Thiazole derivative compound and application thereof

Abstract

The present invention relates to a novel thiazole derivative compound, a compound selected from pharmaceutically acceptable salts thereof, solvates thereof or stereoisomers thereof, and medical uses thereof. The present invention provides a TGF [beta] R1 (ALK5) inhibitor that selectively inhibits only TGF [beta] R1 without interfering with the normal TGF [beta] signal, and that novel TGF [beta] R1 inhibitors are useful for a variety of indications (e.g., anti-cancer drugs).

Description

Technical Field

[0001] The present disclosure relates to a thiazole derivative compound and a medical use thereof. The thiazole derivative compound is a novel TGFβR1 (ALK5) inhibitor. Background Art

[0002] The transforming growth factor β (TGFβ) superfamily of growth factors is involved in cell growth inhibition, tissue homeostasis, extracellular matrix (ECM) remodeling, endothelial-mesenchymal transition (EMT), cell migration and invasion, immune regulation, and numerous signaling pathways that regulate a variety of biological processes, including mesenchymal-epithelial transition.

[0003] Regarding ECM remodeling, TGFβ signaling can increase the number of fibroblasts and ECM deposition, while TGFβ ligands can regulate the function of regulatory T cells, the growth of immune precursor cells, and the maintenance of homeostasis in the immune system.

[0004] In normal epithelial cells, TGFβ is a potent growth inhibitor and cell differentiation promoter, but with the occurrence and development of tumors, TGFβ can become a promoter of tumorigenesis by stimulating angiogenesis, changing the matrix environment, and inducing local and systemic immunosuppression.

[0005] Therefore, TGFβ is considered a therapeutic target for a variety of clinical indications, but despite the efforts of many groups to develop TGFβ therapeutics, no safe and effective TGFβ therapeutics have yet been developed.

[0006] Therefore, there is a need to develop therapeutic drugs for various indications (e.g., immuno-oncology drugs) by developing low-molecular-weight TGFβR1 (activin receptor-like kinase 5 (ALK5)) selective inhibitors, which are effective in TGFβ therapeutic drugs with few side effects and are becoming therapeutic targets for various clinical indications. Summary of the invention

[0007] Technical Purpose

[0008] The object of the present disclosure is to provide a compound selected from a novel thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof or a stereoisomer thereof.

[0009] Another object of the present disclosure is to provide a pharmaceutical composition for treating or preventing cancer diseases, the pharmaceutical composition comprising a compound as an active ingredient, the compound being selected from a thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0010] Another object of the present disclosure is to provide a health functional food composition for improving or preventing cancer diseases, wherein the health functional food composition comprises a compound as an active ingredient, wherein the compound is selected from a thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0011] Another object of the present disclosure is to provide a reagent composition for inhibiting the expression of transforming growth factor β (TGFβ), the reagent composition comprising a compound as an active ingredient, the compound being selected from a thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0012] Technical Solution

[0013] To achieve the above object, the present disclosure provides a compound selected from the group consisting of a thiazole derivative compound represented by the following Chemical Formula 1, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0014] [Chemical formula 1]

[0015]

[0016] In chemical formula 1, A 1 O or S, A 2 CH or N, R 1 and R 2 The alkyl groups may be the same or different and each may be one of the following: (C1-C4)alkyl, (C1-C4)alkylene, (C1-C4)alkoxy, trifluoromethyl (CF 3 ), halogen, NR 11 R 12 , unsubstituted or substituted (C3-C8)cycloalkyl, unsubstituted or substituted (C5-C10)aryl, and unsubstituted or substituted heteroaryl containing 5 to 10 atoms of one or more heteroatoms selected from the group consisting of N, O and S; R 11 and R 12 may be the same or different and each is any one of the following: hydrogen, (C1-C5) alkyl, (C3-C8) cycloalkyl; the substituted (C3-C8) cycloalkyl, substituted (C5-C10) aryl, or 5 to 10 atoms of substituted heteroaryl is substituted by (C1-C5) alkyl; n is one of 0 to 3, Ar is unsubstituted or substituted (C5-C10) aryl or 5 to 10 atoms of unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, the substituted (C5-C10) aryl or 5 to 10 atoms of substituted heteroaryl is substituted by R 3 Replacement, R 3 For-R 3-1or -(C1-C5)alkyl-R 3-1 , R 3-1 is hydrogen, halogen, hydroxyl, cyano, (C1-C5) alkyl, (C1-C5) alkoxy, -CONR 31-1 R 31-2 、-COOR 32 、-NHSO 2 R 33 、-SO 2 R 34 、-SO 2 NR 35-1 R 35-2 、-COR 36 、-NH-(C1-C3)alkyl-R 37 , as well as Any of the R 31-1 , R 31-2 , R 32 , R 33 , R 34 , R 35-1 and R 35-2 may be the same or different and are each hydrogen, hydroxy, trifluoromethyl, (C1-C5)alkyl, (C3-C8)cycloalkyl, -SO 2 -(C1-C3)alkyl, -(C1-C3)alkyl-R 301 as well as R 301 is (C1-C4) alkylamino, di[(C1-C4) alkyl]amino, (C3-C8) cycloalkyl, as well as Any of the R 3001 is hydrogen or (C1-C5) alkyl, R 302 It is a halogen.

[0017] R 303 and R 304 may be the same or different and are each hydrogen or (C1-C3) alkyl, R 36 and R 37 may be the same or different and each is R 305 is hydrogen or (C1-C5) alkyl, R 306 is any one of hydrogen, amino, (C1-C4) alkylamino and di[(C1-C4) alkyl]amino, R 38 and R 39 The groups may be the same or different and are each any one of hydrogen, (C1-C3) alkyl, and -(C1-C3) alkyl-(C1-C3) alkoxy.

[0018] In addition, the present disclosure provides a pharmaceutical composition for treating or preventing cancer diseases, the pharmaceutical composition comprising a compound as an active ingredient, the compound being selected from a thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0019] In addition, the present disclosure provides a health functional food composition for improving or preventing cancer diseases, the health functional food composition comprising a compound as an active ingredient, the compound being selected from a thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0020] In addition, the present disclosure provides an agent composition for inhibiting the expression of transforming growth factor β (TGFβ), the agent composition comprising a compound as an active ingredient, the compound being selected from a thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0021] Beneficial Effects

[0022] The present disclosure relates to a compound and its use, wherein the compound is selected from a novel thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof or a stereoisomer thereof, wherein the compound selectively inhibits only TGFβR1 without interfering with normal TGFβ signaling, and the compound has a therapeutic effect on a variety of related cancer diseases, and thus the compound can be widely used in treatment methods in medical institutions such as hospitals. DETAILED DESCRIPTION

[0023] Hereinafter, the present disclosure will be described in detail.

[0024] The present disclosure provides a compound selected from a thiazole derivative compound represented by the following Chemical Formula 1, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0025] [Chemical formula 1]

[0026]

[0027] In chemical formula 1, A 1 O or S, A 2 CH or N, R 1 and R 2 The alkyl groups may be the same or different and each may be one of the following: (C1-C4)alkyl, (C1-C4)alkylene, (C1-C4)alkoxy, trifluoromethyl (CF 3 ), halogen, NR 11 R 12, unsubstituted or substituted (C3-C8)cycloalkyl, unsubstituted or substituted (C5-C10)aryl, and unsubstituted or substituted heteroaryl containing 5 to 10 atoms of one or more heteroatoms selected from the group consisting of N, O and S; R 11 and R 12 may be the same or different and each is any one of the following: hydrogen, (C1-C5) alkyl, (C3-C8) cycloalkyl; the substituted (C3-C8) cycloalkyl, substituted (C5-C10) aryl, or 5 to 10 atoms of substituted heteroaryl is substituted by (C1-C5) alkyl; n is one of 0 to 3, Ar is unsubstituted or substituted (C5-C10) aryl or 5 to 10 atoms of unsubstituted or substituted heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, the substituted (C5-C10) aryl or 5 to 10 atoms of substituted heteroaryl is substituted by R 3 Replacement, R 3 For-R 3-1 or -(C1-C5)alkyl-R 3-1 , R 3-1 is hydrogen, halogen, hydroxyl, cyano, (C1-C5) alkyl, (C1-C5) alkoxy, -CONR 31-1 R 31-2 、-COOR 32 、-NHSO 2 R 33 、-SO 2 R 34 、-SO 2 NR 35-1 R 35-2 、-COR 36 、-NH-(C1-C3)alkyl-R 37 , as well as Any of the R 31-1 , R 31-2 , R 32 , R 33 , R 34 , R 35-1 and R 35-2 may be the same or different and are each hydrogen, hydroxy, trifluoromethyl, (C1-C5)alkyl, (C3-C8)cycloalkyl, -SO 2 -(C1-C3)alkyl, -(C1-C3)alkyl-R 301 as well as R 301 is (C1-C4) alkylamino, di[(C1-C4) alkyl]amino, (C3-C8) cycloalkyl, as well as Any of the R3001 is hydrogen or (C1-C5) alkyl, R 302 It is a halogen.

[0028] R 303 and R 304 may be the same or different and are each hydrogen or (C1-C3) alkyl, R 36 and R 37 may be the same or different and each is R 305 is hydrogen or (C1-C5) alkyl, R 306 is any one of hydrogen, amino, (C1-C4) alkylamino and di[(C1-C4) alkyl]amino, and R 38 and R 39 The groups may be the same or different and are each any one of hydrogen, (C1-C3) alkyl, and -(C1-C3) alkyl-(C1-C3) alkoxy.

[0029] In Chemical Formula 1, R 1 (C1-C3) alkyl, (C1-C3) alkylene, methoxy, trifluoromethyl (CF 3 ), bromine (Br), (C3-C6) cycloalkyl and NR 11 R 12 Any of the R 11 and R 12 may be the same or different and each is any one of hydrogen, (C1-C3) alkyl and cyclopropyl, R 2 for or naphthyl, A 3 CH or N, R 21 is hydrogen or methyl, n is one of 0 to 2, Ar is as well as Any of the R 3 For-R 3-1 or -(C1-C3)alkyl-R 3-1 , R 3-1 is hydrogen, fluorine, chlorine, hydroxyl, cyano, (C1-C3) alkyl, (C1-C3) alkoxy, -CONR 31-1 R 31-2 、-COOR 32 、-NHSO 2 R 33 、-SO 2 R 34 、-SO 2 NR 35-1 R 35-2 、-COR 36 、-NH-(C1-C3)alkyl-R 37 , as well as Any of the R 31-1 , R 31-2 , R 32 , R 33 , R 34 , R 35-1 and R 35-2 may be the same or different and are each hydrogen, hydroxy, trifluoromethyl, (C1-C3) alkyl, (C3-C6) cycloalkyl, -SO 2 CH 3 、-(C1-C3)alkyl-R 301 as well as R 301 Methylamino, dimethylamino, cyclopropyl, as well as Any of the R 3001 is hydrogen or (C1-C3) alkyl, R 302 is fluorine, R 303 and R 304 may be the same or different and each is hydrogen or methyl, R 36 and R 37 may be the same or different and each is R 305 is (C1-C3) alkyl, R 306 is any one of hydrogen, amino and methylamino, R 38 and R 39 The groups may be the same or different and are each any one of hydrogen, (C1-C3) alkyl and -(C1-C3) alkyl-methoxy.

[0030] In Chemical Formula 1, R 1 Methyl, ethyl, isopropyl, ethylene, methoxy, trifluoromethyl (CF 3 ), bromine (Br), cyclopropyl, cyclopentyl, cyclohexyl and NR 11 R 12 Any of the R 11 and R 12 may be the same or different and each is any one of hydrogen, methyl and cyclopropyl, R 2 for as well as One of: n is one of 0 to 2, Ar is as well as Any of the R 3 For-R 3-1 or -(C1-C3)alkyl-R 3 -1 , R 3-1 is hydrogen, fluorine, chlorine, hydroxyl, cyano, methyl, methoxy, -CONR 31-1 R31-2 、-COOR 32 、-NHSO 2 R 33 、-SO 2 R 34 、-SO 2 NR 35-1 R 35-2 、-COR 36 、-NH-(C1-C2)alkyl-R 37 , as well as Any of the R 31-1 and R 31-2 may be the same or different and each is hydrogen, methyl, isopropyl, hydroxyl, -SO 2 CH 3 、-(C1-C2)alkyl-R 301 as well as Any of the R 301 For dimethylamino, cyclopropyl, as well as Any of the R 3001 is one of methyl, ethyl and isopropyl, R 302 is fluorine, R 303 and R 304 is methyl, R 32 is one of hydrogen, methyl and -(C1-C2)alkyl-dimethylamino, R 33 is one of methyl, ethyl, cyclopropyl and trifluoromethyl, R 34 is one of hydroxyl, methyl, ethyl, cyclopropyl and trifluoromethyl, R 35-1 and R 35-2 may be the same or different and each is one of hydrogen, methyl and cyclopropyl, R 36 for R 305 is methyl, R 306 is amino or methylamino, R 37 for R 38 Methyl or -CH 2 CH 2 OCH 3 , and R 39 It may be hydrogen or methyl.

[0031] The compound represented by Chemical Formula 1 may be selected from the following group of compounds.

[0032] (1) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0033] (2) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0034] (3) Methyl 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate

[0035] (4) 4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0036] (5) 4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0037] (6) 4-phenyl-5-((2-(pyridin-3-ylamino)pyridin-4-yl)oxy)thiazol-2-amine

[0038] (7) 5-((2-((6-fluoropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0039] (8) 4-phenyl-5-((2-(pyridin-4-ylamino)pyridin-4-yl)oxy)thiazol-2-amine

[0040] (9) 6-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0041] (10) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylbenzamide

[0042] (11) 5-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0043] (12) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzenesulfonamide

[0044] (13) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylbenzenesulfonamide

[0045] (14) N-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0046] (15) 5-((2-((3-(methylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0047] (16) N-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopropanesulfonamide

[0048] (17) 4-phenyl-5-((2-((3-((trifluoromethyl)sulfonyl)phenyl)amino)pyridin-4-yl)oxy)thiazol-2-amine

[0049] (18) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid

[0050] (19) 5-((2-((3-((methylsulfonyl)methyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0051] (20) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-cyclopropylbenzenesulfonamide

[0052] (21) 5-((2-((3-fluorobenzyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0053] (22) 2-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide

[0054] (23) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0055] (24) 5-((2-((2-methoxypyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0056] (25) 5-((2-(Benzylamino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0057] (26) 4-phenyl-5-((2-((pyridin-4-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine

[0058] (27) 5-((2-((2-chloropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0059] (28) 4-phenyl-5-((2-(pyridin-3-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine

[0060] (29) (3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0061] (30) 5-((2-((2-fluoropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0062] (31) 5-((2-((6-methoxypyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0063] (32) 5-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0064] (33) 6-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0065] (34) 5-((2-((3-(ethylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0066] (35) 5-((2-((6-chloropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0067] (36) N-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide

[0068] (37) 5-((2-((1-methyl-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0069] (38) 5-((2-((1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0070] (39) 4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0071] (40) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0072] (41) 2-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0073] (42) 2-(4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0074] (43) 2-(5-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0075] (44) 2-(3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0076] (45) 3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0077] (46) 3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0078] (47) 4-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0079] (48) 3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0080] (49) 4-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0081] (50) 2-(3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0082] (51) 3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0083] (52) 3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0084] (53) 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0085] (54) 2-(4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0086] (55) 2-(5-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0087] (56) 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0088] (57) 3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0089] (58) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0090] (59) 2-(4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0091] (60) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0092] (61) 2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0093] (62) 5-((2-((1-(methylsulfonyl)-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0094] (63) 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0095] (64) 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0096] (65) 2-(5-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0097] (66) 2-methyl-2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoic acid

[0098] (67) N,N-Dimethyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0099] (68) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid

[0100] (69) N-methyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0101] (70) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(3-(methylsulfonyl)phenyl)pyridin-2-amine

[0102] (71) N-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0103] (72) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((trifluoromethyl)sulfonyl)phenyl)pyridin-2-amine

[0104] (73) N-methyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0105] (74) N,N-Dimethyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0106] (75) N-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopropanesulfonamide

[0107] (76) N-Cyclopropyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0108] (77) N-(3-(ethylsulfonyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0109] (78) (3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0110] (79) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((methylsulfonyl)methyl)phenyl)pyridin-2-amine

[0111] (80) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-ylmethyl)pyridin-2-amine

[0112] (81) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-ylmethyl)pyridin-2-amine

[0113] (82) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-yl)pyridin-2-amine

[0114] (83) N-(6-fluoropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0115] (84) N-(6-chloropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0116] (85) N-(6-methoxypyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0117] (86) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-yl)pyridin-2-amine

[0118] (87) N-(2-fluoropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0119] (88) N-(2-methoxypyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0120] (89) N-(2-chloropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0121] (90) 6-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0122] (91) 5-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0123] (92) 5-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0124] (93) 2-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide

