention also includes the use of the compounds according to the invention for treating and / or preventing sequelae of renal insufficiency such as pulmonary edema, heart failure, uremia, anemia, electrolyte abnormalities (e.g., hyperkalemia, hypernatremia) and disorders of bone and carbohydrate metabolism.

[0187] The present invention also includes the use of compounds according to the invention for treating and / or preventing sequelae of renal insufficiency, such as pulmonary edema, heart failure, uremia, anemia, electrolyte abnormalities (e.g., hyperkalemia, hypernatremia) and disorders of bone and carbohydrate metabolism.

[0188] The compounds according to the invention are further suitable for the treatment and / or prevention of polycystic kidney disease (PCKD) and syndrome of inappropriate ADH secretion (SIADH).

[0189] Furthermore, the compounds according to the invention are also useful in the treatment of metabolic syndrome, hypertension, resistant hypertension, acute and chronic heart failure, coronary heart disease, stable and unstable angina, peripheral and cardiovascular disorders, arrhythmias, atrial and ventricular arrhythmias and conduction disorders such as atrioventricular block of degree I to III (AB block I to III), supraventricular tachyarrhythmias, atrial fibrillation, atrial flutter, ventricular fibrillation, ventricular flutter, ventricular tachyarrhythmias, polymorphic ventricular tachycardia, atrial and ventricular extrasystoles, atrioventricular junctional premature contractions, sick sinus syndrome, syncope, atrioventricular nodal reentrant tachycardia, Wolff-Parkinson-White syndrome, acute coronary syndrome (ACS), autoimmune heart diseases (pericarditis, endocarditis, valvulitis, aortitis, cardiomyopathy), shock, such as cardiogenic shock, septic shock and anaphylactic shock, aneurysms, boxer's cardiomyopathy (premature ventricular contractions (PVCs)). )), thromboembolic disorders and ischemia, such as myocardial ischemia, myocardial infarction, stroke, cardiac hypertrophy, transient and ischemic attacks, pre-eclampsia, inflammatory cardiovascular disorders, spasm of coronary and peripheral arteries, edema formation, such as pulmonary edema, cerebral edema, renal edema or edema caused by heart failure, peripheral circulatory disorders, reperfusion injury, arterial and venous thrombosis, myocardial insufficiency, endothelial dysfunction, for example, for the prevention of restenosis after thrombolytic therapy, percutaneous transluminal coronary angioplasty (PTA), transluminal coronary angioplasty (PTCA), heart transplantation and bypass surgery, as well as micro- and macrovascular damage (vasculitis), elevated levels of fibrinogen and low-density lipoprotein (LDL) and elevated concentrations of plasminogen activator inhibitor 1 (PAI-1), and for the treatment and / or prevention of erectile dysfunction and female sexual dysfunction.

[0190] Furthermore, the compounds according to the invention are also suitable for the treatment and / or prevention of asthmatic disorders, pulmonary arterial hypertension (PAH) and other types of pulmonary hypertension (PH) (including pulmonary hypertension associated with left heart disease, HIV, sickle cell anemia, thromboembolism (CTEPH), sarcoidosis, COPD or pulmonary fibrosis), chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), acute lung injury (ALI), alpha 1-antitrypsin deficiency (AATD), pulmonary fibrosis, emphysema (e.g. cigarette smoke-induced emphysema) and cystic fibrosis (CF).

[0191] The compounds described in the present invention are also active compounds for controlling the central nervous system disorders characterized by the disorder of NO / cGMP system.They are particularly suitable for improving perception, concentration, learning or memory after cognitive impairment, such as mild cognitive impairment, age-related learning and memory impairment, age-related memory loss, vascular dementia, craniocerebral injury, stroke, dementia that occurs after stroke (post-stroke dementia), post-traumatic craniocerebral injury, general concentration disorder, concentration disorder in children with learning and memory problems, Alzheimer's disease, dementia with Lewy bodies, dementia with frontal lobe degeneration including Pick's syndrome, Parkinson's disease, progressive dementia with corticobasal degeneration, amyotrophic lateral sclerosis (ALS), Huntington's chorea, demyelination, multiple sclerosis, thalamic degeneration, Creutzfeldt-Jakob dementia, HIV dementia, schizophrenia with dementia or Korsakoff's psychosis and other conditions / diseases / syndrome. They are also suitable for treating and / or preventing central nervous system disorders, such as anxiety, tension and depression, conditions of CNS-related dysfunction and sleep disorders, and for controlling pathological disorders of the intake of food, recreational and addictive substances.

[0192] The compounds according to the present invention are also suitable for controlling cerebral blood flow, making them effective drugs for controlling migraine.They are also suitable for preventing and controlling the sequelae of cerebral infarction (cerebral hemorrhage), such as stroke, cerebral ischemia and craniocerebral injury.The compounds according to the present invention can also be used to control pain conditions and tinnitus.

[0193] The compounds according to the present invention are also suitable for treating and / or preventing fibrotic disorders of internal organs, such as lungs, heart, kidney, bone marrow and especially liver, as well as dermatological fibrosis and fibrotic eye disorders.In the context of the present invention, the term fibrotic disorder particularly includes the following terms: liver fibrosis, liver cirrhosis, pulmonary fibrosis, endomyocardial fibrosis, nephropathy, glomerulonephritis, renal interstitial fibrosis, fibrotic lesions resulting from diabetes, myelofibrosis and similar fibrotic disorders, scleroderma, morphea, keloid, hypertrophic scar (even after surgical procedures), nevi, diabetic retinopathy, proliferative vitreoretinopathy and connective tissue disorders (for example, sarcoidosis).

[0194] The compounds according to the invention are also suitable for controlling post-operative scarring, for example as a result of glaucoma surgery.

[0195] The compounds according to the invention can also be used cosmetically for aging and keratinized skin.

[0196] Furthermore, the compounds according to the invention are suitable for treating and / or preventing hepatitis, neoplasms, osteoporosis, glaucoma and gastroparesis.

[0197] The present invention further provides the use of the compounds according to the invention for treating and / or preventing disorders, in particular the disorders mentioned above.

[0198] The present invention further provides the use of a compound according to the invention for the treatment and / or prevention of chronic renal damage, acute and chronic renal insufficiency, diabetic, inflammatory or hypertensive nephropathy, fibrotic disorders, heart failure, angina pectoris, hypertension, pulmonary hypertension, ischemia, vascular disorders, thromboembolic disorders, arteriosclerosis, sickle cell anemia, erectile dysfunction, benign prostatic hyperplasia, urinary disorders associated with benign prostatic hyperplasia, Huntington's, dementia, Alzheimer's and Creutzfeldt-Jakob disease.

[0199] The present invention further provides a method for the treatment and / or prevention of disorders, in particular the disorders mentioned above, using an effective amount of at least one of the compounds according to the invention.

[0200] The present invention further provides methods for treating and / or preventing chronic kidney disease, acute and chronic renal insufficiency, diabetic, inflammatory or hypertensive nephropathy, fibrotic disorders, heart failure, angina pectoris, hypertension, pulmonary hypertension, ischemia, vascular disorders, thromboembolic disorders, arteriosclerosis, sickle cell anemia, erectile dysfunction, benign prostatic hyperplasia, urinary disorders associated with benign prostatic hyperplasia, Huntington's, dementia, Alzheimer's and Creutzfeldt-Jakob disease.

[0201] In another embodiment, the compounds of the present invention may be used to treat or prevent uterine fibroids (uterine leiomyomas or fibroids) in women.

[0202] Uterine fibroids are benign tumors of the myometrium, the smooth muscle layer of the uterus. They grow slowly over a woman's lifetime and depend on the female sex hormones estradiol and progesterone [Kawaguchi K et al., Immunohistochemical analysis of estrogen receptors, progesterone receptors, and Ki-67 in leiomyoma and myometrium during the menstrual cycle and pregnancy. Virchows Arch A Pathol Anat Histopathol. 1991;419(4):309-15.] The peak prevalence of uterine fibroids, approximately 70% and over 80%, is seen in white American and African American women, respectively, from age 35 until menopause, when uterine leiomyoma involutes due to declining hormone levels [Baird DD et al., High cumulative incidence of uterine leiomyoma in black and white women: Ultrasound evidence. Am J Obstet Gynecol. 2003 Jan;188(1):100-7.] Approximately 30% and 45% of Caucasian American and African American women, respectively, exhibit clinically relevant symptoms of fibroids: heavy menstrual bleeding and menstrual cycle-related pain [David M et al. Myoma-associated pain frequency and intensity: a retrospective evaluation of 1548 myoma patients. Eur J Obstet Gynecol Reprod Biol. 2016 Apr;199:137-40]. Heavy menstrual bleeding, in this regard, is defined as blood loss of more than 80 mL during a menstrual bleeding period [Fraser IS et al. The FIGO Recommendations on Terminologies and Definitions for Normal and Abnormal Uterine Bleeding, Semin Reprod Med 2011;29(5):383-390].Submucosal locations of uterine fibroids, such as those located beneath the endometrium, appear to have an even more severe impact on uterine bleeding, which can lead to anemia in affected women [Yang JH et al. Impact of submucous myoma on the severity of anemia. Fertil Steril. 2011 Apr;95(5):1769-72]. Furthermore, uterine fibroids severely affect the quality of life of affected women due to their symptoms [Downes E et al. The burden of uterine fibroids in five European countries. Eur J Obstet Gynecol Reprod Biol. 2010 Sep;152(1):96-102].

[0203] To date, it is unclear how uterine fibroids cause heavy menstrual bleeding. Dysregulated genes in uterine fibroids compared with normal myometrium may provide clues to understanding the underlying mechanisms. In a published internal study, we found that TDO2, a tryptophan 2,3-dioxygenase, was highly upregulated [Tsibris JC et al., Insights from gene arrays on the development and growth regulation of uterine leiomyomata. Fertil Steril. July 2002;78(1):114-21.]. TDO2 metabolizes the substrate L-tryptophan to L-kynurenine, which can be further metabolized to kynurenic acid. Both L-kynurenine and kynurenic acid are physiological ligands and activators of the aryl hydrocarbon receptor (AHR) [Opitz CA et al. An endogenous tumor-promoting ligand of the human aryl hydrocarbon receptor Nature. 2011 Oct 5;478(7368):197-203].

[0204] L-kynurenine regulates at least two physiological processes that are dysregulated in uterine fibroids. Synthesized by upregulation of IDO (indoleamine-2,3-dioxygenase) or TDO2 and acting through the AHR receptor, L-kynurenine suppresses the immune system, thus preventing immune cells from recognizing and eliminating tumor cells [Munn DH Blocking IDO activity to enhance anti-tumor immunity. Front Biosci (Elite ed.). 2012 January 1;4:734-45]. Furthermore, upregulation of L-kynurenine leads to vasodilation of blood vessels, thus directly increasing blood loss and bleeding [Wang Y et al. Kynurenine is an endothelium-derived relaxing factor produced during inflammation. Nature Medicine 16, 279-285 (2010)].

[0205] In summary, upregulation of L-kynurenine through activation of its physiological receptor AHR appears to support the growth of uterine fibroids by local suppression of the immune system and may cause heavy menstrual bleeding by vasodilation of endometrial vessels in close proximity to the tumor.

[0206] Therefore, systemic or local application of compounds of the present invention that inhibit AHR activation and thus block the effects of L-kynurenine derived from uterine fibroids represents a new and effective treatment option for uterine fibroids.

[0207] The compounds of the present invention can be used to inhibit, block, reduce or decrease AHR activation by exogenous and / or endogenous ligands for reducing tumor growth and modulating dysregulated immune responses, for example, blocking immunosuppression and increasing immune cell activation and infiltration in the context of cancer and cancer immunotherapy. The method comprises administering to a mammal, including a human, in need thereof, an amount of a compound of the present invention, or a pharmaceutically acceptable salt, isomer, polymorph, metabolite, hydrate, solvate or ester thereof, effective to treat the disorder.

[0208] The present invention also provides methods for treating a variety of other disorders in which AHR is involved, including, but not limited to, inflammation, vaccination for infectious diseases and cancer, viral infections, obesity and diet-induced obesity, steatosis, metabolic disorders, fatty liver, and uterine fibroids.

[0209] These disorders are well characterized in humans, but also exist in other mammals with similar etiologies and can be treated by administering the pharmaceutical compositions of the present invention.

[0210] As used herein, the terms "treating" or "treatment" are used conventionally, e.g., the management or care of a subject for the purpose of combating, alleviating, reducing, ameliorating, or ameliorating the condition of a disease or disorder, e.g., liquid and solid tumors.

[0211] According to a further aspect, the present invention covers compounds of general formula (I) as defined above, or stereoisomers, tautomers, N-oxides, hydrates, solvates and salts thereof, in particular pharmaceutically acceptable salts thereof, or mixtures thereof, for use in the treatment or prevention of diseases, in particular cancer or conditions involving a dysregulated immune response or other disorders associated with abnormal AHR signaling.

[0212] The pharmaceutical activity of the compounds according to the invention can be explained by their activity as AHR inhibitors.

[0213] According to a further aspect, the present invention covers the use of a compound of general formula (I) as defined above, or a stereoisomer, tautomer, N-oxide, hydrate, solvate and salt thereof, in particular a pharmaceutically acceptable salt thereof, or a mixture thereof, for treating or preventing a disease, in particular cancer or a condition involving a dysregulated immune response or other disorder associated with abnormal AHR signaling, in particular liquid and solid tumors.

[0214] According to a further aspect, the present invention covers the use of a compound of formula (I) as defined above, or a stereoisomer, tautomer, N-oxide, hydrate, solvate or salt thereof, in particular a pharmaceutically acceptable salt thereof, or a mixture thereof, for the prevention or treatment of a disease, in particular cancer or a condition involving a dysregulated immune response or other disorder associated with abnormal AHR signaling, in particular liquid and solid tumors.

[0215] According to a further aspect, the present invention covers the use of a compound of general formula (I) as defined above, or a stereoisomer, tautomer, N-oxide, hydrate, solvate and salt thereof, in particular a pharmaceutically acceptable salt thereof, or a mixture thereof, in a method for treating or preventing a disease, in particular cancer or a condition involving a dysregulated immune response or other disorder associated with abnormal AHR signaling, in particular liquid and solid tumors.

[0216] According to a further aspect, the present invention covers the use of a compound of general formula (I) as defined above, or its stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, in particular pharmaceutically acceptable salts thereof, or mixtures thereof, for the preparation of a pharmaceutical composition, preferably a medicament, for the prevention or treatment of a disease, in particular cancer or a condition involving a dysregulated immune response or other disorder associated with abnormal AHR signaling, in particular liquid and solid tumors.

[0217] According to a further aspect, the present invention covers a method for treating or preventing a disease, in particular cancer or a condition involving a dysregulated immune response or other disorder associated with abnormal AHR signaling, in particular liquid and solid tumors, using an effective amount of a compound of the above general formula (I), or its stereoisomers, tautomers, N-oxides, hydrates, solvates and salts, in particular pharmaceutically acceptable salts thereof, or mixtures thereof.

[0218] According to a further aspect, the present invention covers pharmaceutical compositions, in particular medicaments, comprising a compound of the above general formula (I), or its stereoisomers, tautomers, N-oxides, hydrates, solvates, salts, in particular pharmaceutically acceptable salts, or mixtures thereof, and one or more excipients, in particular one or more pharmaceutically acceptable excipients. Conventional procedures for preparing such pharmaceutical compositions in suitable dosage forms can be utilized.

[0219] The present invention further covers pharmaceutical compositions, in particular medicaments, comprising at least one compound according to the invention, conventionally together with one or more pharmaceutically suitable excipients, and the use thereof for the above-mentioned purposes.

[0220] The compounds according to the invention can have systemic and / or local activity, and for this purpose they can be administered in any suitable manner, for example via the oral, parenteral, pulmonary, nasal, sublingual, lingual, buccal, rectal, vaginal, dermal, transdermal, conjunctival, auricular route, or as an implant or stent.

[0221] For these administration routes, the compounds according to the invention can be administered in suitable dosage forms.

[0222] For oral administration, the compounds according to the invention can be formulated into dosage forms known in the art that deliver the compounds of the invention rapidly and / or in a modified manner, such as tablets (uncoated or coated, for example, with a slow-dissolving or soluble enteric or controlled-release coating), orally disintegrating tablets, films / wafers, films / lyophilisates, capsules (for example, hard or soft gelatin capsules), dragees, granules, pellets, powders, emulsions, suspensions, aerosols or solutions. The compounds according to the invention can be incorporated into such dosage forms in crystalline and / or amorphous and / or dissolved form.

[0223] Parenteral administration can be achieved by bypassing the absorption step (e.g., intravenously, intraarterially, intracardially, intrathecally, or intralumbarly) or by including absorption (e.g., intramuscularly, subcutaneously, intradermally, transdermally, or intraperitoneally). Suitable dosage forms for parenteral administration are, inter alia, injection and infusion preparations in the form of solutions, suspensions, emulsions, lyophilisates, or sterile powders.

[0224] Examples of suitable forms for other administration routes are pharmaceutical forms for inhalation (in particular powder inhalers, nebulizers), nose drops, nasal solutions or nasal sprays; tablets / films / wafers / capsules for lingual, sublingual or buccal administration; suppositories; eye drops, eye ointments, eye baths, eye inserts, ear drops, ear sprays, ear powders, ear rinses, ear tampons; vaginal capsules, aqueous suspensions (lotions, shaking mixtures), lipophilic suspensions, emulsions, ointments, creams, transdermal therapeutic systems (e.g. patches), milks, pastes, foams, powders, implants or stents.

[0225] The compounds according to the invention can be incorporated into the mentioned dosage forms. This can be done in a manner known per se by mixing with pharmaceutically suitable excipients. Pharmaceutically suitable excipients include, in particular: Fillers and carriers (e.g., cellulose, microcrystalline cellulose (e.g., Avicel®, etc.), lactose, mannitol, starch, calcium phosphate (e.g., Di-Cafos®, etc.)); ointment bases (e.g., petrolatum, paraffin, triglycerides, wax, wool wax, wool wax alcohol, lanolin, hydrophilic ointments, polyethylene glycol); suppository bases (e.g., polyethylene glycol, cocoa butter, hard fat), solvents (e.g., water, ethanol, isopropanol, glycerol, propylene glycol, medium-chain triglyceride fatty oils, liquid polyethylene glycol, paraffin); surfactants, emulsifiers, dispersing agents or wetting agents (e.g., sodium dodecyl sulfate, lecithin, phospholipids, fatty alcohols (e.g., Lanette®, etc.), sorbitan fatty acid esters (e.g., Span®, etc.), polyoxyethylene sorbitan fatty acid esters (e.g., Tween®, etc.), polyoxyethylene fatty acid glycerides (e.g., Cremophor®, etc.), polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, glycerol fatty acid esters, poloxamers (e.g., Pluronic®, etc.), buffers, acids and bases (e.g., phosphates, carbonates, citric acid, acetic acid, hydrochloric acid, sodium hydroxide solution, ammonium carbonate, trometamol, triethanolamine); isotonic agents (e.g., glucose, sodium chloride), Adsorbents (e.g., highly dispersible silica), viscosity enhancing agents, gel forming agents, thickeners and / or binders (e.g., polyvinylpyrrolidone, methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, starch, carbomer, polyacrylic acid (e.g., Carbopol®), alginates, gelatin); Disintegrants (e.g., modified starch, sodium carboxymethylcellulose, sodium starch glycolate (e.g., Explotab®, etc.), cross-linked polyvinylpyrrolidone, croscarmellose sodium (e.g., AcDiSol®, etc.)), Flow regulators, lubricants, glidants and release agents (e.g., magnesium stearate, stearic acid, talc, highly disperse silica (e.g., Aerosil®, etc.)), coating materials (e.g., sugars, shellac) and film-forming agents or dispersion films that dissolve rapidly or in a modified manner (e.g., polyvinylpyrrolidone (e.g., Kollidon®), polyvinyl alcohol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, ethyl cellulose, hydroxypropyl methylcellulose phthalate, cellulose acetate, cellulose acetate phthalate, polyacrylates, polymethacrylates (e.g., Eudragit®), capsule materials (e.g., gelatin, hydroxypropyl methylcellulose), synthetic polymers (e.g., polylactides, polyglycolides, polyacrylates, polymethacrylates (e.g., Eudragit®, etc.), polyvinylpyrrolidones (e.g., Kollidon®, etc.), polyvinyl alcohols, polyvinyl acetates, polyethylene oxides, polyethylene glycols, and copolymers and block copolymers thereof); plasticizers (e.g., polyethylene glycol, propylene glycol, glycerol, triacetin, triacetyl citrate, dibutyl phthalate); penetration enhancers, stabilizers (e.g., antioxidants such as ascorbic acid, ascorbyl palmitate, sodium ascorbate, butylhydroxyanisole, butylhydroxytoluene, propyl gallate); Preservatives (e.g., parabens, sorbic acid, thiomersal, benzalkonium chloride, chlorhexidine acetate, sodium benzoate), colorants (e.g., inorganic pigments, e.g., iron oxide, titanium dioxide); Flavorings, sweeteners, flavorings and / or odor masking agents.

[0226] The present invention further relates to pharmaceutical compositions comprising at least one compound according to the invention, conventionally together with one or more pharmaceutically suitable excipients, and to their use according to the invention.

[0227] According to another aspect, the present invention covers pharmaceutical combinations, in particular medicaments, comprising at least one compound of general formula (I) according to the invention and at least one or more further active ingredients, in particular for the treatment and / or prevention of cancer or conditions involving a dysregulated immune response or other disorders associated with abnormal AHR signaling, general name disorders, in particular liquid and solid tumors.

[0228] The term "combination" in the present invention is used as known to those skilled in the art, and the combination can be a fixed combination, a loose combination or a kit-of-parts.

[0229] " Fixed combination " in the present invention is used as known by those skilled in the art, and is defined as, for example, the combination in which the first active ingredient, for example, one or more compounds of general formula (I) of the present invention, and the additional active ingredient are present together in one unit dosage or single entity.One example of " fixed combination " is the pharmaceutical composition in which the first active ingredient and the additional active ingredient are present in a mixture, for example, a formulation, for simultaneous administration.Another example of " fixed combination " is the pharmaceutical combination in which the first active ingredient and the additional active ingredient are not mixed but are present in one unit.

[0230] In the present invention, the term "unfixed combination" or "kit of parts" is used as known by those skilled in the art, and is defined as the combination of the first active ingredient and the additional active ingredient in two or more units.An example of the unfixed combination or kit of parts is the combination of the first active ingredient and the additional active ingredient that are separately present.The components of the unfixed combination or kit of parts can be administered separately, sequentially, simultaneously, simultaneously or chronologically staggered.

[0231] Effective dosages of the compounds of the present invention can be readily determined for treating each desired indication based on standard laboratory techniques known for evaluating compounds useful in treating cancer or conditions involving a dysregulated immune response or other disorders associated with abnormal AHR signaling, by standard toxicity tests and standard pharmacological assays to determine the treatment of the above-identified conditions in mammals, and comparing the results of these with those of known active ingredients or pharmaceuticals used to treat these conditions. The amount of active ingredient to be administered in the treatment of one of these conditions can vary widely depending on considerations such as the particular compound and dosage unit used, the mode of administration, the duration of treatment, the age and sex of the patient being treated, and the nature and severity of the condition being treated.

[0232] The total amount of active ingredient to be administered generally ranges from about 0.001 mg / kg to about 200 mg / kg body weight per day, preferably from about 0.01 mg / kg to about 20 mg / kg body weight per day. Clinically useful dosing schedules range from one to three times daily administration to once every four weeks. Additionally, "drug holidays," during which the patient does not receive the drug for a period of time, can be beneficial to the overall balance between pharmacological effect and tolerability. A unit dosage can contain from about 0.5 mg to about 1500 mg of active ingredient and can be administered once or multiple times daily, or less than once daily. The average daily dosage for administration by injection, including intravenous, intramuscular, subcutaneous, and parenteral injections, as well as for use with infusion techniques, will preferably be 0.01 to 200 mg / kg total body weight. An average daily rectal administration regimen will preferably be 0.01 to 200 mg / kg total body weight. An average daily vaginal administration regimen will preferably be 0.01 to 200 mg / kg total body weight. The average daily topical dosage regimen is preferably 0.1 to 200 mg administered 1 to 4 times daily. The transdermal concentration will preferably be that required to maintain a daily dose of 0.01 to 200 mg / kg. The average daily inhalation dosage regimen will preferably be 0.01 to 100 mg / kg of total body weight.

[0233] Naturally, the specific initial and subsequent administration regimens for each patient will vary depending on the nature and severity of the condition as determined by the attending diagnostician, the activity of the specific compound used, the age and general condition of the patient, the duration of administration, the route of administration, the excretion rate of the drug, the combination of drugs, etc. The desired mode of treatment and frequency of administration of the compounds of the present invention or pharmaceutically acceptable salts or esters thereof or compositions thereof can be ascertained by one skilled in the art using conventional therapeutic trials. DETAILED DESCRIPTION OF THE INVENTION

[0234] Experimental Section NMR peak forms are stated as they appear in the spectra, without taking into account possible higher order effects. Multiplicities are stated according to the signal forms that appear in the spectra, without taking into account higher order NMR spectroscopic effects. NMR signal multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, qi, quin = quintet, b, br = broad signal, m = multiplet. NMR signal: shift (ppm). Multiplicity combinations can be, for example, dd = doublet of doublets.

[0235] Chemical names were generated using ACD / Name software from ACD / Labs. In some cases, commonly accepted names of commercially available reagents were used in place of ACD / Name-generated names.

[0236] Table 1 lists the abbreviations used in this paragraph and in the Examples section unless explained in the text. Other abbreviations have their customary meanings to those skilled in the art.

[0237] Table 1: Abbreviations ACN Acetonitrile AcOH acetic acid BPR back pressure regulator CDCl3 deuterated chloroform DAD Diode Array Detector DCM dichloromethane DEA Diethylamine DIPEA N,N-Diisopropylethylamine DMA N,N-dimethylacetamide DME 1,2-dimethoxyethane DMF N,N-dimethylformamide DMSO-d6 Deuterated Dimethyl Sulfoxide DMSO dimethyl sulfoxide EtOAc ethyl acetate EtOH ethanol Eq equivalent ESI electrospray ionization Example HATU (7-Aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate HBTU O-Benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate HPLC High Pressure Liquid Chromatography KA kynurenic acid LCMS Liquid Chromatography Coupled with Mass Spectrometry LPS lipopolysaccharide mL milliliter min. M molar concentration mCPBA metachloroperbenzoic acid MeLi Methyllithium MS mass spectrometry MTBE Methyl tert-butyl ether MTP Microtiter Plate n-BuLi n-butyllithium NMP N-methyl-2-pyrrolidone p pressure PBMC peripheral blood mononuclear cells Pd2(dba)3 tris(dibenzylideneacetone)dipalladium(0) Pd / C Palladium activated carbon (10% with 50% water) PLC Pressure Liquid Chromatography PyBOB (benzotriazol-1-yl)oxytripyrrolidinophosphonium hexafluorophosphate RP-HPLC Reversed-phase high-pressure liquid chromatography Rt retention time rt, rt room temperature sat. saturation T3P 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane 2,4,6-trioxide tBuBrettPhos Pd G3 [(2-di-tert-butylphosphino-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate tBuBrettPhos 2-(di-tert-butylphosphino)-2',4',6'-triisopropyl-3,6-dimethoxy-1,1'-biphenyl TEA Triethylamine THF tetrahydrofuran TFA trifluoroacetic acid TLC thin layer chromatography TNFa tumor necrosis factor alpha μM micromolar UPLC Ultra-High Performance Chromatography Xantphos 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene Xphos 2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl XPhos Pd G1 [2-(2-aminoethyl)phenyl](chloro)palladium-dicyclohexyl(2',4',6'-triisopropyl[biphenyl]-2-yl)phosphine (1:1) XPhos Pd G4 Methanesulfonato(2-dicyclohexylphosphino-2',4',6'-tri-isopropyl-1,1'-biphenyl)(2'-methylamino-1,1'-biphenyl-2-yl)palladium(II)

[0238] Various aspects of the invention described in this application are illustrated by the following examples, which are not intended to be limiting of the invention in any way.

[0239] The example test experiments described herein serve to illustrate the invention, but the invention is not limited to the examples shown.

[0240] Experimental Section - General Part All reagents whose synthesis is not described in the experimental section are commercially available, or are known compounds, or can be formed from known compounds by known methods by those skilled in the art.

[0241] The compounds and intermediates produced by the methods of the present invention may require purification. Purification of organic compounds is well known to those skilled in the art, and several methods for purifying the same may exist. In some cases, purification may not be necessary. In some cases, compounds can be purified by crystallization. In some cases, impurities can be stirred out using an appropriate solvent. In some cases, compounds can be purified by chromatography, particularly flash column chromatography, using, for example, a pre-packed silica gel cartridge, such as a Biotage SNAP cartridge KP-Sil® or KP-NH®, in combination with a Biotage automated purification system (SP4® or Isolera Four®) and an eluent, such as a gradient of hexane / ethyl acetate or DCM / methanol. In some cases, compounds can be purified by preparative HPLC using, for example, a Waters automated purification system equipped with a diode array detector and / or an online electrospray ionization mass spectrometer in combination with an appropriate pre-packed reverse-phase column and an eluent, such as a gradient of water and acetonitrile, which may contain additives such as trifluoroacetic acid, formic acid, or aqueous ammonia.

[0242] In some cases, such purification methods can provide compounds of the present invention having sufficiently basic or acidic functionality in the form of a salt, such as a trifluoroacetate or formate salt in the case of a sufficiently basic compound of the present invention, or an ammonium salt in the case of a sufficiently acidic compound of the present invention. These salts can be converted to their free base or free acid forms, respectively, by various methods known to those skilled in the art, and can be used as salts in subsequent biological assays. It should be understood that the specific form (e.g., salt, free base, etc.) of a compound of the present invention isolated and described herein is not necessarily the only form in which the compound can be applied to biological assays to quantify specific biological activity.

[0243] UPLC / MS method Method 1: Instrument: Waters Acquity UPLCMS SingleQuad; Column: Acquity UPLC BEH C18 1.7 μm, 50 x 2.1 mm; Eluent A: water + 0.1% by volume formic acid (99%), Eluent B: acetonitrile; Gradient: 0–1.6 min, 1–99% B, 1.6–2.0 min, 99% B; Flow rate: 0.8 mL / min; Temperature: 60 °C; DAD scan: 210–400 nm.

[0244] Method 2: Instrument: Waters Acquity UPLCMS SingleQuad; Column: Acquity UPLC BEH C18 1.7 μm, 50 x 2.1 mm; Eluent A: water + 0.2% (v / v) aqueous ammonia (32%), Eluent B: acetonitrile; Gradient: 0–1.6 min, 1–99% B, 1.6–2.0 min, 99% B; Flow rate: 0.8 mL / min; Temperature: 60 °C; DAD scan: 210–400 nm.

[0245] Method 3: Column: XBridge BEH C18 2.5 μm 2.1 × 50 mm; Run time: 4.70 min; Solvent: A) 10 mM ammonium bicarbonate pH 10, B) MeCN; Gradient: 2 to 98% B at 4.00 min, hold at 98% B until 4.70 min

[0246] Method 4: Instrument: Waters Acquity UPLCMS SingleQuad; Column: Acquity UPLC BEH C18 1.7 μm, 50 x 2.1 mm; Eluent A: water + 0.1% by volume formic acid (99%), Eluent B: acetonitrile, Gradient: 0–1.7 min, 1–45% B, 1.7–1.72 min, 45–99% B, 1.72–2.0 min, 99% B; Flow rate: 0.8 ml / min; Temperature: 60 °C; DAD scan: 210–400 nm.

[0247] Method 5: Instrument: Waters Acquity UPLCMS SingleQuad; Column: Acquity UPLC CSH C18 1.7 μm, 50 x 2.1 mm; Eluent A: water + 0.2% (v / v) aqueous ammonia (32%), Eluent B: acetonitrile; Gradient: 0–1.6 min, 1–99% B, 1.6–2.0 min, 99% B; Flow rate: 0.8 ml / min; Temperature: 60 °C; DAD scan: 210–400 nm.