[0125] (94) N-Benzyl-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0126] (95) N-(4-fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0127] (96) N-(3-fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0128] (97) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(1-(methylsulfonyl)-1H-pyrazol-4-yl)pyridin-2-amine

[0129] (98) N-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0130] (99) N-(1-methyl-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0131] (100) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(1H-pyrazol-4-yl)pyridin-2-amine

[0132] (101) 6-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0133] (102) 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0134] (103) N-(4-methoxyphenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0135] (104) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(piperazin-1-yl)phenyl)pyridin-2-amine

[0136] (105) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(2-(piperidin-1-yl)ethoxy)phenyl)pyridin-2-amine

[0137] (106) N-(3-methoxy-4-(4-methylpiperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0138] (107) 1,1,1-trifluoro-N-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0139] (108) N-(4-(4-(2-methoxyethyl)piperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0140] (109) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0141] (110) 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0142] (111) 2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)acetonitrile

[0143] (112) N-(3-((1H-tetrazolyl-5-yl)methyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0144] (113) 3-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propionitrile

[0145] (114) N-(3-(2-(2H-tetrazolyl-5-yl)ethyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0146] (115) 2-(3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0147] (116) 3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0148] (117) 3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0149] (118) 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0150] (119) 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0151] (120) 2-(4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0152] (121) 2-(5-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0153] (122) N-(3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)ethanesulfonamide

[0154] (123) N-(3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide

[0155] (124) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0156] (125) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0157] (126) 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0158] (127) N-(6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)methanesulfonamide

[0159] (128) N-(4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0160] (129) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0161] (130) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate

[0162] (131) Methyl 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate

[0163] (132) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0164] (133) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0165] (134) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0166] (135) 3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0167] (136) 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0168] (137) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0169] (138) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-hydroxynicotinamide

[0170] (139) 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-hydroxybenzamide

[0171] (140) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(methylsulfonyl)nicotinamide

[0172] (141) 2-(3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0173] (142) 3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0174] (143) 3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0175] (144) 3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0176] (145) 3-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0177] (146) 6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0178] (147) 4-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0179] (148) N-methyl-4-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0180] (149) 6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0181] (150) N-methyl-6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0182] (151) 3-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0183] (152) 4-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0184] (153) 2-(3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0185] (154) 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0186] (155) 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0187] (156) 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0188] (157) 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0189] (158) 2-(4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0190] (159) 2-(5-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0191] (160) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0192] (161) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0193] (162) Methyl 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate

[0194] (163) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0195] (164) 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0196] (165) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0197] (166) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0198] (167) 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0199] (168) 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0200] (169) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0201] (170) Methyl 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate

[0202] (171) 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0203] (172) 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0204] (173) 6-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0205] (174) 6-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0206] (175) 4-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0207] (176) 6-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0208] (177) 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0209] (178) 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0210] (179) 4-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0211] (180) 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0212] (181) 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0213] (182) 2-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0214] (183) 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0215] (184) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0216] (185) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0217] (186) 2-(4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0218] (187) 2-(5-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0219] (188) N-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)ethanesulfonamide

[0220] (189) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0221] (190) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0222] (191) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate

[0223] (192) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0224] (193) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0225] (194) 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0226] (195) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0227] (196) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-isopropylnicotinamide

[0228] (197) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(4-methylpiperazin-1-yl)methanone

[0229] (198) (3-aminopyrrolidin-1-yl)(6-(4-(2-ethyl-4-phenylthiazol-5-yloxy)pyridin-2-ylamino)pyridin-3-yl)methanone

[0230] (199) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(pyrrolidin-1-yl)ethyl)nicotinamide

[0231] (200)(6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(3-(methylamino)pyrrolidin-1-yl)methanone

[0232] (201) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-methylpiperazin-1-yl)ethyl)nicotinamide

[0233] (202) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-isopropylpiperazin-1-yl)ethyl)nicotinamide

[0234] (203) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-ethylpiperazin-1-yl)ethyl)nicotinamide

[0235] (204) 5-(3-aminopyrrolidin-1-yl)-N-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)pyridin-2-amine

[0236] (205)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-isopropylpiperazin-1-yl)ethyl)benzene-1,4-diamine

[0237] (206)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-methylpiperazin-1-yl)ethyl)benzene-1,4-diamine

[0238] (207)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-ethylpiperazin-1-yl)ethyl)benzene-1,4-diamine

[0239] (208)N1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(Pyrrolidin-1-yl)ethyl)benzene-1,4-diamine

[0240] (209)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-methylpiperazin-1-yl)ethyl)pyridine-2,5-diamine

[0241] (210)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(Pyrrolidin-1-yl)ethyl)pyridine-2,5-diamine

[0242] (211)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-ethylpiperazin-1-yl)ethyl)pyridine-2,5-diamine

[0243] (212)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-isopropylpiperazin-1-yl)ethyl)pyridine-2,5-diamine

[0244] (213) N-(5-(1H-pyrazol-4-yl)pyridin-2-yl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0245] (214) N-(4-(3-aminopyrrolidin-1-yl)phenyl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0246] (215) 4-((2-ethyl-4-phenylthiazol-5-yl)oxy)-N-(4-(3-(methylamino)pyrrolidin-1-yl)phenyl)pyridin-2-amine

[0247] (216) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid methyl ester

[0248] (217) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0249] (218) 3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0250] (219) 2-(3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0251] (220) 3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0252] (221) 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0253] (222) 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0254] (223) 2-(4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0255] (224) 2-(5-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0256] (225) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0257] (226) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0258] (227) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0259] (228) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0260] (229) 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0261] (230) 3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0262] (231) 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0263] (232) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0264] (233) 3-((4-((2-(methylamino)-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0265] (234) 3-((4-((2-amino-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0266] (235) 3-((4-((2-(dimethylamino)-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0267] (236) 3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide

[0268] (237) 3-((6-((2-methyl-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide

[0269] (238) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzenesulfonamide

[0270] (239) 3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide

[0271] (240) 3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide

[0272] (241) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)picolinamide

[0273] (242) 2-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)isonicotinamide

[0274] (243) 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzamide

[0275] (244) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)nicotinic acid

[0276] (245) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)nicotinamide

[0277] (246) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzoic acid

[0278] (247) 3-((4-((2-amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0279] (248) 4-((4-((2-amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0280] (249) 3-((4-((2-amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0281] (250) 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0282] (251) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0283] (252) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0284] (253) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0285] (254) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0286] (255) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0287] (256) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0288] (257) 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0289] (258) 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0290] (259) 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0291] (260) 5-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0292] (261) 5-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0293] (262) 5-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0294] (263) 4-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0295] (264) 4-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0296] (265) 4-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0297] (266) 2-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinic acid

[0298] (267) 2-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide

[0299] (268) 2-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylisonicotinamide

[0300] (269) N-(2-(dimethylamino)ethyl)-6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0301] (270) N-(Cyclopropylmethyl)-6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0302] (271) 2-(dimethylamino)ethyl 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0303] (272) N-(3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0304] (273) 2-(Dimethylamino)ethyl 3-(6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamido)-5-fluorobenzoate

[0305] (274) 3-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0306] (275) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0307] (276) 2-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide

[0308] (277) 3-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0309] (278) 6-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0310] (279) 6-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0311] (280) 2-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylisonicotinamide

[0312] (281) 3-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0313] (282) 6-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0314] (283) 3-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0315] (284) 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0316] (285) 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0317] (286) 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0318] (287) 3-((4-((2-isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0319] (288) 6-((4-((2-isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0320] (289) 3-((4-((4-(6-methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0321] (290) 6-((4-((2-isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0322] (291) 3-((4-((4-(6-methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0323] (292) 3-((4-((2-(methylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0324] (293) 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0325] (294) 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0326] (295) 4-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0327] (296) 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0328] (297) 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0329] (298) 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0330] (299) 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0331] (300) 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0332] (301) 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0333] (302) 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0334] (303) 3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0335] (304) 2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)acetonitrile

[0336] (305) N-(3-((1H-tetrazolyl-5-yl)methyl)phenyl)-4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-amine

[0337] (306) 3-(3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propionitrile

[0338] (307) N-(3-(2-(2H-tetrazolyl-5-yl)ethyl)phenyl)-4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-amine

[0339] (308) Methyl 2-methyl-2-(3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoate

[0340] (309) 2-Methyl-2-(3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoic acid

[0341] (310) 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0342] (311) N-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide

[0343] (312) 4-((2-ethyl-4-phenylthiazol-5-yl)oxy)-N-(5-(3-(methylamino)pyrrolidin-1-yl)pyridin-2-yl)pyridin-2-amine.

[0344] In addition, the present disclosure provides a pharmaceutical composition for treating or preventing cancer diseases, the pharmaceutical composition comprising a compound as an active ingredient, the compound being selected from a thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0345] The cancer disease can be selected from the group consisting of lung cancer, breast cancer, ovarian cancer, uterine cancer, pancreatic cancer, lung cancer, stomach cancer, liver cancer, colorectal cancer, skin cancer, head and neck cancer, brain cancer, laryngeal cancer, prostate cancer, bladder cancer, esophageal cancer, thyroid cancer, kidney cancer and rectal cancer, but is not limited thereto.

[0346] The cancer disease may be a cancer disease associated with transforming growth factor β (TGFβ).

[0347] The pharmaceutical composition can selectively inhibit transforming growth factor beta receptor 1 (TGFβR1).

[0348] In another exemplary embodiment of the present disclosure, the pharmaceutical composition may further comprise one or more additives selected from the group consisting of suitable carriers, excipients, disintegrants, sweeteners, coating agents, expanders, lubricants, glydents, flavoring agents, antioxidants, buffers, bacteriostats, diluents, dispersants, surfactants, binders and friction reducers commonly used in the manufacture of pharmaceutical compositions.

[0349] Specifically, as carrier, excipient and diluent, lactose, glucose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginic acid salt, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talcum, magnesium stearate and mineral oil can be used, solid preparations for oral administration include tablets, pills, acid agents, granules and capsules, wherein, these solid preparations can be prepared by mixing at least one or more excipients (such as starch, calcium carbonate, sucrose or lactose and gelatin) in the composition. Except simple excipients, lubricants, such as magnesium stearate and talcum can also be used. For oral liquid preparations, suspensoids, liquids, emulsions and syrups can be used, except commonly used simple diluents (such as water and liquid paraffin), various excipients, such as humectants, sweeteners, spices and preservatives can also be included. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized agents, and suppositories. As non-aqueous solvents and suspensions, propylene glycol, polyethylene glycol, vegetable oils (e.g., olive oil), and injectable esters (e.g., ethyl oleate) can be used. As the base of suppositories, witepsol, macrogol, tween 61, cocoa butter, laurin butter, and glycerin gelatin can be used.

[0350] According to an exemplary embodiment of the present disclosure, the pharmaceutical composition can be administered to a subject in a conventional manner by intravenous, intraarterial, intraperitoneal, intramuscular, intraarterial, intraperitoneal, intrasternal, transdermal, nasal, inhalation, topical, rectal, oral, intraocular or intradermal routes.

[0351] The dosage of the active ingredient according to the present disclosure may vary according to the condition and body weight of the subject, the type and severity of the disease, the drug form, and the route and duration of administration, and may be appropriately selected by those skilled in the art, and the daily dosage may be 0.01 mg / kg to 200 mg / kg, preferably 0.1 mg / kg to 200 mg / kg, more preferably 0.1 mg / kg to 100 mg / kg. It may be administered once a day or divided into multiple doses, but the scope of the present disclosure is not limited thereto.

[0352] In addition, the present disclosure provides a health functional food composition for improving or preventing cancer diseases, the health functional food composition comprising a compound as an active ingredient, the compound being selected from a thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0353] The cancer disease can be selected from the group consisting of lung cancer, breast cancer, ovarian cancer, uterine cancer, pancreatic cancer, lung cancer, stomach cancer, liver cancer, colorectal cancer, skin cancer, head and neck cancer, brain cancer, laryngeal cancer, prostate cancer, bladder cancer, esophageal cancer, thyroid cancer, kidney cancer and rectal cancer, but is not limited thereto.

[0354] Health functional foods may contain various nutritional supplements, vitamins, minerals (electrolytes), flavorings (such as synthetic flavorings and natural flavorings), colorants and fillers (cheese, chocolate, etc.), pectin acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol and carbonating agents used in carbonated beverages.

[0355] In addition, it can also contain pulp for making natural juice, synthetic juice and vegetable beverage. These ingredients can be used independently or in combination. In addition, the health functional food composition can be in any form of meat, sausage, bread, chocolate, candy, snacks, sweets, pizza, instant noodles, chewing gum, ice cream, soup, beverage, tea, functional water, drink, alcohol and vitamin complex.

[0356] In addition, health functional foods may further include food additives, unless otherwise specified, whose suitability as “food additives” is determined by standards and guidelines related to corresponding items according to general rules and general test methods of the Korean Food Additives Codex approved by the Ministry of Food and Drug Safety.

[0357] Items listed in the Korean Food Additive Codex can include, for example, chemically synthesized compounds such as ketones, glycine, potassium citrate, niacin and cinnamic acid; natural additives such as persimmon pigment, licorice extract, crystalline cellulose, sorghum pigment and guar gum; and mixed preparations such as sodium L-glutamate preparations, noodle alkali agents, preservatives and tar coloring agents.

[0358] Here, the content of the active ingredient added to the food during the manufacture of the health functional food can be appropriately adjusted as needed, and preferably, the active ingredient can be added so as to be contained in an amount of 1 to 90 parts by weight in 100 parts by weight of the food.

[0359] In addition, the present disclosure provides an agent composition for inhibiting the expression of transforming growth factor β (TGFβ), the agent composition comprising a compound as an active ingredient, the compound being selected from a thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0360] The reagent composition can selectively inhibit transforming growth factor β receptor 1 (TGFβR1).

[0361] Example

[0362] Hereinafter, the present disclosure will be described in detail by examples to help understand the present disclosure. However, the embodiments described below are only intended to explain the present invention, and the scope of the present disclosure is not limited to the following embodiments. The embodiments of the present disclosure are provided to more completely explain the present disclosure to those skilled in the art.

[0363] [Synthesis Example] NMR and MS data of compounds

[0364] (1) A-1: ​​3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0365]

[0366] (2) A-2: 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0367]

[0368] (3) A-3: methyl 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate

[0369]

[0370] (4) A-4: 4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0371]

[0372] (5) A-5: 4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0373]

[0374] (6) A-6: 4-phenyl-5-((2-(pyridin-3-ylamino)pyridin-4-yl)oxy)thiazol-2-amine

[0375]

[0376] (7) A-7: 5-((2-((6-fluoropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0377]

[0378] (8) A-8: 4-phenyl-5-((2-(pyridin-4-ylamino)pyridin-4-yl)oxy)thiazol-2-amine

[0379]

[0380] (9) A-9: 6-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0381]

[0382] (10) A-10: 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylthiazol-5-yl)oxy Benzamide

[0383]

[0384] (11) A-11: 5-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinyl amine

[0385]

[0386] (12) A-12: 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzene Sulfonamide

[0387]

[0388] (13) A-13: 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylthiazol-5-yl Benzenesulfonamide

[0389]

[0390] (14) A-14: N-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl) Methanesulfonamide

[0391]

[0392] (15) A-15: 5-((2-((3-(methylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazole-2-yl amine

[0393]

[0394] (16) A-16: N-3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopentane Propanesulfonamide

[0395]

[0396] (17) A-17: 4-phenyl-5-((2-((3-((trifluoromethyl)sulfonyl)phenyl)amino)pyridin-4-yl)oxy) Thiazol-2-amine

[0397]

[0398] (18) A-18: 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid

[0399]

[0400] (19) A-19: 5-((2-((3-((methylsulfonyl)methyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthio Oxazol-2-amine

[0401]

[0402] (20) A-20: 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-cyclopropyl Benzenesulfonamide

[0403]

[0404] (21) A-21: 5-((2-((3-fluorobenzyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0405]

[0406] (22) A-22: 2-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide

[0407]

[0408] (23) A-23: 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzene Formamide

[0409]

[0410] (24) A-24: 5-((2-((2-methoxypyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazole-2- amine

[0411]

[0412] (25) A-25: 5-((2-(Benzylamino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0413]

[0414] (26) A-26: 4-phenyl-5-((2-((pyridin-4-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine

[0415]

[0416] (27) A-27: 5-((2-((2-chloropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0417]

[0418] (28) A-28: 4-phenyl-5-((2-((pyridin-3-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine

[0419]

[0420] (29) A-29: (3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methyl Sulfonamide

[0421]

[0422] (30) A-30: 5-((2-((2-fluoropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0423]

[0424] (31) A-31: 5-((2-((6-methoxypyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazole-2-yl amine

[0425]

[0426] (32) A-32: 5-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0427]

[0428] (33) A-33: 6-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinyl amine

[0429]

[0430] (34) A-34: 5-((2-((3-(ethylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazole- 2-Amine

[0431]

[0432] (35) A-35: 5-((2-((6-chloropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0433]

[0434] (36) A-36: N-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)- 1,1,1-Trifluoromethanesulfonamide

[0435]

[0436] (37) A-37: 5-((2-((1-methyl-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazole- 2-Amine

[0437]

[0438] (38) A-38: 5-((2-((1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0439]

[0440] (39) A-39: 4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0441]

[0442] (40) A-40: 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0443]

[0444] (41) A-41: 2-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl) Propan-2-ol

[0445]

[0446] (42) A-42: 2-(4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine- 2-yl)propan-2-ol

[0447]

[0448] (43) A-43: 2-(5-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine- 2-yl)propan-2-ol

[0449]

[0450] (44) A-44: 2-(3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino 1-(4-(4-(2-yl)phenyl)propan-2-ol

[0451]

[0452] (45) A-45: 3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) Benzenesulfonamide

[0453]

[0454] (46) A-46: 3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) Benzamide

[0455]

[0456] (47) A-47: 4-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) Benzamide

[0457]

[0458] (48) A-48: 3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) benzoic acid

[0459]

[0460] (49) A-49: 4-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) benzoic acid

[0461]

[0462] (50) A-50: 2-(3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzene 2-Methyl)propan-2-ol

[0463]

[0464] (51) A-51: 3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonate Amide

[0465]

[0466] (52) A-52: 3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzyl Amide

[0467]

[0468] (53) A-53: 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonate Amide

[0469]

[0470] (54) A-54: 2-(4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine pyridin-2-yl)propan-2-ol

[0471]

[0472] (55) A-55: 2-(5-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine pyridin-2-yl)propan-2-ol

[0473]

[0474] (56) A-56: 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzyl acid

[0475]

[0476] (57) A-57: 3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzyl acid

[0477]

[0478] (58) A-58: 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0479]

[0480] (59) A-59: 2-(4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine- 2-yl)propan-2-ol

[0481]

[0482] (60) A-60: 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0483]

[0484] (61) A-61: 2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl) Propan-2-ol

[0485]

[0486] (62) A-62: 5-((2-((1-(methylsulfonyl)-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenyl Thiazol-2-amine

[0487]

[0488] (63) A-63: 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide)

[0489]

[0490] (64) A-64: 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0491]

[0492] (65) A-65: 2-(5-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine- 2-yl)propan-2-ol

[0493]

[0494] (66) A-66: 2-methyl-2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino 1-(4-(4-amino)phenyl)propionic acid

[0495]

[0496] (67) A-67: N,N-dimethyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino Benzamide

[0497]

[0498] (68) A-68: 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid

[0499]

[0500] (69) A-69: N-methyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzene Formamide

[0501]

[0502] (70) A-70: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(3-(methylsulfonyl)phenyl)pyridine-2-yl amine

[0503]

[0504] (71) A-71: N-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl) Methanesulfonamide

[0505]

[0506] (72) A-72: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((trifluoromethyl)sulfonyl)benzene 1-(2-YL)pyridin-2-amine

[0507]

[0508] (73) A-73: N-methyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzene Sulfonamide

[0509]

[0510] (74) A-74: N,N-dimethyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino Benzenesulfonamide

[0511]

[0512] (75) A-75: N-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopentane Propanesulfonamide

[0513]

[0514] (76) A-76: N-cyclopropyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) Benzenesulfonamide

[0515]

[0516] (77) A-77: N-(3-(ethylsulfonyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridine- 2-Amine

[0517]

[0518] (78) A-78: (3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methyl Sulfonamide

[0519]

[0520] (79) A-79: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((methylsulfonyl)methyl)phenyl) Pyridin-2-amine

[0521]

[0522] (80) A-80: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-ylmethyl)pyridin-2-amine

[0523]

[0524] (81) A-81: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-ylmethyl)pyridin-2-amine

[0525]

[0526] (82) A-82: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-yl)pyridin-2-amine

[0527]

[0528] (83) A-83: N-(6-fluoropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0529]

[0530] (84) A-84: N-(6-chloropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0531]

[0532] (85) A-85: N-(6-methoxypyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridine- 2-Amine

[0533]

[0534] (86) A-86: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-yl)pyridin-2-amine

[0535]

[0536] (87) A-87: N-(2-fluoropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0537]

[0538] (88) A-88: ​​N-(2-methoxypyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridine- 2-Amine

[0539]

[0540] (89) A-89: N-(2-chloropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0541]

[0542] (90) A-90: 6-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0543]

[0544] (91) A-91: 5-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinyl amine

[0545]

[0546] (92) A-92: 5-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0547]

[0548] (93) A-93: 2-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide

[0549]

[0550] (94) A-94: N-Benzyl-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0551]

[0552] (95) A-95: N-(4-fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0553]

[0554] (96) A-96: N-(3-fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0555]

[0556] (97) A-97: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(1-(methylsulfonyl)-1H-pyrazole-4-yl) 1-(2-YL)pyridin-2-amine

[0557]

[0558] (98) A-98: N-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazole-5-yl)- 2-Methyl)oxy)pyridin-2-amine

[0559]

[0560] (99) A-99: N-(1-methyl-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyrazol-4-yl Pyridine-2-amine

[0561]

[0562] (100) A-100: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(1H-pyrazol-4-yl)pyridin-2-amine

[0563]

[0564] (101) A-101: 6-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridinemethyl Amide

[0565]

[0566] (102) A-102: 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridinemethyl Amide

[0567]

[0568] (103) A-103: N-(4-methoxyphenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0569]

[0570] (104) A-104: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(piperazin-1-yl)phenyl)pyrrolidone Pyridine-2-amine

[0571]

[0572] (105) A-105: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(2-(piperidin-1-yl)ethoxy) 1-(4-(4-(2-yl)phenyl)pyridin-2-amine

[0573]

[0574] (106) A-106: N-(3-methoxy-4-(4-methylpiperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiophene) oxazol-5-yl)oxy)pyridin-2-amine

[0575]

[0576] (107) A-107: 1,1,1-trifluoro-N-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridine-2- 4-(4-amino)phenyl)methanesulfonamide

[0577]

[0578] (108) A-108: N-(4-(4-(2-methoxyethyl)piperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiophene) oxazol-5-yl)oxy)pyridin-2-amine

[0579]

[0580] (109) A-109: 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0581]

[0582] (110) A-110: 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0583]

[0584] (111) A-111: 2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzene (Methyl)acetonitrile

[0585]

[0586] (112) A-112: N-(3-((1H-tetrazolyl-5-yl)methyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl) Oxy)pyridin-2-amine

[0587]

[0588] (113) A-113: 3-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzene (Methyl) propionitrile

[0589]

[0590] (114) A-114: N-(3-(2-(2H-tetrazol-5-yl)ethyl)phenyl)-4-((2-methyl-4-phenylthiazole ... 2-Methyl)oxy)pyridin-2-amine

[0591]

[0592] (115) A-115: 2-(3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzene 2-Methyl)propan-2-ol

[0593]

[0594] (116) A-116: 3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonyl Amide

[0595]

[0596] (117) A-117: 3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzyl Amide

[0597]

[0598] (118) A-118: 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonyl Amide

[0599]

[0600] (119) A-119: 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzyl Amide

[0601]

[0602] (120) A-120: 2-(4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine pyridin-2-yl)propan-2-ol

[0603]

[0604] (121) A-121: 2-(5-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine pyridin-2-yl)propan-2-ol

[0605]

[0606] (122) A-122: N-(3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzene ETHYLSULFONAMIDE

[0607]

[0608] (123) A-123: N-(3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzene 1,1,1-trifluoromethanesulfonamide

[0609]

[0610] (124) A-124: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine Formamide

[0611]

[0612] (125) A-125: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methyl Pyridinecarboxamide

[0613]

[0614] (126) A-126: 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methyl Benzamide

[0615]

[0616] (127) A-127: N-(6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine pyridin-3-yl)methanesulfonamide

[0617]

[0618] (128) A-128: N-(4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzene Methanesulfonamide

[0619]

[0620] (129) A-129: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinoyl amine

[0621]

[0622] (130) A-130: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid Methyl ester

[0623]

[0624] (131) A-131: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine Methyl formate

[0625]

[0626] (132) A-132: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0627]

[0628] (133) A-133: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methyl Niacinamide

[0629]

[0630] (134) A-134: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine Formic acid

[0631]

[0632] (135) A-135: 3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzyl acid

[0633]

[0634] (136) A-136: 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzyl acid

[0635]

[0636] (137) A-137: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine Formic acid

[0637]

[0638] (138) A-138: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-hydroxy Niacinamide

[0639]

[0640] (139) A-139: 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-hydroxy Benzamide

[0641]

[0642] (140) A-140: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N- (Methylsulfonyl) niacinamide

[0643]

[0644] (141) A-141: 2-(3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzene 2-Methyl)propan-2-ol

[0645]

[0646] (142) A-142: 3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonate Amide

[0647]

[0648] (143) A-143: 3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzyl Amide

[0649]

[0650] (144) A-144: 3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzyl acid

[0651]

[0652] (145) A-145: 3-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino) Benzenesulfonamide

[0653]

[0654] (146) A-146: 6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino) Niacinamide

[0655]

[0656] (147) A-147: 4-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino) Benzamide

[0657]

[0658] (148) A-148: N-methyl-4-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridine-2- 1-(4-amino)benzamide

[0659]

[0660] (149) A-149: 6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino) niacin

[0661]

[0662] (150) A-150: N-methyl-6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridine-2- nicotinamide

[0663]

[0664] (151) A-151: 3-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino) benzoic acid

[0665]

[0666] (152) A-152: 4-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino) benzoic acid

[0667]

[0668] (153) A-153: 2-(3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino 1-(4-(4-(2-yl)phenyl)propan-2-ol

[0669]

[0670] (154) A-154: 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) Benzenesulfonamide

[0671]

[0672] (155) A-155: 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) Benzamide

[0673]

[0674] (156) A-156: 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) Benzenesulfonamide

[0675]

[0676] (157) A-157: 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) Benzamide

[0677]

[0678] (158) A-158: 2-(4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino 2-Yl)pyridin-2-yl)propan-2-ol

[0679]

[0680] (159) A-159: 2-(5-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino 2-Yl)pyridin-2-yl)propan-2-ol

[0681]

[0682] (160) A-160: 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) Pyridinecarboxamide

[0683]

[0684] (161) A-161: 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)- N-Methylpicolinamide

[0685]

[0686] (162) A-162: 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) Methyl picolinate

[0687]

[0688] (163) A-163: 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) Niacinamide

[0689]

[0690] (164) A-164: 4-((4-((2-dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)- N-Methylbenzamide

[0691]

[0692] (165) A-165: 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) niacin

[0693]

[0694] (166) A-166: 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)- N-Methylnicotinamide

[0695]

[0696] (167) A-167: 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) benzoic acid

[0697]

[0698] (168) A-168: 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) benzoic acid

[0699]

[0700] (169) A-169: 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) Picolinic acid

[0701]

[0702] (170) A-170: Methyl 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate ester

[0703]

[0704] (171) A-171: 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0705]

[0706] (172) A-172: 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0707]

[0708] (173) A-173: 6-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinoyl amine

[0709]

[0710] (174) A-174: 6-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0711]

[0712] (175) A-175: 4-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzyl acid

[0713]

[0714] (176) A-176: 6-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methyl Niacinamide

[0715]

[0716] (177) A-177: 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinoyl amine

[0717]

[0718] (178) A-178: 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0719]

[0720] (179) A-179: 4-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzyl acid

[0721]

[0722] (180) A-180: 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methyl Niacinamide

[0723]

[0724] (181) A-181: 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonyl amine

[0725]

[0726] (182) A-182: 2-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzene 2-Methyl)propan-2-ol

[0727]

[0728] (183) A-183: 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoyl amine

[0729]

[0730] (184) A-184: 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonyl amine

[0731]

[0732] (185) A-185: 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoyl amine

[0733]

[0734] (186) A-186: 2-(4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine pyridin-2-yl)propan-2-ol

[0735]

[0736] (187) A-187: 2-(5-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine pyridin-2-yl)propan-2-ol

[0737]

[0738] (188) A-188: N-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzene ETHYLSULFONAMIDE

[0739]

[0740] (189) A-189: 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methyl Benzamide

[0741]

[0742] (190) A-190: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0743]

[0744] (191) A-191: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate

[0745]

[0746] (192) A-192: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0747]

[0748] (193) A-193: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methyl Niacinamide

[0749]

[0750] (194) A-194: 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0751]

[0752] (195) A-195: 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0753]

[0754] (196) A-196: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-isopropyl Niacinamide

[0755]

[0756] (197) A-197: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine-3-yl 4-Methylpiperazine-1-yl)methanone

[0757]

[0758] (198) A-198: (3-aminopyrrolidin-1-yl)(6-(4-(2-ethyl-4-phenylthiazol-5-yloxy)pyridine- 2-amino)pyridin-3-yl)methanone

[0759]

[0760]

[0761] (199) A-199: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2- (Pyrrolidin-1-yl)ethyl)nicotinamide

[0762]

[0763] (200) A-200: (6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine- 3-(Methylamino)pyrrolidin-1-yl)methanone

[0764]

[0765] (201) A-201: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2- (4-Methylpiperazin-1-yl)ethyl)nicotinamide

[0766]

[0767] (202) A-202: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2- (4-Isopropylpiperazin-1-yl)ethyl)nicotinamide

[0768]

[0769] (203) A-203: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2- (4-ethylpiperazin-1-yl)ethyl)nicotinamide

[0770]

[0771] (204) A-204: 5-(3-aminopyrrolidin-1-yl)-N-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy) Pyridin-2-yl)pyridin-2-amine

[0772]

[0773] (205)A-205:N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-iso 1-Propylpiperazin-1-yl)ethyl)benzene-1,4-diamine

[0774]

[0775] (206)A-206:N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-methyl 1-(2-piperazine-1-yl)ethyl)benzene-1,4-diamine

[0776]

[0777] (207)A-207:N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-ethyl 1-(2-piperazine-1-yl)ethyl)benzene-1,4-diamine

[0778]

[0779] (208)A-208:N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(pyrrole 1-Alkyl)ethyl)benzene-1,4-diamine

[0780]

[0781] (209)A-209:N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-methyl 1-(2-piperazine-1-yl)ethyl)pyridine-2,5-diamine

[0782]

[0783] (210)A-210:N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(pyrrole (alkyl-1-yl)ethyl)pyridine-2,5-diamine

[0784]

[0785] (211)A-211:N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-ethyl 1-(2-piperazine-1-yl)ethyl)pyridine-2,5-diamine

[0786]

[0787] (212)A-212:N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-iso propylpiperazin-1-yl)ethyl)pyridine-2,5-diamine

[0788]

[0789] (213) A-213: N-(5-(1H-pyrazol-4-yl)pyridin-2-yl)-4-((2-ethyl-4-phenylthiazol-5-yl) Oxy)pyridin-2-amine

[0790]

[0791] (214) A-214: N-4-(3-aminopyrrolidin-1-yl)phenyl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy 1-(2-YL)pyridin-2-amine

[0792]

[0793] (215) A-215: 4-((2-ethyl-4-phenylthiazol-5-yl)oxy)-N-(4-(3-(methylamino)pyrrolidine-1- 1-(4-(4-(2-yl)phenyl)pyridin-2-amine

[0794]

[0795] (216) A-216: 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine Methyl formate

[0796]

[0797] (217) A-217: 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine Formic acid

[0798]

[0799] (218) A-218: 3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonyl Amide

[0800]

[0801] (219) A-219: 2-(3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzene 2-Methyl)propan-2-ol

[0802]

[0803] (220) A-220: 3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzyl Amide

[0804]

[0805] (221) A-221: 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonyl Amide

[0806]

[0807] (222) A-222: 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzyl Amide

[0808]

[0809] (223) A-223: 2-(4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine pyridin-2-yl)propan-2-ol

[0810]

[0811] (224) A-224: 2-(5-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine pyridin-2-yl)propan-2-ol

[0812]

[0813] (225) A-225: 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methyl Pyridinecarboxamide

[0814]

[0815] (226) A-226: 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridine Formamide

[0816]

[0817] (227) A-227: 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinoyl amine

[0818]

[0819] (228) A-228: 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methyl Niacinamide

[0820]

[0821] (229) A-229: 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methyl Benzamide

[0822]

[0823] (230) A-230: 3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzyl acid

[0824]

[0825] (231) A-231: 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzyl acid

[0826]

[0827] (232) A-232: 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0828]

[0829] (233) A-233: 3-((4-((2-(methylamino)-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino Benzenesulfonamide

[0830]

[0831] (234) A-234: 3-((4-((2-amino-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzene Sulfonamide

[0832]