[0248] Experimental Section - Intermediates Intermediate 1 Methyl (2-cyanophenyl)carbamate [ka] 2-Aminobenzonitrile (CAS 1885-29-6, 3.84 g, 32.5 mmol) and potassium carbonate (13.5 g, 97.5 mmol) were solubilized in tetrahydrofuran (190 mL), and methyl carbonochloridate (CAS 79-22-1, 5.0 mL, 65 mmol) was added. The mixture was stirred at 80 °C overnight. The mixture was filtered, washed with tetrahydrofuran, and concentrated under reduced pressure to give 6.01 g of the title compound (80% purity, 84% yield). LC-MS (Method 2):R t =0.77min;MS(ESIneg):m / z=175[MH] - . 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=3.69(s,3H),7.33(td,1H),7.52(d,1H),7.63-7.71(m,1H),7.79(dd,1H),9.77(s,1H).

[0249] Intermediate 2 Ethyl (2-cyano-6-fluorophenyl)carbamate [ka] 2-Amino-3-fluorobenzonitrile (500 mg, 3.67 mmol) was stirred in ethyl carbonochloridate (7.0 mL, 73 mmol) overnight at 100° C. The mixture was cooled to rt and concentrated under reduced pressure. LC-MS (Method 2):R t =0.81min;MS(ESIneg):m / z=207[MH] - 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.23(t,3H),4.13(q,2H),7.45-7.52(m,1H),7.65-7.74(m,2H),9.70(br s,1H).

[0250] Intermediate 3 Methyl (2-cyano-6-methylphenyl)carbamate [ka] 2-Amino-3-methylbenzonitrile (1.00 g, 7.57 mmol) and potassium carbonate (3.14 g, 22.7 mmol) were solubilized in toluene, and methyl carbonochloridate (1.2 mL, 15 mmol) was added. The mixture was stirred at 80° C. overnight and at 120° C. for 24 hours. The mixture was cooled to rt and filtered. The solid was washed with DCM, and the filtrate was concentrated under reduced pressure to give 1.55 g of the title compound (90% purity, 97% yield). The compound was used without further purification. LC-MS (Method 2):R t =0.78min;MS(ESIpos):m / z=191[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=2.23(s,3H),3.62-3.69(m,3H),7.35(t,1H),7.57-7.62(m,1H),7.67(d,1H),9.42-(s 1H).

[0251] Intermediate 4 Methyl (2-cyano-5-methylphenyl)carbamate [ka] 2-Amino-4-methylbenzonitrile (1.00 g, 7.57 mmol) and potassium carbonate (3.14 g, 22.7 mmol) were solubilized in THF (19 mL), and methyl carbonochloridate (1.2 mL, 15 mmol) was added. The mixture was stirred at 80 °C overnight. The reaction mixture was cooled to rt and filtered. The solid was washed with THF, and the filtrate was concentrated under reduced pressure to give 1.50 g of the title compound (95% pure, 99% yield) without further purification. LC-MS (Method 2):R t =0.92min;MS(ESIneg):m / z=189[MH] - 1H-NMR (400MHz, DMSO-d6): δ[ppm]=2.36(s,3H),3.68(s,3H),7.13-7.17(m,1H),7.33(s,1H),7.67(d,1H),9.69(s,1H).

[0252] Intermediate 5 Methyl (2-cyano-5-fluorophenyl)carbamate [ka] 2-Amino-4-fluorobenzonitrile (1.00 g, 7.35 mmol) and potassium carbonate (3.05 g, 22.0 mmol) were solubilized in toluene (20 mL), and methyl carbonochloridate (1.1 mL, 15 mmol) was added. The mixture was stirred at 120 °C overnight. The mixture was cooled to rt and filtered. The solid was washed with toluene, and the filtrate was concentrated under reduced pressure to give the title compound 1 g (72% yield). The compound was used without further purification. LC-MS (method 2): Rt=0.87 min; MS (ESIneg): m / z=193[MH] - 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=3.71(s,3H),7.21(td,1H),7.47(dd,1H),7.90(dd,1H),9.98(s,1H).

[0253] Intermediate 6 Methyl (2-cyano-4-methylphenyl)carbamate [ka] 2-Amino-5-methylbenzonitrile (1.00 g, 7.57 mmol) and potassium carbonate (3.14 g, 22.7 mmol) were solubilized in THF (19 mL), and methyl carbonochloridate (1.2 mL, 15 mmol) was added. The mixture was stirred at 80 °C overnight. The reaction mixture was cooled to rt and filtered. The solid was washed with THF, and the filtrate was concentrated under reduced pressure to give 1.55 g of the title compound (95% purity, 102% yield). LC-MS (Method 2):R t =0.93min;MS(ESIpos):m / z=191[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=2.31(s,3H),3.67(s,3H),7.37(d,1H),7.46-7.50(m,1H),7.61(dd,1H),9.64(s,1H).

[0254] Intermediate 7 Methyl (2-cyano-4-fluorophenyl)carbamate [ka] 2-Amino-5-fluorobenzonitrile (1.00 g, 7.35 mmol) and potassium carbonate (3.05 g, 22.0 mmol) were solubilized in THF (20 mL), and methyl carbonochloridate (1.1 mL, 15 mmol) was added. The mixture was stirred at 80 °C overnight. The mixture was cooled to rt and filtered. The solid was washed with THF, and the filtrate was concentrated under reduced pressure to give 1.6 g of the title compound. The compound was used without further purification. LC-MS (method 2): Rt=0.81 min; MS (ESIneg): m / z=193[MH] - 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=3.68(s,3H),7.49-7.62(m,2H),7.82(dd,1H),9.77(s,1H).

[0255] Intermediate 8 Ethyl (3-bromo-2-cyanophenyl)carbamate [ka] 2-Amino-6-bromobenzonitrile (1.50 g, 7.61 mmol) was stirred in ethyl carbonochloridate (11 mL, 110 mmol) at reflux for 6 hours. The reaction mixture was cooled to rt and concentrated under reduced pressure to give 2.21 g of the title compound. The compound was used without further purification. LC-MS (Method 2):R t =1.05min;MS(ESIneg):m / z=267[MH] -

[0256] Intermediate 9 Ethyl (3-chloro-2-cyanophenyl)carbamate [ka] 2-Amino-6-chlorobenzonitrile (1.75 g, 11.5 mmol) was stirred in ethyl carbonochloridate (20 mL, 210 mmol) at reflux for 6 hours. The mixture was cooled to RT and concentrated under reduced pressure to give 3.00 g of the crude title compound. The compound was used without further purification. LC-MS (Method 2):R t =1.06min;MS(ESIneg):m / z=223[MH] - 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.25(t,3H),4.16(q,2H),7.51(d,2H),7.68(dd,1H),9.95(s,1H).

[0257] Intermediate 10 Ethyl [2-cyano-3-(trifluoromethyl)phenyl]carbamate [ka] 2-Amino-6-(trifluoromethyl)benzonitrile (500 mg, 2.69 mmol) was stirred in ethyl carbonochloridate (5.0 mL, 52 mmol) at reflux for 4 hours. The reaction mixture was cooled to rt and concentrated under reduced pressure to give 740 mg of the crude title compound. The compound was used without further purification. LC-MS (Method 2):R t =1.10min;MS(ESIneg):m / z=257[MH] -

[0258] Intermediate 11 2-Amino-6-cyclopropylbenzonitrile [ka] 2-Amino-6-bromobenzonitrile (500 mg, 2.54 mmol) was solubilized in 1,4-dioxane (25 mL). Cyclopropylboronic acid (262 mg, 3.05 mmol), cesium carbonate (71 μL, 10 mmol), and bis(diphenylphosphino)ferrocene-dichloropalladium(II)-dichloromethane complex (414 mg, 508 μmol) were added, and the reaction was stirred at 130° C. for 10 minutes under microwave irradiation. The reaction mixture was filtered, and the solid was washed with dioxane. The filtrate was concentrated under reduced pressure to give 748 mg of the title compound. This compound was used without further purification. LC-MS (Method 2):R t =0.99min;MS(ESIneg):m / z=157[MH] - 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=0.65-0.71(m,2H),0.96-1.03(m,2H),1.94-2.05(m,1H),5.90(s,2H),6.15(d,1H),6.56(dd,1H),7.15(t,1H).

[0259] Intermediate 12 Ethyl (2-cyano-3-cyclopropylphenyl)carbamate [ka] 2-Amino-6-cyclopropylbenzonitrile (700 mg, 4.42 mmol) was stirred in ethyl carbonochloridate (6.3 mL, 66 mmol) at reflux for 4 hours. The reaction mixture was cooled to rt and concentrated under reduced pressure to give 901 mg (88% yield) of the title compound. The compound was used without further purification. LC-MS (Method 2):R t =1.11 min;MS(ESIpos):m / z=231[M+H] +

[0260] Intermediate 13 Methyl (2-cyano-3-methylphenyl)carbamate [ka] 2-Amino-6-methylbenzonitrile (500 mg, 3.78 mmol) and potassium carbonate (1.57 g, 11.3 mmol) were dissolved in THF (9.6 mL), and methyl carbonochloridate (580 μL, 7.6 mmol) was carefully added. The mixture was stirred at 80 °C overnight. The reaction mixture was cooled to rt and filtered. The solid was washed with THF, and the filtrate was concentrated under reduced pressure to give 788 mg of the title compound. The compound was used without further purification. LC-MS (Method 2):R t =0.89min;MS(ESIneg):m / z=189[MH] - 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=2.46(s,3H),3.68(s,3H).,7.24(d,1H),7.33(d,1H),7.50-7.58(m,1H),9.69(s,1H).

[0261] Intermediate 14 Methyl (2-cyano-3-fluorophenyl)carbamate [ka] 2-Amino-6-fluorobenzonitrile (150 mg, 1.10 mmol) and potassium carbonate (457 mg, 3.31 mmol) were stirred in toluene (2.8 mL), and methyl carbonochloridate (170 μL, 2.2 mmol) was added. The mixture was stirred at 120 °C overnight. The reaction mixture was cooled to rt and filtered. The filtrate was concentrated under reduced pressure to give 52 mg of the title compound (100% purity, 24% yield). The compound was used without further purification. LC-MS (method 2): Rt=0.83 min; MS (ESIpos): m / z=193[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=3.70(s,3H),7.22-7.31(m,1H),7.39(d,1H),7.72(td,1H),10.04(s,1H).

[0262] Intermediate 15 2-Phenyl[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (2.00 g, 11.4 mmol) and benzohydrazide (CAS 613-94-5, 1.85 g, 13.6 mmol) were stirred in N-methylpyrrolidone (50 mL) at 120° C. for 4 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 2.09 g of the title compound (90% purity, 63% yield). LC-MS (Method 2):R t =0.66min;MS(ESIpos):m / z=263[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=7.39-7.49(m,2H),7.54-7.61(m,3H),7.69-7.76(m,1H),8.21-8.27(m,3H),12.34(s,1H)

[0263] Intermediate 16 5-chloro-2-phenyl[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-Phenyl[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (2.10 g, 8.02 mmol) was solubilized in phosphorus(V) oxychloride (40 mL, 430 mmol), N,N-diisopropylethylamine (2.8 mL, 16 mmol) was carefully added, and the mixture was stirred at 110 °C overnight. The mixture was concentrated, and the residue was diluted with dichloromethane. The precipitated product was filtered off and washed with dichloromethane to give 1.83 g of the title compound (100% pure, 81% yield). C-MS (method 2):R t =1.39min;MS(ESIpos):m / z=281[M+H] + 1 H-NMR(500MHz,DMSO-d6):δ[ppm]=7.59-7.64(m,3H),7.87(td,1H),7.96-8.01(m,1H),8.03-8.07(m,1H),8.29-8.33(m,2H),8.53(dd,1H)

[0264] Intermediate 17 2-(4-chlorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (129 mg, 733 μmol) and 4-chlorobenzohydrazide (CAS 536-40-3, 150 mg, 879 μmol) were stirred in N-methylpyrrolidone (3.2 mL) at 120° C. for 4 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 265 mg of the title compound (90% purity, 110% yield). LC-MS (Method 2):R t =0.80min;MS(ESIpos):m / z=297[M+H]+ 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=7.39-7.49(m,2H),7.63-7.68(m,2H),7.72(ddd,1H),8.20-8.26(m,3H),12.38(br s,1H)

[0265] Intermediate 18 5-chloro-2-(4-chlorophenyl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(4-Chlorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (430 mg, 1.45 mmol) was solubilized in phosphorus(V) oxychloride (22 mL, 230 mmol), N,N-diisopropylethylamine (2.5 mL, 14 mmol) was carefully added, and the mixture was stirred at 110 °C overnight. The mixture was concentrated, and the residue was diluted with dichloromethane. The precipitated product was filtered off and washed with dichloromethane to give 518 mg (113% yield) of the title compound. LC-MS (Method 2):R t =1.53min;MS(ESIpos):m / z=315[M+H] + 1H-NMR(400 MHz,DMSO-d6)δ[ppm]:1.207(0.47),1.218(1.66),1.234(1.88),1.252(15.57),1. 269(16.00),1.273(11.31),1.288(15.50),1.305(14.52),3.072(0.63),3.083(0.8 2), 3.091(1.92), 3.101(2.04), 3.109(2.03), 3.119(1.91), 3.138(0.63), 3.492(0.74), 3.519(0.76), 3.549(2.19), 3.563(1.30), 3.577(3.13), 3.589(1.76), 3.596( 1.43), 3.606(1.26), 3.622(0.50), 5.944(1.56), 7.416(0.48), 7.481(0.44), 7.501(0.52), 7.631(0.99), 7.652(1.10), 7.665(1.19), 7.686(1.24), 7.718(0.41), 7.8 70(0.50), 7.983(0.46), 8.034(0.69), 8.209(0.61), 8.215(1.14), 8.236(1.03), 8.287(1.20), 8.308(1.14), 8.504(0.49), 8.523(0.47), 9.428(0.44), 12.433(0.60).

[0266] Intermediate 19 2-(3-Fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (150 mg, 851 μmol) and 3-fluorobenzohydrazide (CAS 499-55-8, 197 mg, 1.28 mmol) were stirred in N,N-dimethylformamide (3.0 mL) at 120° C. overnight. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 221 mg of the title compound (98% purity, 91% yield). LC-MS (Method 2):R t=0.67min;MS(ESIpos):m / z=281[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=7.37-7.49(m,3H),7.64(td,1H),7.73(ddd,1H),7.90-7.98(m,1H),8.08(dt,1H),8.24(dd,1H),12.39(br s,1H)

[0267] Intermediate 20 5-chloro-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(3-Fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (1.35 g, 4.82 mmol) was solubilized in phosphorus(V) oxychloride (10 mL, 110 mmol), N,N-diisopropylethylamine (8.4 mL, 48 mmol) was carefully added, and the mixture was stirred at 110 °C overnight. The mixture was concentrated, and the residue was diluted with dichloromethane. The precipitated product was filtered off and washed with dichloromethane to give 1.27 g of the title compound (99% purity, 87% yield). LC-MS (Method 2):R t =1.42min;MS(ESIpos):m / z=299[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=7.43-7.49(m,1H),7.67(td,1H),7.88(dd d,1H),7.96-8.02(m,2H),8.03-8.07(m,1H),8.15(dt,1H),8.50-8.56(m,1H)

[0268] Intermediate 21 2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (1.04 g, 5.93 mmol) and 1-methyl-1H-pyrazole-4-carbohydrazide (CAS 170020-91-4, 831 mg, 5.93 mmol) were stirred in N,N-dimethylformamide (21 mL) at 120° C. for 20 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 943 mg of the title compound (95% purity, 57% yield). LC-MS (Method 2):R t =0.47min;MS(ESIpos):m / z=267[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=3.94(s,3H),7.36-7.42(m,1H),7.44(d,1H),7.70(ddd,1H),8.01(d,1H),8.16(dd,1H),8.42(s,1H),12.26(s 1H)

[0269] Intermediate 22 5-chloro-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(1-Methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (943 mg, 3.54 mmol) was solubilized in phosphorus(V) oxychloride (10 mL, 107 mmol), N,N-diisopropylethylamine (6.2 mL, 35 mmol) was carefully added, and the mixture was stirred at 110 °C overnight. The mixture was concentrated, and the residue was diluted with dichloromethane. The precipitated product was filtered off and washed with dichloromethane to give 963 mg of the title compound (96% purity, 92% yield). LC-MS (Method 2):R t =0.97min;MS(ESIpos):m / z=285[M+H] + 1H-NMR(400MHz,DMSO-d6):δ[ppm]=3.96(s,3H),7.84(ddd,1H),7.96(td,1H),7.99-8.04(m,1H),8.09(s,1H),8.45(dd,1H),8.53(s,1H)

[0270] Intermediate 23 2-(4-Methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (2.00 g, 11.4 mmol) and 4-methoxybenzohydrazide (CAS 3290-99-1, 1.89 g, 11.4 mmol) were stirred in N,N-dimethylformamide (40 mL) at 120° C. for 20 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 3.23 g of the title compound (95% purity, 93% yield). LC-MS (Method 2):R t =0.69min;MS(ESIpos):m / z=293[M+H] + 1 H-NMR (400 MHz, DMSO-d6): δ [ppm] = 3.85 (s, 3H), 7.10-7.15 (m, 2H), 7.37-7.47 (m, 2H), 7.71 (ddd, 1H), 8.14-8.19 (m, 2H), 8.22 (dd, 1H) (NH protons not visible)

[0271] Intermediate 24 5-chloro-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(4-Methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (305 mg, 1.00 mmol) was solubilized in phosphorus(V) oxychloride (5 mL, 54 mmol), N,N-diisopropylethylamine (1.8 mL, 10 mmol) was carefully added, and the mixture was stirred at 110 °C overnight. The mixture was concentrated, and the residue was diluted with dichloromethane. The precipitated product was filtered off and washed with dichloromethane to give 173 mg of the title compound (100% purity, 53% yield). LC-MS (Method 2):R t =1.38min;MS(ESIpos):m / z=311[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=3.87(s,3H),7.12-7.18(m,2H),7.86(td,1H),7.97(td,1H),8.01-8.06(m,1H),8.20-8.27(m,2H),8.51(dd,1H)

[0272] Intermediate 25 2-(4-Methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazoline-5(6H)-thione [ka] 2-Isothiocyanatobenzonitrile (CAS 81431-98-3, 100.0 mg, 624 μmol) and 4-methoxybenzohydrazide (CAS 3290-99-1, 103.4 mg, 624 μmol) were solubilized in isopropanol (20 mL, 261 mmol), and the mixture was stirred at reflux for 8 hours. The reaction mixture was filtered and washed with isopropanol to give 177 mg of the title compound (75% purity, 69% yield). LC-MS (method 2): Rt=0.63 min; MS (ESIpos): m / z=309[M+H] + 1H-NMR(400MHz,DMSO-d6):δ[ppm]=3.86(s,3H),7.14(d,2H),7.51-7.58(m,1H ),7.67(d,1H),7.75-7.84(m,1H),8.16-8.22(m,2H),8.28(dd,1H),13.96(br s,1H)

[0273] Intermediate 26 2-(2-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (500 mg, 2.84 mmol) and 2-methylbenzohydrazide (CAS 7658-80-2, 426 mg, 2.84 mmol) were stirred in N,N-dimethylformamide (130 mL) at 120° C. for 20 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 666 mg of the title compound (79% purity, 67% yield). LC-MS (Method 2):R t =0.72min;MS(ESIpos):m / z=277[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=2.70(s,3H),7.35-7.48(m,5H),7.72(ddd,1H),8.09-8.14(m,1H),8.23(dd,1H),12.3(s,1H)

[0274] Intermediate 27 5-chloro-2-(2-methylphenyl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(2-Methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (666 mg, 2.41 mmol) was solubilized in phosphorus(V) oxychloride (11 mL, 120 mmol), N,N-diisopropylethylamine (4.2 mL, 24 mmol) was carefully added, and the mixture was stirred at 110 °C overnight. The mixture was concentrated, and the residue was diluted with dichloromethane. The precipitated product was filtered off and washed with dichloromethane to give 648 mg of the title compound (100% pure, 91% yield). LC-MS (Method 2):R t =1.47min;MS(ESIpos):m / z=295[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=2.75(s,3H),7.36-7.51(m,3H),7.87(ddd ,1H),7.94-8.00(m,1H),8.03-8.07(m,1H),8.13-8.21(m,1H),8.52(dd,1H).

[0275] Intermediate 28 2-[2-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (250 mg, 1.42 mmol) and 2-(trifluoromethyl)benzohydrazide (CAS 344-95-6, 348 mg, 1.70 mmol) were stirred in N,N-dimethylformamide (3 mL) at 120° C. for 15 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 401 mg (86% yield) of the title compound. LC-MS (Method 2):R t =0.70min;MS(ESIpos):m / z=331[M+H] + 1H-NMR(400 MHz,DMSO-d6)δ[ppm]:1.229(0.63),2.331(2.77),2.518(11.72),2.523(7.45),2.727(3.41),2.888(4.04),2.934(0.55),3.072(2.77),3.365(1.35),3.383(0.55),3.868(1.50),6.834(1.66),6.852(3.09),6.870(1.90),6.872(1.90),6.925(3.01),6.944(3.41),7.022(7.60),7.042(8.55),7.049(3.80),7.070(2.53),7.097(5.15),7.099(5.07),7.117(10.06),7.135(6.42),7.138(5.78),7.181(0.71),7.261(0.71),7.284(2.14),7.287(2.38),7.305(2.85),7.322(1.58),7.325(1.43),7.400(2.38),7.402(2.53),7.421(4.99),7.429(4.36),7.438(3.80),7.440(3.96),7.450(6.89),7.465(6.18),7.485(5.78),7.511(3.09),7.566(0.71),7.648(1.19),7.667(2.61),7.685(2.30),7.699(3.01),7.716(10.77),7.733(12.28),7.736(12.75),7.748(10.22),7.774(8.79),7.792(8.00),7.800(6.89),7.820(5.15),7.840(10.69),7.859(8.71),7.885(2.61),7.904(1.19),7.953(5.39),7.965(9.82),7.985(8.63),8.006(0.79),8.101(0.48),8.175(3.96),8.178(4.20),8.195(3.96),8.198(3.64),10.172(1.74),10.571(3.09),10.662(16.00),10.909(1.82),11.254(0.55).

[0276] Intermediate 29 5-chloro-2-[2-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazoline [ka] 2-[2-(Trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (401 mg, 1.21 mmol) was solubilized in phosphorus(V) oxychloride (4.0 mL, 43 mmol), N,N-diisopropylethylamine (2.1 mL, 12 mmol) was carefully added, and the mixture was stirred at 110 °C overnight. The mixture was poured into ice and stirred for 1 h. The precipitated product was filtered off, washed with water, and dried under reduced pressure at 60 °C to give 232 mg (55% yield) of the title compound. LC-MS (Method 2):R t =1.38min;MS(ESIpos):m / z=349[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=7.81-7.86(m,1H),7.88-7.93(m,2H),7.99-8.04(m,3H),8.04-8.10(m,1H),8.50(dd,1H).

[0277] Intermediate 30 2-(3-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (1.50 g, 8.51 mmol) and 3-methylbenzohydrazide (CAS 13050-47-0, 1.28 g, 8.51 mmol) were stirred in N,N-dimethylformamide (30 mL) at 120° C. for 18 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 50° C. to give 1.87 g of the title compound (79% yield, 100% purity). LC-MS (method 3): Rt=0.73 min, MS (ESIpos): m / z=277(M+H) + 1 H-NMR(400 MHz,methanol-d4):δ[ppm]=2.44(s,3H),7.30-7.47(m,4H),7.67-7.73(m,1H),8.07(d,1H),8.12(s,1H),8.35(d,1H),NH not observed

[0278] Intermediate 31 5-chloro-2-(3-methylphenyl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(3-Methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (1.87 g, 6.77 mmol) was solubilized in phosphorus(V) oxychloride (21 mL, 230 mmol), N,N-diisopropylethylamine (12 mL, 68 mmol) was carefully added, and the mixture was stirred at 100 °C for 3 h and then left at room temperature for an additional 72 h. The mixture was concentrated, and the residue was diluted with water. The precipitated product was filtered off, washed with water, and dried under vacuum at 50 °C to give a mixture of product and starting material, which was reused. This was again dissolved in phosphorus(V) oxychloride (21 mL, 230 mmol), and N,N-diisopropylethylamine (12 mL, 68 mmol) was carefully added. The mixture was stirred at 100 °C for 4 h. The solvent was evaporated, and the residue was slowly added to ice. The solid precipitate was filtered off, washed with water, and dried under reduced pressure at 50°C to give the crude material as a brown solid. This was suspended in dichloromethane, and the solid was filtered off to give the starting material (120 mg). The filtrate was concentrated under reduced pressure to give 929.3 mg of the title compound (80% purity, 47% yield). LC-MS (method 3): Rt=1.17 min, MS (ESIpos): m / z=295(M+H) + 1H-NMR(400 MHz,DMSO-d6):δ[ppm]=2.43(s,3H),7.31-7.49(m,2H),7.81-7.86(m,1H),7.92-8.12(m,4H),8.48-8.52(m,1H)

[0279] Intermediate 32 2-[3-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (1.50 g, 8.51 mmol) and 3-(trifluoromethyl)benzohydrazide (CAS 22227-25-4, 1.74 g, 8.51 mmol) were stirred in N,N-dimethylformamide (30 mL) at 120° C. for 18 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 1.72 g of the title compound (61% yield, 94% purity). LC-MS (method 3): Rt=0.79 min, MS (ESIpos): m / z=331 (M+H) + 1 H-NMR (400 MHz, DMSO-d6): δ[ppm]=7.39(t,1H),7.43(d,1H),7.66-7.72(m,1H),7.81(t,1H),7.89(s,1H),8.23(dd,1H),8.43(s,1H),8.48(d,1H).

[0280] Intermediate 33 5-chloro-2-[3-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazoline [ka] 2-[3-(Trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (1.70 g, 67% purity, 3.45 mmol) was added to phosphorus(V) oxychloride (20 mL, 210 mmol) at room temperature, and N,N-diisopropylethylamine (6.0 mL, 34 mmol) was added slowly. The reaction mixture was warmed to 100 °C and stirred for 18 h. The solvent was evaporated, the residue was poured into ice water, and dichloromethane was added. The aqueous layer was extracted three times with dichloromethane. The organic layers were combined, dried over magnesium sulfate, and the solvent was evaporated to give 1.88 g of the title compound (119% yield, 76% purity). LC-MS (method 3): Rt=1.19 min, (ESIpos): m / z=349(M+H) + 1 H-NMR(400 MHz,DMSO-d6)δ[ppm]=7.82-7.87(m,2H),7.93-8.04(m,3H),8.47-8.57(m,3H).

[0281] Intermediate 34 2-(2-Fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (1.50 g, 8.51 mmol) and 2-fluorobenzohydrazide (CAS 446-24-2, 1.31 g, 8.51 mmol) were stirred in N,N-dimethylformamide (30 mL) at 120° C. for 18 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 50° C. to give 1.66 g of the title compound (69% yield, 99% purity). LC-MS (method 3): Rt=0.59 min, MS (ESIpos): m / z=281 (M+H) + 1H-NMR(400 MHz,DMSO-d6):δ[ppm]=7.36-7.46(m,4H),7.55-7.61(m,1H),7.67-7.72(m,1H),8.16-8.22(m,2H),12.32(s,1H)

[0282] Intermediate 35 5-chloro-2-(2-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(2-Fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (1.66 g, 5.92 mmol) was solubilized in phosphorus(V) oxychloride (20 mL, 210 mmol), and N,N-diisopropylethylamine (10 mL, 59 mmol) was carefully added. The mixture was stirred at 100 °C for 3 h and then allowed to stand at room temperature for an additional 72 h. The mixture was concentrated, and the residue was diluted with warm water. The precipitated solid was filtered off, washed with water, and dried under vacuum at 50 °C to give a mixture of product and starting material as a brown solid. This was suspended in dichloromethane, and the solid was filtered off. The filtrate was concentrated under reduced pressure to give 1.01 g of the title compound (90% pure, 51% yield). LC-MS (method 3): Rt=1.04 min, MS (ESIpos): m / z=299 (M+H) + 1 H-NMR(400 MHz,DMSO-d6):δ[ppm]=7.36-7.47(m,2H),7.59-7.66(m,1H),7.82-7.87(m,1H),7.93-7.99(m,1H),8.03(d,1H),8.27(td,1H),8.49(d,1H),NH not observed

[0283] Intermediate 36 2-(4-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (1.50 g, 8.51 mmol) and 4-methylbenzohydrazide (CAS 3619-22-5, 1.28 g, 8.51 mmol) were stirred in N,N-dimethylformamide (30 mL) at 120° C. for 18 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 50° C. to give 1.43 g of the title compound (61% yield, 91% purity). LC-MS (method 3): Rt=0.71 min, MS (ESIpos): m / z=277(M+H) + 1 H-NMR(400 MHz,DMSO-d6):δ[ppm]=2.37(s,3H),7.32-7.45(m,4H),7.68(t,1H),8.09(d,2H),8.19(d,1H),12.26(br s,1H)

[0284] Intermediate 37 5-chloro-2-(4-methylphenyl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(4-Methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (340 mg, 1.23 mmol) was added to phosphorus(V) oxychloride (10 mL, 110 mmol) at room temperature, and N,N-diisopropylethylamine (2.1 mL, 12 mmol) was added slowly. The reaction mixture was warmed to 100 °C and stirred for 72 h. The solvent was evaporated, and the residue was poured into ice water. The aqueous layer was extracted three times with dichloromethane. The organic layers were combined, dried over magnesium sulfate, and the solvent was evaporated to give 471 mg of the title compound (114% yield, 87% purity). LC-MS (method 3): Rt=1.14 min, MS (ESIpos): m / z=295(M+H) + 1H-NMR (400 MHz, CDCl3): δ[ppm]=2.44(s,3H),7.34(d,2H),7.75(t,1H),7.86(t,1H),8.01(d,1H),8.28(d,2H),8.60(d,1H).

[0285] Intermediate 38 2-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (250 mg, 1.42 mmol) and 4-(trifluoromethyl)benzohydrazide (CAS 339-59-3, 348 mg, 1.70 mmol) were stirred in N,N-dimethylformamide (3 mL) at 120° C. for 15 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 491 mg (100% yield) of the title compound. LC-MS (Method 2):R t =0.83min;MS(ESIpos):m / z=331[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=7.40-7.49(m,2H),7.73(ddd,1H),7.96(d,2H),8.25(dd,1H),8.44(d,2H),12.41(s,1H).

[0286] Intermediate 39 5-chloro-2-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazoline [ka] 2-[4-(Trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (491 mg, 1.49 mmol) was solubilized in phosphorus(V) oxychloride (5.0 mL, 54 mmol), N,N-diisopropylethylamine (2.6 mL, 15 mmol) was carefully added, and the mixture was stirred at 110 °C overnight. The mixture was poured into ice and stirred for 1 h. The precipitated product was filtered off, washed with water, and dried under reduced pressure at 60 °C to give 475 mg (92% yield) of the title compound. 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=7.89(ddd,1H),7.97-8.03(m,3H),8.05-8.09(m,1H),8.51(d,2H),8.55(dd,1H).

[0287] Intermediate 40 2-(2-chlorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (1.75 g, 9.93 mmol) and 2-chlorobenzohydrazide (CAS 5814-05-1, 1.69 g, 9.93 mmol) in N,N-dimethylformamide (30 mL) were stirred at 120° C. for 96 hours and at 140° C. for an additional 18 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 50° C. to give 1.93 g of the title compound (65% yield, 75% purity). UPLC2-MS (short basic, 2~98%): Rt=0.61 min, MS (ESIpos): m / z=297 (M+H) + 1 H-NMR (400 MHz, MeOD-d3): δ[ppm]=7.40-7.55(m,4H),7.58-7.62(m,1H),7.69-7.75(m,1H),7.91-7.95(m,1H),8.30-8.34(m,1H).

[0288] Intermediate 41 5-chloro-2-(2-chlorophenyl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(2-Chlorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (170 mg, 573 μmol) was added to phosphorus(V) oxychloride (10 mL, 110 mmol) at room temperature, and N,N-diisopropylethylamine (1000 μL, 5.7 mmol) was added slowly. The reaction mixture was warmed to 100° C. and stirred for 72 hours. The solvent was evaporated and azeotroped three times with toluene to give 2.69 g of the title compound as a dark brown oil. The material was carried on to the next step without further purification. UPLC2-MS (short basic, 2~98%): Rt=1.07 min, MS (ESIpos): m / z=317 (M+H) + .