[0833] (235) A-235: 3-((4-((2-(dimethylamino)-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl) Amino)benzenesulfonamide

[0834]

[0835] (236) A-236: 3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonyl amine

[0836]

[0837] (237) A-237: 3-((6-((2-methyl-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonyl amine

[0838]

[0839] (238) A-238: 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzenesulfonyl amine

[0840]

[0841] (239) A-239: 3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonyl amine

[0842]

[0843] (240) A-240: 3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonyl amine

[0844]

[0845] (241) A-241: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)picolinamide

[0846]

[0847] (242) A-242: 2-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)isonicotinamide amine

[0848]

[0849] (243) A-243: 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzoyl amine

[0850]

[0851] (244) A-244: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)nicotinic acid

[0852]

[0853] (245) A-245: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)nicotinamide

[0854]

[0855] (246) A-246: 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzoic acid

[0856]

[0857] (247) A-247: 3-((4-((2-amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (4-amino)benzenesulfonamide

[0858]

[0859] (248) A-248: 4-((4-((2-amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- 1-(4-amino)benzoic acid

[0860]

[0861]

[0862] (249) A-249: 3-((4-((2-amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- 1-(4-amino)benzoic acid

[0863]

[0864] (250) A-250: 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (4-amino)benzenesulfonamide

[0865]

[0866] (251) A-251: 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- nicotinamide

[0867]

[0868] (252) A-252: 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- nicotinic acid

[0869]

[0870] (253) A-253: 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (amino)-N-methylnicotinamide

[0871]

[0872] (254) A-254: 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (4-(2-amino)picolinic acid

[0873]

[0874] (255) A-255: 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2-yl 1-(4-(2-amino)-picolinamide

[0875]

[0876] (256) A-256: 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (4-(2-Methyl)-1-amino)-N-methylpicolinamide

[0877]

[0878] (257) A-257: 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- 1-(4-amino)benzoic acid

[0879]

[0880] (258) A-258: 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- 1-(4-amino)benzamide

[0881]

[0882] (259) A-259: 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- 1-(2-Methyl)amino)-N-methylbenzamide

[0883]

[0884] (260) A-260: 5-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- nicotinic acid

[0885]

[0886] (261) A-261: 5-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- nicotinamide

[0887]

[0888] (262) A-262: 5-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (amino)-N-methylnicotinamide

[0889]

[0890] (263) A-263: 4-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (4-(2-amino)picolinic acid

[0891]

[0892] (264) A-264: 4-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- 1-(4-(2-amino)-picolinamide

[0893]

[0894] (265) A-265: 4-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (4-(2-Methyl)-1-amino)-N-methylpicolinamide

[0895]

[0896] (266) A-266: 2-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- 1-(4-(2-amino)-isonicotinic acid

[0897]

[0898] (267) A-267: 2-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (4-(2-(4-(2-amino)-isonicotinamide))

[0899]

[0900] (268) A-268: 2-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (4-(2-(4-(2-nitrophenyl)amino)-N-methylisonicotinamide)

[0901]

[0902] (269) A-269: N-(2-(dimethylamino)ethyl)-6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiophene) (oxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0903]

[0904] (270) A-270: N-(cyclopropylmethyl)-6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazole-5- 2-YL)OXY)PYRIDIN-2-YL)AMINAMIDE

[0905]

[0906] (271) A-271: 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- 2-(Dimethylamino)ethyl nicotinate

[0907]

[0908] (272) A-272: N-(3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine- 2-amino)phenyl)methanesulfonamide

[0909]

[0910] (273) A-273: 3-(6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine- 2-(Dimethylamino)ethyl 5-fluorobenzoate

[0911]

[0912] (274) A-274: 3-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- 1-(4-amino)benzamide

[0913]

[0914] (275) A-275: 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- nicotinamide

[0915]

[0916] (276) A-276: 2-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (4-(2-(4-(2-amino)-isonicotinamide))

[0917]

[0918] (277) A-277: 3-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (4-amino)benzenesulfonamide

[0919]

[0920] (278) A-278: 6-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- 1-(4-(2-amino)-picolinamide

[0921]

[0922] (279) A-279: 6-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (4-(2-Methyl)-1-amino)-N-methylpicolinamide

[0923]

[0924] (280) A-280: 2-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (4-(2-(4-(2-nitrophenyl)amino)-N-methylisonicotinamide)

[0925]

[0926] (281) A-281: 3-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- 1-(2-Methyl)amino)-N-methylbenzamide

[0927]

[0928] (282) A-282: 6-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (amino)-N-methylnicotinamide

[0929]

[0930] (283) A-283: 3-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyrrolidone (2-pyridin-2-yl)amino)benzenesulfonamide

[0931]

[0932] (284) A-284: 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyrrolidone (2-pyridin-2-yl)amino)nicotinamide

[0933]

[0934] (285) A-285: 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyrrolidone pyridin-2-yl)amino)nicotinic acid

[0935]

[0936] (286) A-286: 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyrrolidone (2-pyridin-2-yl)amino)-N-methylnicotinamide

[0937]

[0938] (287) A-287: 3-((4-((2-isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (4-amino)benzenesulfonamide

[0939]

[0940] (288) A-288: 6-((4-((2-isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- nicotinamide

[0941]

[0942] (289) A-289: 3-((4-((4-(6-methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyrrolidone (2-pyridin-2-yl)amino)benzenesulfonamide

[0943]

[0944] (290) A-290: 6-((4-((2-isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- nicotinamide

[0945]

[0946] (291) A-291: 3-((4-((4-(6-methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyrrolidone (2-pyridin-2-yl)amino)benzamide

[0947]

[0948] (292) A-292: 3-((4-((2-(methylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine- 2-amino)benzenesulfonamide

[0949]

[0950] (293) A-293: 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0951]

[0952] (294) A-294: 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinoyl amine

[0953]

[0954] (295) A-295: 4-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzyl acid

[0955]

[0956] (296) A-296: 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzyl Amide

[0957]

[0958] (297) A-297: 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methyl Benzamide

[0959]

[0960] (298) A-298: 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonyl Amide

[0961]

[0962] (299) A-299: 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)pyridine Formamide

[0963]

[0964] (300) A-300: 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzyl acid

[0965]

[0966] (301) A-301: 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)pyridine Formic acid

[0967]

[0968] (302) A-302: 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methyl Pyridinecarboxamide

[0969]

[0970] (303) A-303: 3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine-2- (4-amino)benzenesulfonamide

[0971]

[0972] (304) A-304: 2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzene (Methyl)acetonitrile

[0973]

[0974] (305) A-305: N-(3-((1H-tetrazolyl-5-yl)methyl)phenyl)-4-((2-methyl-4-(6-methylpyridine-2- 1-(2-YL)thiazol-5-yl)oxy)pyridin-2-amine

[0975]

[0976] (306) A-306: 3-(3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridine- 2-amino)phenyl)propionitrile

[0977]

[0978] (307) A-307: N-(3-(2-(2H-tetrazolyl-5-yl)ethyl)phenyl)-4-((2-methyl-4-(6-methylpyridine- 2-yl)thiazol-5-yl)oxy)pyridin-2-amine

[0979]

[0980] (308) A-308: 2-methyl-2-(3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy 2-Yl)pyridin-2-yl)amino)phenyl)propionic acid methyl ester

[0981]

[0982] (309) A-309: 2-methyl-2-(3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy 1-(4-yl)pyridin-2-yl)amino)phenyl)propionic acid

[0983]

[0984] (310) A-310: 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzene Formamide

[0985]

[0986] (311) A-311: N-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzene 1,1,1-trifluoromethanesulfonamide

[0987]

[0988] (312) A-312: 4-((2-ethyl-4-phenylthiazol-5-yl)oxy)-N-(5-(3-(methylamino)pyrrolidine-1- 1-(2-yl)pyridin-2-yl)pyridin-2-amine

[0989]

[0990] [Synthesis Example 2] Method for synthesizing novel thiazole derivative compounds

[0991] 1. Synthesis of Intermediates 1-6 and 1-6'

[0992]

[0993] (1) Preparation of 2-((2-chloropyridin-4-yl)oxy)-1-acetophenone (1-3)

[0994] To a solution of 2-bromo-1-acetophenone (1-1) (9.22 g, 46.3 mmol) in acetone (129 mL) was added 2-chloropyridin-4-ol (1-2) (5.00 g, 38.6 mmol) and K 2 CO 3 (8.00 g, 57.9 mmol). After stirring at room temperature for 4 hours, the reaction mixture was poured into water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. 2 Purification by column chromatography (hexane:EtOAc=2:1) ​​gave 1-3 (6.00 g, 63%) as a yellow solid.

[0995]

[0996] (2) Preparation of 2-bromo-2-((2-chloropyridin-4-yl)oxy)-1-phenylethyl-1-one (1-4)

[0997] At room temperature, 3 AlCl was slowly added to a solution of 1-3 (6.00 g, 24.2 mmol) in (242 mL). 3 (1.29 g, 9.69 mmol) and Br 2 (1.87 mL, 36.3 mmol). The mixture was stirred at room temperature for 2 hours. The reaction mixture was washed with saturated NaHCO 3 The organic layer was quenched and extracted with EtOAc. 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=4:1) gave 1-4 (5.74 g, 73%) as a yellow solid.

[0998]

[0999] (3) Preparation of 5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazol-2-amine (1-5)

[1000] A mixture of 1-4 (4.70 g, 14.4 mmol) and thiourea (2.19 g, 28.8 mmol) in EtOH (144 mL) was heated at 80 °C for 10 min. After cooling to room temperature, the reaction mixture was concentrated in vacuo. The residue was purified by NH—SiO 2 Purification by column chromatography (DCM:MeOH=100:1) gave 1-5 (2.72 g, 62%) as a light yellow solid.

[1001]

[1002] (4) Preparation of tert-butyl (5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazol-2-yl)carbamate (1-6') and tert-butyl 5-(2-chloropyridin-4-yloxy)-4-phenylthiazol-2-ylcarbamate (1-6)

[1003] To a solution of 1-5 (2.72 g, 8.95 mmol) in THF (90 mL) was added Boc 2O (5.86 g, 26.9 mmol), TEA (3.74 mL, 26.9 mmol) and DMAP (438 mg, 3.58 mmol). The mixture was stirred at room temperature for 18 hours. The reaction mixture was poured into water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=7:1 to 4:1) gave 1-6 (1.50 g, 30%) and 1-6′ (1.10 g, 30%) as a light yellow solid.

[1004]

[1005] 2. Synthesis of A-1

[1006]

[1007] (1) Preparation of tert-butyl (4-phenyl-5-((2-((3-sulfamoylphenyl)amino)pyridin-4-yl)oxy)thiazol-2-yl)carbamate (1-7)

[1008] To a solution of a mixture of compound 1-6 and compound 1-6' (200 mg, 0.50 mmol) in DMF (5.0 mL) at room temperature were added 3-aminobenzenesulfonamide (128 mg, 0.74 mmol) and K 2 CO 3 (205 mg, 1.49 mmol). The mixture was degassed by purging with argon and refilling with argon several times. After adding BrettPhos Pd G1, methyl tert-butyl ether adduct (185 mg, 0.20 mmol), the reaction mixture was heated at 100 ° C for 4 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=3:2) gave 1-7 (140 mg, 52%) as a brown solid.

[1009]

[1010] (2) Preparation of A-1

[1011] To a solution of 1-7 in DCM (3 mL) was added TFA (0.2 mL, 2.60 mmol) and stirred at room temperature for 18 h. The reaction mixture was washed with saturated NaHCO 3The aqueous solution was quenched and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=3:2 to 1:1) gave A-1 (52 mg, 45%) as a white solid.

[1012] The following A-2 to A-38 were synthesized using the procedure described for the synthesis of A-1.

[1013] 3. Synthesis of A-39

[1014]

[1015] (1) Preparation of 4-((4-((2-((tert-butyloxycarbonyl)amino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (1-9)

[1016] To a solution of (4-(4-(2-(tert-butoxycarbonylamino)-4-phenylthiazol-5-yloxy)pyridin-2-ylamino)benzoate (hereinafter referred to as Compound 1-8) in THF (5.0 mL) and water (5.0 mL) was added LiOH·H 2 O (42.0 mg, 1.01 mmol). After stirring at 50° C. for 4 days, the reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was acidified with 2N HCl aqueous solution. The precipitated solid was collected by filtration to give 1-9 (185 mg, 72%) as a brown solid.

[1017]

[1018] (2) Preparation of A-39

[1019] To a solution of 1-9 in DCM (3.7 mL) was added TFA (0.57 mL, 7.33 mmol) at 0°C. After stirring at 40°C for 3 h, the reaction mixture was cooled to room temperature and washed with saturated NaHCO 3 The solution was quenched and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue was triturated with DCM. The precipitated solid was collected by filtration to give A-39 (37.4 mg, 25%) as a beige solid.

[1020] The following A-40 was synthesized using the procedure described for the synthesis of A-39.

[1021] 4. Synthesis of A-41

[1022]

[1023] (1) Preparation of 2-bromo-5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazole (1-10)

[1024] To a solution of 1-5 (460 mg, 1.51 mmol) was added copper (II) bromide (338 mg, 1.51 mmol) and tert-butyl nitrite (0.27 mL, 2.27 mmol) at 0°C. The reaction mixture was stirred at 0°C for 30 minutes. The reaction mixture was quenched with aqueous ammonia and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=3:1) gave 1-10 (358 mg, 64%) as a yellow solid.

[1025] (2) Preparation of N-(5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazol-2-yl)-1,1-diphenylmethanimine (1-11)

[1026] To a solution of 1-10 in dioxane (2.7 mL) was added diphenylformimine (0.07 mL, 0.41 mmol), Xantphos (16.0 mg, 0.03 mmol) and Cs 2 CO 3 (266 mg, 0.82 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. Pd 2 (dba) 3 (16.0 mg, 0.03 mmol), the reaction mixture was heated at 100°C for 18 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=5:1) gave compound 1-11 (62.0 mg, 49%) as a yellow solid.

[1027]

[1028] (3) Preparation of 2-(3-((4-((2-((diphenylmethylene)amino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (1-12)

[1029] To a solution of 1-11 in DMF (2.7 mL) was added 2-(3-aminophenyl)propan-2-ol (30.0 mg, 0.20 mmol) and K 2 CO 3 (55.0 mg, 0.40 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (24.0 mg, 0.03 mmol), the reaction mixture was heated at 100 °C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=1:1) gave 1-12 (15.4 mg, 20%) as a yellow solid.

[1030]

[1031] (4) Preparation of A-41

[1032] To a solution of 1-12 (15.0 mg, 0.03 mmol) in MeOH (0.50 mL) was added NH 2 OH·HCl (3.58 mg, 0.05 mmol). After stirring at room temperature for 3 hours, the reaction mixture was concentrated in vacuo. The residue was washed with NH—SiO 2 Purification by column chromatography (DCM:MeOH=100:1 to 50:1) gave A-41 (2.20 mg, 20%) as a white solid.

[1033] The following A-42 and A-43 were synthesized using the procedure described for the synthesis of A-41.

[1034] 5. Synthesis of A-44

[1035]

[1036] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-N-cyclopropyl-4-phenylthiazol-2-amine (2-1)

[1037] A mixture of compound 1-4 and 1-cyclopropylthiourea (142 mg, 1.23 mmol) in EtOH (6.1 mL) was heated at 80°C for 10 minutes. After cooling to room temperature, the reaction mixture was concentrated in vacuo. The residue was filtered through SiO 2 Purification by column chromatography (hexane:EtOAc=2:1) ​​gave 2-1 (74.0 mg, 35%) as a yellow solid.

[1038]

[1039] (2) Preparation of A-44

[1040] To a solution of 2-1 (70.0 mg, 0.20 mmol) in DMF (4.1 mL) was added 2-(3-aminophenyl)propan-2-ol (46.0 mg, 0.31 mmol) and K 2 CO 3 (84.0 mg, 0.61 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (37.0 mg, 0.04 mmol), the reaction mixture was heated at 100 °C for 2 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (DCM only) afforded A-44 (19.6 mg, 21%) as a cream solid.

[1041] The following A-45 to A-47 were synthesized using the procedure described for the synthesis of A-44.

[1042] 6. Synthesis of A-48

[1043]

[1044] (1) Preparation of methyl 3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate (2-2)

[1045] To a solution of 2-1 (200 mg, 0.58 mmol) in DMF (12 mL) was added methyl 3-aminobenzoate (132 mg, 0.87 mmol) and K 2 CO 3 (241 mg, 1.75 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G1 (207 mg, 0.23 mmol), the reaction mixture was heated at 100 °C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2Purification by column chromatography (hexane:EtOAc=4:1) gave 2-2 (103 mg, 39%) as a yellow solid.

[1046]

[1047] (2) Preparation of A-48

[1048] To a solution of 2-2 (60.0 mg, 0.13 mmol) in THF (2.0 mL) and water (0.65 mL) was added LiOH·H 2 O (55.0 mg, 1.31 mmol). After stirring at room temperature for 18 hours, the reaction mixture was concentrated in vacuo. The residue was acidified with 2N HCl aqueous solution. The precipitated solid was collected by filtration to give A-48 (1.0 mg, 1.7%) as a cream solid.

[1049] The following A-49 was synthesized using the procedure described for the synthesis of A-48.

[1050] 7. Synthesis of A-50

[1051]

[1052] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-N-methyl-4-phenylthiazol-2-amine (3-1)

[1053] A mixture of 1-4 (300 mg, 0.92 mmol) and 1-methylthiourea (120 mg, 1.38 mmol) in EtOH (10 mL) was stirred at 80 °C for 10 min. After cooling to room temperature, the solvent was removed in vacuo. The residue was dissolved in EtOAc and washed with water. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=4:1) gave 3-1 (58.0 mg, 20%) as a yellow oil.

[1054]

[1055] (2) Preparation of A-50

[1056] To a solution of 3-1 (57.0 mg, 0.18 mmol) in DMF (2.0 mL) was added 2-(3-aminophenyl)propan-2-ol (41.0 mg, 0.27 mmol) and K 2 CO 3(74.0 mg, 0.54 mmol). The mixture was degassed by purging with argon and refilling with argon several times. After adding BrettPhos Pd G3 (30.0 mg, 0.04 mmol), the reaction mixture was heated at 100 °C for 18 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=1:1) gave A-50 (3.4 mg, 39%) as a milky white solid.

[1057] The following A-51 to A-55 were synthesized using the procedure described for the synthesis of A-50.

[1058] 8. Synthesis of A-56 and A-56 Salt

[1059]

[1060] (1) Preparation of methyl 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate (3-2)

[1061] To a solution of 3-1 (800 mg, 2.52 mmol) in DMF (20.0 mL) was added methyl 4-aminobenzoate (570 mg, 3.78 mmol) and K 2 CO 3 (1.04 g, 7.55 mmol). The mixture was degassed by purging with argon and refilling with argon several times. After adding BrettPhos Pd G1 (580 mg, 0.63 mmol), the reaction mixture was heated at 100 °C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue was purified by MPLC column chromatography (hexane: EtOAc = 7:3) to give 3-2 (630 mg, 58%) as a brown oil.

[1062]

[1063] (2) Preparation of A-56

[1064] To THF / H 2 To a mixture of 3-2 (630 mg, 1.46 mmol) in 2H2O (v / v=1 / 1, 30.0 mL) was added LiOH·H 2O (1.22 g, 29.1 mmol) was added and stirred at room temperature to 50°C for 5 days. After cooling to room temperature, the reaction mixture was neutralized with 1N HCl aqueous solution and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane: EtOAc = 2:3) and trituration with DCM gave A-56 (180 mg, 30%) as a cream solid.

[1065] (3) Preparation of A-56_Salt

[1066] To a solution of A-56 (30.0 mg, 0.07 mmol) in MeOH (1.5 mL) was added HCl (2 M in MeOH, 0.08 mL, 0.15 mmol). The reaction mixture was stirred at room temperature for 2 hours and the solvent was removed in vacuo. The precipitated solid was filtered and washed with EtO. 2 After washing, A-56_salt (17.0 mg, 52%) was obtained as a yellow solid.

[1067]

[1068] The following A-57 was synthesized using the procedure described for the synthesis of A-56.

[1069] 9. Synthesis of A-58

[1070]

[1071] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-methyl-4-phenylthiazole (4-1)

[1072] To a solution of 1-10 (1.50 g, 4.08 mmol) in dioxane (37 mL) and water (3.7 mL) at room temperature were added methylboronic acid (733 mg, 12.2 mmol), Sphos (837 mg, 2.04 mmol) and K 2 CO 3 (1.69 mg, 12.2 mmol). The mixture was degassed by purging with Ar and refilling with Ar multiple times. Pd(OAc) was added 2 (229 mg, 1.02 mmol), the reaction mixture was heated at 100°C for 18 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2Purification by column chromatography (hexane:EtOAc=10:1 to 7:1) gave 4-1 (403 mg, 33%) as a yellow solid.

[1073]

[1074] (2) Preparation of A-58

[1075] To a solution of 4-1 (18.0 mg, 0.06 mmol) in DMF (1.2 mL) was added 3-aminobenzenesulfonamide (15.0 mg, 0.09 mmol) and K 2 CO 3 (25.0 mg, 0.18 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (10.8 mg, 0.01 mmol), the reaction mixture was heated at 100 °C for 4 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (hexane:EtOAc=1:1) gave A-58 (6.6 mg, 25%) as a milky white solid.

[1076] The following A-59 to A-108 were synthesized using the procedure described for step 2 of the synthesis of A-58.

[1077] 10. Synthesis of A-109

[1078]

[1079] (1) Preparation of methyl 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate (4-2)

[1080] To a solution of 4-1 (50.0 mg, 0.17 mmol) in DMF (3.3 mL) was added methyl 3-aminobenzoate (37.0 mg, 0.25 mmol) and K 2 CO 3 (68.0 mg, 0.50 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G1 (44.0 mg, 0.05 mmol), the reaction mixture was heated at 100 °C for 4 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=3:1) gave 4-2 (61.0 mg, 88%) as a yellow oil.

[1081]

[1082] (2) Preparation of A-109

[1083] To a solution of 4-2 (61.0 mg, 0.15 mmol) in THF / water (v / v=1 / 1, 3 mL) was added LiOH·H 2 O (61.0 mg, 1.46 mmol). After stirring at room temperature for 18 hours, the reaction mixture was concentrated in vacuo. The residue was acidified with 2N HCl aqueous solution. The precipitated solid was collected by filtration to give A-109 (21 mg, 36%) as a cream solid.

[1084] The following A-110 was synthesized using the procedure described for the synthesis of A-109.

[1085] 11. Synthesis of A-111 and A-112

[1086]

[1087] (1) Preparation of A-111

[1088] To a solution of 4-1 (300 mg, 0.99 mmol) in DMF (9.9 mL) was added 2-(3-aminophenyl)acetonitrile (196 mg, 1.49 mmol) and K 2 CO 3 (411 mg, 2.97 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (269 mg, 0.30 mmol), the reaction mixture was heated at 100 °C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 After purification by column chromatography (hexane:EtOAc=1:4), A-111 (343 mg, 87%) was obtained as a light yellow solid.

[1089] (2) Preparation of A-112

[1090] To a solution of A-111 (150 mg, 0.376 mmol) in dioxane (4.7 mL) was added Bu2 SnO (187 mg, 0.75 mmol) and Me 3 S N 3 (0.25 mL, 1.88 mmol). The mixture was heated at 120 °C for 4 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (EtOAc only) afforded A-112 (23.5 mg, 14%) as a cream solid.

[1091] The following A-113 was synthesized using the procedure described for the synthesis of A-111.

[1092] The following A-114 was synthesized using the procedure described for the synthesis of A-112.

[1093] 12. Synthesis of A-115

[1094]

[1095] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-cyclopropyl-4-phenylthiazole (5-1)

[1096] To a solution of 1-10 (358 mg, 0.97 mmol) in dioxane (7.3 mL) and water (2.4 mL) at room temperature were added cyclopropylboronic acid (335 mg, 3.90 mmol) and K 2 CO 3 (404 mg, 2.92 mmol). The mixture was degassed by purging with Ar and refilling with Ar multiple times, and then PdCl was added at room temperature 2 (dppf) (143 mg, 0.20 mmol). The reaction mixture was stirred at 90°C for 18 hours. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=1:1) gave 5-1 (92.0 mg, 29%) as a white solid.

[1097]

[1098] (2) Preparation of A-115

[1099] To a solution of 5-1 (20 mg, 0.06 mmol) in DMF (1.2 mL) was added 2-(3-aminophenyl)propan-2-ol (14.0 mg, 0.09 mmol) and K 2 CO 3 (25.0 mg, 0.18 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (11.0 mg, 0.01 mmol), the reaction mixture was heated at 100 °C for 2 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=2:1) ​​gave A-115 (10.7 mg, 40%) as a yellow solid.

[1100] The following A-116 to A-131 were synthesized using the procedure described for the synthesis of A-115.

[1101] 13. Synthesis of A-132 and A-133

[1102]

[1103] (1) Preparation of A-132

[1104] To a solution of A-130 (50.0 mg, 0.11 mmol) in THF (0.94 mL) and water (0.19 mL) was added LiOH·H 2 O (27.0 mg, 1.12 mmol). The reaction mixture was stirred at room temperature for 4 hours. After cooling to 0°C, the reaction mixture was acidified with 1N HCl aqueous solution and concentrated in vacuo to give A-132 (40.0 mg, 83%) as a white solid, which was used in the next step without further purification.

[1105] (2) Preparation of A-133

[1106] A mixture of A-132 (40.0 mg, 0.09 mmol), HATU (53.0 mg, 0.14 mmol), DIPEA (0.049 mL, 0.28 mmol) and methylamine (2.0 M in THF, 0.07 mL, 0.14 mmol) in DMF (0.93 mL) was stirred for 2 hours at room temperature. The reaction mixture was taken up with EtOAc and washed with water and brine. The organic layer was purified by Na 2 SO 4Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (DCM:MeOH=10:1) gave A-133 (35.0 mg, 85%) as a white solid.

[1107] The following A-134 to A-136 were synthesized using the procedure described for step 1 of the synthesis of A-132.

[1108] 14. Synthesis of A-138

[1109]

[1110] To a solution of A-130 (50.0 mg, 0.11 mmol) in THF (1.0 mL) and MeOH (1.0 mL) was added NaOH (22.0 mg, 0.56 mmol) and aq. NH 2 OH (50 wt%, 0.17 mL, 0.11 mmol). The mixture was heated at 50 °C for 2 hours. After cooling to room temperature, the reaction mixture was concentrated in vacuo. The residue was acidified with 2N HCl aqueous solution at 0 °C. The precipitated solid was collected by filtration to give A-138 (8.9 mg, 18%) as a white solid.

[1111] The following A-139 was synthesized using the procedure described for the synthesis of A-138.

[1112] 15. Synthesis of A-140

[1113]

[1114] At room temperature, to a solution of A-132 (35.0 mg, 0.08 mmol) in DMF (1.6 mL) was added methanesulfonamide (9.28 mg, 0.10 mmol), DMAP (10.9 mg, 0.09 mmol), 2-chloro-1-methylpyridinium iodide (31.0 mg, 0.12 mmol) and TEA (34.0 μL, 0.24 mmol). The mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue was triturated with DCM and hexanes, the precipitated solid was collected by filtration and dried in vacuo to afford A-140 (11.0 mg, 27%) as a light red solid.

[1115] 16. Synthesis of A-141

[1116]

[1117] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-methoxy-4-phenylthiazole (6-1)

[1118] To a solution of 1-10 (60.0 mg, 0.16 mmol) in MeOH (1.6 mL) was added sodium methoxide (25 wt% in MeOH, 0.15 mL, 0.65 mmol) at room temperature. After stirring for 4 h, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=3:1) gave 5-((2-chloropyridin-4-yl)oxy)-2-methoxy-4-phenylthiazole (6-1) (13.0 mg, 25%) as a yellow solid.

[1119] MS Calcd.:318.78;MS Found:319.02(M+H + ).

[1120] (2) Preparation of A-141

[1121] To a solution of 6-1 (13 mg, 0.0410 mmol) in DMF (1.0 mL) was added 2-(3-aminophenyl)propan-2-ol (9.3 mg, 0.0610 mmol) and K 2 CO 3 (17.0 mg, 0.122 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (7.4 mg, 8.16 μmol), the reaction mixture was heated at 100 °C for 2 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=3:1) gave A-141 (1.1 mg, 6%) as a yellow solid.

[1122] The following A-142 to A-144 were synthesized using the procedure described for the synthesis of A-141.

[1123] 17. Synthesis of A-145

[1124]

[1125] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-4-phenyl-2-(trifluoromethyl)thiazole (7-1)

[1126] To a solution of 1-10 (200 mg, 0.54 mmol) in DMF (11 mL) was added methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (0.35 mL, 2.72 mmol), CuI (518 mg, 2.72 mmol) and AsPh 3 (67.0 mg, 0.22 mmol). The mixture was degassed by purging with Ar and refilling with Ar multiple times. Pd 2 (dba) 3 (25.0 mg, 0.03 mmol), the reaction mixture was heated at 100°C for 1 hour. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=20:1) gave 7-1 (95.0 mg, 49%) as a yellow solid.

[1127] (2) Preparation of A-145

[1128] To a solution of 7-1 (100 mg, 0.28 mmol) in DMF (2.8 mL) was added 3-aminobenzenesulfonamide (72.0 mg, 0.14 mmol) and K 2 CO 3 (116 mg, 0.84 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (47.0 mg, 0.06 mmol), the reaction mixture was heated at 100 °C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=1:1) gave A-145 (10.0 mg, 7%) as a white solid.

[1129] The following A-146 to A-148 were synthesized using the procedure described for step 2 of the synthesis of A-145.

[1130] 18. Synthesis of A-149 and A-150

[1131]

[1132] (1) Preparation of methyl 6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate (7-2)

[1133] To a solution of 7-1 (184.3 mg, 0.52 mmol) in DMF (2.0 mL) was added methyl 6-aminonicotinate (86.0 mg, 0.57 mmol) and K 2 CO 3 (214.0 mg, 1.55 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (187.0 mg, 0.21 mmol), the reaction mixture was heated at 100 °C for 14 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=1:1) gave 7-2 (127.6 mg, 52%) as a crude yellow solid.

[1134] MS Calcd:472.44; MS Found:473.14(M+H + ).

[1135] (2) Preparation of A-149

[1136] To a solution of 7-2 (127.6 mg, 0.27 mmol) in THF (2.0 mL) and water (2.0 mL) was added LiOH·H 2 O (34.0 mg, 0.81 mmol). The mixture was heated at 50 °C for 12 hours. After cooling to room temperature, the reaction mixture was concentrated in vacuo. The residue was acidified with 1N HCl aqueous solution. The precipitated solid was collected by filtration to give A-149 (66.6 mg, 54%) as a white solid.

[1137] (3) Preparation of A-150

[1138] To a solution of A-149 (30.0 mg, 0.07 mmol) in DMF (4.0 mL) at room temperature were added HATU (37.3 mg, 0.11 mmol), DIPEA (0.02 mL, 0.11 mmol) and a 2M methylamine solution in THF (0.05 mL, 0.11 mmol). The mixture was stirred at room temperature for 17 hours. The organic layer was purified by Na 2 SO 4Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (DCM:MeOH=10:1) gave A-150 (3.1 mg, 10%) as a white solid.

[1139] The following A-151 and A-152 were synthesized using the procedure described for the synthesis of A-149.

[1140] 19. Synthesis of A-153

[1141]

[1142] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-N,N-dimethyl-4-phenylthiazol-2-amine (8-1)

[1143] To a solution of compound 1-10 (100 mg, 0.27 mmol) in DMF (5.50 mL) was added dimethylamine (2 M in THF, 0.20 mL, 0.41 mmol) and stirred at 80°C for 18 hours. The reaction mixture was washed with water and extracted with EtOAc. The combined organic layers were purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 After purification by column chromatography (hexane:EtOAc=3:2), (8-1) (32 mg, 36%) was obtained as a yellow oil.

[1144]

[1145] (2) Preparation of A-153

[1146] To a solution of compound 8-1 (30.0 mg, 0.09 mmol) in DMF (1.0 mL) were added 2-(3-aminophenyl)propan-2-ol (21.0 mg, 0.14 mmol) and K 2 CO 3 (37.0 mg, 0.27 mmol). The mixture was degassed by purging with argon and refilling with argon several times. After adding BrettPhos Pd G3 (15.0 mg, 0.02 mmol), the reaction mixture was heated at 100 °C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=1:1) gave A-153 (1.3 mg, 3%) as a white solid.

[1147] The following A-154 to A-164 were synthesized using the procedure described for the synthesis of A-153.

[1148] 20. Synthesis of A-165 and A-166

[1149]

[1150] (1) Preparation of A-165

[1151] To a solution of 8-2 (100 mg, 0.22 mmol) in THF (2.2 mL) and water (2.2 mL) was added LiOH·H 2 O (94.0 mg, 2.24 mmol). The mixture was heated at 50 °C for 18 hours. After cooling to room temperature, the reaction mixture was concentrated in vacuo. The residue was acidified with 2N HCl aqueous solution. The precipitated solid was collected by filtration to give A-165 (19.5 mg, 20%) as a yellow solid.

[1152] (2) Preparation of A-166

[1153] To a solution of A-165 (60.0 mg, 0.14 mmol) in DMF (1.4 mL) was added HATU (79.0 mg, 0.21 mmol), MeNH 2 (2M in THF, 10.4 μL, 0.201 mmol) and DIPEA (73.0 μL, 0.42 mmol). The mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo.The residue was triturated with DCM and the resulting solid was filtered to afford A-166 (26.0 mg, 42%) as a beige solid.