[0289] Intermediate 42 2-(3-chlorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (1.60 g, 9.08 mmol) and 3-chlorobenzohydrazide (CAS 1673-47-8, 1.55 g, 9.08 mmol) were stirred in N,N-dimethylformamide (30 mL) at 120° C. for 72 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 50° C. to give 2.38 g of the title compound (88% yield, 96% purity). UPLC2-MS (short basic, 2~98%): Rt=0.74 min, MS (ESIpos): m / z=297 (M+H) + . 1H-NMR(400 MHz,DMSO-d6):δ[ppm]=7.39(t,1H),7.43(d,1H),7.56-7.62(m,2H),7.67-7.72(m,1H),8.13-8.18(m,2H),8.21(d,1H),12.34(br s,1H)

[0290] Intermediate 43 5-chloro-2-(3-chlorophenyl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(3-Chlorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (700 mg, 2.36 mmol) was added to phosphorus(V) oxychloride (15 mL, 160 mmol) at room temperature, and N,N-diisopropylethylamine (6.2 mL, 35 mmol) was added slowly. The reaction mixture was warmed to 100 °C and stirred for 24 h. The solvent was evaporated, and the residue was poured into ice water. The aqueous layer was extracted three times with dichloromethane. The organic layers were combined, dried over magnesium sulfate, and the solvent was evaporated to give 1.31 g of the title compound (79% yield, 45% purity). UPLC2-MS (short basic, 2~98%): Rt=1.20 min, MS (ESIpos): m / z=315 / 317 (M+H) + (Product) and 0.73 min, 40.04%. MS (ESI pos): m / z = 297 / 299 (M + H) + (Starting material)

[0291] Intermediate 44 2-(2-Methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (1.00 g, 5.68 mmol) and 2-methoxybenzohydrazide (CAS 7466-54-8, 1.13 g, 6.81 mmol) in N-methylpyrrolidone (25 mL) were stirred at 120° C. for 8 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 846 mg of the title compound (95% purity, 48% yield). LC-MS (Method 2):R t =0.65min;MS(ESIpos):m / z=293[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=3.87(s,3H),7.12(td,1H),7.22(d,1H),7.38-7.43(m, 1H),7.45(d,1H),7.49-7.56(m,1H),7.71(ddd,1H),7.92(dd,1H),8.20(dd,1H),12.31(br s,1H).

[0292] Intermediate 45 5-chloro-2-(2-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(2-Methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (846 mg, 2.89 mmol) was solubilized in phosphorus(V) oxychloride (14 mL, 150 mmol), N,N-diisopropylethylamine (5.0 mL, 29 mmol) was carefully added, and the mixture was stirred at 110 °C overnight. The mixture was poured into ice and stirred for 1 h. The organic solvent was evaporated, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60 °C to give 455 mg of the title compound (100% purity, 51% yield). 1H-NMR(400MHz,DMSO-d6):δ[ppm]=3.90(s,3H),7.15(td,1H),7.26(d,1H),7.53- 7.60(m,1H),7.86(ddd,1H),7.95-8.02(m,2H),8.03-8.07(m,1H),8.50(dd,1H). LC-MS (Method 2):R t =1.22 min;MS(ESIpos):m / z=311[M+H] +

[0293] Intermediate 46 2-(1H-pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (250 mg, 1.42 mmol) and 1H-pyrazole-3-carbohydrazide (CAS 26275-64-9, 215 mg, 1.70 mmol) in N,N-dimethylformamide (3 mL) were stirred at 120° C. for 15 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 290 mg (81% yield) of the title compound. LC-MS (Method 2):R t =0.46min;MS(ESIpos):m / z=253[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=6.86-6.97(m,1H),7.38-7.50(m,2H),7.71(br t,1H),7.92(s,1H),8.21(d,1H),12.32(br s,1H),13.31(br s,1H).

[0294] Intermediate 47 5-chloro-2-(1H-pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(1H-Pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (290 mg, 1.15 mmol) was solubilized in phosphorus(V) oxychloride (3.6 mL, 38 mmol), N,N-diisopropylethylamine (2.0 mL, 11 mmol) was carefully added, and the mixture was stirred at 110 °C overnight. The mixture was poured into ice and stirred for 1 h. The organic solvent was evaporated, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60 °C to give 320 mg of the title compound (38% purity, 39% yield). LC-MS (Method 2):R t =0.89min;MS(ESIpos):m / z=271[M+H] +1H-NMR(400 MHz,DMSO-d6)δ[ppm]:1.211(0.61),1.227(0.90),1.249(6.94),1.265(8.14),1.277(6.62),1.282(2.63),1.294(6.39),2.5 18(4.33),2.523(2.80),3.105(0.86),3.116(0.84),3.124(0.84),3.134(0.84),3.577(0.48),3.587(0.50),3.593(0.67),3. 603 (0.65), 3.609 (0.46), 3.620 (0.48), 5.655 (0.82), 5.923 (1.07), 6.897 (13.77), 6.903 (16.00), 6.977 (5.84), 6.982 (6.16), 7.398 (2.80), 7.400 (3.03), 7.418 (5.49), 7.436 (3.15), 7.438 (3.41), 7.464 (5.11), 7.483 (6.14), 7.528 (0.50), 7.694 (3.5 5), 7.698(3.68), 7.712(3.53), 7.716(4.58), 7.719(3.28), 7.733(2.52), 7.736(2.48), 7.845(2.02), 7.849(12.36), 7.854(11.58), 7.863(2.14), 7.866(2.35), 7.868(1.58), 7.882(1.58), 7.886(1.58), 7.911(5.28), 7.916(5.28), 7.955(1.26), 7.95 9 (1.32), 7.973 (0.97), 7.976 (2.31), 7.980 (2.12), 7.994 (1.70), 7.998 (1.62), 8.033 (2.69), 8.035 (2.88), 8.054 (1.58), 8.196 (4.39), 8.199 (4.60), 8.215 (4.44), 8.218 (4.08), 8.490 (1.96), 8.493 (2.02), 8.508 (1.79), 8.512 (1.83), 12.344 (6.43).

[0295] Intermediate 48 2-(1-methyl-1H-pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (503 mg, 2.86 mmol) and 1-methyl-1H-pyrazole-3-carbohydrazide (400 mg, 2.86 mmol) in DMF (10 mL) were stirred at 120° C. for 20 hours. Water was added to the mixture, and the solid was filtered, washed with water, and dried under reduced pressure at 60° C. to give 630 mg of the title compound, which was used without further purification. LC-MS (method 2): Rt=0.48 min; MS (ESIpos): m / z=267[M+H] +

[0296] Intermediate 49 5-chloro-2-(1-methyl-1H-pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(1-Methyl-1H-pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (630 mg, 2.37 mmol) was stirred in phosphorus(V) oxychloride (6.0 mL), N,N-diisopropylethylamine (4.1 mL, 24 mmol) was carefully added, and the mixture was stirred at 110° C. for 3 hours. The mixture was poured into ice and stirred for 1 hour. The solid was filtered, washed with water, and dried under reduced pressure at 60° C. to give 485 mg of the title compound, which was used without further purification. LC-MS (method 2): Rt=1.00 min; MS (ESIpos): m / z=285[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=3.99(s,3H),6.94(d,1H),7.86(ddd,1H),7.91(d,1H),7.94-8.00(m,1H),8.01-8.06(m,1H),8.50(dd,1H).

[0297] Intermediate 50 2-(5-methyl-1H-pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (250 mg, 1.42 mmol) and 5-methyl-1H-pyrazole-3-carbohydrazide (CAS 40535-14-6, 199 mg, 1.42 mmol) were stirred in N,N-dimethylformamide (5 mL) at 120° C. for 40 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 202 mg of the title compound (70% purity, 37% yield), which was used without further purification. LC-MS (Method 2):R t =0.50min;MS(ESIpos):m / z=267[M+H] + 1 H-NMR(400 MHz,DMSO-d6)δ[ppm]:2.287(5.95),2.321(16.00),2.522(2.27),2.669(0.49),2.726(9.97),2.885(12.16),6.469(1.0 2),6.624(4.56),6.698(0.50),7.000(0.65),7.019(0.81),7.064(0.40),7.081(0.78),7.101(0.56),7.390(4.84),7.40 8 (9.71), 7.428 (6.36), 7.437 (8.19), 7.457 (9.00), 7.684 (3.63), 7.703 (5.86), 7.722 (2.90), 7.948 (2.32), 7.966 (0.81), 8.177 (7.58), 8.180 (7.78), 8.197 (7.49), 10.547 (0.83), 10.616 (0.92), 12.290 (3.21), 12.970 (4.45), 13.552 (0.53).

[0298] Intermediate 51 5-chloro-2-(5-methyl-1H-pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(5-Methyl-1H-pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (200 mg, 751 μmol) was solubilized in phosphorus(V) oxychloride (3.5 mL, 38 mmol), N,N-diisopropylethylamine (1.3 mL, 7.5 mmol) was carefully added, and the mixture was stirred at 110 °C for 2 days. The mixture was poured onto ice and stirred for 2 hours. It was extracted with dichloromethane. The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give 130 mg of the title compound (92% purity, 61% yield), which was used without further purification. LC-MS (Method 2):R t =0.96min;MS(ESIpos):m / z=285[M+H] + 1H-NMR(400 MHz,DMSO-d6)δ[ppm]:1.196(0.46),1.205(0.89),1.213(0.54),1.220(1.05),1.237(2.31), 1.246(7.31),1.255(4.73),1.262(7.78),1.269(7.33),1.286(6.85),2.310(0.57),2.331(1 6.00), 2.518(1.93), 2.523(1.23), 2.664(0.41), 2.669(0.56), 3.114(0.95), 3.124(0.98), 3.133(0.96), 3.143(0.93), 3.568(0.50), 3.585(0.82), 3.594(0.86), 3.601(1.00), 3.611(1. 00), 3.618(0.82), 3.627(0.79), 3.643(0.46), 5.759(1.14), 6.723(4.86), 6.725(4.93), 7.838(1.15), 7.841(1.23), 7.856(1.84), 7.858(2.29), 7.861(1.65), 7.875(1.64), 7.878(1.63 ),7.948(1.21),7.952(1.27),7.969(2.33),7.973(2.04),7.987(1.62),7.990(1.52),8.025(3.12),8.044(1.71),8.085(0.44),8.472(2.07),8.474(2.24),8.492(2.09),8.494(1.94).

[0299] Intermediate 52 2-(1-methyl-1H-pyrazol-5-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (71.2 mg, 404 μmol) and 1-methyl-1H-pyrazole-5-carbohydrazide (85.0 mg, 607 μmol) in DMF (850 μL) were stirred at 120° C. overnight. The reaction mixture was cooled to rt and diluted with water. The solid was filtered, washed with water, and dried under reduced pressure at 60° C. to give 78.0 mg (72% yield) of the title compound without further purification. LC-MS (method 2): Rt=0.53 min; MS (ESIpos): m / z=267[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.29(s,3H),6.99(d,1H),7.40-7.44(m,1H),7.46(d,1H),7.60(d,1H),7.73(ddd,1H),8.22(dd,1H),12.43(s,1H).

[0300] Intermediate 53 5-chloro-2-(1-methyl-1H-pyrazol-5-yl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(1-Methyl-1H-pyrazol-5-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (78.0 mg, 293 μmol) was solubilized in phosphorus(V) oxychloride (1.1 mL, 11 mmol), N,N-diisopropylethylamine (510 μL, 2.9 mmol) was carefully added, and the mixture was stirred at 110° C. overnight. The mixture was cooled to RT, poured onto ice, and stirred for 1 h. The solid was filtered, washed with water, and dried under reduced pressure at 60° C. to give 50.0 mg (60% yield) of the title compound without further purification. LC-MS (method 2): Rt=1.13 min; MS (ESIpos): m / z=286[M+H] + 1H-NMR (400MHz, DMSO-d6): δ[ppm]=4.35(s,3H),7.07(d,1H),7.64(d,1H),7.88(ddd,1H),7.97-8.03(m,1H),8.04-8.09(m,1H),8.52(dd,1H).

[0301] Intermediate 54 2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (209 mg, 1.19 mmol) and 1-ethyl-3-methyl-1H-pyrazole-4-carbohydrazide (CAS 1177272-66-0, 200 mg, 1.19 mmol) were stirred in N,N-dimethylformamide (4.2 mL) at 120° C. for 20 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 200 mg of the title compound (purity 98%, yield 56%). LC-MS (Method 2):R t =0.56 min;MS(ESIpos):m / z=295[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=1.41(t,3H),2.54(s,3H),4.15(q,2H),7.34-7.56(m,2H),7.70(ddd,1H),8.15(dd,1H),8.35(s,1H),12.26(br s,1H).

[0302] Intermediate 55 5-chloro-2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(1-Ethyl-3-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (200 mg, 678 μmol) was solubilized in phosphorus(V) oxychloride (1.9 mL, 20 mmol), N,N-diisopropylethylamine (1.2 mL, 6.8 mmol) was carefully added, and the mixture was stirred at 110 °C overnight. The mixture was poured into ice and stirred for 2 h. The precipitated product was filtered off, washed with water, and dried under reduced pressure at 60 °C to give 128 mg of the title compound (66% purity, 40% yield), which was used without further purification. LC-MS (Method 2):R t =1.18 min;MS(ESIpos):m / z=313[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1,42(t,3H),2,53(s,3H),4,16(q,2H),7,84(td,1H),7,95(td,1H),8,02(d,1H),8,44(dd,1H),8,45(s,1H).

[0303] Intermediate 56 2-(1-ethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (229 mg, 1.30 mmol) and 1-ethyl-1H-pyrazole-4-carbohydrazide (CAS 512809-51-7, 200 mg, 1.30 mmol) were stirred in N,N-dimethylformamide (4.6 mL) at 120° C. for 20 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 244 mg of the title compound (100% purity, 67% yield). LC-MS (Method 2):R t =0.52min;MS(ESIpos):m / z=281[M+H] + 1H-NMR(400MHz,DMSO-d6):δ[ppm]=1.44(t,3H),4.24(q,2H),7.34-7.51(m,2H),7.70(ddd,1H),8.03(d,1H),8.17(dd,1H),8.46(s,1H),12.26(br s,1H).

[0304] Intermediate 57 5-chloro-2-(1-ethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(1-Ethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (244 mg, 872 μmol) was solubilized in phosphorus(V) oxychloride (2.4 mL, 26 mmol), N,N-diisopropylethylamine (1.5 mL, 8.7 mmol) was carefully added, and the mixture was stirred at 110°C overnight. The mixture was poured into ice and stirred for 2 hours. The precipitated product was filtered off, washed with water, and dried under reduced pressure at 60°C to give 133 mg of the title compound (85% purity, 43% yield), which was used without further purification. LC-MS (Method 2):R t =1.06min;MS(ESIpos):m / z=299[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1,45(t,3H),4,25(q,2H),7,84(td,1H),7,96(td,1H),8,02(dd,1H),8,10(s,1H),8,45(dd,1H),8,57(s,1H).

[0305] Intermediate 58 2-(1,5-dimethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (229 mg, 1.30 mmol) and 1,5-dimethyl-1H-pyrazole-4-carbohydrazide (CAS 864948-68-5, 200 mg, 1.30 mmol) were stirred in N,N-dimethylformamide (4.6 mL) at 120° C. for 20 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 287 mg of the title compound (80% purity, 63% yield). LC-MS (Method 2):R t =0.52min;MS(ESIpos):m / z=281[M+H] + 1 H-NMR(400 MHz,DMSO-d6)δ[ppm]:2.518(2.95),2.523(1.96),2.707(15.66),2.727(0.94),2.888(1.08),3.757(4.5 7),3.829(16.00),7.090(0.60),7.371(0.92),7.373(1.03),7.391(1.90),7.409(1.20),7.411(1.33),7 .423(1.90), 7.444(2.14), 7.674(1.11), 7.678(1.14), 7.693(1.11), 7.696(1.54), 7.698(1.13), 7.713(0.85), 7.717(0.85), 7.934(5.92), 7.969(0.42), 8.177(1.54), 8.181(1.61), 8.198(1.58), 8.200(1.47).

[0306] Intermediate 59 5-chloro-2-(1,5-dimethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(1,5-Dimethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (287 mg, 1.02 mmol) was solubilized in phosphorus(V) oxychloride (2.9 mL, 31 mmol), N,N-diisopropylethylamine (1.8 mL, 10 mmol) was carefully added, and the mixture was stirred at 110 °C overnight. The mixture was poured into ice and stirred for 2 hours. The precipitated product was filtered off, washed with water, and dried under reduced pressure at 60 °C to give 237 mg of the title compound (50% purity, 39% yield). The compound was used without further purification. LC-MS (Method 2):R t =1.10min;MS(ESIpos):m / z=299[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=2,70(s,3H),3,83(s,3H),7,84(td,1H),7,96(dd,1H),8,01(s,1H),8,02(d,1H),8,47(dd,1H).

[0307] Intermediate 60 2-(1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (500 mg, 2.84 mmol) and 1H-pyrazole-4-carbohydrazide (358 mg, 2.84 mmol) in DMF (10 mL) were stirred at 120° C. overnight. 1H-Pyrazole-4-carbohydrazide (358 mg, 2.84 mmol) was added, and the reaction was again stirred at 120° C. overnight. The reaction mixture was cooled to rt and diluted with water. The solid was filtered, washed with water, and dried under reduced pressure at 60° C. to give 430 mg (60% yield) of the title compound. LC-MS (method 2): Rt=0.46 min; MS (ESIpos): m / z=253[M+H] + 1H-NMR (400MHz, DMSO-d6): δ[ppm]=7.35-7.48(m,2H),7.70(ddd,1H),8.09(br s,1H),8.18(dd,1H),8.44(br s,1H),12.25(br s,1H),13.31(br s,1H).

[0308] Intermediate 61 5-chloro-2-(1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(1H-Pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (215 mg, 852 μmol) was solubilized in phosphorus(V) oxychloride (2.8 mL, 30 mmol), N,N-diisopropylethylamine (1.5 mL, 8.5 mmol) was carefully added, and the mixture was stirred at 110° C. overnight. The mixture was carefully poured onto ice and stirred for 1 hour. The solid was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 208 mg (90% yield) of the title compound. The compound was used without further purification. LC-MS (Method 2):R t =0.87min;MS(ESIpos):m / z=271[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=7.84(ddd,1H),7.93-7.99(m,1H),8.00-8.04(m,1H),8.35(s,2H),8.47(dd,1H).

[0309] Intermediate 62 2-chloro-4-hydrazinoquinazoline [ka] 2,4-Dichloroquinazoline (1 g, 5.02 mmol) was dissolved in THF (20 mL). Hydrazine hydrate (293 μL, 6.03 mmol) and triethylamine (2.52 mL, 18.09 mmol) were added. As the reaction mixture became viscous, additional THF (10 mL) was added. The reaction mixture was stirred at rt overnight. Water (50 mL) and ethyl acetate (50 mL) were added to the reaction mixture. The layers were separated, and the aqueous phase was extracted twice with ethyl acetate (15 mL). The combined organic phases were washed with saturated aqueous ammonium chloride, dried over magnesium sulfate, and concentrated in vacuo to give 925 mg of the title compound, which was used without further purification. LC-MS (Method 2):R t =0.60min;MS(ESIpos):m / z=195[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.84(br s,2H),7.46-7.51(m,1H),7.60(d,1H),7.73-7.80(m,1H),8.18(br d,1H),10.12(br s,1H).

[0310] Intermediate 63 N'-(2-chloroquinazolin-4-yl)-2-methyl-1,3-oxazole-4-carbohydrazide [ka] To a stirred solution of 2-methyl-1,3-oxazole-4-carboxylic acid (5 g, 39.3 mmol) in DMF (75 mL) was added N,N-diisopropylethylamine (10.15 g, 78.6 mmol), and the reaction mixture was cooled to 0 °C. HATU (22.4 g, 58.9 mmol) was added, followed by 2-chloro-4-hydrazinoquinazoline (7.63 g, 0.125 mol). The reaction mixture was stirred for 1 hour and quenched with ice. The precipitate was filtered and washed with water and petroleum ether to give the title compound. The crude material was used without further purification.

[0311] Intermediate 64 2-(2-methyl-1,3-oxazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] N'-(2-chloroquinazolin-4-yl)-2-methyl-1,3-oxazole-4-carbohydrazide (8.2 g, 28.7 mmol) was stirred at reflux in acetic acid (82 mL) for 6 hours. The reaction mixture was then cooled to rt and diluted with ice-cold water. The precipitate was filtered and washed with water and petroleum ether to give the title compound. The crude material was used without further purification.

[0312] Intermediate 65 5-chloro-2-(2-methyl-1,3-oxazol-4-yl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(2-Methyl-1,3-oxazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (3.3 g, 12.3 mmol) and N,N-diisopropylethylamine (9.53 g, 74.0 mmol) were stirred at reflux in POCl (114 mL) for 4 hours. The reaction was cooled to rt and diluted with DCM and ice-cold water. The aqueous phase was extracted with DCM. The organic phase was dried (NaSO), filtered, and concentrated under reduced pressure to give the title compound without further purification.

[0313] Intermediate 66 2-(4-Fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (500 mg, 2.84 mmol) and 4-fluorobenzohydrazide (CAS 456-06-4, 437 mg, 2.84 mmol) were stirred in N,N-dimethylformamide (10 mL) at 120° C. for 20 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 725 mg of the title compound (purity 96%, yield 88%). LC-MS (Method 2):R t =0.70min;MS(ESIpos):m / z=281[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=7.38-7.48(m,4H),7.72(ddd,1H),8.20-8.30(m,3H),12.35(br s,1H).

[0314] Intermediate 67 5-chloro-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(4-Fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (725 mg, 2.59 mmol) was solubilized in phosphorus(V) oxychloride (8.0 mL, 86 mmol), N,N-diisopropylethylamine (4.5 mL, 26 mmol) was carefully added, and the mixture was stirred at 110 °C overnight. The mixture was poured into ice and stirred for 1 h. The organic solvent was evaporated, and the solid was filtered off, washed with water, and dried under reduced pressure at 60 °C to give 725 mg of the title compound (99% purity, 93% yield). LC-MS (Method 2):R t =1.41 min;MS(ESIpos):m / z=299[M+H] + 1H-NMR (400MHz, DMSO-d6): δ[ppm]=7.41-7.48(m,2H),7.87(ddd,1H),7.96-8.02(m,1H),8.03-8.07(m,1H),8.31-8.38(m,2H),8.49-8.55(m,1H).

[0315] Intermediate 68 2-(3-Methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (2.00 g, 11.4 mmol) and 3-methoxybenzohydrazide (CAS 5785-06-8, 2.26 g, 13.6 mmol) in N-methylpyrrolidone (50 mL) were stirred at 120° C. for 4 hours. Water was added to the mixture, and the precipitated product was filtered off, washed with water, and dried under reduced pressure at 60° C. to give 2.63 g of the title compound (93% purity, 74% yield). LC-MS (Method 2):R t =0.64 min;MS(ESIpos):m / z=293[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=3.88(s,3H),7.12(ddd,1H),7.38-7.53(m,3H),7.69-7.75(m,2H),7.83(dt,1H),8.24(dd,1H),12.35(s,1H)

[0316] Intermediate 69 5-chloro-2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(3-Methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (2.63 g, 8.99 mmol) was solubilized in phosphorus(V) oxychloride (26 mL, 282 mmol), N,N-diisopropylethylamine (16 mL, 90 mmol) was carefully added, and the mixture was stirred at 110 °C overnight. The mixture was evaporated, and the residue was diluted with ethyl acetate. The precipitated product was filtered off to give 2.86 g of the title compound (100% purity, 100% yield). LC-MS (Method 2):R t =1.36min;MS(ESIpos):m / z=311[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=3.89(s,3H),7.17(ddd,1H),7.53(t,1H),7 .79(dd,1H),7.84-7.92(m,2H),7.98(td,1H),8.03-8.08(m,1H),8.53(dd,1H)

[0317] Intermediate 70 N 2 -(tert-Butoxycarbonyl)-N-propan-2-yl-D-alaninamide [ka] N-(tert-Butoxycarbonyl)-D-alanine (100 mg, 529 μmol), propan-2-amine (90 μL, 1.1 mmol), sodium bicarbonate (133 mg, 1.59 mmol), and HATU (402 mg, 1.06 mmol) in dichloromethane (1.5 mL) were stirred overnight at rt. The solid was filtered and washed with DCM. The filtrate was diluted with water and extracted with DCM / MeOH (9 / 1). The organic layer was dried (silicone filter) and concentrated under reduced pressure to give 97 mg of the title compound (100% pure, 80% yield) without further purification. 1H-NMR (400MHz, DMSO-d6): δ[ppm]=1.03(dd,6H),1.13(d,3H),1.37(s,9H),3.69-3.98(m,2H),6.75(br d,1H),7.56(br d,1H).

[0318] Intermediate 71 N 2 -(tert-Butoxycarbonyl)-N-cyclopropyl-D-alaninamide [ka] N-(tert-Butoxycarbonyl)-D-alanine (100 mg, 529 μmol), cyclopropanamine (60.4 mg, 1.06 mmol), sodium bicarbonate (133 mg, 1.59 mmol), and HATU (402 mg, 1.06 mmol) in dichloromethane (1.5 mL) were stirred overnight at rt. The solid was filtered and washed with DCM. The mixture was diluted with water and extracted with DCM / MeOH (9 / 1). The organic layer was dried (silicone filter) and concentrated under reduced pressure to give 155 mg of the title compound (100% pure, 96% yield) without further purification. 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=0.34-0.40(m,2H),0.58-0.61(m,2H),0.75-0.82(m,1H),1.11(d,3H),1.36(s,9H),3.79-3.90(m,1H),6.77(br d,1H),7.83(br d,1H).

[0319] Intermediate 72 N 2 -(tert-Butoxycarbonyl)-N-ethyl-D-alaninamide [ka] N-(tert-Butoxycarbonyl)-D-alanine (100 mg, 529 μmol), ethanamine (530 μL, 2.0 M in THF, 1.1 mmol), sodium bicarbonate (133 mg, 1.59 mmol), and HATU (402 mg, 1.06 mmol) in DCM (1.5 mL) were stirred overnight at rt. The mixture was diluted with water and extracted with DCM / MeOH (9 / 1). The organic layer was dried (silicone filter) and concentrated under reduced pressure to give 155 mg of the title compound (100% pure, 94% yield) without further purification. 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=0.99(t,3H),1.14(d,3H),1.37(s,9H),3.01-3.09(m,2H),3.88(br t,1H),6.81(br d,1H),7.73(br s,1H).

[0320] Intermediate 73 N 2 -(tert-Butoxycarbonyl)-N-methyl-D-alaninamide [ka] N-(tert-Butoxycarbonyl)-D-alanine (100 mg, 529 μmol), methanamine (530 μL, 2.0 M in THF, 1.1 mmol), sodium bicarbonate (133 mg, 1.59 mmol), and HATU (402 mg, 1.06 mmol) in DCM (1.5 mL) were stirred overnight at rt. The mixture was diluted with water and extracted with DCM / MeOH (9 / 1). The organic layer was dried (silicone filter) and concentrated under reduced pressure to give 110 mg of the title compound (100% pure, 92% yield) without further purification. 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.14(d,3H),1.37(s,9H),2.56(d,3H),3.82-3.95(m,1H),6.85(br d,1H),7.70(br d,1H).

[0321] Intermediate 74 tert-Butyl [(2R)-1-(cyclobutylamino)-1-oxopropan-2-yl]carbamate [ka] N-(tert-Butoxycarbonyl)-D-alanine (100 mg, 529 μmol), cyclobutanamine (75.2 mg, 1.06 mmol), sodium bicarbonate (133 mg, 1.59 mmol), and HATU (402 mg, 1.06 mmol) in DCM (1.5 mL) were stirred overnight at rt. The mixture was diluted with water and extracted with DCM / MeOH (9 / 1). The organic layer was dried (silicone filter) and concentrated under reduced pressure to give 168 mg of the title compound (75% purity, 98% yield) without further purification. 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.12(d,3H),1.37(s,9H),1.54-1.69(m,2H),1.77-1. 96(m,2H),2.06-2.19(m,2H),3.87(quin,1H),4.15(sxt,1H),6.73-6.81(m,1H),7.98(br d,1H).

[0322] Intermediate 75 N 2 -(tert-Butoxycarbonyl)-N,N-dimethyl-D-alaninamide [ka] N-(tert-Butoxycarbonyl)-D-alanine (100 mg, 529 μmol), N-methylmethanamine (530 μL, 2.0 M in THF, 1.1 mmol), sodium bicarbonate (133 mg, 1.59 mmol), and HATU (402 mg, 1.06 mmol) in DCM (1.5 mL) were stirred overnight at rt. The mixture was diluted with water and extracted with DCM / MeOH (9 / 1). The organic layer was dried (silicone filter) and concentrated under reduced pressure to give 155 mg of the title compound without further purification. 1H-NMR (400MHz, DMSO-d6): δ[ppm]=1.11(d,3H),1.36(s,9H),2.81(s,3H),2.99(s,3H),4.40(quin,1H),6.89(br d,1H).

[0323] Intermediate 76 N 2 -(tert-Butoxycarbonyl)-N-(2-hydroxyethyl)-D-alaninamide [ka] N-(tert-Butoxycarbonyl)-D-alanine (100 mg, 529 μmol), 2-aminoethan-1-ol (64.6 mg, 1.06 mmol), sodium bicarbonate (133 mg, 1.59 mmol), and HATU (402 mg, 1.06 mmol) in DCM (1.5 mL) were stirred overnight at rt. The mixture was diluted with water and extracted with DCM / MeOH (9 / 1). The aqueous phase was lyophilized to give 600 mg of the crude title compound, which was used without further purification.

[0324] Intermediate 77 N 2 -(tert-Butoxycarbonyl)-N-(3-hydroxypropyl)-D-alaninamide [ka] N-(tert-Butoxycarbonyl)-D-alanine (100 mg, 529 μmol), 3-aminopropan-1-ol (79.4 mg, 1.06 mmol), sodium bicarbonate (133 mg, 1.59 mmol), and HATU (402 mg, 1.06 mmol) in DCM (1.5 mL) were stirred overnight at rt. The mixture was diluted with water and extracted with DCM / MeOH (9 / 1). The aqueous layer was lyophilized to give 58 mg of the crude title compound, which was used without further purification.

[0325] Intermediate 78 N-Propan-2-yl-D-alaninamide hydrochloride [ka] N 2 -(tert-Butoxycarbonyl)-N-propan-2-yl-D-alaninamide (97.0 mg, 421 μmol) was solubilized in dichloromethane (5.6 mL) and methanol (1.4 mL). HCl (1.6 mL, 4.0 M in dioxane, 6.3 mmol) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure to give 97 mg of the title compound. The compound was used without further purification.

[0326] Intermediate 79 N-Cyclopropyl-D-alaninamide hydrochloride [ka] N 2 -(tert-Butoxycarbonyl)-N-cyclopropyl-D-alaninamide (155 mg, 766 μmol) was dissolved in dichloromethane (5.0 mL) and methanol (2.0 mL), HCl (2.9 mL, 4.0 M in dioxane, 11 mmol) was added, and the mixture was stirred at rt overnight. The reaction mixture was concentrated under reduced pressure to give 116 mg of the title product, which was used without further purification.

[0327] Intermediate 80 N-Ethyl-D-alaninamide hydrochloride [ka] N 2 155 mg (766 μmol) of tert-butoxycarbonyl-N-ethyl-D-alaninamide was dissolved in 5.0 mL of dichloromethane and 2.0 mL of methanol. HCl (2.9 mL, 4.0 M in dioxane, 11 mmol) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure to give 101 mg of the title compound, which was used without further purification.

[0328] Intermediate 81 N-Methyl-D-alaninamide hydrochloride [ka] N 2 -(tert-Butoxycarbonyl)-N-methyl-D-alaninamide (110 mg, 544 μmol) was dissolved in dichloromethane (5.0 mL) and methanol (2.0 mL), HCl (2.0 mL, 4.0 M in dioxane, 8.2 mmol) was added, and the mixture was stirred at rt overnight. The reaction mixture was concentrated under reduced pressure to give 70 mg of the title compound, which was used without further purification.

[0329] Intermediate 82 N-Cyclobutyl-D-alaninamide hydrochloride [ka] tert-Butyl [(2R)-1-(cyclobutylamino)-1-oxopropan-2-yl]carbamate (168 mg, 75% purity, 520 μmol) was dissolved in dichloromethane (4.8 mL) and methanol (1.9 mL), HCl (1.9 mL, 4.0 M in dioxane, 7.8 mmol) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure to give 158 mg of the title compound, which was used without further purification.