[1154] The following A-167 to A-169 were synthesized using the procedure described for the synthesis of A-165.

[1155] 21. Synthesis of A-170 and A-171

[1156]

[1157] (1) Preparation of A-170

[1158] To a solution of A-3 (104 mg, 0.25 mmol) in ACN (2.5 mL) at 0°C, copper (II) bromide (56.0 mg, 0.25 mmol) and tert-butyl nitrite (38.0 mg, 0.37 mmol) were added. The mixture was stirred at 0°C for 30 minutes. The reaction mixture was quenched with aqueous ammonia and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=3:1) gave A-170 (47.8 mg, 40%) as a light yellow solid.

[1159] (2) Preparation of A-171

[1160] To a solution of methyl 3-(4-(2-bromo-4-phenylthiazol-5-yloxy)pyridin-2-ylamino)benzoate (7.50 mg, 0.02 mmol) in THF (0.23 mL) and water (0.08 mL) was added lithium hydroxide hydrate (6.52 mg, 0.16 mmol) at room temperature. After stirring at room temperature for 18 hours, the reaction mixture was concentrated in vacuo. The residue was acidified with 2N HCl aqueous solution. The precipitated solid was collected by filtration to give A-171 (1.50 mg, 21%) as a white solid.

[1161] 22. Synthesis of A-172

[1162]

[1163] To a solution of 1-13 (15.0 mg, 0.03 mol) in water (0.24 mL) and EtOH (1.4 mL) was added NaOH (1.34 mg, 0.03 mmol), DMSO (3.55 μL, 0.05 mmol) and hydrogen peroxide (30 wt%, 3.92 μL, 0.05 mmol) at room temperature. After stirring at room temperature for 30 minutes, the reaction mixture was quenched with ammonia and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (DCM:EtOAc=1:1) gave A-172 (11.0 mg, 71%) as a yellow solid.

[1164] 23. Synthesis of A-173

[1165]

[1166] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-(cyclopent-1-en-1-yl)-4-phenylthiazole (9-1)

[1167] To a solution of 1-10 (300 mg, 0.82 mmol) in dioxane (6.1 mL) and water (2.0 mL) at room temperature were added cyclopentenylboronic acid (100 mg, 0.90 mmol) and K 2 CO 3 (189 mg, 1.37 mmol). The mixture was degassed by purging with Ar and refilling with Ar multiple times. PdCl was added 2 After addition of (dppf) (119 mg, 0.16 mmol), the reaction mixture was heated at 90°C for 18 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=10:1) gave 9-1 (125 mg, 42%) as a brown oil.

[1168]

[1169] (2) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-cyclopentyl-4-phenylthiazole (9-2)

[1170] To a solution of 9-1 (125 mg, 0.35 mmol) in MeOH (3.5 mL) was added PtO 2 (96.0 mg, 0.42 mmol). The mixture was stirred at room temperature under H 2 Stir under atmosphere (balloon) for 2 hours. The reaction mixture was filtered through a pad of Celite. The filtrate was concentrated in vacuo to give 9-2 (113 mg, 90%) as a yellow oil, which was used in the next step without further purification.

[1171]

[1172] (3) Preparation of A-173

[1173] To a solution of 9-2 (113 mg, 0.32 mmol) in DMF (6.3 mL) was added 6-aminonicotinamide (48.0 mg, 0.35 mmol) and K 2 CO 3(131 mg, 0.95 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (86.0 mg, 95.0 μmol), the reaction mixture was heated at 100 °C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (EtOAc only) afforded A-173 (39.0 mg, 27%) as a white solid.

[1174] The following A-174 to A-176 were synthesized using the procedure described for the synthesis of A-173.

[1175] 24. Synthesis of A-177

[1176]

[1177] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-(cyclohex-1-en-1-yl)-4-phenylthiazole (10-1)

[1178] 1-10 (1.0 g, 2.72 mmol), 2-cyclohexenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.7 mL, 3.26 mmol), K 2 CO 3 (1.12 g, 8.16 mmol) and PdCl 2 A solution of (dppf) (398 mg, 0.54 mmol) was flushed with argon and the mixture was stirred at 90°C for 18 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (EtOAc:hexane=1:10) gave 10-1 (728 mg, 72%) as a yellow solid.

[1179]

[1180] (2) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-cyclohexyl-4-phenylthiazole (10-2)

[1181] To a mixture of 10-1 (710 mg, 1.92 mmol) in MeOH (19 mL) was added PtO 2(524 mg, 2.3 mmol) and heated to 40 ℃ under H supplied by latex balloon. 2 Stir under atmosphere for 1 hour. The mixture was filtered through a Celite pad and washed with MeOH. The filtrate was concentrated in vacuo to give 10-2 (210 mg, 30%) as a white solid.

[1182]

[1183] (3) Preparation of A-177

[1184] To a solution of 10-2 (50.0 mg, 0.13 mmol) in DMF (1.3 mL) was added 6-aminonicotinamide (22 mg, 0.16 mmol) and K 2 CO 3 (55 mg, 0.4 mmol). The mixture was degassed by purging with argon and refilling with argon several times. After adding BrettPhos Pd G3 (36.0 mg, 0.04 mmol), the reaction mixture was heated at 100 °C for 3 hours. After cooling to room temperature, the reaction mixture was washed with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (DCM:MeOH=9:1) gave A-177 (1.8 mg, 2%) as a pink solid.

[1185] The following A-178 to A-180 were synthesized using the procedure described for the synthesis of A-177.

[1186] 25. Synthesis of A-181

[1187]

[1188] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-4-phenyl-2-vinylthiazole (11-1)

[1189] To a solution of 1-10 (900 mg, 2.45 mmol) in 1,4-dioxane (22 mL) and water (2.2 mL) at room temperature were added 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (754 mg, 4.90 mmol) and Na 2 CO 3 (778 mg, 7.34 mmol). The mixture was degassed by purging with Ar and refilling with Ar multiple times. PdCl was added 2After addition of (dppf) (269 mg, 0.37 mmol), the reaction mixture was heated at 100°C for 18 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=10:1) gave 11-1 (443 mg, 58%) as a yellow solid.

[1190]

[1191] (2) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-ethyl-4-phenylthiazole (11-2)

[1192] A mixture of 11-1 (443 mg, 1.41 mmol) and Pd / C (10 wt %, 150 mg, 0.14 mmol) in MeOH (14 mL) was stirred at room temperature under H 2 Stirred under atmosphere (balloon) for 1 h. After filtering through a pad of Celite, the filtrate was concentrated in vacuo and 11-2 (333 mg, 75%) was obtained as a yellow oil which was used without further purification.

[1193]

[1194] (3) Preparation of A-181

[1195] To a solution of 11-2 (30.0 mg, 0.0950 mmol) in DMF (1.9 mL) was added 3-aminobenzenesulfonamide (24.0 mg, 0.14 mmol) and K 2 CO 3 (39.0 mg, 0.284 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (17.0 mg, 0.02 mmol), the reaction mixture was heated at 100 °C for 4 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=1:1) gave A-181 (21 mg, 49%) as a white solid.

[1196] The following A-182 to A-190 were synthesized using the procedure described for the synthesis of A-181.

[1197] 26. Synthesis of A-191 to A-193

[1198]

[1199] (1) Preparation of A-191

[1200] 11-2 (200 mg, 0.63 mmol), methyl 6-aminonicotinate (96.0 mg, 0.63 mmol) and K in DMF (6.31 mL) were prepared by purging with Ar and refilling with Ar multiple times. 2 CO 3 (87.0 mg, 0.63 mmol) was degassed. After adding BrettPhos Pd G3 (572 mg, 0.63 mmol), the reaction mixture was stirred at 100 °C for 4 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The separated organic layer was purified by MgSO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=1:1) gave A-191 (120 mg, 44%) as a yellow solid.

[1201] (2) Preparation of A-192

[1202] To a solution of methyl 6-(4-(2-ethyl-4-phenylthiazol-5-yloxy)pyridin-2-ylamino)nicotinate (70.0 mg, 0.16 mmol) in THF (1.29 mL) and water (0.32 mL) was added LiOH·H 2 O (39.0 mg, 1.62 mmol). The reaction mixture was stirred at 50 ° C for 24 hours. After cooling to 0 ° C, the reaction mixture was acidified with 1N HCl aqueous solution and concentrated in vacuo to give A-192 (90.0 mg, quantitative) as a white solid, which was used in the next step without further purification.

[1203] (3) Preparation of A-193

[1204] A mixture of A-192 (50.0 mg, 0.12 mmol), HATU (68.0 mg, 0.18 mmol), DIPEA (0.06 mL, 0.36 mmol) and methylamine (0.09 mL, 0.18 mmol) in DMF (1.19 mL) was stirred for 2 hours at room temperature. The reaction mixture was dissolved in EtOAc and washed with water and brine. The separated organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2Purification by column chromatography (DCM:MeOH=10:1) gave A-193 (43.0 mg, 83%) as a white solid.

[1205] The following A-194 and A-195 were synthesized using the procedure described for the synthesis of A-192.

[1206] The following A-196 to A-215 were synthesized using the procedure described for the synthesis of A-191 or A-193.

[1207] 27. Synthesis of A-216 and A-217

[1208]

[1209] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-4-phenyl-2-(prop-1-en-2-yl)thiazole (12-1)

[1210] 1-10 (40.0 mg, 0.11 mmol), potassium isopropenyl trifluoroborate (24.0 mg, 0.16 mmol), Na 2 CO 3 (81.0 mg, 0.76 mmol) and PdCl 2 A solution of (dppf) (8.9 mg, 0.01 mmol) was flushed with argon and the mixture was stirred at 60°C for 8 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (EtOAc:hexane=1:4) gave 12-1 (24.0 mg, 67%) as a yellow oil.

[1211]

[1212] (2) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-isopropyl-4-phenylthiazole (12-2)

[1213] To a mixture of 12-1 (300 mg, 0.91 mmol) in DCM (10 mL) was added 10% Pd / C (97.0 mg, 0.09 mmol) and stirred at room temperature under H supplied by a latex balloon. 2 Stir under atmosphere for 30 minutes. The mixture was filtered through a Celite pad and washed with DCM. The filtrate was concentrated in vacuo to give 12-2 (170 mg, 56%) as a colorless oil.

[1214]

[1215] (3) Preparation of A-216

[1216] To a solution of 12-2 (80.0 mg, 0.24 mmol) in DMF (2.4 mL) was added methyl 6-aminopicolinate (55.0 mg, 0.36 mmol) and K 2 CO 3 (100 mg, 0.72 mmol). The mixture was degassed by purging with argon and refilling with argon several times. After adding BrettPhos Pd G3 (65.0 mg, 0.07 mmol), the reaction mixture was heated at 100 °C for 3 hours. After cooling to room temperature, the reaction mixture was washed with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=3:1) gave A-216 (41.0 mg, 38%) as a yellow solid.

[1217] (4) Preparation of A-217

[1218] To a solution of A-216 (41.0 mg, 0.09 mmol) in THF (0.9 mL) and water (0.9 mL) was added LiOH·H 2 O (38.0 mg, 0.91 mmol). The reaction mixture was stirred at 50°C for 18 hours. After cooling to 0°C, the reaction mixture was acidified with 1N HCl aqueous solution and concentrated in vacuo to give A-217 (24.0 mg, 60%) as a yellow solid.

[1219] The following A-218 to A-229 were synthesized using the procedure described for the synthesis of A-216.

[1220] The following A-230 to A-232 were synthesized using the procedure described for the synthesis of A-217.

[1221] 28. Synthesis of A-233

[1222]

[1223] (1) Preparation of 2-((2-chloropyridin-4-yl)oxy)-1-(naphthalen-2-yl)ethan-1-one (13-2)

[1224] 13-1 (1.50 g, 11.58 mmol), 2-bromo-1-(naphthalen-2-yl)ethanone (3.46 g, 13.89 mmol) and K in acetone (20 mL) were added at room temperature.2 CO 3 The mixture of 2-(2.40 g, 17.37 mmol) was stirred for 18 hours. The reaction mixture was washed with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Drying, filtration and concentration in vacuo gave 13-2 (2.77 g, 80%) as a yellow foam which was used in the next step without further purification.

[1225]

[1226] (2) Preparation of 2-bromo-2-((2-chloropyridin-4-yl)oxy)-1-(naphthalen-2-yl)ethan-1-one (13-3)

[1227] At 0°C, 3 To a solution of 13-2 (230 mg, 0.77 mmol) in 1% Br (8.0 mL) was added 2 (0.06 mL, 1.16 mmol) and AlCl 3 (21.0 mg, 0.15 mol). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was washed with saturated NaHCO at 0°C. 3 The organic layer was washed with aqueous solution and extracted with EtOAc. 2 SO 4 Drying, filtration and concentration in vacuo gave 13-3 (300 mg, quantitative) as a yellow foam which was used in the next step without further purification.

[1228]

[1229] (3) Preparation of 5-((2-chloropyridin-4-yl)oxy)-N-methyl-4-(naphthalen-2-yl)thiazol-2-amine (13-4)

[1230] A mixture of 13-3 (480 mg, 1.27 mmol) and 1-methylthiourea (115 mg, 1.27 mmol) in EtOH (13.0 mL) was stirred at 75 °C for 20 min. After cooling to room temperature, the solvent was removed in vacuo. The residue was dissolved in EtOAc and washed with water. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (DCM) gave 13-4 (160 mg, 34%) as a yellow solid.

[1231]

[1232] (4) Preparation of A-233

[1233] To a solution of 13-4 (80.0 mg, 0.22 mmol) in DMF (5.0 mL) was added K 2 CO 3 (90.0 mg, 0.65 mmol) and 3-aminobenzenesulfonamide (56.0 mg, 0.33 mmol). The mixture was degassed by purging with argon and refilling with argon several times. After adding BrettPhos Pd G3 (39.0 mg, 0.04 mmol), the reaction mixture was heated at 100 ° C for 5 hours. After cooling to room temperature, the reaction mixture was washed with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (DCM:MeOH=98:2) gave A-233 (8.2 mg, 7%) as a beige solid.

[1234] 29. Synthesis of A-234

[1235]

[1236] (1) Preparation of 5-(2-chloropyridin-4-yloxy)-4-(naphthalen-2-yl)thiazol-2-amine (13-5)

[1237] A mixture of 13-2 and thiourea (61.0 mg, 0.80 mmol) in EtOH (7.9 mL) was heated at 70 °C for 20 min. After cooling to room temperature, the solvent was removed in vacuo. The residue was dissolved in EtOAc and washed with water. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (DCM only) gave 13-5 (120 mg, 42%) as a yellow solid.

[1238]

[1239] (2) Preparation of di-tert-butyl 5-(2-chloropyridin-4-yloxy)-4-(naphthalen-2-yl)thiazol-2-ylcarbamate (13-6)

[1240] 13-5 (300 mg, 0.85 mmol), Boc 2A mixture of 2-nitropropene (2.34 mL, 1.02 mmol), TEA (0.14 mL, 1.02 mmol) and DMAP (10.4 mg, 0.08 mmol) was stirred for 18 h. The reaction mixture was quenched with water and extracted with DCM. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo.The residue was purified by MPLC (hexanes / EtOAc) to give 13-6 (330 mg, 70%) as a yellow foam.

[1241]

[1242] (3) Preparation of tert-butyl 4-(naphthalen-2-yl)-5-(2-(3-sulfamoylphenylamino)pyridin-4-yloxy)thiazol-2-ylcarbamate (13-7)

[1243] To a solution of 13-6 (200 mg, 0.36 mmol) in DMF (8 mL) was added K 2 CO 3 (150 mg, 1.08 mmol) and 3-aminobenzenesulfonamide (93.0 mg, 0.54 mmol). The mixture was degassed by purging with argon and refilling with argon several times. After adding BrettPhos Pd G3 (65.0 mg, 0.07 mmol), the reaction mixture was heated at 100 ° C for 18 hours. After cooling to room temperature, the reaction mixture was washed with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=4:1) gave 13-7 (120 mg, 56%) as a dark brown solid.

[1244]

[1245] (4) Preparation of A-234

[1246] To a solution of 13-7 (120 mg, 0.20 mmol) in DCM (5.0 mL) was added TFA (0.18 mL, 2.03 mmol) and stirred at room temperature for 18 h. The reaction mixture was washed with saturated NaHCO 3 The aqueous solution was neutralized and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2Purification by column chromatography (DCM:MeOH=95:5) gave A-234 (10.0 mg, 10%) as a beige solid.