[0330] Intermediate 83 N,N-Dimethyl-D-alaninamide hydrochloride [ka] N 2-(tert-Butoxycarbonyl)-N,N-dimethyl-D-alaninamide (153 mg, 70% purity, 495 μmol) was dissolved in dichloromethane (5.0 mL) and methanol (1.5 mL), HCl (1.9 mL, 4.0 M in dioxane, 7.4 mmol) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure to give 133 mg of the title compound, which was used without further purification.

[0331] Intermediate 84 N-(2-hydroxyethyl)-D-alaninamide hydrochloride [ka] N 2 -(tert-Butoxycarbonyl)-N-(2-hydroxyethyl)-D-alaninamide (600 mg, 20% purity, 517 μmol) was dissolved in dichloromethane (4.7 mL) and methanol (1.9 mL), HCl (1.9 mL, 4.0 M in dioxane, 7.7 mmol) was added, and the mixture was stirred at rt overnight. The reaction mixture was concentrated under reduced pressure to give 90 mg of the title compound, which was used without further purification.

[0332] Intermediate 85 N-(3-hydroxypropyl)-D-alaninamide hydrochloride [ka] N 2 -(tert-Butoxycarbonyl)-N-(3-hydroxypropyl)-D-alaninamide (58.0 mg, 235 μmol) was dissolved in dichloromethane (2.2 mL) and methanol (870 μL), HCl (880 μL, 4.0 M in dioxane, 3.5 mmol) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure to give 45 mg of the title compound, which was used without further purification.

[0333] Intermediate 86 2-(Pyridin-2-yl)[1,2,4]triazolo[1,5-c]quinazoline-5(6H)-thione [ka] 2-Isothiocyanatobenzonitrile (CAS 81431-98-3, 500 mg, 3.12 mmol) and pyridine-2-carbohydrazide (CAS 1452-63-7, 428 mg, 3.12 mmol) were solubilized in 100 mL of ethanol, and the reaction mixture was stirred at reflux overnight. The precipitated product was filtered off, washed with ethanol, and dried at 40 °C to give 769 mg of the title compound (90% purity, 79% yield). LC-MS (Method 2):R t =0.50min;MS(ESIpos):m / z=280[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=7.54-7.61(m,2H),7.69(d,1H),7.78-7.85(m,1H),8.04(td,1H),8.29-8.35(m,2H),8.77-8.82(m,1H),14.08(br s,1H).

[0334] Intermediate 87 2-(Pyridin-3-yl)[1,2,4]triazolo[1,5-c]quinazoline-5(6H)-thione [ka] 2-Isothiocyanatobenzonitrile (CAS 81431-98-3, 500 mg, 3.12 mmol) and pyridine-3-carbohydrazide (CAS 553-53-7, 428 mg, 3.12 mmol) were solubilized in ethanol (100 mL), and the mixture was stirred at reflux overnight. The reaction mixture was filtered and washed with ethanol to give 754 mg of the title compound (95% purity, 82% yield). LC-MS (Method 2):R t =0.49min;MS(ESIpos):m / z=280[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=7.53-7.59(m,1H),7.64(ddd,1H),7.69(d,1H),7 .78-7.86(m,1H),8.32(dd,1H),8.57(dt,1H),8.77(dd,1H),9.40(dd,1H),14.09(br s,1H).

[0335] Intermediate 88 2-(Pyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazoline-5(6H)-thione [ka] 2-Isothiocyanatobenzonitrile (250 mg, 1.56 mmol) and pyridine-4-carbohydrazide (214 mg, 1.56 mmol) were solubilized in ethanol (50 mL), and the mixture was stirred at reflux overnight. The reaction was filtered, and the solid was washed with ethanol and dried under reduced pressure to give 367 mg of the title compound (100% purity, 84% yield). 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=7.53-7.60(m,1H),7.69(d,1H),7.80-7.86(m,1H),8.13-8.18(m,2H),8.31(dd,1H),8.80-8.84(m,2H),14.12(br s,1H).

[0336] Intermediate 89 2-(pyridazin-4-yl)[1,2,4]triazolo[1,5-c]quinazoline-5(6H)-thione [ka] 2-Isothiocyanatobenzonitrile (CAS 81431-98-3, 100 mg, 624 μmol) and pyridazine-4-carbohydrazide (CAS 56932-26-4, 86.2 mg, 624 μmol) were solubilized in ethanol (2 mL), and the reaction mixture was stirred at reflux overnight. The precipitated product was filtered off, washed with ethanol, and dried to give 138 mg of the title compound (67% purity, 53% yield). LC-MS (Method 1):R t =0.71 min;MS(ESIpos):m / z=281[M+H] +

[0337] Intermediate 90 2-[4-(dimethylamino)phenyl][1,2,4]triazolo[1,5-c]quinazoline-5(6H)-thione [ka] 2-Isothiocyanatobenzonitrile (CAS 81431-98-3, 186 mg, 1.16 mmol) and 4-(dimethylamino)benzohydrazide (CAS 19353-92-5, 208 mg, 1.16 mmol) were solubilized in ethanol (37 mL), and the reaction mixture was stirred at reflux overnight. The precipitated product was filtered off, washed with ethanol, and dried to give 288 mg of the title compound (86% purity, 66% yield). LC-MS (Method 2):R t =0.62min;MS(ESIpos):m / z=322[M+H] + 1H-NMR(400 MHz,DMSO-d6)δ[ppm]:1.035(0.39),1.052(0.67),1.070(0.41),2.518(0.77),2.523(0.50), 2.948(0.51),2.997(0.77),3.014(9.62),3.020(16.00),6.767(0.97),6.789(0.96),6.843( 0.20), 6.850(1.84), 6.855(0.57), 6.867(0.60), 6.872(1.91), 6.879(0.21), 7.251(0.23), 7.270(0.42), 7.287(0.60), 7.306(0.49), 7.506(0.41), 7.508(0.43), 7.526(0.83), 7.544(0. 48), 7.546(0.49), 7.635(0.19), 7.651(0.80), 7.671(1.01), 7.761(0.57), 7.765(0.57), 7.779(0.55), 7.782(0.75), 7.785(0.50), 7.800(0.39), 7.804(0.37), 7.872(0.45), 7.893(0.43 ),8.052(0.23),8.059(2.30),8.064(0.62),8.077(0.62),8.082(2.11),8.089(0.26),8.098(0.23),8.118(0.21),8.261(0.75),8.264(0.78),8.281(0.73),8.284(0.68),10.864(0.29).

[0338] Intermediate 94 2-(furan-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (200 mg, 1.14 mmol) and furan-2-carbohydrazide (143 mg, 1.14 mmol) in DMF (4.0 mL) were stirred at 120° C. for 20 hours. The reaction was diluted with water, and the mixture was filtered. The solid was washed with water and dried under reduced pressure at 60° C. to give 247 mg of the title compound (80% purity, 69% yield). LC-MS (method 2): Rt=0.55 min; MS (ESIpos): m / z=253[M+H] + 1 H-NMR (400 MHz, DMSO-d6): δ [ppm] = 6.74 (dd, 1H), 7.25 (dd, 1H), 7.38-7.43 (m, 1H), 7.45 (d, 1H), 7.72 (ddd, 1H), 7.96 (dd, 1H), 8.19 (dd, 1H). (One proton is invisible.)

[0339] Intermediate 95 5-chloro-2-(furan-2-yl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(Furan-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (247 mg, 981 μmol) was solubilized in phosphorus(V) oxychloride (4.4 mL, 48 mmol), N,N-diisopropylethylamine (1.7 mL, 9.8 mmol) was carefully added, and the mixture was stirred at 110° C. for 5 h. The mixture was cooled to rt and concentrated under reduced pressure. The crude material was solubilized in DCM, poured onto ice, and stirred for 10 min. The solid was filtered, washed with water, and dried under reduced pressure at 60° C. to give 196 mg of the title compound (80% purity, 59% yield) without further purification. LC-MS (Method 2):R t =1.15min;MS(ESIpos):m / z=271[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=6.78(dd,1H),7.38(dd,1H),7.86(ddd,1H),7.96-8.07(m,3H),8.46-8.52(m,1H).

[0340] Intermediate 96 Ethyl [2-(2-chloroquinazolin-4-yl)hydrazino](oxo)acetate [ka] To a stirred suspension of 2-chloro-4-hydrazinylquinazoline (200 mg, 1.03 mmol) in dichloromethane (2 mL) was added triethylamine (0.43 mL, 3.08 mmol). At -5 °C, ethyl chloro(oxo)acetate (132 μL, 1.18 mmol) was added dropwise. The reaction mixture was stirred at -5 °C to 0 °C for 1 h. The precipitate was filtered off and washed with a small amount of water. The precipitate in the filtrate was filtered again, and the second filtrate and the second precipitate were combined and the pH was adjusted to 6 with hydrochloric acid (0.5 M HCl, 0.6 mL). Dichloromethane (40 mL) was added, the layers were separated, and the aqueous phase was extracted with dichloromethane. The combined organic phases were washed twice with water, dried over magnesium sulfate, and concentrated to give about 138 mg of the title compound containing about 0.35 moles of trimethylamine, which was used in the next step without purification. LC-MS (Method 1):R t =0.81 min;MS(ESIpos):m / z=295[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.32(t,3H),4.33(q,2H),7.49-7.65(m,2H),7.79(br s,1H),8.20(br d,1H),10.16(br s,2H).

[0341] Intermediate 97 Ethyl 5-oxo-5,6-dihydro[1,2,4]triazolo[1,5-c]quinazoline-2-carboxylate [ka] Ethyl [2-(2-chloroquinazolin-4-yl)hydrazino](oxo)acetate (13.6 g, 46.0 mmol) was stirred at reflux in acetic acid (136 mL) for 6 hours. The reaction mixture was then cooled to room temperature and diluted with ice-cold water. The precipitate was filtered, and the solid was washed with water and petroleum ether to give the title compound without further purification.

[0342] Intermediate 98 Ethyl 5-chloro[1,2,4]triazolo[1,5-c]quinazoline-2-carboxylate [ka] Ethyl 5-oxo-5,6-dihydro[1,2,4]triazolo[1,5-c]quinazoline-2-carboxylate (11.4 g, 46.4 mmol) and N,N-diisopropylethylamine (36.0 g, 278 mmol) were stirred in POCl3 (114 mL). The reaction mixture was heated to reflux for 4 h. The reaction mixture was cooled to rt and concentrated under reduced pressure. The crude mixture was diluted with DCM (200 mL) and ice-cold water. The aqueous phase was extracted with dichloromethane, and the combined organic phases were dried (sodium sulfate), filtered, and concentrated under reduced pressure to give the title compound without further purification.

[0343] Intermediate 99 Ethyl 5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-2-carboxylate [ka] Ethyl 5-chloro[1,2,4]triazolo[1,5-c]quinazoline-2-carboxylate (500 mg, 1.81 mmol), (3R)-3-aminoazepan-2-one (255 mg, 1.99 mmol), and N,N-diisopropylethylamine (630 μL, 3.6 mmol) in DMF (8.1 mL) were stirred at 60° C. for 2 hours. The reaction was cooled to rt and diluted with water. The solid was filtered, washed with water, and dried under reduced pressure at 60° C. to give 486 mg (73% yield) of the title compound. LC-MS (Method 2):R t =1.08min;MS(ESIpos):m / z=369[M+H] + 1H-NMR(400MHz,DMSO-d6):δ[ppm]=1.26-1.35(m,1H),1.39(t,3H),1.48-1.61(m,1H),1.79-1.94(m,2H),1.97-2.06(m,1H),2.26-2.35(m,1H),3. 10-3.21(m,1H),3.30-3.41(m,1H),4.47(q,2H),4.82(dd,1H),7.48(ddd ,1H),7.66-7.71(m,1H),7.74-7.80(m,2H),8.24(dd,1H),8.29(dd,1H).

[0344] Intermediate 100 7-Fluoro-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Ethyl (2-cyano-6-fluorophenyl)carbamate (200 mg, 961 μmol) and 3-fluorobenzohydrazide (178 mg, 1.15 mmol) in DMF (2.1 mL) were stirred at 120° C. overnight. The reaction was cooled to rt and diluted with water. The solid was filtered, washed with water, and dried under reduced pressure at 60° C. to give 240 mg (84% yield) of the title compound without further purification. LC-MS (method 2): Rt=0.64 min; MS (ESIpos): m / z=299[M+H] +

[0345] The following intermediates were prepared similarly:

[0346] [Table 1A] [Table 1B] [Table 1C] [Table 1D] [Table 1E] [Table 1F] [Table 1G] [Table 1H] [Table 1I] [Table 1J] [Table 1K] [Table 1L] [Table 1M]

[0347] Intermediate 133 5-chloro-7-fluoro-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 7-Fluoro-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (100 mg, 335 μmol) was solubilized in phosphorus(V) oxychloride (1.1 mL, 12 mmol), N,N-diisopropylethylamine (580 μL, 3.4 mmol) was carefully added, and the mixture was stirred at 110°C overnight. The reaction mixture was cooled to rt, poured onto ice, and stirred for 1 h. The solid was filtered, washed with water, and dried under reduced pressure at 60°C to give 91.0 mg of the title compound (97% purity, 83% yield). The compound was used without further purification. LC-MS (Method 2):R t=1.40min;MS(ESIpos):m / z=317[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=7.43-7.50(m,1H),7.68(td,1H),7.84-7.92(m,2H),8.00(ddd,1H),8.15(dt,1H),8.31-8.37(m,1H).

[0348] The following intermediates are the same as those used in the preparation:

[0349] Table 2A Table 2B Table 2C Table 2D Table 2E Table 2F Table 2G

Table 2H

Table 2I

[0350] Intermediate 166 Benzyl 6-{[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-5-oxo-1,4-diazepane-1-carboxylate [ka] 5-Chloro-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazoline (211 mg, 739 μmol), benzyl 6-amino-5-oxo-1,4-diazepane-1-carboxylate (292 mg, 1.11 mmol), and N,N-diisopropylethylamine (260 μL, 1.5 mmol) were stirred in DMSO (3.0 mL) at 60° C. for 2 h. The mixture was cooled to RT and diluted with water. The solid was filtered, washed with water, and dried under reduced pressure at 60° C. to give 182 mg of the title compound (55% purity, 26% yield), which was used without further purification. LC-MS (method 2): Rt=1.08 min; MS (ESIpos): m / z=512[M+H] +

[0351] Intermediate 167 Benzyl 6-{[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-5-oxo-1,4-diazepane-1-carboxylate, Enantiomer 1 [ka] Chiral HPLC separation of benzyl 6-{[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-5-oxo-1,4-diazepane-1-carboxylate was performed (instrument: Labomatic HD5000, Labocord-5000; Gilson GX-241, Labcol Vario 4000; column: Chiralpak IA 5μ 250 × 30 mm; eluent: methanol + 0.1% (v / v) diethylamine (99%) / ethanol 50:50%; flow rate: 40.0 mL / min; UV 254 nm).

[0352] Retention time of enantiomer 1: 5.73 min; [α] 20 D :-96°(c=1) in DMSO. Instrument: Agilent HPLC 1260; Column: Chiralpak IA 3μ 100 x 4,6 mm; Eluent: Methanol + 0.1% (v / v) diethylamine (99%) / ethanol 50:50; Flow rate: 1.4 mL / min; Temperature: 25 °C; DAD 254 nm

[0353] Intermediate 168 Benzyl 6-{[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-5-oxo-1,4-diazepane-1-carboxylate, Enantiomer 2 [ka] The title compound was prepared as described for Intermediate 162. Retention time of enantiomer 2: 9.64 min; [α] 20 D :+95°(c=1) in DMSO

[0354] The following intermediates were prepared similarly to intermediate 161:

[0355] [Table 3A] [Table 3B]

[0356] Intermediate 173 Ethyl (2-chloro-6-cyanophenyl)carbamate [ka] 2-Amino-3-chlorobenzonitrile (928 mg, 6.08 mmol) in ethyl carbonochloridate (9.3 mL, 97 mmol) was stirred at reflux for 48 h. The reaction mixture was cooled to rt and concentrated under reduced pressure to give 1.36 g (99% yield) of the title compound, which was used without further purification. LC-MS (Method 2):R t =0.89min;MS(ESIpos):m / z=225[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.23(t,3H),4.13(q,2H),7.49(t,1H),7.89(ddd,2H),9.71(br s,1H).

[0357] Intermediate 174 Ethyl [2-cyano-6-(trifluoromethyl)phenyl]carbamate [ka] 2-Amino-3-(trifluoromethyl)benzonitrile (500 mg, 2.69 mmol) in ethyl carbonochloridate (3.0 mL, 31 mmol) was stirred at reflux for 7 days. The mixture was cooled to rt and concentrated under reduced pressure to give 621 mg (90% yield) of the title compound, which was used without further purification. LC-MS (Method 2):R t =1.01 min;MS(ESIpos):m / z=259[M+H] +

[0358] Intermediate 175 Ethyl (2-cyano-6-methoxyphenyl)carbamate [ka] 2-Amino-3-methoxybenzonitrile (500 mg, 3.37 mmol) in ethyl carbonochloridate (4.8 mL, 51 mmol) was stirred at reflux for 18 hours. The reaction mixture was cooled to rt and concentrated under reduced pressure to give 450 mg (61% yield) of the title compound, which was used without further purification. LC-MS (method 2): Rt=0.85 min; MS (ESIpos): m / z=221[M+H] + 1 H NMR(400MHz,DMSO-d6)δppm=9.13(br s,1 H),7.31-7.52(m,3 H),4.08(q,2 H),3.83(s,3 H),1.20(t,3 H).

[0359] Intermediate 176 2-Amino-3-cyclopropylbenzonitrile [ka] 2-Amino-3-bromobenzonitrile (500 mg, 2.54 mmol) was solubilized in 1,4-dioxane (27 mL). Cyclopropylboronic acid (262 mg, 3.05 mmol), cesium carbonate (3.31 g, 10.2 mmol), and bis(diphenylphosphino)ferrocene (dichloropalladium(II)) were added. * Dichloromethane complex (414 mg, 508 μmol) was added and the reaction was stirred at 130 °C for 10 minutes under microwave irradiation. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The crude material was purified by flash column chromatography to give 275 mg of the title compound (91% purity, 62% yield). LC-MS (Method 2):R t =1.04min;MS(ESIpos):m / z=159[M+H] +

[0360] Intermediate 177 Ethyl (2-cyano-6-cyclopropylphenyl)carbamate [ka] 2-Amino-3-cyclopropylbenzonitrile (275 mg, 1.74 mmol) in ethyl carbonochloridate (2.5 mL, 26 mmol) was stirred at reflux for 4 h. The reaction mixture was cooled to rt and concentrated under reduced pressure to give 380 mg of the title compound (85% purity, 81% yield), which was used without further purification. LC-MS (Method 2):R t =1.00min;MS(ESIneg):m / z=229[MH] -

[0361] Intermediate 178 Ethyl (2-bromo-6-cyanophenyl)carbamate [ka] 2-Amino-3-bromobenzonitrile (5.00 g, 25.4 mmol) in ethyl carbonochloridate (29 mL, 300 mmol) was stirred at reflux for 18 hours. The mixture was cooled to RT and concentrated under reduced pressure to give 6.20 g (84% purity, 76% yield) of the title compound, which was used without further purification. LC-MS (Method 2):R t =0.90min;MS(ESIpos):m / z=269[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.23(br t,3H),4.13(q,2H),7.41(t,1H),7.91(dd,1H),8.00-8.12(m,1H),9.66(br s,1H).

[0362] Intermediate 179 Ethyl (2,4-dibromo-6-cyanophenyl)carbamate [ka] 2-Amino-3,5-dibromobenzonitrile (750 mg, 2.72 mmol) in ethyl carbonochloridate (5.0 mL, 52 mmol) was stirred at reflux for 18 hours. The mixture was concentrated under reduced pressure to give 851 mg of the title compound (66% purity, 59% yield), which was used without further purification. LC-MS (method 2): Rt=1.07 min; MS (ESIpos): m / z=347[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.29(t,3H),4.19(q,2H),8.32(d,1H),8.42(d,1H),9.78(br s,1H).

[0363] Intermediate 180 Ethyl (2-cyano-5-methoxyphenyl)carbamate [ka] 2-Amino-4-methoxybenzonitrile (100 mg, 675 μmol) in ethyl carbonochloridate (1.4 mL, 15 mmol) was stirred for 18 h at 100° C. The reaction mixture was cooled to rt and concentrated under reduced pressure to give 406 mg (74% yield) of the title compound, which was used without further purification. LC-MS (method 2): Rt=0.96 min; MS (ESIpos): m / z=221[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.24(t,3H),3.81(s,3H),4.14(q,2H),6.88(dd,1H),7.09(d,1H),7.70(d,1H),9.66(s,1H).

[0364] Intermediate 181 Ethyl (2-cyano-4,5-dimethoxyphenyl)carbamate [ka] 2-Amino-4,5-dimethoxybenzonitrile (300 mg, 1.68 mmol) in ethyl carbonochloridate (2.9 mL, 31 mmol) was stirred at reflux for 6 h. The reaction mixture was cooled to rt and concentrated under reduced pressure to give 402 mg of the title compound (100% pure, 95% yield), which was used without further purification. LC-MS (Method 2):R t =0.88 min;MS(ESIpos):m / z=251[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.23(t,3H),3.80(s,3H),3.78(s,3H)4.12(q,2H),7.05(s,1H),7.30(s,1H),9.48(br s,1H).

[0365] Intermediate 182 Ethyl [2-cyano-5-(trifluoromethyl)phenyl]carbamate [ka] 2-Amino-4-(trifluoromethyl)benzonitrile (100 mg, 537 μmol) in ethyl carbonochloridate (1.0 mL) was stirred for 18 hours at 110° C. The reaction mixture was cooled to rt and concentrated under reduced pressure to give 136 mg (98% yield) of the title compound, which was used without further purification. LC-MS (method 2): Rt=1.14 min; MS (ESIneg): m / z=257[MH] - 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.26(t,3H),4.17(q,2H),7.67(d,1H),7.93(s,1H),8.06(d,1H),10.09(s,1H).

[0366] Intermediate 183 Ethyl (5-bromo-2-cyanophenyl)carbamate [ka] 2-Amino-4-bromobenzonitrile (400 mg, 2.03 mmol) in ethyl carbonochloridate (4.0 mL, 6.1 mmol) was stirred for 18 h at 110° C. The reaction mixture was cooled to rt and concentrated under reduced pressure to give 406 mg (74% yield) of the title compound, which was used without further purification. LC-MS (method 2): Rt=1.10 min; MS (ESIpos): m / z=269[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.25(t,3H),4.16(q,2H),7.54(dd,1H),7.76(d,1H),7.79(d,1H),9.93(s,1H).

[0367] Intermediate 184 Ethyl (2-cyano-4-fluorophenyl)carbamate [ka] 2-Amino-5-fluorobenzonitrile (300 mg, 2.20 mmol) was stirred in ethyl carbonochloridate (8.7 mL) at reflux for 6 h. The mixture was cooled to rt and concentrated under reduced pressure to give 463 mg of the title compound (99% purity, 100% yield), which was used without further purification. LC-MS (Method 2):R t =0.93min;MS(ESIpos):m / z=207[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.25(t,3H),4.15(q,2H),7.49-7.55(m,1H),7.55-7.62(m,1H),7.83(dd,1H),9.74(s,1H).

[0368] Intermediate 185 Ethyl (4-chloro-2-cyanophenyl)carbamate [ka] 2-Amino-5-chlorobenzonitrile (150 mg, 983 μmol) in ethyl carbonochloridate (3.9 mL) was stirred at reflux for 6 h. The mixture was cooled to rt and concentrated under reduced pressure to give 205 mg of the title compound (100% pure, 93% yield), which was used without further purification. LC-MS (Method 2):R t =1.06min;MS(ESIneg):m / z=212[MH] - 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.25(t,3H),4.15(q,2H),7.54(d,1H),7.74(dd,1H),7.99(d,1H),9.85(s,1H).

[0369] Intermediate 186 Ethyl (2-cyano-4-methoxyphenyl)carbamate [ka] 2-Amino-5-methoxybenzonitrile (300 mg, 2.02 mmol) was stirred in ethyl carbonochloridate (8.0 mL) at reflux for 6 h. The mixture was cooled to rt and concentrated under reduced pressure to give 439 mg of the title compound (96% purity, 94% yield), which was used without further purification. LC-MS (Method 2):R t =0.92min;MS(ESIpos):m / z=221[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.23(t,3H),3.79(s,3H),4.11(q,2H),7.24(dd,1H),7.35(d,1H),7.38(d,1H),9.47(br s,1H).

[0370] Intermediate 187 Ethyl (4-bromo-2-cyanophenyl)carbamate [ka] 2-Amino-5-bromobenzonitrile (600 mg, 3.05 mmol) was stirred in ethyl carbonochloridate (12 mL) at reflux for 6 h. The mixture was cooled to rt and concentrated under reduced pressure to give 835 mg of the title compound, which was used without further purification. LC-MS (Method 2):R t =1.09min;MS(ESIneg):m / z=267[MH] - 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.25(t,3H),4.15(q,2H),7.47(d,1H),7.86(dd,1H),8.09(d,1H),9.84(s,1H).

[0371] Intermediate 188 Ethyl (2-cyano-3-fluorophenyl)carbamate [ka] 2-Amino-6-fluorobenzonitrile (500 mg, 3.67 mmol) in ethyl carbonochloridate (7.0 mL, 73 mmol) was stirred for 18 h at 100° C. The mixture was cooled to rt and concentrated under reduced pressure to give 755 mg (99% yield) of the title compound, which was used without further purification. LC-MS (Method 2):R t =0.96min;MS(ESIneg):m / z=207[MH] - 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.25(t,3H),4.16(q,2H),7.23-7.32(m,1H),7.38(d,1H),7.72(td,1H),10.00(s,1H).

[0372] Intermediate 189 Ethyl (2-cyano-3-methoxyphenyl)carbamate [ka] 2-Amino-6-methoxybenzonitrile (200 mg, 1.35 mmol) in ethyl carbonochloridate (2.4 mL, 25 mmol) was stirred at reflux for 18 h. The mixture was cooled to RT and concentrated under reduced pressure to give 276 mg of the title compound (75% purity, 70% yield), which was used without further purification. LC-MS (Method 2):R t =0.94min;MS(ESIneg):m / z=219[MH] -

[0373] Intermediate 190 Ethyl 1-(propan-2-yl)-1H-pyrazole-4-carboxylate [ka] Ethyl 1H-pyrazole-4-carboxylate (100 mg, 714 μmol) was solubilized in anhydrous DMF (1.0 mL) and the mixture was cooled to 0°C. Sodium hydride (37.1 mg, 60% purity in mineral oil, 928 μmol) was added, and the reaction mixture was stirred at 0°C for 15 minutes. 2-Iodopropane (85 μL, 860 μmol) was then added, and the mixture was stirred at room temperature for 18 hours. Saturated aqueous sodium bicarbonate was added, and the mixture was extracted with ethyl acetate. The organic layer was dried over a silicone filter and concentrated under reduced pressure to give 120 mg (92% yield) of the title compound, which was used without further purification. LC-MS (Method 2):R t =0.93min;MS(ESIpos):m / z=183[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.26(t,3H),1.41(d,6H),4.20(q,2H),4.55(spt,1H),7.84(s,1H),8.34(s,1H).

[0374] Intermediate 191 1-(Propan-2-yl)-1H-pyrazole-4-carbohydrazide [ka] Ethyl 1-(propan-2-yl)-1H-pyrazole-4-carboxylate (60.0 mg, 329 μmol) was solubilized in ethanol (1.2 mL), hydrazine monohydrate (32 μL, 660 μmol) was added, and the mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure to give 57 mg of the title compound, which was used without further purification. 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.40(d,6H),4.00-4.42(br s,2H),4.49(spt,1H),7.82(s,1H),8.17(s,1H),9.28(s,1H).

[0375] Intermediate 192 5-Methyl-1,3,4-oxadiazole-2-carbohydrazide [ka] Ethyl 5-methyl-1,3,4-oxadiazole-2-carboxylate (50.0 mg, 320 μmol) and hydrazine hydrate (78 μL, 1.6 mmol) were stirred in ethanol (2.0 mL) at rt for 18 h. The reaction mixture was then poured into water and lyophilized to give 30.0 mg (66% yield) of the title compound, which was used without further purification.

[0376] Intermediate 193 Ethyl 4-chloro-2-(trifluoromethoxy)benzoate [ka] 4-Chloro-2-(trifluoromethoxy)benzoic acid (1.00 g, 4.16 mmol) in thionyl chloride (1.7 mL, 24 mmol) was stirred at rt for 15 min. At 0 °C, ethanol (8.3 mL) was carefully added under strong gas evolution. After 30 min, the reaction was stirred at 80 °C for 2.5 h. The reaction was allowed to cool to rt and concentrated in vacuo. Saturated aqueous sodium bicarbonate solution (25 mL) was added, and the aqueous phase was extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated to give 1.12 g of the title compound, which was used in the next step without further purification. LC-MS (Method 1):R t =1.40min;MS(ESIpos):m / z=269[m+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.30(t,3H),4.33(q,2H),7.68(dd,1H),7.72-7.74(m,1H),7.97(d,1H).

[0377] Intermediate 194 Ethyl 5-chloro-2-(trifluoromethoxy)benzoate [ka] 5-Chloro-2-(trifluoromethoxy)benzoic acid (370 mg, 1.54 mmol) was dissolved in ethanol (3.5 mL). Thionyl chloride (640 μL, 8.8 mmol) was carefully added in an ice bath under gas evolution, and stirring was continued for 145 min on an ice bath. This was stirred under reflux for 2 h and at rt overnight. The reaction mixture was concentrated in vacuo. The residue was treated twice with dichloromethane and concentrated under reduced pressure to give 401 mg (97%) of the title compound, which was used in the next step without further purification. LC-MS (Method 1):R t =1.42min;MS(ESIpos):m / z=269[m+H] + 1H-NMR (400MHz, DMSO-d6): δ[ppm]=1.30(t,3H),4.33(q,2H),7.58(qd,1H),7.83(dd,1H),7.95(d,1H).

[0378] Intermediate 195 4-Chloro-2-(trifluoromethoxy)benzohydrazide [ka] Ethyl 4-chloro-2-(trifluoromethoxy)benzoate (1.12 g, 4.15 mmol) and hydrazine hydrate (2.0 mL, 42 mmol) in ethanol (18 mL) were stirred at 80° C. for 22 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. Saturated aqueous ammonium chloride solution (50 mL) was added, and it was extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated to give 579 mg of the title compound, which was used in the next step without further purification. LC-MS (Method 1):R t =0.84min;MS(ESIpos):m / z=255[m+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.54(br s,2H),7.55-7.57(m,2H),7.60-7.62(m,1H),9.65(br s,1H).

[0379] Intermediate 196 5-(trifluoromethyl)pyridine-3-carbohydrazide [ka] Ammonium 5-(trifluoromethyl)nicotinate (500 mg, 2.40 mmol) was suspended in ethanol (3.0 mL). Sulfuric acid (96%, 147 μL, 2.8 mmol) was added and stirred under reflux for 23 hours. Thionyl chloride (350 μL, 4.8 mmol) was added and the reaction mixture was stirred under reflux overnight. The reaction mixture was cooled to RT, and hydrazine hydrate (930 μL, 19 mmol) was added and stirred at RT overnight. It was then stirred under reflux overnight. The reaction mixture was cooled to RT and concentrated under reduced pressure. Water was added, and the aqueous phase was extracted four times with 1-butanol. The combined organic phases were dried over magnesium sulfate and concentrated. The residue was purified by HPLC. The collected aqueous fractions were concentrated under reduced pressure. Dichloromethane was added and evaporated under reduced pressure. This was repeated once more to give 149 mg (30%) of the title compound, which was used in the next step without further purification. LC-MS (Method 2):R t =0.56 min;MS(ESIpos):m / z=206[m+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.67(br s,2H),8.52(s,1H),9.11-9.16(m,1H),9.23-9.26(m,1H),10.20(br s,1H).

[0380] Intermediate 197 3-(Methanesulfonyl)benzohydrazide [ka] Methyl 3-(methanesulfonyl)benzoate (100 mg, 467 μmol) was dissolved in methanol (2.3 mL). Hydrazine hydrate (114 μL, 2.33 mmol) was added, and this was heated in a microwave reactor (high absorption) at 140° C. for 1 hour. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between saturated aqueous ammonium chloride and ethyl acetate. The layers were separated, and the aqueous phase was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, concentrated under reduced pressure, and dried under vacuum at 50° C. to give 54 mg (49%) of the title compound, which was used in the next step without further purification. LC-MS (Method 1):R t =0.47min;MS(ESIpos):m / z=215[m+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=3.26(s,3H),4.60(br s,2H),7.75(t,1H),8.06(ddd,1H),8.13(ddd,1H),8.33(t,1H),10.05(s,1H).

[0381] Intermediate 198 6-(trifluoromethyl)pyridine-2-carbohydrazide [ka] Methyl 6-(trifluoromethyl)pyridine-2-carboxylate (648 mg, 3.16 mmol) was dissolved in methanol (15 mL). Hydrazine hydrate (730 μL, 15 mmol) was added and heated in a microwave reactor (high absorption) at 140° C. for 1 h. The reaction mixture was cooled to rt and concentrated under reduced pressure. The residue was partitioned between saturated aqueous ammonium chloride solution (15 mL) and ethyl acetate (15 mL). The layers were separated and the aqueous phase was extracted with ethyl acetate (2 times 15 mL). The combined organic layers were washed with brine (10 mL), dried over magnesium sulfate and concentrated under reduced pressure to give the title compound 624, which was used in the next step without further purification. LC-MS (Method 2):Rt =0.67min;MS(ESIpos):m / z=206[m+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.66(br s,2H),8.08(dd,1H),8.21-8.30(m,2H),9.92(br s,1H).

[0382] Intermediate 199 5-chloro-2-(trifluoromethoxy)benzohydrazide [ka] Ethyl 5-chloro-2-(trifluoromethoxy)benzoate (397 mg, 1.48 mmol) was dissolved in ethanol (3.2 mL) and hydrazine hydrate (360 μL, 7.4 mmol) was added. This was stirred at a bath temperature of 90° C. for 70 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. This residue and the residue of a second batch synthesized under similar conditions (ethyl 5-chloro-2-(trifluoromethoxy)benzoate, 58 mg, 216 μmol) were added. The combined residues were treated twice with dichloromethane and concentrated under reduced pressure to give 374 mg of the title compound, which was used in the next step without further purification. LC-MS (Method 2):R t =0.84min;MS(ESIpos):m / z=255[m+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.54(br s,2H),7.48(qd,1H),7.58(d,1H),7.66(dd,1H),9.69(br s,1H).

[0383] Intermediate 200 4-Methoxythiophene-3-carbohydrazide [ka] Methyl 4-methoxythiophene-3-carboxylate (938 mg, 4.45 mmol) was dissolved in ethanol (32.3 mL) and hydrazine hydrate (1.33 mL, 27.2 mmol) was added. This was stirred at a bath temperature of 85° C. for 44 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to give 935 mg (99.7%) of the title compound, which was used in the next step without further purification. LC-MS (Method 2):R t =0.56min;MS(ESIpos):m / z=173[m+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=3.84(s,3H),4.49(br s,2H),6.73(d,1H),7.96(d,1H),8.76(s,1H).

[0384] Intermediate 201 Thiophene-3-carbohydrazide [ka] Methylthiophene-3-carboxylate (800 mg, 5.63 mmol) was dissolved in ethanol (16 mL) and hydrazine hydrate (1.37 mL, 28.1 mmol) was added. This was stirred under reflux for 90 hours. The reaction mixture was cooled to rt and concentrated under reduced pressure. The residue was dissolved in ethanol and concentrated to dryness. This process was repeated to give 795 mg (94%) of the title compound, which was used in the next step without further purification. 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.46(br s,2H),7.49(dd,1H),7.58(dd,1H),8.09(dd,1H),9.59(s,1H).

[0385] Intermediate 202 2-Methylthiophene-3-carbohydrazide [ka] Methyl 2-methylthiophene-3-carboxylate (350 mg, 2.24 mmol) was dissolved in 1-butanol (3.5 mL) and hydrazine hydrate (545 μL, 11.2 mmol) was added. This was stirred at a bath temperature of 120° C. for 20 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was treated with dichloromethane and concentrated to dryness under reduced pressure to give 340 mg (97%) of the title compound, which was used in the next step without further purification. LC-MS (Method 2):R t =0.57min;MS(ESIpos):m / z=157[m+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=2.62(s,3H),4.80(br s,2H),7.24-7.29(m,2H),9.36(s,1H).

[0386] Intermediate 203 5-Methylthiophene-3-carbohydrazide [ka] Methyl 5-methylthiophene-3-carboxylate (950 mg, 6.08 mmol) was dissolved in ethanol (9.5 mL) and hydrazine hydrate (1.48 mL, 30.4 mmol) was added. This was stirred under reflux for 6 hours and at room temperature over the weekend. The reaction mixture was concentrated under reduced pressure. The residue was treated with dichloromethane and concentrated to dryness to give 830 mg (87%) of the title compound, which was used in the next step without further purification. LC-MS (Method 2):R t =0.61 min;MS(ESIpos):m / z=157[m+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=2.43(d,3H),4.42(br s,2H),7.17(t,1H),7.82(d,1H),9.49(s,1H).

[0387] Intermediate 204 7-chloro-2-(pyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Ethyl (2-chloro-6-cyanophenyl)carbamate (500 mg, 2.23 mmol) and pyridine-4-carbohydrazide (366 mg, 2.67 mmol) in DMF (24 mL) were stirred at 120° C. for 18 hours. The reaction was cooled to rt, and water was added to the mixture. The suspension was filtered, washed with water, and dried under reduced pressure at 60° C. to give 582 mg (88% yield) of the title compound. LC-MS (Method 2):R t =0.55min;MS(ESIpos):m / z=298[M+H] +

[0388] The following intermediates were prepared similarly to intermediate 204:

[0389] [Table 4A] [Table 4B] [Table 4C] [Table 4D] [Table 4E] [Table 4F] [Table 4G] [Table 4H] [Table 4I] [Table 4J] [Table 4K] [Table 4L] [Table 4M] [Table 4N] [Table 4O] [Table 4P] [Table 4Q] [Table 4R]

[0390] Intermediate 253 2-(4-Methoxyphenyl)-5-oxo-5,6-dihydro[1,2,4]triazolo[1,5-c]quinazoline-10-carbonitrile [ka] 10-Bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (50 mg, 0.14 mmol), bis[cinnamylpalladium(II) chloride] (3.5 mg, 0.007 mmol), 1,1'-ferrocenediyl-bis(diphenylphosphine) (3.7 mg, 0.007 mmol), and zinc cyanide (15.8 mg, 0.14 mmol) were added to a 5 mL reaction vessel, which was then sealed and flushed with argon. Degassed N,N-dimethylacetamide (1 mL) and N,N-diisopropylethylamine (47 μL, 0.27 mmol) were added, and the mixture was heated at 80 °C overnight. The mixture was cooled to RT, and the precipitate was filtered and washed with water. The solid material was dissolved in DCM and loaded onto a 2 g silica column, the column was washed with a DCM:MeOH mixture (9:1), the eluent was collected and the solvent was removed under reduced pressure to give the title compound (43.9 mg, 0.12 mmol, 87%). LC-MS (Method 1):R t =1.00min;MS(ESIpos):m / z=318.3[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ3.85(s,3 H)7.13-7.20(m,2 H)7.70(d,1 H)7.76-8.02(m,2 H)8.15-8.21(m,2 H)

[0391] Intermediate 254 2-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5,6-dihydro[1,2,4]triazolo[1,5-c]quinazoline-10-carbonitrile [ka] 10-Bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (177 mg, 0.51 mmol), bis[cinnamylpalladium(II) chloride] (13.2 mg, 0.026 mmol), 1,1'-ferrocenediyl-bis(diphenylphosphine) (14.2 mg, 0.026 mmol), and zinc cyanide (60.2 mg, 0.51 mmol) were added to a 5 mL reaction vessel, which was then sealed and flushed with argon. Degassed N,N-dimethylacetamide (2 mL) and N,N-diisopropylethylamine (179 μL, 1.03 mmol) were added, and the mixture was heated at 80 °C overnight. The mixture was cooled to RT, diluted with DCM, washed with NaHCO (saturated aqueous solution), and the aqueous phase was extracted twice with DCM. The combined organic phases were dried by passing through a water-repellent filter and purified by RP-HPLC (column: X-Brigde C18 5μ100 × 30 mm; acetonitrile / water + 0.1% formic acid) to give the title compound (32 mg, 0.10 mmol, 19%). LC-MS (Method 1):R t =1.00min;MS(ESIpos):m / z=292.2[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ3.96(s,3 H)7.70(dd,1 H)7.81(t,1 H)7.88(d,1 H)7.99(d,1 H)8.38(s,1 H)12.47-12.70(m,1 H)

[0392] Intermediate 255 2-(4-Fluorophenyl)-5-oxo-5,6-dihydro[1,2,4]triazolo[1,5-c]quinazoline-10-carbonitrile [ka] 10-Bromo-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (157 mg, 0.43 mmol), bis[cinnamylpalladium(II) chloride] (11.3 mg, 0.022 mmol), 1,1'-ferrocenediyl-bis(diphenylphosphine) (12.1 mg, 0.022 mmol), and zinc cyanide (51.3 mg, 0.44 mmol) were added to a 5 mL reaction vessel, which was then sealed and flushed with argon. Degassed N,N-dimethylacetamide (2 mL) and N,N-diisopropylethylamine (152 μL, 0.87 mmol) were added, and the mixture was heated at 80 °C overnight. The mixture was cooled to RT, diluted with DCM, washed with NaHCO (saturated aqueous solution), and the aqueous phase was extracted twice with DCM. The combined organic phases were dried through a water-repellent filter and purified by RP-HPLC (column: X-Brigde C18 5μ100×30 mm; acetonitrile / water+0.1% formic acid) to give the title compound (53 mg, 0.16 mmol, 36%). LC-MS (Method 1):R t =1.02min;MS(ESIpos):m / z=306.1[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ7.39-7.50(m,2 H)7.73(d,1 H)7.81-7.94(m,2 H)8.28(dd,2 H)12.54-12.79(m,1 H) Intermediate 256 2-(3-Fluorophenyl)-5-oxo-5,6-dihydro[1,2,4]triazolo[1,5-c]quinazoline-10-carbonitrile [ka]

[0393] 10-Bromo-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (152 mg, 0.43 mmol), bis[cinnamylpalladium(II) chloride] (11.0 mg, 0.021 mmol), 1,1'-ferrocenediyl-bis(diphenylphosphine) (11.7 mg, 0.021 mmol), and zinc cyanide (50.0 mg, 0.43 mmol) were added to a 5 mL reaction vessel, which was then sealed and flushed with argon. Degassed N,N-dimethylacetamide (2 mL) and N,N-diisopropylethylamine (147 μL, 0.74 mmol) were added, and the mixture was heated at 80 °C overnight. The mixture was cooled to RT, diluted with DCM, washed with NaHCO (saturated aqueous solution), and the aqueous phase was extracted twice with DCM. The combined organic phases were dried through a water-repellent filter and purified by RP-HPLC (column: X-Brigde C18 5μ100×30 mm; acetonitrile / water+0.1% formic acid) to give the title compound (77 mg, 0.21 mmol, 50%). LC-MS (Method 1):R t =1.02min;MS(ESIpos):m / z=306.1[M+H] + 1 H-NMR(400MHz,DMSO-d6):δppm 7.40-7.48(m,1 H)7.65-7.76(m,2 H)7.83-7.95(m,3 H)8.09(dt,J=7.98,1.08 Hz,1 H)12.72(br s,1 H)

[0394] Intermediate 257 2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (800 mg, 4.54 mmol) and 2-(trifluoromethoxy)benzohydrazide (1.00 g, 4.54 mmol) were dissolved in DMF (16 mL). This was stirred at 120° C. for 72 hours and at 130° C. for 96 hours. The reaction mixture was cooled to rt, and water (20 mL) was added and stirred for 15 minutes. The precipitate was filtered off, washed twice with water, and dried under vacuum at 50° C. to give 1.05 g (67%) of the title compound, which was used in the next step without further purification. LC-MS (Method 1):R t =1.15 min;MS(ESIpos):m / z=347[m+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=7.40-7.48(m,2H),7.58-7.65(m,2H),7.68-7.75(m,2H),8.20(dd,1H),8.28(dd,1H),12.41(br s,1H).

[0395] The following intermediates were prepared similarly to intermediate 256:

[0396] [Table 5A] [Table 5B] [Table 5C] [Table 5D] [Table 5E] [Table 5F] [Table 5G]

[0397] Intermediate 274 2-(Imidazo[1,2-a]pyridin-7-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (700 mg, 3.97 mmol) and imidazo[1,2-a]pyridine-7-carbohydrazide (700 mg, 3.97 mmol) were suspended in DMF (20 mL). This was stirred at 120° C. for 24 hours. Imidazo[1,2-a]pyridine-7-carbohydrazide (100 mg, 0.57 mmol) was added, and this was stirred at 120° C. for 24 hours. The reaction mixture was cooled to rt and poured into water (100 mL). The precipitate was filtered off, washed four times with water, and dried under vacuum at 50° C. to give 1.02 g of crude product. 100 mg of the crude product in DMF (2.5 mL) was stirred at 120° C. over the weekend. The reaction mixture was cooled to rt and poured into water. The precipitate was filtered off, washed three times with water, and dried under vacuum at 50° C. to give 88 mg of crude product. All two crude products were combined and stirred in DMF (20 mL) at 130° C. for 120 h. The reaction mixture was allowed to reach rt and poured into water. The precipitate was filtered off, washed three times with water, and dried under vacuum at 50° C. to give 919 mg of the title compound, which was used in the next step without further purification. LC-MS (Method 2):R t =.56 min;MS(ESIpos):m / z=303[m+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=7.42-7.49(m,2H),7.66(dd,1H),7.70-7.77(m,2H),8.11(s,1H),8.27(dd,1H),8.34(s,1H),8.72(d,1H),12.39(br s,1H).

[0398] Intermediate 275 Methyl 2-(4-methoxyphenyl)-5-oxo-5,6-dihydro[1,2,4]triazolo[1,5-c]quinazoline-10-carboxylate [ka] 10-Bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (396 mg, 1.07 mmol) was suspended in methanol / THF (13.2 mL, 10:1) in an autoclave (50 mL). Triethylamine (300 μL, 2.1 mmol) and 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (90 mg, 110 μmol) were added. The reaction mixture was purged with carbon monoxide three times at room temperature. The autoclave was then filled with carbon monoxide up to 12.7 bar and stirred at room temperature for 30 min. The pressure remained constant at 12.6 bar, allowing the carbon monoxide to be released, and the autoclave was evacuated under vacuum. The autoclave was filled with carbon monoxide up to 14.2 bar at an internal temperature of 20 °C. The reaction mixture was stirred at an internal temperature of 100° C. for 24 hours. The reaction mixture was cooled to room temperature and carbon monoxide was removed. The reaction mixture was concentrated and digested in ethyl acetate / dichloromethane. The insoluble residue was filtered off, washed with ethyl acetate and a few drops of dichloromethane, and the filtrate was concentrated under reduced pressure to give 326 mg (87%) of the title product. LC-MS (Method 2):R t =0.67min;MS(ESIpos):m / z=351[M+H] + 1 H-NMR(400 MHz,DMSO-d6)δ[ppm]=3.85(s,3H),4.01(s,3H),7.11-7.17(m,2H),7.43(dd,1H),7.54(dd,1H),7.76(dd,1H),8.08-8.14(m,2H).

[0399] Intermediate 276 5,7-Dichloro-2-(pyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 7-Chloro-2-(pyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (482 mg, 1.62 mmol) in POCl (5.0 mL, 54 mmol) and N,N-diisopropylethylamine (2.8 mL, 16 mmol) was stirred overnight at 110° C. The mixture was poured onto ice, and the solid was filtered, washed with water, and dried under reduced pressure at 60° C. to give 530 mg of the title compound (39% purity, 40% yield), which was used without further purification. LC-MS (Method 2):R t =1.19min;MS(ESIpos):m / z=316[M+H] +

[0400] The following intermediates were prepared similarly to intermediate 275:

[0401] [Table 6A] [Table 6B] [Table 6C] [Table 6D] [Table 6E] [Table 6F] [Table 6G] [Table 6H] [Table 6I] [Table 6J] [Table 6K] [Table 6L] [Table 6M] [Table 6N] [Table 6O] [Table 6P] [Table 6Q] [Table 6R] [Table 6S]

[0402] Intermediate 329 5-chloro-2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazoline [ka] 2-[2-(Trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (600 mg, 1.73 mmol) was suspended in phosphorus trichloride (4.8 mL, 51.13 mmol). N,N-Diisopropylethylamine (3.0 mL, 17 mmol) was added, and the mixture was stirred at 110° C. for 4.5 h. The reaction mixture was cooled to rt, poured into ice / water, and stirred for 30 min. The precipitate was filtered, washed three times with water, and dried overnight under vacuum at 50° C. to give 585 mg (93%) of the title compound, which was used in the next step without further purification. LC-MS (Method 2):R t =1.48min;MS(ESIpos):m / z=365[m+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=7.61-7.69(m,2H),7.72-7.77(m,1H),7.89(ddd,1H),8.00(ddd,1H),8.05-8.08(m,1H),8.40(dd,1H),8.50(dd,1H).

[0403] The following intermediates were prepared similarly to intermediate 328:

[0404] [Table 7A] [Table 7B] [Table 7C] [Table 7D] [Table 7E] [Table 7F]

[0405] Intermediate 346 5-chloro-2-(imidazo[1,2-a]pyridin-7-yl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(Imidazo[1,2-a]pyridin-7-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (110 mg, 364 μmol) was suspended in phosphorus trichloride (1.0 mL, 10.7 mmol). N,N-Diisopropylethylamine (630 μL, 3.6 mmol) was added, and the mixture was stirred at 110° C. for 6 hours. Phosphorus trichloride (1.0 mL, 10.7 mmol) was added, and the mixture was stirred at 110° C. for 6 hours. The reaction mixture was cooled to rt, poured into ice / water, and stirred for several minutes. The precipitate was filtered, washed three times with water, and dried under vacuum at 50° C. overnight to give 89 mg of the title compound, which was used in the next step without further purification. LC-MS (Method 2):R t =1.04min;MS(ESIpos):m / z=321[m+H] +

[0406] Intermediate 347 Methyl 5-chloro-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazoline-10-carboxylate [ka] Methyl 2-(4-methoxyphenyl)-5-oxo-5,6-dihydro[1,2,4]triazolo[1,5-c]quinazoline-10-carboxylate (20.0 mg, 57.1 μmol) was solubilized in POCl (190 μL, 2.0 mmol), N,N-diisopropylethylamine (99 μL, 570 μmol) was carefully added, and the mixture was stirred at 110°C for 4 h. The mixture was cooled to RT and poured onto ice. The solid was filtered, washed with water, and dried under reduced pressure at 60°C to give 14.5 mg of the title compound (70% purity, 48% yield), which was used without further purification. LC-MS (Method 2):R t =1.34min;MS(ESIpos):m / z=369[M+H] +

[0407] Intermediate 348 Benzyl (6R)-6-{[7-chloro-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-5-oxo-1,4-diazepane-1-carboxylate [ka] 5,7-Dichloro-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazoline (75.0 mg, 235 μmol), benzyl (6R)-6-amino-5-oxo-1,4-diazepane-1-carboxylate hydrochloride (77.5 mg, 258 μmol), and N,N-diisopropylethylamine (120 μL, 700 μmol) in DMSO (1.6 mL) were stirred at 60° C. for 2 hours. The reaction was quenched with water, and the solid was filtered, washed with water, and dried under reduced pressure at 60° C. to give 100 mg of the title compound (95% purity, 74% yield). LC-MS (Method 2):R t =1.17 min;MS(ESIpos):m / z=546[M+H] + 1 H-NMR (400 MHz, DMSO-d6): δ [ppm] = 3.01-3.21 (m, 1H), 3.37-3.56 (m, 2H), 3.96 (s, 3H), 4.06-4.16 (m, 1H), 4.35-4.50 (m, 1H), 4.89-5.21 (m, 3H), 6.98-7.45 (m, 6H), 7.86 (br d, 1H), 8.07 (d, 2H), 8.22 (dd, 1H), 8.31-8.44 (m, 1H), 8.49 (s, 1H). (One proton is invisible.)

[0408] The following intermediates were prepared similarly to intermediate 347:

[0409] [Table 8A] [Table 8B] [Table 8C] Table 8D Table 8E Table 8F Table 8G Table 8H

Table 8I

Table 8L

Table 8M

Table 8O

Table 8P

Table 8Q

Table 8R

Table 8S

[0410] Intermediate 387 Benzyl (6R)-5-oxo-6-({2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepane-1-carboxylate [ka] 5-Chloro-2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazoline (87.0 mg, 239 μmol) was suspended in DMSO (0.95 mL). Benzyl (6R)-6-amino-5-oxo-1,4-diazepane-1-carboxylate hydrochloride (1:1) (107 mg, 358 μmol) and N,N-diisopropylethylamine (125 μL, 720 μmol) were added. This was stirred at 60°C for 2 hours. The reaction mixture was cooled, and the solid was filtered off, washed with DMSO (2 × 0.5 mL), and washed twice with water. This was dried under vacuum at 50°C to give 67.5 mg (48%) of the title product, which was used in the next step without further purification. The filtrate was purified by HPLC to give 23 mg (16%) of the title product. LC-MS (Method 2):R t =1.47min;MS(ESIpos):m / z=592[m+H] + [α] 20 D :-83.2°(c=1.00,DMSO) 1 H-NMR (400 MHz, DMSO-d6): δ [ppm] = 2.91-3.11 (m, 1H), 3.11-3.32 (m, 2H and water signals), 3.45-3.56 (m, 1H), 4.12-4.30 (m, 1H), 4.63-4.81 (m, 1H), 4.87-4.99 (m, 1H), 5.22 (br s, 2H), 7.13-7.53 (m, 6H), 7.59-7.69 (m, 3H), 7.69-7.90 (m, 3H), 8.29 (br d, 1H), 8.37 (dd, 1H), 8.41-8.56 (m, 1H).

[0411] Intermediate 388 (3R)-3-{[2-(4-methoxyphenyl)-7-(prop-1-en-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one [ka] (3R)-3-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (100 mg, 208 μmol) and XPhosPd G4 (89.4 mg, 104 μmol) were dissolved in 1,4-dioxane (5.0 mL), Na2CO3 (270 μL, 2.0 M, 540 μmol) was added, and the mixture was degassed by bubbling argon through it for 5 minutes. After degassing, 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (69.8 mg, 415 μmol) was added, and the reaction tube was sealed. The mixture was stirred at 100 °C for 2 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with EtOAc. The organic layer was dried (silica filter) and concentrated under reduced pressure. The crude material was purified by preparative HPLC to give 34.2 mg of the title compound (95% purity, 35% yield). LC-MS (Method 2):R t =1.49min;MS(ESIpos):m / z=443[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=1.21-1.40(m,2H),1.49-1.64(m,1H),1.80-1.96(m,2H),1.97-2.14(m,2H),3.19(br s,1H),3.86(s,3H),4.70-4.88(m,1H),5.20(s,1H),5.30(s,1H),7.14(d,2H) ,7.36-7.44(m,1H),7.57-7.76(m,1H),7.58-7.94(m,1H),8.14-8.27(m,4H).

[0412] Intermediate 389 (3R)-3-{[2-(4-methoxyphenyl)-7-(3,3,3-trifluoroprop-1-en-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one [ka] (3R)-3-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (20.0 mg, 41.5 μmol) and Xphos Pd G4 (1.79 mg, 2.08 μmol) were solubilized in 1,4-dioxane (1.0 mL), and Na2CO3 (54 μL, 2.0 M, 110 μmol) was added. The mixture was degassed by bubbling argon through it for 5 minutes. After degassing, 4,4,5,5-tetramethyl-2-(3,3,3 trifluoroprop-1-en-2-yl)-1,3,2-dioxaborolane (18 μL, 83 μmol) was added, and the reaction tube was sealed. The mixture was stirred at 100 °C for 18 hours. The reaction was cooled to rt, and water was added. The mixture was extracted with EtOAc and the combined organic layers were dried (silica filter) and concentrated under reduced pressure to give 29 mg of the title compound, which was used without further purification. LC-MS (method 2): Rt=1.48 min; MS (ESIpos): m / z=497[M+H] +

[0413] Intermediate 390 Methyl 3-amino-N-(tert-butoxycarbonyl)-D-alaninate [ka] Under a nitrogen atmosphere, to a solution of 3-amino-N-(tert-butoxycarbonyl)-D-alanine (220 g, 1.08 mol, 1.00 equiv.) in MeOH (3.60 L) and DCM (360 mL) cooled to 10 °C, diazomethyl(trimethyl)silane (2.0 M in n-hexane, 583 mL, 1.08 equiv.) was added dropwise at 10-20 °C. The mixture was stirred at 10-20 °C for 20 h and concentrated under reduced pressure at 25 °C. MTBE was added to the residue, stirred for 30 min, filtered, and the filtrate was concentrated under reduced pressure at 25 °C to give 290 g of the target compound (70% purity, 43% yield), which was used without further purification. 1H NMR (CDCl3): δ[ppm]=5.45-5.64(m,1H),4.12-4.22(m,1H),3.64(s,3H),2.93(d,J=4.4 Hz,2H),1.33(s,9H).

[0414] Intermediate 391 9H-Fluoren-9-ylmethyl(2-oxoethyl)carbamate [ka] A mixture of 9H-fluoren-9-ylmethyl (2-hydroxyethyl)carbamate (200 g, 706 mmol, 1.00 equiv.) and 2-iodoxybenzoic acid (260 g, 929 mmol, 1.32 equiv.) in ethyl acetate (2.00 L) was stirred at 75-78 °C under a nitrogen atmosphere. DMSO (110 g, 1.41 mol, 110 mL, 2.00 equiv.) was added, and the mixture was stirred at 75-78 °C for 15 h. The reaction mixture was cooled to 10-20 °C, and ethyl acetate (4.00 L) was added. This mixture was stirred for 30 min, filtered, and the filtrate was washed with sodium thiosulfate solution (10%), saturated sodium bicarbonate solution, and brine. The organic layer was dried and concentrated under reduced pressure. The residue was triturated with MTBE, filtered, and the solid was dried under reduced pressure to give the target compound (683 g, 86% yield), which was used without further purification. 1H NMR (400 MHz, CDCl3): δ[ppm]=9.66(s,1H),7.78(d,J=7.6 Hz,2H),7.61(d,J=7.6 Hz,2H),7.42(t,J=7.6 Hz,2H),7.33(t,J=7.6 Hz,2H),5.48(s,1H),4.44(d,J=7.2 Hz,2H),4.24(t,J=6.8 Hz,1H),4.15(d,J=5.2 Hz,2H).

[0415] Intermediate 392 Methyl N-(tert-butoxycarbonyl)-3-[(2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}ethyl)amino]-D-alaninate [ka] To a mixture of 9H-fluoren-9-ylmethyl (2-oxoethyl)carbamate (310 g, 1.10 mol, 1.00 equiv.) and methyl 3-amino-N-(tert-butoxycarbonyl)-D-alaninate (434 g, 1.37 mol, 1.24 equiv.) in DCM (3.10 L) cooled to 5 °C, trimethoxymethane (352 g, 3.31 mol, 363 mL, 3.01 equiv.) was added at 5-15 °C and stirred for 1 h. Sodium triacetoxyborohydride (350 g, 1.65 mol, 1.50 equiv.) was added to the mixture under a nitrogen atmosphere, which was stirred for 1 h at 5-15 °C. Saturated sodium bicarbonate solution was added to the mixture and stirred for 1 h. The aqueous phase was extracted with ethyl acetate, and the organic phase was dried and concentrated under reduced pressure. The residue was purified by flash chromatography to give 297 g (55% yield) of the target compound. 1H NMR (400 MHz, CDCl3): δ[ppm]=7.76(d,J=7.2 Hz,2H),7.60(d,J=7.2 Hz,2H),7.40(t,J=7.2 Hz,2H),7.31(t,J=7.2 Hz,2H),5.43(d,J=6.8 Hz,1H),5.29(s,1H),4.32-4.52(m,3H),4.22(t,J=6.4 Hz,1H),3.73(s,3H),3.20-3.32(m,1H),3.03-3.12(m,1H),2.91-3.01(m,2H),2.66-2.85(m,2H),1.45(s,9H).

[0416] Intermediate 394 Benzyl (6R)-6-[(tert-butoxycarbonyl)amino]-5-oxo-1,4-diazepane-1-carboxylate [ka] A mixture of methyl 3-{[(benzyloxy)carbonyl](2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}ethyl)amino}-N-(tert-butoxycarbonyl)-D-alaninate (300 g, 486 mmol, 1.00 equiv.) and piperidine (331 g, 3.89 mol, 384 mL, 8.00 equiv.) in DMF (3.00 L) was stirred at 15-20 °C for 39 h. The reaction mixture was poured into water and extracted three times with ethyl acetate. The combined organic phases were washed twice with brine, dried, and concentrated under reduced pressure. The residue was purified by flash chromatography to give 127 g of the target compound (95% purity, 68% yield). 1H NMR(400 MHz, CDCl3):δ[ppm]=7.29-7.62(m,5H),6.59(s,1H),5.82(s,1H),5.22(s, 2H),4.18-4.62(m,3H),3.22-3.52(m,2H),2.84-3.05(m,2H),1.49(s,9H).

[0417] Intermediate 395 Benzyl (6R)-6-amino-5-oxo-1,4-diazepane-1-carboxylate hydrochloride (1:1) [ka] To a mixture of benzyl (6R)-6-[(tert-butoxycarbonyl)amino]-5-oxo-1,4-diazepane-1-carboxylate (127 g, 349 mmol, 1.00 equiv.) in dioxane (500 mL), hydrogen chloride (4.0 M in dioxane, 437 mL, 5.00 equiv.) was added at 15-25 °C, and the mixture was stirred at 15-25 °C for 21 h. MTBE was added to the reaction mixture, which was stirred for 15 min, filtered, and the solid was dried under reduced pressure to give 103.06 g of the target compound (100% purity, 98% yield). 1H NMR (400 MHz, DMSO-d6): δ[ppm]=8.45(s,4H),7.25-7.51(m,5H),5.14(s,2H),4.25(d,J=12.0 Hz,2H),4.10(d,J=12.8 Hz,1H),3.36-3.45(m,1H),3.10-3.29(m,2H),2.82-3.07(br s,1H).

[0418] Intermediate 396 Ethyl 2-(difluoromethoxy)benzoate [ka] Thionyl dichloride (160 μL, 2.2 mmol) was added dropwise to 2-(difluoromethoxy)benzoic acid (100 mg, 532 μmol) under argon, DCM (0.5 mL) was added, and the mixture was stirred at rt for 30 min. The mixture was cooled to 0 °C, and ethanol (880 μL) was added dropwise. The mixture was stirred at 0 °C for 30 min, at reflux for 1 h, and at rt overnight. The mixture was concentrated under reduced pressure to give 95.0 mg (83% yield) of the target compound, which was used without further purification. LC-MS (method 1): Rt=1.17 min; MS (ESIpos): m / z=217[M+H] + 1H-NMR (400MHz, DMSO-d6): δ[ppm]=1.30(t,3H),4.30(q,2H),7.18(t,1H),7.32(dd,1H),7.40(td,1H),7.66(ddd,1H),7.83(dd,1H).

[0419] Intermediate 397 Ethyl 5-fluoro-2-(trifluoromethoxy)benzoate [ka] 5-Fluoro-2-(trifluoromethoxy)benzoic acid (661 mg, 2.95 mmol) was solubilized in ethanol (6.6 mL) under argon, cooled to 0 °C, thionyl dichloride (1.2 mL, 17 mmol) was added dropwise, and the mixture was stirred at reflux for 6 h. The mixture was concentrated under reduced pressure to give 660 mg (89% yield) of the target compound, which was used without further purification. 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.30(t,3H),4.33(q,2H),7.58-7.66(m,2H),7.75(ddd,1H).