[1247] 30. Synthesis of A-235

[1248]

[1249] (1) Preparation of 2-bromo-5-(2-chloropyridin-4-yloxy)-4-(naphthalen-2-yl)thiazole (13-8)

[1250] To a solution of 5-(2-chloropyridin-4-yloxy)-4-(naphthalen-2-yl)thiazol-2-amine in ACN (90 mL) was added CuBr 2 (5.99 g, 26.8 mmol) and isoamyl nitrite (5.40 mL, 40.2 mmol). The reaction mixture was stirred at 0°C for 90 minutes. 4 OH was quenched and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=1:4) gave 13-8 (5.40 g, 48%) as a brown solid.

[1251]

[1252] (2) Preparation of 5-(2-chloropyridin-4-yloxy)-N,N-dimethyl-4-(naphthalen-2-yl)thiazol-2-amine (13-9)

[1253] A mixture of 13-8 (100 mg, 0.24 mmol) and dimethylamine (2M in THF, 0.18 mL, 0.36 mmol) in DCM (5 mL) was stirred at room temperature to 50°C for 2 days. After cooling to room temperature, the reaction mixture was washed with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=3:2) gave 13-9 (23.0 mg, 25%) as a yellow oil.

[1254]

[1255] (3) Preparation of A-235

[1256] To a solution of 13-9 (23.0 mg, 0.06 mmol) in DMF (2 mL) was added K 2 CO 3 (33.0 mg, 0.24 mmol) and 3-aminobenzenesulfonamide (16.0 mg, 0.09 mmol). The mixture was degassed by purging with argon and refilling with argon several times. After adding BrettPhos Pd G3 (11.0 mg, 0.01 mmol), the reaction mixture was heated at 100 ° C for 18 hours. After cooling to room temperature, the reaction mixture was washed with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=1:1) gave A-235 (5.8 mg, 18%) as a light yellow solid.

[1257] 31. Synthesis of A-236

[1258]

[1259] (1) Preparation of 2-(6-chloropyrimidin-4-yloxy)-1-phenylethanone (14-1)

[1260] To a solution of 1-1 (5.03 g, 25.3 mmol) in acetone (46 mL) were added 6-chloropyrimidin-4-ol (3.00 g, 23.0 mmol) and K 2 CO 3 (4.76 g, 34.5 mmol). After stirring at room temperature for 4 hours, the reaction mixture was poured into water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=1:2) gave 14-1 (5.55 g, 97%) as a white solid.

[1261]

[1262] (2) Preparation of 2-bromo-2-(6-chloropyrimidin-4-yloxy)-1-phenylethanone (14-2)

[1263] At room temperature, 3 To a solution of 14-1 (5.55 g, 22.3 mmol) in (74 mL) was slowly added AlCl 3 (1.19 g, 8.93 mmol) and Br 2(1.73 mL, 33.5 mmol). The mixture was stirred at room temperature for 18 h. The reaction mixture was washed with saturated NaHCO 3 The solution was quenched and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=5:1) gave 14-2 (4.71 g, 64%) as a white solid.

[1264]

[1265] (3) Preparation of 5-(6-chloropyrimidin-4-yloxy)-4-phenylthiazol-2-amine (14-3)

[1266] A mixture of 14-2 (4.70 g, 14.4 mmol) and thiourea (1.20 g, 15.8 mmol) in ACN (48 mL) was heated at 80 °C for 30 min. After cooling to room temperature, the reaction mixture was washed with saturated NaHCO 3 The solution was quenched and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Drying, filtration and concentration in vacuo gave 14-3 (4.03 g, 92%) as a yellow solid which was used in the next step without further purification.

[1267]

[1268] (4) Preparation of tert-butyl (tert-butyloxycarbonyl)(5-((6-chloropyrimidin-4-yl)oxy)-4-phenylthiazol-2-yl)carbamate (14-4)

[1269] To a solution of 14-3 (1.00 g, 3.28 mmol) in THF (33 mL) was added Boc 2 O (2.15 g, 9.84 mmol), TEA (1.37 mL, 9.84 mmol) and DMAP (80.0 mg, 0.67 mmol). The mixture was stirred at room temperature for 18 hours. The reaction mixture was poured into water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=5:1 to 3:1) gave 14-4 (1.14 g, 69%) as a yellow solid.

[1270]

[1271] (5) Preparation of tert-butyl 4-phenyl-5-(6-(3-sulfamoylphenylamino)pyrimidin-4-yloxy)-thiazol-2-ylcarbamate (14-5)

[1272] To a solution of 14-4 (300 mg, 0.60 mmol) in DMF (6.0 mL) was added 3-aminobenzenesulfonamide (113 mg, 0.65 mmol) and K 2 CO 3 (246 mg, 1.78 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (162 mg, 0.18 mmol), the reaction mixture was heated at 100 °C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=1:3) gave 14-5 (106 mg, 28%) as a yellow solid.

[1273]

[1274] *Protons from NH were not observed.

[1275] (6) Preparation of A-236

[1276] To a solution of 14-5 (106 mg, 0.17 mmol) in DCM (1.7 mL) was added TFA (0.13 mL, 1.65 mmol) at 0°C. The mixture was stirred at room temperature for 18 h. The reaction mixture was washed with saturated NaHCO 3 The solution was quenched and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (DCM:MeOH=20:1) gave A-236 (7.6 mg, 10%) as a light yellow solid.

[1277] 32. Synthesis of A-237

[1278]

[1279] (1) Preparation of 2-bromo-5-(6-chloropyrimidin-4-yloxy)-4-phenylthiazole (14-6)

[1280] To a solution of 14-3 (400 mg, 1.31 mmol) in ACN (6.6 mL) was added CuBr at 0 °C. 2 (293 mg, 1.31 mmol) and isoamyl nitrite (0.26 mL, 1.97 mmol). After stirring at room temperature for 1 hour, the reaction mixture was concentrated in vacuo. The residue was filtered through SiO 2 Purification by column chromatography (hexane:EtOAc=5:1) gave 14-6 (284 mg, 59%) as a light yellow solid.

[1281]

[1282] (2) Preparation of 5-(6-chloropyrimidin-4-yloxy)-2-methyl-4-phenylthiazole (14-7)

[1283] To a solution of 14-6 (284 mg, 0.77 mmol) in THF (7.7 mL) was added MeZnCl (2M in THF, 0.96 mL, 1.93 mmol) and CuI (103 mg, 0.54 mmol) at room temperature. The mixture was degassed by purging with Ar and refilling with Ar several times. PdCl was added 2 After addition of (dppf) (113 mg, 0.15 mmol), the reaction mixture was refluxed for 1 hour. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=1:1) gave 14-7 (111 mg, 47%) as a yellow solid.

[1284]

[1285] (3) Preparation of A-237

[1286] To a solution of 14-7 (111 mg, 0.37 mmol) in DMF (3.7 mL) was added 3-aminobenzenesulfonamide (69.0 mg, 0.40 mmol) and K 2 CO 3 (152 mg, 1.10 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (99.0 mg, 0.11 mmol), the reaction mixture was heated at 80 °C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=1:3) gave A-237 (38 mg, 24%) as a yellow solid.

[1287] 33. Synthesis of A-238

[1288]

[1289] (1) Preparation of 2-(2-chloropyrimidin-4-yloxy)-1-phenylethanone (15-1)

[1290] To a solution of 1-1 (1.68 g, 8.43 mmol) in acetone (15 mL) was added 2-chloropyrimidin-4-ol (1.00 g, 7.66 mmol) and K 2 CO 3 (1.59 g, 11.5 mmol). After stirring at room temperature for 4 hours, the reaction mixture was poured into water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=1:2) gave 15-1 (1.69 g, 89%) as a white solid.

[1291]

[1292] (2) Preparation of 2-bromo-2-(2-chloropyrimidin-4-yloxy)-1-phenylethanone (15-2)

[1293] At 0°C, 3 AlCl was slowly added to a solution of 15-1 (1.69 g, 6.80 mmol) in 23 mL of 1% paraformaldehyde. 3 (362 mg, 2.72 mmol) and Br 2 (0.525 mL, 10.2 mmol). The mixture was stirred at room temperature for 18 h. The reaction mixture was washed with saturated NaHCO 3 The solution was quenched and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=3:1) gave 15-2 (1.55 g, 70%) as a white solid.

[1294]

[1295] (3) Preparation of 5-(2-chloropyrimidin-4-yloxy)-4-phenylthiazol-2-amine (15-3)

[1296] A mixture of 15-2 (1.55 g, 4.73 mmol) and thiourea (396 mg, 5.21 mmol) in ACN (16 mL) was heated at 80 °C for 30 min. After cooling to room temperature, the reaction mixture was washed with saturated NaHCO 3 The solution was quenched and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Drying, filtration and concentration in vacuo gave 15-3 (1.13 g, 78%) as a yellow solid which was used in the next step without further purification.

[1297]

[1298] (4) Preparation of 2-bromo-5-(2-chloropyrimidin-4-yloxy)-4-phenylthiazole (15-2)

[1299] To a solution of 15-3 (400 mg, 1.31 mmol) in ACN (6.6 mL) was added CuBr at 0 °C. 2 (293 mg, 1.31 mmol) and isoamyl nitrite (0.26 mL, 1.97 mmol). The mixture was stirred at 0°C for 1 hour. The reaction mixture was poured into water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=3:1) gave 15-4 (159 mg, 33%) as a yellow solid.

[1300]

[1301] (5) Preparation of 5-(2-chloropyrimidin-4-yloxy)-2-methyl-4-phenylthiazole (15-5)

[1302] To a solution of 15-4 (159 mg, 0.43 mmol) in THF (4.3 mL) was added MeZnCl (2M in THF, 0.54 mL, 1.08 mmol) and CuI (63.0 mg, 0.30 mmol) at room temperature. The mixture was degassed by purging with Ar and refilling with Ar several times. Pd(dppf)Cl was added 2(63.0 mg, 0.09 mmol), the reaction mixture was refluxed for 1 hour. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=3:1) gave 15-5 (57.0 mg, 44%) as a yellow solid.

[1303]

[1304] (6) Preparation of A-238

[1305] To a solution of 15-5 (57.0 mg, 0.19 mmol) in DMF (1.9 mL) was added 3-aminobenzenesulfonamide (36.0 mg, 0.21 mmol) and K 2 CO 3 (78.0 mg, 0.56 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (51.0 mg, 0.06 mmol), the reaction mixture was heated at 100 °C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (DCM:MeOH=20:1) gave A-238 (8.8 mg, 11%) as a white solid.

[1306] 34. Synthesis of A-239

[1307]

[1308] (1) Preparation of tert-butyl (tert-butyloxycarbonyl)(5-((2-chloropyrimidin-4-yl)oxy)-4-phenylthiazol-2-yl)carbamate (15-6)

[1309] To a solution of 15-3 (700 mg, 3.28 mmol) in THF (23 mL) was added Boc 2 O (1.50 g, 6.89 mmol), TEA (0.96 mL, 6.89 mmol) and DMAP (56.0 mg, 0.46 mmol). The mixture was stirred at room temperature for 18 hours. The reaction mixture was poured into water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=5:1 to 3:1) gave 15-6 (339 mg, 29%) as a yellow solid.

[1310] Compound 15-6: MS Calcd.: 504.99; MS Found: 504.78 (M+H + )

[1311] (2) Preparation of tert-butyl 4-phenyl-5-(2-(3-sulfamoylphenylamino)pyrimidin-4-yloxy)-thiazol-2-ylcarbamate (15-7)

[1312] To a mixed solution of compound 15-6 (339 mg, 0.67 mmol) in DMF (6.0 mL) were added 3-aminobenzenesulfonamide (127 mg, 0.74 mmol) and K 2 CO 3 (278 mg, 2.01 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (183 mg, 0.20 mmol), the reaction mixture was heated at 100 °C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=1:1) gave 15-7 (144 mg, 40%) as a beige solid.

[1313]

[1314] (3) Preparation of A-239

[1315] To a solution of 15-7 (144 mg, 0.27 mmol) in DCM (2.7 mL) was added TFA (0.31 mL, 4.00 mmol) at 0°C. The mixture was stirred at room temperature for 18 h. The reaction mixture was washed with saturated NaHCO 3 The solution was quenched and extracted with DCM. The organic layer was washed with Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (DCM:MeOH=10:1) gave A-239 (5.0 mg, 4%) as a white solid.

[1316] 35. Synthesis of A-240

[1317]

[1318] (1) Preparation of 5-(2-chloropyrimidin-4-yloxy)-4-phenyl-2-vinylthiazole (15-8)

[1319] To a solution of 15-4 (170 mg, 0.46 mmol) in dioxane (2.1 mL) and water (0.21 mL) were added 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (107 mg, 0.69 mmol) and Na 2 CO 3 (147 mg, 1.38 mmol). The mixture was degassed by purging with Ar and refilling with Ar multiple times. Pd(dppf)Cl was added 2 (67.5 mg, 0.09 mmol), the reaction mixture was heated at 80 ° C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=9:1) gave 15-8 (59.0 mg, 41%) as a milky white oil.

[1320]

[1321] (2) Preparation of 5-(2-chloropyrimidin-4-yloxy)-2-ethyl-4-phenylthiazole (15-9)

[1322] A mixture of 15-8 (59.0 mg, 0.19 mmol) and Pd / C (5 wt %, 9.94 mg, 0.09 mmol) in MeOH (3.7 mL) was stirred at room temperature under H 2 Stir under atmosphere (balloon) for 3 hours.After filtering through a pad of Celite, the filtrate was concentrated in vacuo to give 15-9 (51.0 mg, 86%) as a brown oil which was used in the next step without further purification.

[1323]

[1324] (3) Preparation of A-240

[1325] To a solution of 15-9 (51.0 mg, 0.16 mmol) in DMF (2.0 mL) was added 3-aminobenzenesulfonamide (33.2 mg, 0.19 mmol) and K 2 CO3 (66.5 mg, 0.48 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (43.6 mg, 0.05 mmol), the reaction mixture was heated at 100 °C for 4 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (EtOAc only) afforded A-240 (8.5 mg, 12%) as a cream solid.

[1326] The following A-241 to A-246 were synthesized using the procedure described for the synthesis of A-240.

[1327] 36. Intermediate (5-((2-chloropyridin-4-yl)oxy)-4-(6-methylpyridin-2-yl)thiazol-2-yl)amino Preparation of tert-butyl ester (16-6)

[1328]

[1329] (1) Preparation of 2-bromo-1-(6-methylpyridin-2-yl)ethanone (16-2)

[1330] To a solution of 1-(6-methylpyridin-2-yl)ethanone (16-1) (10.0 g, 74.0 mmol) in DCM (148 mL) at 0°C were added HBr (33 wt% in AcOH, 24.35 mL, 148 mmol) and Br 2 (4.58 mL, 89.0 mmol). The mixture was stirred at room temperature for 3 hours. The reaction mixture was washed with saturated NaHCO at 0°C. 3 The solution was neutralized and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Drying, filtration and concentration in vacuo gave 16-2 (15.52 g, 98%) as a yellow oil which was used in the next step without further purification.

[1331]

[1332] (2) Preparation of 4-(6-methylpyridin-2-yl)thiazol-2-amine (16-3)

[1333] To a solution of 16-2 (15.52 g, 72.5 mmol) in acetonitrile (145 mL) was added thiourea (6.07 g, 80.0 mmol) at room temperature. The mixture was heated at 80 °C for 2 h. After cooling to room temperature, the reaction mixture was washed with saturated NaHCO at 0 °C. 3The aqueous solution was neutralized and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Drying, filtration and concentration in vacuo gave 16-3 (12.3 g, 89%) as a yellow solid which was used in the next step without further purification.

[1334]

[1335] (3) Preparation of tert-butyl (tert-butyloxycarbonyl)(4-(6-methylpyridin-2-yl)thiazol-2-yl)carbamate (16-4)

[1336] To a solution of 16-3 (12.3 g, 64.3 mmol) in THF (19 mL) was added Boc 2 O (42.1 g, 193 mmol), DMAP (2.35 g, 19.29 mmol) and TEA (26.7 mL, 193 mmol). The mixture was stirred at room temperature for 18 hours. The reaction mixture was poured into water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=5:1) gave 16-4 (15.78 g, 62%) as a light yellow solid.

[1337]

[1338] (4) Preparation of tert-butyl (5-bromo-4-(6-methylpyridin-2-yl)thiazol-2-yl)(tert-butoxycarbonyl)carbamate (16-5)

[1339] To a solution of 16-4 (15.7 g, 40.1 mmol) in DMF (201 mL) was slowly added NBS (7.85 g, 44.1 mmol) at 0°C. The mixture was stirred at room temperature for 2 h. The reaction mixture was washed with saturated NaHCO 3 The aqueous solution was quenched and extracted with EtOAc. The organic layer was washed several times with brine and then 2 SO 4 Drying, filtration and concentration in vacuo gave 16-5 (16.3 g, 86%) as a brown oil which was used in the next step without further purification.