[0420] Intermediate 398 Ethyl 4-methoxy-2-(trifluoromethoxy)benzoate [ka] 4-Methoxy-2-(trifluoromethoxy)benzoic acid (100 mg, 423 μmol) was solubilized in ethanol (950 μL) under argon, cooled to 0°C, thionyl dichloride (180 μL, 2.4 mmol) was added dropwise, and the mixture was stirred at reflux for 6 h. The mixture was concentrated under reduced pressure to give 110 mg of the target compound (99% pure, 97% yield), which was used without further purification. 1H-NMR (400MHz, DMSO-d6): δ[ppm]=1.29(t,3H),3.87(s,3H),4.28(q,2H),7.00-7.03(m,1H),7.12(dd,1H),7.94(d,1H).

[0421] Intermediate 399 Ethyl 4-fluoro-2-(trifluoromethoxy)benzoate [ka] Thionyl dichloride (1.7 mL, 23 mmol) was added dropwise to 4-fluoro-2-(trifluoromethoxy)benzoic acid (900 mg, 4.02 mmol) under argon, and the mixture was stirred at rt for 15 minutes. The mixture was cooled to 0 °C, and ethanol (9.0 mL) was added dropwise. The mixture was stirred at 80 °C for 2 hours. The mixture was evaporated, diluted with saturated sodium bicarbonate solution, and extracted three times with EtOAc. The combined organic layers were washed with water, dried, and concentrated under reduced pressure to give 1.08 g of the target compound, which was used without further purification. 1 H-NMR (500MHz, DMSO-d6): δ[ppm]=1.31(t,3H),4.32(q,2H),7.46(ddd,1H),7.53-7.56(m,1H),8.04(dd,1H).

[0422] Intermediate 400 Ethyl 4-bromo-2-(trifluoromethoxy)benzoate [ka] 4-Bromo-2-(trifluoromethoxy)benzoic acid (900 mg, 3.16 mmol) was solubilized in ethanol (7.1 mL) under argon and cooled to 0 °C. Thionyl dichloride (1.3 mL, 18 mmol) was added dropwise, and the mixture was stirred at reflux for 2 h and at rt overnight. The mixture was concentrated under reduced pressure to give 1.14 g of the target compound, which was used without further purification. 1H-NMR (400MHz, DMSO-d6): δ[ppm]=1.30(t,3H),4.32(q,2H),7.81(dd,1H),7.83-7.84(m,1H),7.89(d,1H).

[0423] Intermediate 403 Ethyl 2-(1,1,2,2-tetrafluoroethoxy)benzoate [ka] 2-(1,1,2,2-Tetrafluoroethoxy)benzoic acid (500 mg, 2.10 mmol) was dissolved in ethanol (10 mL) under argon and cooled to 0 °C. Thionyl dichloride (0.873 mL, 12 mmol) was added dropwise, and the mixture was stirred at 0 °C for 5 minutes, at reflux for 6 hours, and at room temperature overnight. The mixture was concentrated under reduced pressure to give 544 mg (97% yield) of the title compound, which was used in the next step without further purification. LC-MS (Method 2):R t =1.27min;MS(ESIpos):m / z=267[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.29(t,3H),4.30(q,2H),6.77(tt,1H),7.42-7.46(m,1H),7.50(td,1H),7.71(ddd,1H),7.87(dd,1H).

[0424] Intermediate 404 2-(Dimethylamino)benzohydrazide [ka] Methyl 2-(dimethylamino)benzoate (1.00 g, 5.58 mmol) was solubilized in propan-1-ol (12 mL), hydrazine hydrate (2.0 mL, 42 mmol) was added, and the mixture was stirred at 100° C. for 48 h. The mixture was concentrated under reduced pressure to give 1.00 g of the target compound (94% purity, 94% yield), which was used without further purification. LC-MS (method 2): Rt=0.69 min; MS (ESIpos): m / z=180[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=2.70(s,6H),4.48(br s,2H),6.97(td,1H),7.08(dd,1H),7.34(ddd,1H),7.46(dd,1H),9.78(s,1H).

[0425] Intermediate 405 2-(Difluoromethoxy)benzohydrazide [ka] Ethyl 2-(difluoromethoxy)benzoate (488 mg, 2.26 mmol) was solubilized in ethanol (4.9 mL), hydrazine hydrate (550 μL, 11 mmol) was added, and the mixture was stirred at 90° C. for 20 h. The mixture was concentrated under reduced pressure to give 480 mg of the target compound (90% purity, 95% yield), which was used without further purification. LC-MS (method 2): Rt=0.60 min; MS (ESIpos): m / z=203[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.50(br s,2H),7.16(t,1H),7.21-7.25(m,1H),7.30(td,1H),7.47(dd,1H),7.51(ddd,1H),9.45(s,1H).

[0426] Intermediate 406 5-Fluoropyridine-3-carbohydrazide [ka] Methyl 5-fluoropyridine-3-carboxylate (400 mg, 2.58 mmol) was solubilized in methanol (6.0 mL), hydrazine hydrate (630 μL, 13 mmol) was added, and the mixture was stirred at 60° C. for 4 h. The mixture was concentrated under reduced pressure to give 395 mg of the target compound (100% purity, 99% yield), which was used without further purification. 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.62(br s,2H),8.04(ddd,1H),8.73(d,1H),8.85(t,1H),10.06(br s,1H).

[0427] Intermediate 407 5-Chloropyridine-3-carbohydrazide [ka] Ethyl 5-chloropyridine-3-carboxylate (770 mg, 4.15 mmol) was solubilized in propan-1-ol (12 mL), hydrazine hydrate (1.5 mL, 31 mmol) was added, and the mixture was stirred at 100° C. for 48 h. The mixture was concentrated under reduced pressure to give 705 mg of the target compound (98% purity, 97% yield), which was used without further purification. LC-MS (method 2): Rt=0.48 min; MS (ESIpos): m / z=172[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.63(br s,2H),8.25(dd,1H),8.77(d,1H),8.91(d,1H),10.06(br s,1H).

[0428] Intermediate 408 2-(Trifluoromethyl)pyridine-3-carbohydrazide [ka] Ethyl 2-(trifluoromethyl)pyridine-3-carboxylate (1.90 g, 8.67 mmol) was solubilized in propan-1-ol (15 mL), hydrazine hydrate (3.2 mL, 65 mmol) was added, and the mixture was stirred at 100° C. for 48 h. The mixture was concentrated under reduced pressure to give 705 mg of the target compound (98% purity, 97% yield), which was used without further purification. 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.58(br s,2H),7.77(dd,1H),7.96(dd,1H),8.80(dd,1H),9.72(s,1H).

[0429] Intermediate 409 5-Fluoro-2-(trifluoromethoxy)benzohydrazide [ka] Ethyl 5-fluoro-2-(trifluoromethoxy)benzoate (100 mg, 397 μmol) was solubilized in ethanol (870 μL), hydrazine hydrate (96 μL, 2.0 mmol) was added, and the mixture was stirred at 90° C. for 20 h. The mixture was concentrated under reduced pressure to give 95.0 mg of the target compound (88% purity, 89% yield), which was used without further purification. 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.54(br s,2H),7.38(dd,1H),7.45(ddd,1H),7.48-7.54(m,1H),9.68(s,1H).

[0430] Intermediate 410 5-Bromo-2-(trifluoromethoxy)benzohydrazide [ka] Ethyl 5-bromo-2-(trifluoromethoxy)benzoate (900 mg, 2.87 mmol) was solubilized in methanol (16 mL), hydrazine hydrate (1.4 mL, 29 mmol) was added, and the mixture was stirred in a microwave at 140 °C for 90 min. The reaction mixture was evaporated. The residue was partitioned between saturated ammonium chloride solution and EtOAc. The aqueous phase was extracted three times with EtOAc, and the combined organic phases were washed with water, dried, and concentrated under reduced pressure to give 770 mg (90% yield) of the target compound, which was used without further purification. LC-MS (method 2): Rt=0.86 min; MS (ESIpos): m / z=299[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.54(br s,2H),7.42(ddd,1H),7.69(d,1H),7.78(dd,1H),9.69(br s,1H).

[0431] Intermediate 411 4-Methoxy-2-(trifluoromethoxy)benzohydrazide [ka] Ethyl 4-methoxy-2-(trifluoromethoxy)benzoate (455 mg, 1.72 mmol) was solubilized in ethanol (9.1 mL), hydrazine hydrate (1.3 mL, 26 mmol) was added, and the mixture was stirred at 90° C. for 88 h. The mixture was concentrated under reduced pressure to give 455 mg of the target compound (83% purity, 88% yield), which was used without further purification. 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=3.82(s,3H),4.45(br s,2H),6.92-6.95(m,1H),7.03(dd,1H),7.49(d,1H),9.46(br s,1H).

[0432] Intermediate 412 4-Methoxy-2-(trifluoromethyl)benzohydrazide [ka] Methyl 4-methoxy-2-(trifluoromethyl)benzoate (400 mg, 1.71 mmol) was solubilized in ethanol (3.7 mL), hydrazine hydrate (830 μL, 17 mmol) was added, and the mixture was stirred at 90° C. for 92 h. The mixture was concentrated under reduced pressure to give 408 mg of the target compound (66% purity, 67% yield), which was used without further purification. LC-MS (method 2): Rt=0.70 min; MS (ESIpos): m / z=235[M+H] +

[0433] Intermediate 413 4-Fluoro-2-(trifluoromethoxy)benzohydrazide [ka] Ethyl 4-fluoro-2-(trifluoromethoxy)benzoate (350 mg, 1.39 mmol) was solubilized in 2-methylbutan-2-ol (6.1 mL, 56 mmol), hydrazine hydrate (680 μL, 14 mmol) was added, and the mixture was stirred at 80 °C for 24 h. The mixture was concentrated under reduced pressure. Saturated ammonium chloride solution was added, and this was extracted three times with EtOAc. The combined organic phases were washed with brine, dried, and concentrated under reduced pressure to give 287 mg (87% yield) of the target compound, which was used without further purification. 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.36(s,2H),6.69-6.74(m,2H),7.70(d,1H),7.96(s,1H).

[0434] Intermediate 414 4-Bromo-2-(trifluoromethoxy)benzohydrazide [ka] Ethyl 4-bromo-2-(trifluoromethoxy)benzoate (1.14 g, 87% purity, 3.17 mmol) was solubilized in ethanol (6.9 mL), hydrazine hydrate (770 μL, 16 mmol) was added, and the mixture was stirred at 90° C. for 20 h. The mixture was concentrated under reduced pressure to give 1.09 g of the target compound (65% purity, 75% yield), which was used without further purification.

[0435] 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.53(br s,2H),7.48(d,1H),7.68-7.73(m,2H),9.65(br s,1H).

[0436] Intermediate 415 4-Chloro-2-(difluoromethoxy)benzohydrazide [ka] Methyl 4-chloro-2-(difluoromethoxy)benzoate (500 mg, 2.11 mmol) was solubilized in methanol (9.0 mL), hydrazine hydrate (510 μL, 11 mmol) was added, and the mixture was stirred in a microwave at 140 °C for 90 min. The reaction mixture was evaporated. The residue was partitioned between saturated ammonium chloride solution and EtOAc. The aqueous phase was extracted three times with EtOAc, and the combined organic phases were washed with brine, dried, and concentrated under reduced pressure to give 467 mg (93% yield) of the target compound, which was used without further purification. LC-MS (method 1): Rt=0.76 min; MS (ESIpos): m / z=237[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.55(br s,2H),7.26(t,1H),7.35-7.37(m,1H),7.40(dd,1H),7.49(d,1H),9.49(br s,1H).

[0437] Intermediate 418 4-Cyanobenzohydrazide [ka] Ethyl 4-cyanobenzoate (1.50 g, 8.56 mmol) was solubilized in ethanol (19 mL), hydrazine hydrate (2.1 mL, 43 mmol) was added, and the mixture was stirred at 90° C. for 3 h. The mixture was filtered, washed with EtOH, and the solid was dried under reduced pressure to give 1.13 g (82% yield) of the target compound, which was used without further purification. 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.62(br s, 2H), 7.92-7.99(m, 4H), 10.05(s, 1H).

[0438] Intermediate 419 1,3-Dimethyl-1H-pyrazole-4-carbohydrazide [ka] Ethyl 1,3-dimethyl-1H-pyrazole-4-carboxylate (2.00 g, 11.9 mmol) was solubilized in ethanol (15 mL), hydrazine hydrate (4.8 mL, 60% purity, 59 mmol) was added, and the mixture was stirred at 110 °C for 21 days. After cooling to room temperature, saturated aqueous ammonium chloride solution and ethyl acetate were added. After separation of the organic phase, the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate, filtered through a hydrophobic phase separation filter paper, and concentrated in vacuo. After drying, 330 mg of the target compound (80% purity, 14% yield) was obtained, which was used without further purification. LC-MS (method 2): Rt=0.51 min; MS (ESIpos): m / z=155[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=2.29(s,3H),3.34(s,1H),3.74(s,3H,in water signal),4.27(br s,2H),7.97(s,1H),9.06(s,1H).

[0439] Intermediate 420 2-(1,1,2,2-tetrafluoroethoxy)benzohydrazide [ka] Ethyl 2-(1,1,2,2-tetrafluoroethoxy)benzoate (539 mg, 2.02 mmol) was dissolved in ethanol (4.8 mL), hydrazine hydrate (990 μL, 20 mmol) was added, and the reaction mixture was stirred under reflux for 23 hours. The reaction mixture was allowed to cool and concentrated under reduced pressure. The residue was treated twice with dichloromethane and concentrated under reduced pressure to give 516 mg of the title compound (92% purity, 93% yield), which was used in the next step without further purification. LC-MS (Method 2):R t =0.76min;MS(ESIpos):m / z=253[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=4.45(br s,2H),6.69(tt,1H),7.36(dd,1H),7.41(td,1H),7.51(dd,1H),7.55(ddd,1H),9.48(s,1H).

[0440] Intermediate 421 4-Bromo-2-(difluoromethoxy)benzohydrazide [ka] Methyl 4-bromo-2-(difluoromethoxy)benzoate (445 mg, 1.58 mmol) was dissolved in methanol (4.4 mL), hydrazine hydrate (770 μL, 16 mmol) was added, and the reaction mixture was stirred under reflux for 4 hours. The reaction mixture was allowed to cool and concentrated under reduced pressure. The residue was treated three times with dichloromethane and concentrated under reduced pressure to give 460 mg of the title compound (93% purity, 96% yield), which was used in the next step without further purification. LC-MS (Method 2):R t=0.81 min;MS(ESIpos):m / z=281[M+H] + 1H-NMR (400MHz, DMSO-d6): δ[ppm]=4.52(br s,2H),7.26(t,1H),7.42(d,1H),7.47-7.49(m,1H),7.53(dd,1H),9.49(s,1H).

[0441] Intermediate 422 Ethyl [2-cyano-4-(trifluoromethyl)phenyl]carbamate [ka] 2-Amino-5-(trifluoromethyl)benzonitrile (300 mg, 1.61 mmol) was stirred in ethyl carbonochloridate (6.4 mL) at reflux for 8 hours. The mixture was concentrated under reduced pressure to give 410 mg of the target compound (100% pure, 99% yield), which was used without further purification. LC-MS (Method 2):R t =1.15min;MS(ESIneg):m / z=257[MH] - 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.27(t,3H),4.19(q,2H),7.81(d,1H),8.03(dd,1H),8.29(d,1H),10.14(s,1H).

[0442] Intermediate 423 Ethyl [2-cyano-6-(propan-2-yl)phenyl]carbamate [ka] Ethyl (2-bromo-6-cyanophenyl)carbamate (1.00 g, 3.72 mmol), lithium hydroxide (712 mg, 29.7 mmol) and (4,4'-di-tert-butyl-2,2'-bipyridine-κ 2 N 1 ,N 1’)(bis{3,5-difluoro-2-[5-(trifluoromethyl)pyridin-2-yl-κN]phenyl-κC 1 Iridium(1+) hexafluorophosphate (83.4 mg, 74.3 μmol) was dissolved in (trifluoromethyl)benzene (70 mL) in a reaction vial. In a separate vial, 1,2-dimethoxyethane-dichloronickel (1:1) (40.8 mg, 186 μmol) and 4,4'-di-tert-butyl-2,2'-bipyridine (49.9 mg, 186 μmol) were stirred in N,N-dimethylacetamide (25 mL, 270 mmol) for 5 minutes. The catalyst solution was added to the sealed reaction vial. The mixture was degassed by sparging with argon for 15 minutes. Then, 2-bromopropane (2.4 mL, 26 mmol) and 1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilane (1.1 mL, 3.7 mmol) were added. The vial was stirred in a water bath and irradiated with two 40 W Kessil LED Aquarium lamps (A160WE tuna blue) for 24 hours. The mixture was diluted with water and extracted three times with EtOAc. The combined organic layers were dried and concentrated under reduced pressure. The residue was purified by flash chromatography to give 530 mg of the target compound (98% purity, 60% yield). LC-MS (Method 2):R t =1.06min;MS(ESIpos):m / z=233[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=1.14(d,6H),1.17-1.30(m,3H),3.12-3.23(m,1H),4.06-4.17(m,2H),7.42-7.47(m,1H),7.68(d,2H),9.38(br m,1H).

[0443] Intermediate 424 Di-tert-butyl[2-cyano-6-(trifluoromethyl)phenyl]-2-imidodicarbonate [ka] To a solution of 2-amino-3-(trifluoromethyl)benzonitrile (2.00 g, 10.7 mmol) in dioxane (48 mL) was added N,N-diisopropylethylamine (4.7 mL, 27 mmol; CAS-RN: [7087-68-5]), 4-(N,N-dimethylamino)pyridine (4.7 mL, 27 mmol; CAS-RN: [7087-68-5]), and di-tert-butyl dicarbonate (6.2 mL, 27 mmol; CAS-RN: [24424-99-5]). The reaction mixture was stirred at room temperature for 90 h and then concentrated in vacuo. The resulting residue was purified via Biotage chromatography (50 g SiO SNAP Ultra column, hexane / 0-80% ethyl acetate) to afford 3.89 g (56% yield) of the desired title compound. 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.33(s,18H),7.85(t,1H),8.19(dd,1H),8.34(dd,1H).

[0444] Intermediate 425 2-(1-methyl-1H-pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (503 mg, 2.86 mmol) and 1-methyl-1H-pyrazole-3-carbohydrazide (400 mg, 2.86 mmol) in DMF (10 mL) were stirred at 120° C. for 20 h. Water was added to the mixture, filtered, washed with water, and the solid was dried under reduced pressure at 60° C. to give 630 mg (83% yield) of the target compound, which was used without further purification. LC-MS (method 2): Rt=0.48 min; MS (ESIpos): m / z=267[M+H] +

[0445] The following intermediates were prepared similarly to intermediate 425:

[0446] [Table 9A] [Table 9B] [Table 9C] [Table 9D] [Table 9E] [Table 9F] [Table 9G] [Table 9H] [Table 9I] [Table 9J] [Table 9K] [Table 9L] [Table 9M]

[0447] Intermediate 458 2-[2-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Step 1: Methyl (2-cyanophenyl)carbamate (206 mg, 1.17 mmol) and 2-(methanesulfonyl)benzohydrazide (300 mg, 1.40 mmol) in DMF (8.0 mL) were stirred at 120° C. for 48 hours. The mixture was cooled, poured into water, concentrated on a rotary evaporator, water was added, filtered, washed with water, and the solid was dried under reduced pressure at 50° C. A small sample was purified by HPLC to give 20 mg of pure product. 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=3.73(s,3H),7.30-7.35(m,1H),7.43(d,1H),7.66(ddd,1H),7.85(ddd,1H),7.88-7.94(m,2H),8.13-8.19(m,2H).

[0448] Step 2: The solid (a mixture of the target compound and intermediate) was solubilized in 1,2-dichloroethane (3.0 mL), TFA (230 μL, 2.9 mmol) was added, and the mixture was stirred at 60°C for 7 h. TFA (230 μL, 2.9 mmol) was added, and the mixture was stirred at 90°C for 48 h. The mixture was evaporated, diluted with water, filtered, washed with water, and the solid was dried under reduced pressure at 45°C to give 128 mg of the target compound (95% pure, 61% yield), which was used without further purification. LC-MS (method 2): Rt=0.57 min; MS (ESIpos): m / z=341[M+H] +

[0449] Intermediate 459 7-Bromo-2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-bromo-6-cyanophenyl)carbamate (361 mg, 1.41 mmol) and 4-chloro-2-(trifluoromethoxy)benzohydrazide (360 mg, 1.41 mmol) in DMF (8.0 mL) were stirred at 120° C. for 6 h. TFA (1.1 mL, 14 mmol) was added, and the mixture was stirred at 120° C. for 20 min. Water was added to the mixture, filtered, washed with water, and the solid was dried under reduced pressure at 60° C. to give 470 mg (72% yield) of the target compound, which was used without further purification. LC-MS (method 2): Rt=0.77 min; MS (ESIpos): m / z=459[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=7.36(t,1H),7.75(dd,1H),7.78(d,1H),8.03(dd,1H),8.23(dd,1H),8.33(d,1H),11.51(br s,1H).

[0450] Intermediate 460 2-[5-Bromo-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Methyl (2-cyanophenyl)carbamate (236 mg, 1.34 mmol) and 5-bromo-2-(trifluoromethoxy)benzohydrazide (400 mg, 1.34 mmol) in DMF (8.0 mL) were stirred at 130° C. for 6 h. TFA (1.0 mL, 13 mmol) was added, and the mixture was stirred at 130° C. for 1 h. Water was added to the mixture, filtered, washed with water, and the solid was dried under reduced pressure at 60° C. to give 537 mg (94% yield) of the target compound, which was used without further purification. LC-MS (method 2): Rt=0.86 min; MS (ESIpos): m / z=425[M+H] + 1H-NMR (400MHz, DMSO-d6): δ[ppm]=7.41-7.48(m,2H),7.59(ddd,1H),7.74(ddd,1H),7.91(dd,1H),8.23(dd,1H),8.42(d,1H),12.45(s,1H).

[0451] Intermediate 461 4-[5-oxo-7-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[1,5-c]quinazolin-2-yl]benzonitrile [ka] Methyl [2-cyano-6-(trifluoromethyl)phenyl]carbamate (350 mg, 1.43 mmol) and 4-cyanobenzohydrazide (231 mg, 1.43 mmol) were stirred in DMF (15 ml) at 120° C. for 20 hours. The reaction mixture was cooled to room temperature, and then water was added to the mixture, filtered, washed with water, and the solid was dried under reduced pressure at 50° C. to give 332 mg of raw material, which was stirred in acetic acid (2 ml) at 90° C. for 20 hours. The reaction mixture was cooled to room temperature, water was added, filtered, washed with water, and the solid was dried under reduced pressure to give 281 mg (52% yield) of the target compound, which was used without further purification. LC-MS (method 1): Rt=1.14 min; MS (ESIpos): m / z=356[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=7.60(t,1H),8.06(d,2H),8.11(br d,1H),8.39(d,2H),8.57(d,1H),11.72(br s,1H).

[0452] The following intermediates were prepared according to the procedure described for intermediate 461:

[0453] [Table 10A] [Table 10B] [Table 10C]

[0454] Intermediate 469 2-[4-chloro-2-(difluoromethoxy)phenyl]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] Di-tert-butyl[2-cyano-6-(trifluoromethyl)phenyl]-2-imidodicarbonate (200 mg, 518 μmol) and 4-chloro-2-(difluoromethoxy)benzohydrazide (147 mg, 621 μmol) were stirred in DMF (1.7 ml) at 120° C. for 20 hours. Acetic acid (2 ml) was then added at 100° C., and the reaction mixture was stirred at this temperature for 24 hours. The reaction mixture was cooled to room temperature and added to water. After stirring for 10 minutes, it was filtered, washed with water, and the solid was dried under reduced pressure at 60° C. to give 182 mg (74% yield) of the target compound, which was used without further purification. LC-MS (method 1): Rt=1.33 min; MS (ESIpos): m / z=431[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=7.39(t,1H),7.54-7.62(m,3H),8.10(d,1H),8.21(d,1H),8.50-8.56(m,1H),11.68(br s,1H).

[0455] The following intermediates were prepared similarly to intermediate 469:

[0456] [Table 11]

[0457] Intermediate 472 5-chloro-2-(1-methyl-1H-pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-(1-Methyl-1H-pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (630 mg, 2.37 mmol) was suspended in phosphorus oxychloride (6.0 mL), DIPEA (4.1 mL, 24 mmol) was carefully added, and the mixture was stirred at 110° C. for 3 h. The mixture was poured into ice, stirred for 1 h, filtered, washed with water, and dried under reduced pressure at 60° C. to give 485 mg of the target compound (100% pure, 68% yield), which was used without further purification. LC-MS (method 2): Rt=1.00 min; MS (ESIpos): m / z=285[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=3.99(s,3H),6.94(d,1H),7.86(ddd,1H),7.91(d,1H),7.94-8.00(m,1H),8.01-8.06(m,1H),8.50(dd,1H).

[0458] The following intermediates were prepared similarly to intermediate 472:

[0459] [Table 12A] [Table 12B] [Table 12C] [Table 12D] [Table 12E] [Table 12F] [Table 12G] [Table 12H] [Table 12I] [Table 12J] [Table 12K] [Table 12L] [Table 12M] [Table 12N] [Table 12O] [Table 12P] [Table 12Q] [Table 12R] [Table 12S]

[0460] Intermediate 519 Benzyl (6R)-6-{[2-(5-bromo-2-furyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-5-oxo-1,4-diazepane-1-carboxylate [ka] 2-(5-Bromofuran-2-yl)-5-chloro[1,2,4]triazolo[1,5-c]quinazoline (100 mg, 286 μmol), benzyl (6R)-6-amino-5-oxo-1,4-diazepane-1-carboxylate hydrochloride (94.3 mg, 315 μmol), and N,N-diisopropylethylamine (200 μL, 1.1 mmol) in DMSO (2.0 mL) were stirred at 60° C. for 2 hours. Water was added to the mixture, which was then filtered, washed with water, and dried under reduced pressure at 60° C. to give 144 mg of the target compound (97% purity, 85% yield). LC-MS (Method 2):R t =1.33min;MS(ESIpos):m / z=576[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=2.93-3.13(m,1H),3.21-3.32(m,2H),3.44-3.54(m,1H),4.10-4.27(m,1H),4.52-4.6 6(m,1H),4.87-5.00(m,1H),5.19(s,2H),6.90(d,1H),7.13-7.27(m,2H),7.27-7.52(m,6H),7.59-7.71(m,1H),7.88(br d,1H),8.27(br d,1H),8.35-8.53(m,1H).

[0461] The following intermediates were prepared according to the same procedure as described for intermediate 519 (in some cases preparative PLC was used for purification):

[0462] [Table 13A] [Table 13B] [Table 13C] [Table 13D] [Table 13E] [Table 13F] [Table 13G] [Table 13H] [Table 13I] [Table 13J] [Table 13K]

[0463] Intermediate 543 Benzyl (6R)-6-{[2-(3,4-dimethoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-5-oxo-1,4-diazepane-1-carboxylate [ka] Benzyl (6R)-6-[(2-bromo[1,2,4]triazolo[1,5-c]quinazolin-5-yl)amino]-5-oxo-1,4-diazepane-1-carboxylate (100 mg, 196 μmol), 2-(3,4-dimethoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (104 mg, 392 μmol), and XPhos Pd G4 (8.43 mg, 9.80 μmol) were dissolved in DMF (1.5 mL), treated with potassium carbonate solution (290 μL, 2.0 M, 590 μmol), and stirred at 90 °C overnight. The mixture was poured into water, and the precipitate was filtered, washed with water, and dried under reduced pressure to give the title compound (111.2 mg). The residue was used without further purification. LC-MS (method 2): Rt=1.27 min; MS (ESIpos): m / z=568[M+H] +

[0464] The following intermediates were prepared similarly to intermediate 543:

[0465] [Table 14A] [Table 14B] [Table 14C] [Table 14D] [Table 14E] [Table 14F] [Table 14G]

[0466] Intermediate 558 N-[(E)-(dimethylamino)methylidene]-2-nitrobenzamide [ka] 2-Nitrobenzamide (1.00 g, 6.02 mmol) and 1,1-dimethoxy-N,N-dimethylmethanamine (4.0 mL, 30 mmol) were stirred at 100° C. for 1 h. The mixture was filtered, washed with hexane, and dried under reduced pressure at 50° C. to give 1.03 g of the target compound (100% purity, 78% yield), which was used without further purification. LC-MS (Method 2):R t =0.76 min;MS(ESIpos):m / z=222[M+H] + 1H-NMR (400MHz, DMSO-d6): δ[ppm]=3.03(d,3H),3.20(s,3H),7.63-7.73(m,2H),7.78-7.82(m,1H),7.92(dd,1H),8.58(t,1H).

[0467] Intermediate 559 5-(2-nitrophenyl)-1H-1,2,4-triazole [ka] N-[(E)-(dimethylamino)methylidene]-2-nitrobenzamide (1.03 g, 4.67 mmol), hydrazine-water (1 / 1) (570 μL, 12 mmol), and molecular sieves (3A) were stirred at reflux for 2 h in acetic acid (26 mL, 450 mmol) and butan-1-ol (15 mL). The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with saturated sodium bicarbonate solution, dried, and concentrated under reduced pressure to give 885 mg of the target compound (100% pure, 100% yield), which was used without further purification. LC-MS (Method 4):R t =0.87min;MS(ESIneg):m / z=189[MH] - 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=7.65(td,1H),7.76(td,1H),7.88(dd,1H),7.99(dd,1H),8.62(s,1H).

[0468] Intermediate 560 3-Bromo-5-(2-nitrophenyl)-4H-1,2,4-triazole [ka] 3-(2-Nitrophenyl)-4H-1,2,4-triazole (8.66 g, 45.5 mmol), NBS (17.8 g, 100 mmol), and potassium carbonate (31.5 g, 228 mmol) in DMF (220 mL) were stirred at rt for 2 h. The mixture was evaporated, diluted with ethanol, filtered, and the filtrate was concentrated under reduced pressure to give 33.0 g of the target compound (37% pure), which was used without further purification. 1H-NMR (400MHz, DMSO-d6): δ[ppm]=7.38(td,1H),7.53-7.61(m,2H),7.92-7.95(m,2H).

[0469] Intermediate 561 2-(5-bromo-4H-1,2,4-triazol-3-yl)aniline [ka] 3-Bromo-5-(2-nitrophenyl)-4H-1,2,4-triazole (21.5 g, 79.9 mmol) was dissolved in methanol (520 mL) and THF (160 mL). Platinum / vanadium (7.79 g, 1% purity, 400 μmol) was added, and the mixture was stirred at room temperature under a hydrogen atmosphere for 6 hours. The mixture was filtered and washed with methanol and THF. The filtrate was concentrated under reduced pressure to give 16.9 g of the target compound (90% purity, 80% yield), which was used without further purification. LC-MS (Method 4):R t =1.23min;MS(ESIpos):m / z=239[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=6.47(ddd,1H),6.63(dd,1H),6.90(ddd,1H),7.76(dd,1H),11.07(br s,2H).

[0470] Intermediate 562 2-Bromo[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ka] 2-(5-Bromo-4H-1,2,4-triazol-3-yl)aniline (15.2 g, 63.7 mmol) and di(1H-imidazol-1-yl)methanone (24.7 g, 152.9 mmol) in DMF (250 mL) were stirred at rt overnight. The mixture was evaporated, diluted with ACN / water (95:5), filtered, washed with ACN, and dried under reduced pressure at 60 °C to give 1.99 g of the target compound (95% pure, 11% yield), which was used without further purification. LC-MS (Method 4):R t =1.20min;MS(ESIpos):m / z=265[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=6.97(ddd,1H),7.18(d,1H),7.39(ddd,1H),7.87(dd,1H).

[0471] Intermediate 563 2-Bromo-5-chloro[1,2,4]triazolo[1,5-c]quinazoline [ka] 2-Bromo[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one (4.41 g, 16.6 mmol) in phosphorus oxychloride (54 mL, 580 mmol) and N,N-diisopropylethylamine (29 mL, 170 mmol) was stirred at 110° C. for 4 h. The mixture was poured onto ice, filtered, washed with water, and dried under reduced pressure at 60° C. to give 3.00 g (64% yield) of the target compound, which was used without further purification. LC-MS (Method 2):R t =1.13min;MS(ESIpos):m / z=283[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=7.87(ddd,1H),7.97-8.09(m,2H),8.40-8.47(m,1H).

[0472] Intermediate 564 (3R)-3-[(2-Bromo[1,2,4]triazolo[1,5-c]quinazolin-5-yl)amino]azepan-2-one [ka] 2-Bromo-5-chloro[1,2,4]triazolo[1,5-c]quinazoline (3.00 g, 10.6 mmol), (3R)-3-aminoazepan-2-one hydrochloride (1.92 g, 11.6 mmol), and N,N-diisopropylethylamine (7.4 mL, 42 mmol) were stirred in DMSO (80 mL) at 60° C. for 2 h. The mixture was diluted with water, filtered, washed with water, and dried under reduced pressure at 60° C. to give 3.72 g of the target compound (95% pure, 89% yield), which was used without further purification. LC-MS (Method 2):R t =1.18 min;MS(ESIpos):m / z=375[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=1.24-1.37(m,1H),1.47-1.60(m,1H),1.78-1.91(m,2H),1.96-2.05(m,1H),2.27(br d,1H),3.10-3.20(m,1H),4.78(dd,1H),7.45(ddd,1H),7.63-7.70(m,2H),7.73-7.79(m,1H),8.16-8.23(m,2H).

[0473] Intermediate 565 tert-Butyl 3-[4-(5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylate [ka] (3R)-3-[(2-Bromo[1,2,4]triazolo[1,5-c]quinazolin-5-yl)amino]azepan-2-one (75.0 mg, 200 μmol), tert-butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylate (90.7 mg, 260 μmol), and XPhos Pd G1 (8.26 mg, 9.99 μmol) were solubilized in DMF (1.3 mL) and aqueous KCO (300 μL, 2.0 M, 600 μmol). The mixture was sparged with argon and stirred at 110 °C for 1 h. The mixture was cooled to rt and purified by preparative HPLC to give 46.1 mg of the title compound (100% purity, 45% yield). LC-MS (Method 2):R t =1.24 min;MS(ESIpos):m / z=518[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=1.25-1.38(m,1H),1.42(s,9H),1.48-1.60(m,1H) ,1.80-1.95(m,2H),1.97-2.06(m,1H),2.26-2.34(m,1H),3.10-3.21(m,1H),4.22(br s,2H),4.29-4.37(m,2H),4.82(br dd,1H),5.35(tt,1H),7.44(ddd,1H),7.61(br d,1H),7.63-7.68(m,1H),7.69-7.75(m,1H),8.18-8.26(m,3H),8.66(s,1H).

[0474] Intermediate 566 tert-Butyl 4-[4-(5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate [ka] (3R)-3-{[2-(1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (75.0 mg, 207 μmol), tert-butyl 4-bromopiperidine-1-carboxylate (60.1 mg, 228 μmol), and CsCO (202 mg, 621 μmol) in DMF (440 μL) were stirred at 100° C. for 1 h. The reaction mixture was cooled to rt and purified by preparative HPLC to give 38.8 mg of the title compound (95% purity, 33% yield). LC-MS (Method 2):R t =1.33min;MS(ESIpos):m / z=546[M+H] + 1 H-NMR (400MHz, DMSO-d6): δ[ppm]=1.25-1.38(m,1H),1.43(s,9H),1.48-1.59(m,1H),1.80-1. 95(m,4H),1.97-2.12(m,3H),2.26-2.35(m,1H),2.82-3.03(m,2H),3.10-3.21(m,1H),4.07(br d,2H),4.49(tt,1H),4.82(br dd,1H),7.43(ddd,1H),7.59(d,1H),7.62-7.67(m,1H),7.69-7.74(m,1H),8.10(s,1H),8.19-8.26(m,2H),8.56(s,1H).

[0475] Intermediate 567 Benzyl (6R)-6-[(2-bromo[1,2,4]triazolo[1,5-c]quinazolin-5-yl)amino]-5-oxo-1,4-diazepane-1-carboxylate [ka] 2-Bromo-5-chloro[1,2,4]triazolo[1,5-c]quinazoline (1.00 g, 3.53 mmol) and benzyl (6R)-6-amino-5-oxo-1,4-diazepane-1-carboxylate hydrochloride (1.16 g, 3.88 mmol) were suspended in DMSO (10 mL) and treated with N,N-diisopropylethylamine (2.5 mL, 14 mmol), and the mixture was stirred at 60° C. for 2 h. The mixture was poured into water, and the precipitate was filtered, washed with water, and dried under reduced pressure to give 1.78 g of the target compound (100% pure, 99% yield). LC-MS (Method 2):R t =1.24 min;MS(ESIpos):m / z=510[M+H] +

[0476] Intermediate 568 tert-Butyl 3-[2-(4-methoxyphenyl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-10-yl]azetidine-1-carboxylate [ka] (3R)-3-{[10-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (50.0 mg, 104 μmol), lithium carbonate (46.1 mg, 623 μmol), and (4,4'-di-tert-butyl-2,2'-bipyridine-κB) 2 N 1 ,N 1’ )(bis{3,5-difluoro-2-[5-(trifluoromethyl)pyridin-2-yl-κN]phenyl-κC 1Iridium(1+) hexafluorophosphate (2.33 mg, 2.08 μmol) was dissolved in (trifluoromethyl)benzene (2.0 mL) in a reaction vial. In a separate vial, 1,2-dimethoxyethane-dichloronickel (1:1) (110 μg, 0.52 μmol) and 4,4'-di-tert-butyl-2,2'-bipyridine (140 μg, 0.52 μmol) were stirred in N,N-dimethylacetamide (1000 μL, 11 mmol) for 5 minutes. The catalyst solution was added to the sealed reaction vial. The mixture was degassed under vacuum in an ultrasonic bath for 5 minutes and then purged with argon. Then, tert-butyl 3-bromoazetidine-1-carboxylate (76 μL, 470 μmol) and 1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilane (32 μL, 100 μmol) were added. The vial was stirred in a water bath and irradiated with two 40 W Kessil LED Aquarium lamps (A160WE tuna blue). The mixture was evaporated, diluted with DMSO, and filtered. The solid was diluted with water and extracted three times with DCM. The combined organic layers were dried and concentrated under reduced pressure. The residue was purified by preparative HPLC to give 9.10 mg of the target compound (100% purity, 16% yield). LC-MS (method 2): Rt=1.59 min; MS (ESIpos): m / z=558[M+H] + 1 H-NMR(400MHz,DMSO-d6):δ[ppm]=1.25-1.37(m,1H),1.40(s,9H),1.49-1.62(m,1H),1.80-1.94(m,2 H),1.97-2.07(m,1H),2.27-2.35(m,1H),3.10-3.22(m,1H),3.86(s,3H),3.94-4.05(m,2H),4.51(br t,2H),4.80(br dd,1H),4.99-5.10(m,1H),7.12-7.18(m,2H),7.54(dd,2H),7.65-7.73(m,2H),8.18-8.25(m,3H).

[0477] Intermediate 569 (3R)-3-{[2-(4-methoxyphenyl)-7-(prop-1-en-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one [ka] (3R)-3-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (100 mg, 208 μmol) and XPhos Pd G4 (89.4 mg, 104 μmol) were dissolved in 1,4-dioxane (5.0 mL). Aqueous sodium carbonate (270 μL, 2.0 M, 540 μmol) was added, and the mixture was sparged with argon for 5 minutes. 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (69.8 mg, 415 μmol) was added, and the mixture was stirred at 100 °C for 2 hours. Water was added to the mixture, which was then extracted twice with EtOAc. The combined organic layers were dried, and the solvent was evaporated. The residue was purified by preparative HPLC to give 34.2 mg of the target compound (purity 95%, yield 35%). LC-MS (Method 2):R t =1.49min;MS(ESIpos):m / z=443[M+H] + 1H-NMR (400MHz, DMSO-d6): δ[ppm]=1.21-1.40(m,2H),1.49-1.64(m,1H),1.80-1.96(m,2H),1.97-2.14(m,2H),2.36(s,3H),3.19(br s,1H),3.86(s,3H),4.70-4.88(m,1H),5.20(s,1H),5.30(s,1H),7.14(d,2H) ,7.36-7.44(m,1H),7.57-7.76(m,1H),7.58-7.94(m,1H),8.14-8.27(m,4H).

[0478] Intermediate 570 Benzyl (6R)-6-{[2-(4-methoxyphenyl)-7-(3,3,3-trifluoroprop-1-en-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-5-oxo-1,4-diazepane-1-carboxylate [ka] Benzyl (6R)-6-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-5-oxo-1,4-diazepane-1-carboxylate (194 mg, 315 μmol), 4,4,5,5-tetramethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1,3,2-dioxaborolane (140 μL, 630 μmol), and XPhosPdG4 (13.5 mg, 15.7 μmol) were solubilized in 1,4-dioxane (6.0 mL). Aqueous Na2CO3 (410 μL, 2.0 M, 820 μmol) was added, and the mixture was sparged with argon (with sonication). The reaction mixture was stirred at 100 °C for 5 h. XPhosPdG (13.5 mg, 15.7 μmol), aqueous NaCO (410 μL, 2.0 M, 820 μmol), and 4,4,5,5-tetramethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1,3,2-dioxaborolane (140 μL, 630 μmol) were added again, and the reaction was stirred at 100 °C for an additional 5 h. T...

Claims

1. Compounds of general formula (I): 【Chemical 1】 (In the formula, R 1 teeth, Independently of each other, halogen, cyano, hydroxy, C 1 ~C 4 -Alkyl, C 1 ~C 4 -alkoxy, C 1 ~C 4 -haloalkyl, C 1 ~C 4 -Haloalkoxy, C 1 ~C 4 -hydroxyalkyl, C 1 ~C 4 -alkoxy-C 1 ~C 4 -Alkyl-, C 3 ~C 6 -cycloalkyl, C 3 ~C 6 -cycloalkyl-C 1 ~C 4 -Alkyl-, C 3 ~C 6 -cycloalkyl-O-, 4- to 6-membered heterocycloalkyl, -NR 9 R 10 , R 9 R 10 N-C 1 ~C 4 -Alkyl-, C 1 ~C 3 -Alkyl-S(O) m - or C 1 ~C 3 - optionally substituted 1 to 3 times with alkyl-SO(NH)-, represents phenyl or heteroaryl; R 2 is hydrogen, C 1 ~C 4 -Alkyl, C 1 ~C 4 -haloalkyl or C 3 ~C 6 - represents cycloalkyl; R 3 is hydrogen, C 1 ~C 6 -alkyl, phenyl or phenyl-C 1 ~C 3 represents alkyl, Said C 1 ~C 6 - The alkyl groups are, independently of each other, hydroxy, halogen, C 1 ~C 4 -alkoxy, -S(O) n -C 1 ~C 4 -Alkyl, phenyl-C 1 ~C 3 -alkoxy or -NR 9 R 10 optionally substituted one or more times with The phenyl groups may be, independently of each other, hydroxy, halogen, cyano, C 1 ~C 3 -Alkyl, C 1 ~C 3 -haloalkyl, C 1 ~C 3 -alkoxy or C 1 ~C 3 - optionally substituted one or more times with haloalkoxy, or R 2 and R 3 together with the carbon atoms to which they are attached form a 3- to 6-membered ring, said ring containing O, S, NH, NR a (In the formula, R a is C 1 ~C 4 - represents an alkyl group; R 4 is hydroxy, C 1 ~C 4 -alkoxy or -NR 11 R 12 represents, or R 2 and R 4 together, ＊ -C 2 ~C 5 -Alkanediyl-X 1 - ＊＊ , ＊ -C 1 ~C 2 -Alkanediyl-X 2 -C 1 ~C 3 -Alkanediyl- ＊＊ or ＊ -C 1 ~C 2 -Alkanediyl-X 2 -C 2 ~C 3 -Alkanediyl-X 1 - ＊＊ and form a 5- to 9-membered ring, ＊ is R 2 indicates the point of attachment of said group to ＊＊ is R 4 indicates the point of attachment of said group to R 5 is hydrogen, halogen, cyano, hydroxy, C 1 ~C 4 -Alkyl, C 1 ~C 4 -alkoxy, C 1 ~C 4 -haloalkyl, C 1 ~C 4 -Haloalkoxy, C 3 ~C 6 -cycloalkyl, 4- to 6-membered heterocycloalkyl, -CO 2 -C 1 ~C 4 -Alkyl, -CO-NR 9 R 10 or -NR 9 R 10 represents; R 6 is hydrogen, halogen, cyano, hydroxy, C 1 ~C 4 -Alkyl, C 1 ~C 4 -alkoxy, C 1 ~C 4 -haloalkyl, C 1 ~C 4 -Haloalkoxy, C 3 ~C 6 -cycloalkyl or -NR 9 R 10 represents; R 7 is hydrogen, halogen, cyano, hydroxy, C 1 ~C 4 -Alkyl, C 1 ~C 4 -alkoxy, C 1 ~C 4 -haloalkyl, C 1 ~C 4 -Haloalkoxy, C 3 ~C 6 -cycloalkyl or -NR 9 R 10 represents; R 8 is hydrogen, halogen, cyano, hydroxy, C 1 ~C 4 -Alkyl, C 1 ~C 4 -alkoxy, C 1 ~C 4 -haloalkyl, C 1 ~C 4 -Haloalkoxy, C 3 ~C 6 -cycloalkyl, 1-R 15 -C 3 ~C 6 -cycloalkyl, -CO 2 -C 1 ~C 4 -Alkyl, -CO-NR 9 R 10 , -NR 9 R 10 , C 1 ~C 4 -hydroxyalkyl, C 1 ~C 4 -alkoxy-C 1 ~C 4 -Alkyl-, C 1 ~C 4 -Alkyl-S-, C 1 ~C 4 -Alkyl-S-C 1 ~C 4 -Alkyl-, -S(=O)R', -S(=O) 2 R', -S(=O) 2 NH 2 , -S(=O) 2 NHR', -S(=O) 2 N(R')R'', -S(=O)(=NH)R', 4-6 membered heterocycloalkyl or -OR 16 represents; R 9 and R 10 are the same or different and independently represent hydrogen, C 1 ~C 3 -alkyl or tert-butoxycarbonyl, or Together with the nitrogen atom to which they are attached, they form a 4- to 6-membered nitrogen-containing heterocyclic ring, which ring is free of O, S, NH, NR a (In the formula, R a is C 1 ~C 4 -Alkyl or C 1 ~C 4 -alkoxycarbonyl; R 11 and R 12 are the same or different and independently represent hydrogen, C 1 ~C 4 -Alkyl, C 2 ~C 4 -hydroxyalkyl, C 1 ~C 4 -alkoxy-C 2 ~C 4 -Alkyl-, R 9 R 10 N-C 2 ~C 4 -Alkyl-, C 3 ~C 6 -cycloalkyl, 4- to 7-membered heterocycloalkyl, wherein the 4- to 7-membered heterocycloalkyl groups are each independently selected from hydroxy, oxo, halogen, C 1 ~C 4 -Alkyl, C 1 ~C 4 -alkoxy or -NR 9 R 10 , optionally substituted once or twice with, or Together with the nitrogen atom to which they are attached, they form a 4- to 6-membered nitrogen-containing heterocyclic ring, which ring is free of O, S, NH, NR a (In the formula, R a is C 1 ~C 4 -Alkyl or C 1 ~C 4 -alkoxycarbonyl), which may optionally contain one additional heteroatom selected from, independently of each other, hydroxy, halogen, C 1 ~C 4 -Alkyl, C 1 ~C 4 -alkoxy or -NR 9 R 10 , optionally substituted once or twice with, or Together with the nitrogen atom to which they are attached, they may independently be hydroxy, halogen, C 1 ~C 4 -Alkyl, C 1 ~C 4 -alkoxy or -NR 9 R 10 forming a heterospirocycloalkyl group which is optionally substituted once or twice by Together with the nitrogen atom to which they are attached, they may independently be hydroxy, halogen, C 1 ~C 4 -Alkyl, C 1 ~C 4 -alkoxy or -NR 9 R 10 forming a bridged heterocycloalkyl group which is optionally substituted once or twice; R 13 is hydrogen, C 1 ~C 4 - alkyl, benzyl, 4-methoxybenzyl or tert-butoxycarbonyl; R 14 is hydrogen, C 1 ~C 4 - alkyl, benzyl or 4-methoxybenzyl; R 15 is C 1 ~C 3 -Alkyl or C 1 ~C 3 - represents haloalkyl; R 16 is C 2 ~C 6 -hydroxyalkyl, C 1 ~C 4 -alkoxy-C 2 ~C 6 -Alkyl- or C 3 ~C 6 - represents cycloalkyl; R' and R'' are independently C 1 ~C 6 -Alkyl, C 1 ~C 6 -haloalkyl or C 3 ~C 6 - represents cycloalkyl; X 1 , O, S(O) m or NR 13 represents; X 2 , O, S(O) m or NR 14 represents; m represents 0, 1 or 2; n represents 0, 1 or 2), The polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates thereof, as well as physiologically acceptable salts and solvates of these salts, and mixtures thereof.

2. R 1 but, Independently of each other, halogen, hydroxy, C 1 ~C 4 -Alkyl, C 1 ~C 4 -alkoxy, C 1 ~C 4 -haloalkyl, C 1 ~C 4 -Haloalkoxy, C 3 ~C 6 -cycloalkyl, C 3 ~C 6 -cycloalkyl-C 1 ~C 4 -Alkyl-, C 3 ~C 6 -cycloalkyl-O-, 4- to 6-membered heterocycloalkyl or -NR 9 R 10 , which was occasionally replaced once or twice, represents phenyl or monocyclic heteroaryl; R 2 is hydrogen or C 1 ~C 4 represents alkyl; R 3 But hydrogen, C 1 ~C 4 -alkyl, phenyl or phenyl-methyl, Said C 1 ~C 4 -Alkyl group is hydroxy, methoxy, -S(O) n -methyl, phenyl-methoxy or -NR 9 R 10 , optionally substituted once with the phenyl group is optionally substituted once with hydroxy, or R 2 and R 3 together with the carbon atom to which they are attached form a 3- to 6-membered ring, said ring optionally containing 1 oxygen atom; R 4 is hydroxy, methoxy or -NR 11 R 12 represents, or R 2 and R 4 Together, 【Chemistry 2】 (In the formula, ＊ indicates the point of attachment of said group to the NH group in formula (I). represents a group selected from R 5 But hydrogen, halogens, C 1 ~C 4 - represents alkyl, methoxy, trifluoromethyl or cyclopropyl; R 6 represents hydrogen, halogen or methyl; R 7 represents hydrogen, halogen, methyl or methoxy; R 8 represents hydrogen, halogen or methyl; R 9 and R 10 are the same or different and independently represent hydrogen, methyl or tert-butoxycarbonyl; R 11 and R 12 are the same or different, and independently, hydrogen, C 1 ~C 3 -Alkyl or C 3 ~C 4 -cycloalkyl, wherein C 1 ~C 3 - alkyl groups optionally substituted with hydroxy; R 13 represents hydrogen or methyl; X 3 But CH 2 or NH; n represents 0 or 2; The compounds according to claim 1, their polymorphs, enantiomers, diastereomers, racemates, tautomers, N-oxides, hydrates and solvates, as well as physiologically acceptable salts thereof and solvates of these salts, and mixtures thereof.

3. (3S)-3-[(2-phenyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl)amino]azepan-2-one N 2 -(2-phenyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl)-D-serinamide N 2 -(2-phenyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl)-D-valinamide (2R)-2-[(2-phenyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl)amino]butanamide (3R)-3-[(2-phenyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl)amino]azepan-2-one (3R)-3-{[2-(4-chlorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(4-chlorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3S)-3-{[2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3S)-3-{[2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one 3-{[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3S)-3-{[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one 3-{[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one N 2 -[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-serinamide (2R)-2-{[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (3R)-3-{[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3S)-3-{[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-{[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3S)-3-{[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one 6-{[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one tert-Butyl [(5S)-6-amino-5-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-6-oxohexyl]carbamate N 2 -[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-serinamide N 2 -[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-leucinamide 3-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-3-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one 3-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one N 2 -[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-L-lysineamide 6-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (3R)-3-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3S)-3-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-3-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3S)-3-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3S)-3-{[2-(2-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(2-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one 3-{[2-(2-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one 3-{[2-(2-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (6R)-6-{[2-(2-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[2-(2-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (3R)-3-{[2-(2-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3S)-3-{[2-(2-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-3-{[2-(2-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3S)-3-{[2-(2-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-({2-[2-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(3-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[3-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(2-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(2-chlorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-chlorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(2-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(2-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1H-pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-methyl-1H-pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(5-methyl-1H-pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-methyl-1H-pyrazol-5-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-ethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1,5-dimethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(2-methyl-1,3-oxazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3S)-3-{[2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-{[2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one 3-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one 3-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-serinamide 3-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-methylpyrrolidin-2-one N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-L-alaninamide N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-leucinamide N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-L-valinamide N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-L-tyrosinamide N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-L-serinamide N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]alaninamide 3-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}oxetane-3-carboxamide (2R)-2-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (2R)-2-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-2-phenylacetamide N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-phenylalaninamide N-[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-serine N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide N-[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-leucine N-[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-valine (2R)-2-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanoic acid N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-methionine amide O-Benzyl-N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-threonine amide N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-2-methylalaninamide 1-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}cyclopentane-1-carboxamide 1-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}cyclohexane-1-carboxamide tert-Butyl [(5S)-6-amino-5-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-6-oxohexyl]carbamate N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-methyl-L-alaninamide N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-valinamide Methyl N-[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-valinate N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-propan-2-yl-D-alaninamide N-Cyclopropyl-N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide N-Ethyl-N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-methyl-D-alaninamide N-Cyclobutyl-N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N,N-dimethyl-D-alaninamide N-(2-hydroxyethyl)-N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide N-(3-hydroxypropyl)-N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide (2R)-4-(methanesulfonyl)-2-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (2R)-2-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-4-(methylsulfonyl)butanamide N 2 -[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-L-lysineamide 6-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (3R)-3-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3S)-3-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3S)-3-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3S)-3-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-methylpyrrolidin-2-one (3R)-3-{[2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-methylpyrrolidin-2-one (3R)-3-{[2-(pyridin-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(pyridin-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(pyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(pyridazin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[4-(dimethylamino)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(3-hydroxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(furan-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-methyl-1,2,4-oxadiazol-5-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-ethyl-1,2,4-oxadiazol-5-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[3-(propan-2-yl)-1,2,4-oxadiazol-5-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(3-tert-butyl-1,2,4-oxadiazol-5-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[7-fluoro-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-fluoro-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-fluoro-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-methoxyphenyl)-7-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(3-methoxyphenyl)-7-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-methyl-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-7-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(4-methoxyphenyl)-7-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-methoxyphenyl)-8-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(3-methoxyphenyl)-8-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[8-methyl-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[8-fluoro-2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[8-fluoro-2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3S)-3-{[8-fluoro-2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[8-fluoro-2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-3-{[8-fluoro-2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-{[8-fluoro-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-methoxyphenyl)-9-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(3-methoxyphenyl)-9-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3S)-3-{[2-(3-methoxyphenyl)-9-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(3-methoxyphenyl)-9-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-3-{[9-methyl-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[9-fluoro-2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[9-fluoro-2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one 3-{[9-fluoro-2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one 3-{[9-fluoro-2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-{[10-bromo-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[10-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[10-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[10-bromo-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[10-chloro-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[10-chloro-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[10-chloro-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[10-chloro-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-fluorophenyl)-10-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-10-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-methyl-1H-pyrazol-4-yl)-10-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-fluorophenyl)-10-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[10-cyclopropyl-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[10-cyclopropyl-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[10-cyclopropyl-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-methoxyphenyl)-10-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one 3-{[2-(3-methoxyphenyl)-10-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one 3-{[2-(3-methoxyphenyl)-10-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3S)-3-{[2-(3-methoxyphenyl)-10-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(3-methoxyphenyl)-10-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-3-{[10-methyl-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one N 2 -[10-fluoro-2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide (3R)-3-{[10-fluoro-2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[9-fluoro-2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3S)-3-{[9-fluoro-2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-{[9-fluoro-2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3S)-3-{[9-fluoro-2-(3-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-3-{[2-(3-methoxyphenyl)-10-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3S)-3-{[2-(3-methoxyphenyl)-10-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one 6-{[2-(4-methoxyphenyl)-10-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (3R)-3-{[7-chloro-2-(pyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-chloro-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[1-(propan-2-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(2,3-dichlorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(2,5-difluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(2-ethoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(5-methyl-1,3,4-oxadiazol-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-bromo-2-chlorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(2,4-difluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[4-(methylsulfanyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(4-fluorophenyl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-methoxy-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-cyclopropyl-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-cyclopropyl-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({7-bromo-2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3S)-3-{[7-bromo-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[7-bromo-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-bromo-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-bromo-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-bromo-2-(pyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-bromo-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-({7-bromo-2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)pyrrolidin-2-one (3R)-3-({7-bromo-2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)piperidin-2-one (3R)-3-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-3-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-3-{[7-bromo-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-{[7-bromo-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-3-{[7-bromo-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-3-{[2-(1-methyl-1H-pyrazol-4-yl)-8-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-8-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[8-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[8-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[9-fluoro-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[9-fluoro-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[9-fluoro-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[9-fluoro-2-(2-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[9-chloro-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[9-chloro-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[9-methoxy-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[9-methoxy-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-fluorophenyl)-9-methoxy[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(2-fluorophenyl)-9-methoxy[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-9-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[9-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-10-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[10-fluoro-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[10-methoxy-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one 2-(4-Methoxyphenyl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-10-carbonitrile 2-(1-methyl-1H-pyrazol-4-yl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-10-carbonitrile 2-(4-Fluorophenyl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-10-carbonitrile 2-(3-fluorophenyl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-10-carbonitrile Methyl 2-(4-methoxyphenyl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-7-carboxylate (3R)-3-{[8-cyclopropyl-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one Methyl 2-(4-methoxyphenyl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-10-carboxylate (6R)-6-{[7-chloro-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(2-ethoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(4-bromo-2-chlorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-({2-[4-(methylsulfanyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-{[2-(1-methyl-1H-pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(furan-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-({2-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-{[2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-({2-[2-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-{[2-(2,3-dichlorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-methoxy-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-({7-bromo-2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-bromo-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-bromo-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-methyl-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[8-methoxy-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(4-methoxyphenyl)-8-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(4-methoxyphenyl)-8-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[8-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[8-fluoro-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[9-fluoro-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[9-chloro-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[9-methoxy-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(4-methoxyphenyl)-9-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[10-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[10-bromo-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[10-bromo-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[10-chloro-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(4-methoxyphenyl)-10-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(1-methyl-1H-pyrazol-4-yl)-10-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(4-fluorophenyl)-10-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(3-fluorophenyl)-10-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(3-methoxyphenyl)-10-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(4-methoxyphenyl)-10-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[10-methoxy-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one 6-{[10-chloro-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one 6-{[10-chloro-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one 6-{[10-cyclopropyl-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one 6-{[10-cyclopropyl-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[10-chloro-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[10-chloro-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[10-chloro-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[10-chloro-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[10-cyclopropyl-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[10-cyclopropyl-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (3R)-3-({2-[3-(hydroxymethyl)-1,2,4-oxadiazol-5-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-[(2-{3-[(dimethylamino)methyl]-1,2,4-oxadiazol-5-yl}[1,2,4]triazolo[1,5-c]quinazolin-5-yl)amino]azepan-2-one (3R)-3-({2-[3-(2-hydroxyethyl)-1,2,4-oxadiazol-5-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[4-(S-methylsulfonimidoyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R,R)-3-({2-[4-(S-methylsulfonimidoyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R,S)-3-({2-[4-(S-methylsulfonimidoyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)pyrrolidin-2-one (3R)-3-({2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)piperidin-2-one (3R)-1-methyl-3-({2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)pyrrolidin-2-one N 2 -{2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-D-serinamide (2R)-2-({2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3S)-3-({2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one N-methyl-N 2 -{2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-D-norvaline amide N-butyl-N 2 -{2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}glycinamide N-ethyl-2-({2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (2R)-N-ethyl-2-({2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (2S)-N-Ethyl-2-({2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide N-Propyl-N 2 -{2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-D-alaninamide N 2 -{2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}norleucinamide N 2 -{2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-D-norleucinamide N 2 -{2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-L-norleucinamide N-[2-(dimethylamino)ethyl]-N 2 -{2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-D-alaninamide (3R)-3-({2-[4-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[4-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)pyrrolidin-2-one (3R)-1-methyl-3-({2-[4-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)pyrrolidin-2-one N 2 -{2-[4-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-D-serinamide (2R)-2-({2-[4-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3S)-3-({2-[4-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[4-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)piperidin-2-one (3R)-3-{[2-(4-methoxythiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxythiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-{[2-(4-methoxythiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3S)-3-{[2-(4-methoxythiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxythiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-methylpyrrolidin-2-one (2R)-2-{[2-(4-methoxythiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide N 2 -[2-(4-methoxythiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-methyl-D-norvaline amide (3R)-3-{[2-(thiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(thiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(thiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-{[2-(thiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (2R)-2-{[2-(thiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (3R)-1-methyl-3-{[2-(thiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-{[2-(2-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(2-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(2-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-3-{[2-(2-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-1-methyl-3-{[2-(2-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (2R)-2-{[2-(2-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (3R)-3-{[2-(5-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(5-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(5-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-1-methyl-3-{[2-(5-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-{[2-(5-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one N-methyl-N 2 -[2-(5-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-norvaline amide (2R)-2-{[2-(5-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (3R)-3-({2-[3,5-bis(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[3,5-bis(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)pyrrolidin-2-one (2R)-2-({2-[3,5-bis(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3R)-3-({2-[5-(trifluoromethyl)pyridin-3-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[4-(trifluoromethyl)pyridin-2-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3S)-3-({2-[4-(trifluoromethyl)pyridin-2-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[4-(trifluoromethyl)pyridin-2-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)piperidin-2-one (3R)-3-({2-[4-(trifluoromethyl)pyridin-2-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)pyrrolidin-2-one (2R)-2-({2-[4-(trifluoromethyl)pyridin-2-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide N-methyl-N 2 -{2-[4-(trifluoromethyl)pyridin-2-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-D-norvaline amide (3R)-3-{[2-(3-fluoropyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[6-(trifluoromethyl)pyridin-2-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (2R)-2-({2-[6-(trifluoromethyl)pyridin-2-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3R)-3-({2-[4-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[4-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)pyrrolidin-2-one (3R)-3-({2-[4-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)piperidin-2-one (3S)-3-({2-[4-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (2R)-2-({2-[4-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide N 2 -{2-[4-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-methyl-D-norvaline amide (2R)-2-({2-[3-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (2R)-2-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide 3-(5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)benzonitrile (2R)-2-{[2-(3-cyanophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide 3-(5-{[(3R)-2-oxopyrrolidin-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)benzonitrile 3-(5-{[(3R)-2-oxopiperidin-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)benzonitrile 3-(5-{[(3S)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)benzonitrile (2R)-2-{[2-(4-cyanophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide 4-(5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)benzonitrile 4-(5-{[(3R)-2-oxopyrrolidin-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)benzonitrile 4-(5-{[(3R)-2-oxopiperidin-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)benzonitrile (3R)-3-{[2-(imidazo[1,2-a]pyridin-7-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one N 2 -[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-propan-2-yl-D-alaninamide (3R)-3-{[2-(4-methoxyphenyl)-9-(propan-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-fluorophenyl)-7-(propan-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-fluorophenyl)-7-(propan-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-8-(propan-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-10-(oxetan-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-10-(oxan-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-(4-methoxyphenyl)-7-[1-(trifluoromethyl)cyclopropyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-7-(1-methylcyclopropyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one 2-(4-Methoxyphenyl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-8-carbonitrile 2-(4-Methoxyphenyl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-9-carbonitrile 2-(4-Fluorophenyl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-7-carbonitrile 2-(1-methyl-1H-pyrazol-4-yl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-7-carbonitrile (3R)-3-{[10-(difluoromethyl)-9-methyl-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[8-(difluoromethyl)-9-methyl-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-(difluoromethyl)-9-methyl-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({9-methyl-2-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (6R)-6-({2-[3-(dimethylamino)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-{[2-(3,4-dimethoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(4-methoxy-2-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-({2-[4-(cyclopropyloxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-{[2-(5-bromofuran-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(3-aminophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-({2-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-[(2-{4-[(propan-2-yl)oxy]phenyl}[1,2,4]triazolo[1,5-c]quinazolin-5-yl)amino]-1,4-diazepan-5-one (6R)-6-({2-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-{[10-chloro-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(4-methoxyphenyl)-9-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-chloro-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-chloro-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-chloro-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(4-methoxyphenyl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(4-fluorophenyl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(3-fluorophenyl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-fluoro-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-fluoro-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-fluoro-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(4-methoxyphenyl)-7-(propan-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-({2-(1-methyl-1H-pyrazol-4-yl)-7-[1-(trifluoromethyl)cyclopropyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-({2-(4-methoxyphenyl)-7-[1-(trifluoromethyl)cyclopropyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (3R)-3-({2-[1-(2-methoxyethyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one 3-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azocan-2-one (2S)-2-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (3R)-3-{[2-(1-methyl-1H-1,2,3-triazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one 1-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}cyclopropane-1-carboxamide 4-(5-{[(3S)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)benzonitrile N-butyl-N 2 -{2-[4-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}glycinamide N 2 -{2-[4-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-propyl-D-alaninamide (3R)-3-({2-[4-bromo-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one N-butyl-N 2 -[2-(3-cyanophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]alaninamide (2S)-2-{[2-(3-cyanophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide 3-(5-{[2-oxoazocane-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)benzonitrile (3R)-3-({2-[3-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (2R)-2-{[2-(3-bromophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (3R)-3-({2-[3-(dimethylamino)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one 3-({2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azocan-2-one (2S)-2-({2-[3-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3R)-3-({2-[3-(methylsulfanyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (2S)-2-({2-[2-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (2R)-2-({2-[2-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3R)-3-{[2-(2-bromophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(2-bromophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(2-bromophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-3-({2-[2-(dimethylamino)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3S)-3-({2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)piperidin-2-one (3R)-3-({2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)pyrrolidin-2-one (3R)-1-methyl-3-({2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)pyrrolidin-2-one 3-({2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azocan-2-one (2S)-2-({2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide N-ethyl-2-({2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide N-methyl-N 2 -{2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-D-norvaline amide N-Propyl-N 2 -{2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-D-alaninamide N-butyl-N 2 -{2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}glycinamide N 2 -{2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}norleucinamide N 2 -{2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-D-serinamide (2R)-2-({2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3R)-3-({2-[2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3S)-3-({2-[2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)piperidin-2-one (3R)-3-({2-[2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)pyrrolidin-2-one 3-({2-[2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azocan-2-one (2S)-2-({2-[2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (2R)-2-({2-[2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide N 2 -{2-[2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-methyl-D-norvaline amide (3R)-3-({2-[2-(methylsulfanyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(5-fluoropyridin-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(5-chloropyridin-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(3-fluoropyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-fluoropyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-3-{[2-(3-fluoropyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (2R)-2-{[2-(3-fluoropyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide N-butyl-N 2 -[2-(3-fluoropyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]glycinamide N 2 -[2-(3-fluoropyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-methyl-D-norvaline amide N 2 -[2-(3-fluoropyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-propyl-D-alaninamide (3R)-3-({2-[2-(trifluoromethyl)pyridin-3-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (2R)-2-({2-[2-(trifluoromethyl)pyridin-3-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3R)-3-({2-[4-(trifluoromethyl)pyridin-3-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (2R)-2-({2-[4-(trifluoromethyl)pyridin-3-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3R)-3-({2-[5-fluoro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3S)-3-({2-[5-fluoro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one N 2 -{2-[5-fluoro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-methyl-D-norvaline amide N 2 -{2-[5-fluoro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-propyl-D-alaninamide (2R)-2-({2-[5-fluoro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3R)-3-({2-[5-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3S)-3-({2-[5-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[5-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)piperidin-2-one (3R)-3-({2-[5-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)pyrrolidin-2-one N 2 -{2-[5-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-methyl-D-norvaline amide N 2 -{2-[5-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-propyl-D-alaninamide N-butyl-N 2 -{2-[5-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}glycinamide (2R)-2-({2-[5-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3R)-3-({2-[5-bromo-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3S)-3-({2-[5-bromo-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (2R)-2-({2-[5-bromo-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3R)-3-({2-[4-methoxy-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3S)-3-({2-[4-methoxy-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one N 2 -{2-[4-methoxy-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-methyl-D-norvaline amide (2R)-2-({2-[4-methoxy-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3R)-3-({2-[4-methoxy-2-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3S)-3-({2-[4-methoxy-2-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (2S)-2-({2-[4-methoxy-2-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (2R)-2-({2-[4-methoxy-2-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3R)-3-({2-[4-fluoro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3S)-3-({2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)piperidin-2-one (3R)-3-({2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)pyrrolidin-2-one N-butyl-N 2 -{2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}alaninamide (2S)-2-({2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (2R)-2-({2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (2S)-2-({2-[4-bromo-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3R)-3-({2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3S)-3-({2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)piperidin-2-one (3R)-3-({2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)pyrrolidin-2-one 3-({2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azocan-2-one (3S)-3-({2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1-methylazepan-2-one (2R)-2-({2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (2S)-2-({2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide N-butyl-N 2 -{2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}alaninamide (3R)-3-({2-[1-(difluoromethyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(1-cyclopropyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3,5-dimethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(5-bromofuran-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(4-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-3-{[2-(4-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (2R)-2-{[2-(4-methylthiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (3R)-3-{[2-(4-fluorophenyl)-9-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(2-fluorophenyl)-9-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-9-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-methyl-1H-pyrazol-4-yl)-9-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[9-cyclopropyl-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-8-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[8-methoxy-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[8-methoxy-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-fluoro-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-fluoro-2-(pyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-chloro-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-chloro-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-chloro-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one N 2 -[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-valinamide (2R)-2-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide 4-(7-bromo-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)benzonitrile 4-(7-bromo-5-{[(3S)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)benzonitrile 4-(7-bromo-5-{[(3R)-2-oxopiperidin-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)benzonitrile 4-(7-bromo-5-{[(3R)-2-oxopyrrolidin-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)benzonitrile N 2 -[7-bromo-2-(4-cyanophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-methyl-D-norvaline amide (2R)-2-{[7-bromo-2-(4-cyanophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (2S)-2-{[7-bromo-2-(4-cyanophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (3R)-3-({7-bromo-2-[4-methoxy-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3S)-3-({7-bromo-2-[4-methoxy-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (2R)-2-({7-bromo-2-[4-methoxy-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (2S)-2-({7-bromo-2-[4-methoxy-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3R)-3-({7-bromo-2-[4-methoxy-2-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3S)-3-({7-bromo-2-[4-methoxy-2-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({7-bromo-2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3S)-3-({7-bromo-2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (2R)-2-({7-bromo-2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (2S)-2-({7-bromo-2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3R)-3-({7-bromo-2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3S)-3-({7-bromo-2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (2R)-2-({7-bromo-2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide N 2 -[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-valinamide (3R)-3-{[7-bromo-2-(1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-fluorophenyl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(4-methoxyphenyl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}piperidin-2-one (3R)-3-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-{[2-(4-methoxyphenyl)-7-(propan-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(propan-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[8,9-dimethoxy-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[8,9-dimethoxy-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7,9-dibromo-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7,9-dibromo-2-(3-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7,9-dibromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7,9-dibromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[1-(oxetan-3-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-[(2-{1-[2-(dimethylamino)ethyl]-1H-pyrazol-4-yl}[1,2,4]triazolo[1,5-c]quinazolin-5-yl)amino]azepan-2-one (3R)-3-({2-[1-(oxan-4-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(1-cyclobutyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[3-(trifluoromethyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(1,3-dimethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1,2,5-trimethyl-1H-pyrrol-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one 1,5-dimethyl-3-(5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)-1H-pyrrole-2-carbonitrile (3R)-3-{[2-(1-tert-butyl-1H-pyrazol-5-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(5-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-methyl-1H-imidazol-5-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(2-chlorothiophen-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[4-(cyclopropyloxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-[(2-{4-[(propan-2-yl)oxy]phenyl}[1,2,4]triazolo[1,5-c]quinazolin-5-yl)amino]azepan-2-one (3R)-3-{[2-(4-hydroxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[4-(difluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(4-ethoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[4-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(2-hydroxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one 2-(5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)benzonitrile (3R)-3-{[2-(4-aminophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-aminophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(2-aminophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(2,6-dimethylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3,4-dimethoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-chloro-4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-fluoro-3-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxy-3-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxy-2-methylphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-fluoro-4-hydroxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[2-fluoro-4-(methylsulfanyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(2-fluoro-4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-[(2-{3-fluoro-4-[(propan-2-yl)oxy]phenyl}[1,2,4]triazolo[1,5-c]quinazolin-5-yl)amino]azepan-2-one (3R)-3-{[2-(3,4-difluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(2-fluoro-4-hydroxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-fluoro-4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(5-methylpyridin-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(6-aminopyridin-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(2-fluoropyridin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(6-fluoropyridin-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(2-fluoropyridin-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(5-fluoro-6-methylpyridin-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(pyrimidin-5-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[2-(trifluoromethyl)pyrimidin-5-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(pyridazin-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1,2-thiazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[1-(piperidin-4-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[10-(azetidin-3-yl)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-[(2-{2-[methanesulfinyl]phenyl}[1,2,4]triazolo[1,5-c]quinazolin-5-yl)amino]azepan-2-one (3R)-3-({2-[2-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[2-(S-methylsulfonimidoyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[3-(S-methylsulfonimidoyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one Methyl 2-(1-methyl-1H-pyrazol-4-yl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-7-carboxylate Propan-2-yl 2-(4-methoxyphenyl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-7-carboxylate (3R)-3-{[2-(4-methoxyphenyl)-7-(morpholin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-10-(morpholin-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (6R)-6-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-methyl-1,4-diazepan-5-one Ethyl N-[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninate N-[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanine (3R,R)-3-({2-[3-(S-methylsulfonimidoyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R,S)-3-({2-[3-(S-methylsulfonimidoyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R,R)-3-({2-[2-(S-methylsulfonimidoyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R,S)-3-({2-[2-(S-methylsulfonimidoyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (2R)-N-ethyl-2-({2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (2S)-N-ethyl-2-({2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide N-Cyclohexyl-N2-[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide N-Cyclopentyl-N 2 -[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide (3R)-3-{[7-ethoxy-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-(2,2-difluoropropoxy)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-hydroxy-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-7-(3,3,3-trifluoropropoxy)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one 4-[5-{[(3R)-2-oxoazepan-3-yl]amino}-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-2-yl]benzonitrile (3R)-3-({2-[4-chloro-2-(trifluoromethoxy)phenyl]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[4-chloro-2-(difluoromethoxy)phenyl]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-ethyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-cyclopropyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[1-(propan-2-yl)-1H-pyrazol-4-yl]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(1,3-dimethyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3S)-3-({7-bromo-2-[4-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (6S)-6-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-oxazepan-5-one (3S)-3-({2-[4-bromo-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (2S)-2-({7-bromo-2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-N-propylbutanamide N 2 -{7-bromo-2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-butyl-D-alaninamide (2S)-2-({7-bromo-2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-N-propylbutanamide N 2 -{7-bromo-2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-butyl-L-alaninamide N 2 -{7-bromo-2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-butyl-L-alaninamide (2S)-2-{[2-(pyrazin-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (3R)-3-{[2-(pyrazin-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (2S)-2-{[2-(1-methyl-1H-1,2,3-triazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (2R)-2-{[2-(pyrazin-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide N 2 -{7-bromo-2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-propyl-D-alaninamide N 2 -{7-bromo-2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-propyl-D-alaninamide (2S)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (3S)-3-{[2-(pyrazin-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (2R)-2-({2-[4-bromo-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (2S)-2-({7-bromo-2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (6R)-6-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-oxazepan-5-one (2R)-2-({2-[4-bromo-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3S)-3-({2-[4-bromo-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (2S)-2-({2-[4-bromo-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3R)-3-({2-[4-bromo-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (2R)-2-({2-[2-(1,1,2,2-tetrafluoroethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (2S)-2-({2-[2-(1,1,2,2-tetrafluoroethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)butanamide (3S)-3-({2-[2-(1,1,2,2-tetrafluoroethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[2-(1,1,2,2-tetrafluoroethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one N-butyl-N 2 -{2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-L-alaninamide 4-[5-{[(6R)-5-oxo-1,4-diazepan-6-yl]amino}-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-2-yl]benzonitrile (6R)-6-({2-[4-chloro-2-(trifluoromethoxy)phenyl]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-({2-[4-chloro-2-(difluoromethoxy)phenyl]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-{[2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(1-ethyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-({2-[4-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-({7-bromo-2-[4-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-({2-[1-(propan-2-yl)-1H-pyrazol-4-yl]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one 4-(7-bromo-5-{[(6R)-5-oxo-1,4-diazepan-6-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)benzonitrile 4-(5-{[(6R)-5-oxo-1,4-diazepan-6-yl]amino}[1,2,4]triazolo[1,5-c]quinazolin-2-yl)benzonitrile (6R)-6-({2-[5-fluoro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-({2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one 2-(4-Methoxyphenyl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-7-carbonitrile (3R)-3-({2-[4-methoxy-3-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one N 2 -{7-bromo-2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-butyl-D-alaninamide N-butyl-N 2 -{2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-D-alaninamide N 2 -[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-butyl-L-alaninamide (3R)-3-{[2-(4-methoxyphenyl)-10-(propan-2-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (6R)-6-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one hydrochloride 4,4-dimethyl-3-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (-)-4,4-dimethyl-3-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (+)-4,4-Dimethyl-3-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one 3-(dimethylamino)-N-methyl-N 2 -[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide (6R)-6-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-oxazepan-5-one (3R)-1-methyl-3-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}pyrrolidin-2-one (3R)-3-{[2-(1,5-dimethyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-methyl-1H-pyrazol-3-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[1-(difluoromethyl)-1H-pyrazol-4-yl]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(1H-pyrazol-3-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-ethyl-3,5-dimethyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-1-methyl-3-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1,3-dimethyl-1H-pyrazol-5-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-cyclobutyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(1-cyclopropyl-3,5-dimethyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(3-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-cyclopropyl-1,3-thiazol-2-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[3-methyl-1-(propan-2-yl)-1H-pyrazol-4-yl]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(1-cyclopropyl-3-ethyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-(trifluoromethyl)-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one N-butyl-N 2 -[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide (3R)-3-{[7-methoxy-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)-7-methoxy[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-ethyl-1H-pyrazol-4-yl)-7-methoxy[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-methoxy-2-(1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-methoxy-2-(1-methyl-1H-1,2,3-triazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-cyclopropyl-1H-pyrazol-4-yl)-7-methoxy[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-cyclobutyl-1H-pyrazol-4-yl)-7-methoxy[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-[1-(propan-2-yl)-1H-pyrazol-4-yl]-7-(trifluoromethoxy)[1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one 5-{[(3R)-2-oxoazepan-3-yl]amino}-2-[1-(propan-2-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazoline-7-carbonitrile 2-(1-cyclopropyl-1H-pyrazol-4-yl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-7-carbonitrile 2-(1-cyclobutyl-1H-pyrazol-4-yl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-7-carbonitrile 2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-7-carbonitrile 2-[1-(difluoromethyl)-1H-pyrazol-4-yl]-5-{[(3R)-2-oxoazepan-3-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-7-carbonitrile 5-{[(3R)-2-oxoazepan-3-yl]amino}-2-(1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazoline-7-carbonitrile (3R)-3-{[2-(4-methoxyphenyl)-7-(methylsulfanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-(4-methoxyphenyl)-7-[(propan-2-yl)sulfanyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({2-(1-methyl-1H-pyrazol-4-yl)-7-[(propan-2-yl)sulfanyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[7-(ethylsulfanyl)-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-(ethylsulfanyl)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({7-(methylsulfanyl)-2-[1-(propan-2-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)-7-(methylsulfanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (2R)-2-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-(morpholin-4-yl)propan-1-one N-[2-(dimethylamino)ethyl]-N 2 -{2-[4-(methanesulfonyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-D-alaninamide N 2 -{2-[5-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-[2-(dimethylamino)ethyl]-D-alaninamide N-[2-(dimethylamino)ethyl]-N 2 -[2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide (2R)-2-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-(4-methylpiperazin-1-yl)propan-1-one (2R)-2-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-(morpholin-4-yl)propan-1-one N 2 -[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(morpholin-4-yl)ethyl]-D-alaninamide N 2 -[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(4-methylpiperazin-1-yl)ethyl]-D-alaninamide N 2 -[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(morpholin-4-yl)ethyl]-D-alaninamide N 2 -[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(morpholin-4-yl)ethyl]-D-alaninamide N 2 -[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(4-methylpiperazin-1-yl)ethyl]-D-alaninamide N-(2-amino-2-methylpropyl)-N 2 -[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-(morpholin-4-yl)propan-1-one (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-(4-methylpiperazin-1-yl)propan-1-one N-[2-(dimethylamino)ethyl]-N 2 -[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide (2R)-2-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-(4-methylpiperazin-1-yl)propan-1-one N-(2-amino-2-methylpropyl)-N 2 -[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide N-(2-amino-2-methylpropyl)-N 2 -[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide Formic acid N-[2-(dimethylamino)ethyl]-N 2 -{2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-D-alaninamide (1 / 1) N-[2-(dimethylamino)ethyl]-N 2 -{2-[2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-D-alaninamide (2R)-2-{[2-(1-methyl-1H-1,2,3-triazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide N 2 -[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-butyl-D-alaninamide N 2 -[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-propyl-D-alaninamide (2R)-2-({7-bromo-2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-N-propylbutanamide (2R)-2-({7-bromo-2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-N-ethylbutanamide (2S)-2-({7-bromo-2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-N-ethylbutanamide (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-5-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (2S)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-5-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide N 2 -{7-bromo-2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-propyl-L-alaninamide (2S)-2-({7-bromo-2-[4-chloro-2-(difluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-N-butylbutanamide (2S)-2-{[2-(1-methyl-1H-pyrazol-5-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (2R)-2-{[2-(1-methyl-1H-pyrazol-5-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}butanamide (3S)-3-{[2-(1-methyl-1H-pyrazol-5-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-methyl-1H-pyrazol-5-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one N 2 -[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[3-(dimethylamino)propyl]-D-alaninamide N 2 -[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[3-(dimethylamino)propyl]-D-alaninamide N 2 -{7-bromo-2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}-N-propyl-L-alaninamide (2R)-2-({7-bromo-2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-N-propylbutanamide (2S)-2-({7-bromo-2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-N-butylbutanamide (2R)-2-({7-bromo-2-[4-chloro-2-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-N-butylbutanamide (3R)-3-{[7-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-chloro-2-(1-cyclopropyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({7-chloro-2-[1-(propan-2-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[7-chloro-2-(1-ethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-chloro-2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({7-cyclopropyl-2-[1-(propan-2-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[7-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({7-bromo-2-[1-(propan-2-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[7-bromo-2-(1,5-dimethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-bromo-2-(1-cyclobutyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-bromo-2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({7-bromo-2-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-({7-bromo-2-[1-(difluoromethyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[7-bromo-2-(4-chlorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-bromo-2-(1-ethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({7-bromo-2-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(4-chlorophenyl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one Benzyl (6R)-6-({7-fluoro-2-[1-(propan-2-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-5-oxo-1,4-diazepane-1-carboxylate (6S)-6-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-thiazepan-5-one (6S)-6-({2-[1-(propan-2-yl)-1H-pyrazol-4-yl]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-thiazepan-5-one (6S)-6-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-thiazepan-5-one (6R)-6-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-thiazepan-5-one (6R)-6-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-thiazepan-5-one (3R)-3-{[7-(methanesulfonyl)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-7-(propane-2-sulfonyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-(ethanesulfonyl)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(propane-2-sulfonyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({7-(methanesulfonyl)-2-[1-(propan-2-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)-7-(methanesulfonyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (6R)-6-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1λ 6 ,4-thiazepane-1,1,5-trione (1R*, 6R)-6-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1λ 4 ,4-thiazepane-1,5-dione (6S)-6-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1λ 6 ,4-thiazepane-1,1,5-trione (6S)-6-({2-[1-(propan-2-yl)-1H-pyrazol-4-yl]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1λ 6 ,4-thiazepane-1,1,5-trione (3R)-3-{[7-(S-methanesulfonimidoyl)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (6R)-6-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-imino-1λ 6 ,4-thiazepane-1,5-dione (3R)-3-{[7-(methanesulfonyl)-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-(2-hydroxypropan-2-yl)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-(hydroxymethyl)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-(2-hydroxypropan-2-yl)-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[10-(hydroxymethyl)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({2-(4-methoxyphenyl)-7-[(methylsulfanyl)methyl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one Ethyl N-[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninate Methyl N-[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-valinate Methyl N-[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-valinate N-[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanine N-[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanine N-[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanine N-[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-valine N-[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-valine (2R)-2-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-(morpholin-4-yl)propan-1-one (2R)-1-(4-methylpiperazin-1-yl)-2-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}propan-1-one (2R)-1-[3-(dimethylamino)pyrrolidin-1-yl]-2-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}propan-1-one N-[2-(dimethylamino)ethyl]-N-methyl-N 2 -[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide N-(2-methoxyethyl)-N-methyl-N 2 -[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide N-[2-(4-methylpiperazin-1-yl)ethyl]-N 2 -[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninamide (2R)-2-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-(2-oxa-6-azaspiro[3.3]heptan-6-yl)propan-1-one N 2 -[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(4-methylpiperazin-1-yl)ethyl]-D-alaninamide tert-Butyl 4-{N-[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanyl}piperazine-1-carboxylate tert-Butyl 4-{N-[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanyl}piperazine-1-carboxylate tert-Butyl 4-[2-({N-[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanyl}amino)ethyl]piperazine-1-carboxylate N 2 -[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-(2-methoxyethyl)-D-alaninamide tert-Butyl 4-{N-[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanyl}piperazine-1-carboxylate tert-Butyl [2-({N-[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanyl}amino)ethyl]methylcarbamate tert-Butyl [2-({N-[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanyl}amino)ethyl]methylcarbamate tert-Butyl [2-({N-[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanyl}amino)ethyl]methylcarbamate tert-Butyl 4-[2-({N-[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanyl}amino)ethyl]piperazine-1-carboxylate tert-Butyl 4-[2-({N-[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanyl}amino)ethyl]piperazine-1-carboxylate Methyl 4-{N-[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanyl}piperazine-1-carboxylate N 2 -[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(piperidin-1-yl)ethyl]-D-alaninamide N 2 -[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(piperidin-1-yl)ethyl]-D-alaninamide N 2 -[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(piperidin-1-yl)ethyl]-D-alaninamide (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]propan-1-one (2R)-2-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]propan-1-one (2R)-2-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-[(1R,4R)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]propan-1-one N 2 -[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-(2-hydroxy-2-methylpropyl)-D-alaninamide N 2 -[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-(2-hydroxy-2-methylpropyl)-D-alaninamide (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-[(2S)-2-methylmorpholin-4-yl]propan-1-one (2R)-2-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-[(2S)-2-methylmorpholin-4-yl]propan-1-one (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-[(3R)-3,4-dimethylpiperazin-1-yl]propan-1-one (2R)-2-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-[(3R)-3-methylmorpholin-4-yl]propan-1-one (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-[(3R)-3-methylmorpholin-4-yl]propan-1-one (2R)-2-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-[(3R)-3,4-dimethylpiperazin-1-yl]propan-1-one (2R)-2-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]propan-1-one (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]propan-1-one (2R)-2-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-(2-oxa-6-azaspiro[3.3]heptan-6-yl)propan-1-one (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-(2-oxa-6-azaspiro[3.3]heptan-6-yl)propan-1-one (2R)-2-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl)propan-1-one (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl)propan-1-one tert-Butyl 6-{N-[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanyl}-2,6-diazaspiro[3.3]heptane-2-carboxylate tert-Butyl 6-{N-[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanyl}-2,6-diazaspiro[3.3]heptane-2-carboxylate (2R)-2-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-3-methyl-1-(4-methylpiperazin-1-yl)butan-1-one N 2 -[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-(2-methoxyethyl)-D-valinamide N 2 -[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(4-methylpiperazin-1-yl)ethyl]-D-valinamide (2R)-2-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-3-methyl-1-(morpholin-4-yl)butan-1-one (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-3-methyl-1-(morpholin-4-yl)butan-1-one N 2 -[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(4-methylpiperazin-1-yl)ethyl]-D-valinamide (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-3-methyl-1-(4-methylpiperazin-1-yl)butan-1-one N 2 -[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-(2-methoxyethyl)-D-valinamide 2-(1-methyl-1H-pyrazol-4-yl)-5-{[(6R)-5-oxo-1,4-diazepan-6-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-7-carbonitrile 5-{[(6R)-5-oxo-1,4-diazepan-6-yl]amino}-2-[1-(propan-2-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazoline-7-carbonitrile 2-(1-cyclopropyl-1H-pyrazol-4-yl)-5-{[(6R)-5-oxo-1,4-diazepan-6-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-7-carbonitrile 2-(1-cyclobutyl-1H-pyrazol-4-yl)-5-{[(6R)-5-oxo-1,4-diazepan-6-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-7-carbonitrile 2-[1-(difluoromethyl)-1H-pyrazol-4-yl]-5-{[(6R)-5-oxo-1,4-diazepan-6-yl]amino}[1,2,4]triazolo[1,5-c]quinazoline-7-carbonitrile 5-{[(6R)-5-oxo-1,4-diazepan-6-yl]amino}-2-(1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazoline-7-carbonitrile (6R)-6-{[7-(methanesulfonyl)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-(methanesulfonyl)-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-(ethylsulfanyl)-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-(ethylsulfanyl)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-(ethanesulfonyl)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(4-methoxyphenyl)-7-(propane-2-sulfonyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-(ethanesulfonyl)-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(1-methyl-1H-pyrazol-4-yl)-7-(propane-2-sulfonyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-({7-(methanesulfonyl)-2-[1-(propan-2-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-{[2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)-7-(methanesulfonyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(1-methyl-1H-pyrazol-5-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(4-chlorophenyl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[2-(1,3-dimethyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[2-(1-cyclopropyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-({7-cyclopropyl-2-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-({7-cyclopropyl-2-[1-(propan-2-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-({7-chloro-2-[1-(propan-2-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-{[7-chloro-2-(1-ethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-chloro-2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[7-cyclopropyl-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-({2-[1-(propan-2-yl)-1H-pyrazol-4-yl]-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-{[7-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(1-cyclopropyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[7-chloro-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-chloro-2-(1-cyclopropyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[2-(1-methyl-1H-pyrazol-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-({7-bromo-2-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-{[2-(1,5-dimethyl-1H-pyrazol-4-yl)-7-fluoro[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[2-(4-methoxyphenyl)-7-methyl[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-({7-fluoro-2-[1-(propan-2-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6S)-6-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[7-bromo-2-(4-fluorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-bromo-2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(1,3-dimethyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-bromo-2-(1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-bromo-2-(4-chlorophenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-({7-bromo-2-[1-(difluoromethyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-{[7-bromo-2-(1,5-dimethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-bromo-2-(1-ethyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-({7-bromo-2-[1-(propan-2-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6R)-6-({7-bromo-2-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (6S)-6-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-({7-bromo-2-[1-(propan-2-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)-1,4-diazepan-5-one (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-(piperazin-1-yl)propan-1-one hydrogen chloride (1 / 1) (2R)-2-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-(piperazin-1-yl)propan-1-one N 2 -[7-Bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(methylamino)ethyl]-D-alaninamide hydrochloride (1 / 1) (2R)-2-{[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-(piperazin-1-yl)propan-1-one hydrogen chloride (1 / 1) N 2 -[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(methylamino)ethyl]-D-alaninamide N 2 -[2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(methylamino)ethyl]-D-alaninamide hydrochloride (1 / 1) N 2 -[7-Bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(methylamino)ethyl]-D-alaninamide hydrochloride (1 / 1) N 2 -[7-Bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(piperazin-1-yl)ethyl]-D-alaninamide hydrochloride (1 / 2) N 2 -[7-Bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-N-[2-(piperazin-1-yl)ethyl]-D-alaninamide hydrochloride (1 / 2) (6R)-6-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-methyl-1,4-diazepan-5-one (6R)-6-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-methyl-1,4-diazepan-5-one (3R)-3-{[7-(3-methoxy-3-methylbutoxy)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-(2-hydroxy-2-methylpropoxy)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-(cyclobutyloxy)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-(cyclopropyloxy)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-(3-hydroxy-3-methylbutoxy)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-7-(2-oxopyrrolidin-1-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(4-methoxyphenyl)-7-(oxetan-3-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-(methoxymethyl)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-(methoxymethyl)-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-(dimethylamino)-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[7-(dimethylamino)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-{[2-(1,5-dimethyl-1H-pyrazol-4-yl)-7-fluoro[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one (3R)-3-({7-fluoro-2-[1-(propan-2-yl)-1H-pyrazol-4-yl][1,2,4]triazolo[1,5-c]quinazolin-5-yl}amino)azepan-2-one (3R)-3-{[7-(methanesulfonimidoyl)-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}azepan-2-one Ethyl N-[2-(1-methyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninate Ethyl N-[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alaninate Methyl 4-{N-[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]-D-alanyl}piperazine-1-carboxylate (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-[(1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]propan-1-one (2R)-2-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-[(1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]propan-1-one (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-[(1R,4R)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]propan-1-one (2R)-2-{[7-bromo-2-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-[(2R)-2-methylmorpholin-4-yl]propan-1-one (2R)-2-{[7-bromo-2-(4-methoxyphenyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1-[(2R)-2-methylmorpholin-4-yl]propan-1-one (6R)-6-{[7-bromo-2-(1-cyclopropyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6S)-6-{[7-bromo-2-(1-cyclopropyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[7-chloro-2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one (6R)-6-{[2-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro[1,2,4]triazolo[1,5-c]quinazolin-5-yl]amino}-1,4-diazepan-5-one 3. The compound according to claim 1 or 2, selected from the group consisting of: a polymorph, enantiomer, diastereomer, racemate, tautomer, N-oxide, hydrate or solvate thereof, or a physiologically acceptable salt thereof or a solvate of such a salt, or a mixture thereof.

4. A method for preparing a compound of general formula (I) according to any one of claims 1 to 3, comprising the step of: 【Chemistry 3】 (In the formula, R 1 , R 5 , R 6 , R 7 and R 8 is as defined for compounds of general formula (I) according to any one of claims 1 to 2) The intermediate compound of general formula (VII): 【Chemistry 4】 (In the formula, R 2 , R 3 and R 4 is as defined for compounds of general formula (I) according to any one of claims 1 to 2) By reacting with the compound Thereby, the general formula (I): 【Chemistry 5】 (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 is as defined for compounds of general formula (I) according to any one of claims 1 to 2) obtaining a compound of formula (I).

5. 4. A compound according to any one of claims 1 to 3 for use in the treatment or prevention of a disease.

6. 4. A pharmaceutical composition comprising a compound according to any one of claims 1 to 3 and one or more pharmaceutically acceptable excipients.

7. one or more compounds according to any one of claims 1 to 3 as a first active ingredient, and one or more pharmaceutically active anti-cancer compounds, or one or more pharmaceutically active immune checkpoint inhibitors 10. A pharmaceutical combination comprising:

8. 10. A composition comprising a compound according to any one of claims 1 to 3 for treating or preventing a disease, wherein the disease is cancer or a condition involving a dysregulated immune response, such as liquid and solid tumors, or other disorders associated with abnormal AHR signaling.

9. 10. Use of a compound according to any one of claims 1 to 3 for the preparation of a medicament for treating or preventing a disease, wherein the disease is cancer or a condition involving a dysregulated immune response, such as liquid and solid tumors, or other disorders associated with abnormal AHR signaling.

10. General formula (V): 【Chemistry 6】 (In the formula, R 1 , R 5 , R 6 , R 7 and R 8 is as defined for compounds of general formula (I) according to claim 1 or 2, However, R 1 is phenyl or 4-chlorophenyl, R 5 , R 6 , R 7 and R 8 does not simultaneously represent hydrogen, The compound is not 5,9-dichloro-2-(2-furyl)[1,2,4]triazolo[1,5-c]quinazoline. Compound.

11. For preparing a compound of general formula (I) according to claim 1 or 2, General formula (V) 【Chemistry 7】 (In the formula, R 1 , R 5 , R 6 , R 7 and R 8 is as defined for the compounds of general formula (I) according to claim 1 or 2) Use of compounds.

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