[1340]

[1341] (5) Preparation of Compound 16-6

[1342] At 100 °C, 16-5 (15.5 g, 33.0 mmol), 2-chloropyridin-4-ol (4.70 g, 36.2 mmol) and K 2 CO 3 The mixture of (9.11 g, 65.9 mmol) was stirred for 150 minutes. The reaction of the consumed compound 16-5 was checked every hour by LC-MS. The mixture was poured into water and extracted with EtOAc. The organic layer was washed several times with brine and then purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (hexane:EtOAc=2:1) ​​gave 16-6 (6.4 g, 37%) as a yellow solid.

[1343]

[1344] *Protons from NH were not observed.

[1345] 37. Synthesis of A-247

[1346]

[1347] (1) Preparation of tert-butyl 4-(6-methylpyridin-2-yl)-5-(2-(3-sulfamoylphenylamino)pyridin-4-yloxy)thiazol-2-ylcarbamate (16-7)

[1348] To a solution of 16-6 (150 mg, 0.36 mmol) in DMF (7.2 mL) at room temperature were added 3-aminobenzenesulfonamide (92.0 mg, 0.54 mmol) and Cs 2 CO 3 (350 mg, 1.07 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (97.0 mg, 0.11 mmol), the reaction mixture was heated at 100 °C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (EtOAc only to EtOAc:MeOH=50:1) gave 16-7 (44.0 mg, 22%) as a yellow solid.

[1349]

[1350] (2) Preparation of A-247

[1351] To a solution of 16-7 (44.0 mg, 0.08 mmol) in DCM (1.6 mL) was added TFA (0.122 mL, 1.59 mmol) at 0°C. After stirring at room temperature for 1 hour, the reaction mixture was washed with saturated NaHCO 3 The organic layer was quenched and extracted with 5% MeOH / DCM. 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (EtOAc only and EtOAc:MeOH=10:1) gave A-247 (7.0 mg, 19%) as a light orange solid.

[1352] The following A-248 and A-249 were synthesized using the procedure described for the synthesis of A-247.

[1353] 38. Synthesis of A-250

[1354]

[1355] (1) Preparation of 5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)thiazol-2-amine (16-8)

[1356] To a solution of 16-6 (6.4 g, 15.28 mmol) in DCM (153 mL) was added TFA (23.54 mL, 306 mmol) at 0°C. After stirring at room temperature for 5 h, the reaction mixture was washed with saturated NaHCO 3 The aqueous solution was neutralized and extracted with DCM. The organic layer was washed with Na 2 SO 4 Drying, filtration and concentration in vacuo gave 16-8 (4.3 g, 88%) as a red solid which was used in the next step without further purification.

[1357]

[1358] (2) Preparation of 2-bromo-5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)thiazole (16-9)

[1359] At 0°C, CuBr in acetonitrile (100 mL) was added 2 To a solution of 16-8 (4.3 g, 13.49 mmol) (3.01 g, 13.49 mmol) and isoamyl nitrite (2.72 mL, 20.23 mmol) was added 16-8 (4.3 g, 13.49 mmol) in acetonitrile (170 mL). The reaction mixture was stirred at room temperature for 2 hours and then washed with NH4 OH (100 mL) and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=5:1 to 3:1) gave 16-9 (1.57 g, 30%) as a yellow solid.

[1360]

[1361] (3) Preparation of 5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)-2-vinylthiazole (17-1)

[1362] To a solution of 16-9 (1.57 g, 4.10 mmol) in THF (41 mL) was added tributyl(vinyl)tin (1.91 mL, 6.56 mmol) at room temperature. The mixture was degassed by Ar, and then PdCl was added. 2 (PPh 3 ) 2 (576 mg, 0.82 mmol). The mixture was heated at 80°C for 4 hours. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=7:1 to 5:1) gave 17-1 (510 mg, 37%) as a yellow solid.

[1363]

[1364] (4) Preparation of 5-(2-chloropyridin-4-yloxy)-2-ethyl-4-(6-methylpyridin-2-yl)thiazole (17-2)

[1365] 17-1 and PtO in MeOH (18 mL) were mixed at room temperature. 2 A mixture of (70.0 mg, 0.31 mmol) in H 2 Stir under 4% CO atmosphere (balloon) for 3 hours. After filtering through a Celite pad, the filtrate was concentrated in vacuo. The residue was filtered through SiO 2 Purification by column chromatography (EA only) gave 17-2 (456 mg, 89%) as a yellow solid.

[1366]

[1367] (5) Preparation of A-250

[1368] To a solution of 17-2 (456 mg, 1.37 mmol) in DMF (13 mL) at room temperature were added 3-aminobenzenesulfonamide (355 mg, 2.06 mmol) and Cs 2 CO 3 (1.3 g, 4.12 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (374 mg, 0.41 mmol), the reaction mixture was heated at 80 ° C for 2 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was washed with NH-SiO 2 Purification by column chromatography (hexane:EA=1:2 to 1:4) gave A-250 (151 mg, 23%) as a white solid.

[1369] The following A-251 to A-273 were synthesized using the procedure described for step 5 of the synthesis of A-250.

[1370] 39. Synthesis of A-274

[1371]

[1372] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazole (18-1)

[1373] To a solution of 16-9 (50 mg, 0.13 mmol) in dioxane (3 mL) at room temperature were added cyclopropyltributyltin (86.5 mg, 0.26 mmol) and PdCl 2 (PPh 3 ) 2 (18.3 mg, 0.03 mmol). The mixture was heated at 100°C for 4 hours. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=3:1) gave 18-1 (20.0 mg, 44.5%) as a yellow liquid.

[1374]

[1375] (2) Preparation of A-274

[1376] To a solution of 18-1 (20.0 mg, 0.06 mmol) in DMF (1.0 mL) was added 3-aminobenzamide (10.0 mg, 0.07 mmol) and K 2 CO 3 (24.1 mg, 0.18 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (21.0 mg, 0.02 mmol), the reaction mixture was heated at 100 °C for 2 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (DCM:MeOH=10:1) gave A-274 (3.4 mg, 13.0%) as a milky white solid.

[1377] The following A-275 to A-282 were synthesized using the procedure described for the synthesis of A-274.

[1378] 40. Synthesis of A-283

[1379]

[1380] (1) Preparation of 5-(2-chloropyridin-4-yloxy)-N,N-dimethyl-4-(6-methylpyridin-2-yl)thiazol-2-amine (19-1)

[1381] To a solution of 16-9 (290 mg, 0.76 mmol) in DMF (3.0 mL) was added dimethylamine (2.0 M in THF, 0.57 mL, 1.14 mmol). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was washed with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Drying, filtration and concentration in vacuo gave 19-1 (100 mg, 38%) as a yellow oil which was used in the next step without further purification.

[1382]

[1383] (2) Preparation of A-283

[1384] To a solution of 19-1 (100 mg, 0.29 mmol) in DMF (3.0 mL) was added 3-aminobenzenesulfonamide (74.0 mg, 0.43 mmol) and K 2 CO 3(120 mg, 0.87 mmol). The mixture was degassed by purging with argon and refilling with argon several times. After adding BrettPhos Pd G3 (52.0 mg, 0.06 mmol), the reaction mixture was heated at 100 °C for 2 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (DCM:MeOH=98:2) gave A-283 (55.4 mg, 40%) as a milky white solid.

[1385] The following A-284 to A-286 were synthesized using the procedure described for the synthesis of A-283.

[1386] 41. Synthesis of A-287

[1387]

[1388] (1) Preparation of 5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)-2-(prop-1-en-2-yl)thiazole (20-1)

[1389] To a solution of 16-9 (400 mg, 1.05 mmol) in THF (5.2 mL) and water (5.2 mL) was added potassium isopropenyl trifluoroborate (232 mg, 1.57 mmol) and Na 2 CO 3 (776 mg, 7.32 mmol). The mixture was degassed by purging with Ar and refilling with Ar multiple times. PdCl was added 2 After addition of (dppf) (86.0 mg, 0.11 mmol), the reaction mixture was heated at 60°C for 18 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=4:1) gave 20-1 (133 mg, 37%) as a yellow oil.

[1390]

[1391] (2) Preparation of 5-(2-chloropyridin-4-yloxy)-2-isopropyl-4-(6-methylpyridin-2-yl)thiazole (20-2)

[1392] To a solution of 20-1 (173 mg, 0.503 mmol) in DCM (2.5 mL) and MeOH (2.5 mL) was added Pd / C (10 wt%, 54.0 mg, 0.05 mmol) at room temperature. The mixture was stirred at room temperature under H 2 Stir under 4% CO atmosphere (balloon) for 18 h. After filtering through a Celite pad, the filtrate was concentrated in vacuo. The residue was filtered through SiO 2 Purification by column chromatography (hexane:EtOAc=3:1) gave 20-2 (60.0 mg, 35%) as a colorless oil.

[1393]

[1394] (3) Preparation of A-287

[1395] To a solution of 20-2 (60.0 mg, 0.17 mmol) in DMF (3.5 mL) at room temperature were added 3-aminobenzenesulfonamide (45.0 mg, 0.26 mmol) and Cs 2 CO 3 (170 mg, 0.52 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (47.0 mg, 0.05 mmol), the reaction mixture was heated at 80 °C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (hexane:EtOAc=1:2) gave A-287 (22.2 mg, 27%) as a white solid.

[1396] The following A-288 was synthesized using the procedure described for the synthesis of A-287.

[1397] 42. Synthesis of A-289

[1398]

[1399] (1) Preparation of 5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)-2-(trifluoromethyl)thiazole (21-1)

[1400] To a solution of 16-9 (0.45 g, 1.18 mmol) in DMF (3 mL) was added CuI (403.1 mg, 2.12 mmol), HMPA (0.41 mL, 2.35 mmol) and methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (0.45 mL, 3.53 mmol) at room temperature. The mixture was heated at 90 °C for 0.5 h. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=5:1) gave 21-1 (50.0 mg, 11%) as a yellow liquid.

[1401]

[1402] (2) Preparation of A-289

[1403] To a solution of 21-1 (38.0 mg, 0.10 mmol) in DMF (2.0 mL) at room temperature were added 3-aminobenzenesulfonamide (26.0 mg, 0.15 mmol) and Cs 2 CO 3 (100 mg, 0.31 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (26.0 mg, 0.15 mmol), the reaction mixture was heated at 80 °C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (hexane:EtOAc=1:4) gave A-289 (12.0 mg, 23%) as a white solid.

[1404] The following A-290 and A-291 were synthesized using the procedure described for the synthesis of A-289.

[1405] 43. Synthesis of A-292

[1406]

[1407] (1) Preparation of N-methyl-4-(6-methylpyridin-2-yl)thiazol-2-amine (22-1)

[1408] To a solution of 16-2 (2.00 g, 9.34 mmol) in EtOH (31 mL) was added 1-methylthiourea (842 mg, 9.34 mmol) at room temperature. The mixture was heated at 80 ° C for 1 hour. After cooling to room temperature, the reaction mixture was concentrated in vacuo and 22-1 (1.70 g, 89%) was obtained as a yellow solid, which was used in the next step without further purification.

[1409]

[1410] (2) Preparation of 5-bromo-N-methyl-4-(6-methylpyridin-2-yl)thiazol-2-amine (22-2)

[1411] To a solution of 22-1 (2.00 g, 9.74 mmol) in DMF (49 mL) was slowly added NBS (1.73 g, 9.74 mmol) at 0°C. The mixture was stirred at room temperature for 1 hour. The reaction mixture was washed with saturated NaHCO 3 The solution was quenched and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue was triturated with ether and hexanes. The solid was filtered and dried to give 22-2 (1.60 g, 58%) as a yellow solid.

[1412]

[1413] (3) Preparation of 5-(2-chloropyridin-4-yloxy)-N-methyl-4-(6-methylpyridin-2-yl)thiazol-2-amine (22-3)

[1414] At 100 °C, 22-2 (1.00 g, 3.52 mmol), 2-chloropyridin-4-ol (501 mg, 3.87 mmol) and K 2 CO 3 The mixture of (501 mg, 3.87 mmol) was stirred for 1 hour. The reaction mixture was poured into water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with NH-SiO 2 Purification by column chromatography (hexane:EtOAc=1:1) gave 22-3 (542 mg, 46%) as a yellow solid.

[1415]

[1416] (4) Preparation of A-292

[1417] To a solution of 22-3 (250 mg, 0.75 mmol) in DMF (15 mL) at room temperature were added 3-aminobenzenesulfonamide (194 mg, 1.13 mmol) and Cs 2 CO 3 (734 mg, 2.25 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (204 mg, 0.22 mmol), the reaction mixture was heated at 80 °C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (DCM:MeOH=10:1) gave A-292 (4.0 mg, 1%) as a light yellow solid.

[1418] 44. Synthesis of A-293 and A-294

[1419]

[1420] (1) Preparation of 5-(2-chloropyridin-4-yloxy)-2-cyclopropyl-4-phenyloxazole (23-1)

[1421] To a solution of 1-4 (700 mg, 2.14 mmol) in EtCN (20 mL) at room temperature was added cyclopropanesulfonamide (1.00 g, 11.8 mmol). The mixture was heated at 120 °C for 18 h. After cooling to room temperature, the reaction mixture was washed with saturated NaHCO 3 The solution was quenched and extracted with EtOAc. The organic layer was washed with brine and purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=4:1) gave 23-1 (180 mg, 27%) as a colorless oil.

[1422]

[1423] (2) Preparation of 6-(4-(2-cyclopropyl-4-phenyloxazol-5-yloxy)pyridin-2-ylamino)nicotinate (23-2)

[1424] To a solution of 23-1 (40.0 mg, 0.13 mmol) in DMF (5.0 mL) was added methyl 6-aminonicotinate (40.0 mg, 0.26 mmol) and K 2 CO 3(60.0 mg, 0.43 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (40.0 mg, 44.0 μmol), the reaction mixture was heated at 100 °C for 2 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=4:1) gave 23-2 (30.0 mg, 55%) as a yellow solid.

[1425]

[1426] (3) Preparation of A-293

[1427] To a solution of 23-2 (30.0 mg, 0.07 mmol) in THF (5.0 mL) and water (5.0 mL) was added LiOH·H 2 O (50.0 mg, 2.09 mmol). The mixture was heated at 50 ° C for 18 hours. After cooling to room temperature, the reaction mixture was concentrated in vacuo. The residue was acidified with 2N HCl aqueous solution. The precipitated solid was collected by filtration to give A-293 (21.0 mg, 72%) as a cream solid.

[1428] (4) Preparation of A-294

[1429] To a solution of A-293 (15.0 mg, 36.0 μmol) in DMF (5.0 mL) was added HATU (30.0 mg, 79.0 μmol), NH 4 Cl (50.0 mg, 0.94 mmol) and DIPEA (0.20 mL, 1.15 mmol). The mixture was stirred at room temperature for 18 hours. The reaction mixture was poured into water. The resulting solid was filtered and triturated with DCM and hexane. The precipitated solid was collected by filtration and dried in vacuo to give A-294 (4.0 mg, 19%) as a white solid.

[1430] The following A-295 to A-302 were synthesized using the procedure described for the synthesis of A-293.

[1431] 45. Synthesis of A-303

[1432]

[1433] (1) Preparation of 5-(2-chloropyridin-4-yloxy)-2-methyl-4-(6-methylpyridin-2-yl)thiazole (24-1)

[1434] To a solution of 16-9 (200 mg, 0.52 mmol) in THF (5.2 mL) was added CuI (70.0 mg, 0.37 mmol) and Pd(dppf)Cl at room temperature. 2 (76.0 mg, 0.11 mmol). The mixture was degassed by purging with Ar and refilling with Ar multiple times. MeZnCl was added 2 After addition of 4% paraformaldehyde (2M in THF, 0.65 mL, 1.31 mmol), the reaction mixture was refluxed for 1 hour. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=2:1) ​​gave 24-1 (90.0 mg, 54%) as a beige solid.

[1435]

[1436] (2) Preparation of A-303

[1437] To a solution of 24-1 (90.0 mg, 0.28 mmol) in DMF (5.7 mL) at room temperature were added 3-aminobenzenesulfonamide (73.0 mg, 0.42 mmol) and Cs 2 CO 3 (277 mg, 0.85 mmol). The mixture was degassed by purging with Ar and refilling with Ar several times. After adding BrettPhos Pd G3 (77.0 mg, 0.08 mmol), the reaction mixture was heated at 80 °C for 3 hours. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was purified by Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue is washed with water by SiO 2 Purification by column chromatography (hexane:EtOAc=2:1) ​​gave A-303 (5.0 mg, 4%) as a white solid.

[1438] The following A-304 to A-309 were synthesized using the procedure described for the synthesis of A-303.

[1439] The following A-62 and A-137 were synthesized using the procedure described for the synthesis of A-1.

[1440] The following A-310 was synthesized using the procedure described for the synthesis of A-50.

[1441] The following A-311 was synthesized using the procedure described for the synthesis of A-191.

[1442] The following A-312 was synthesized using the procedure described for the synthesis of A-193.

[1443] [Example 1] LanthaScreen Eu kinase binding assay

[1444] 4 μL of 4X test compound in 4% DMSO and 4 μL of 4X kinase in kinase buffer were added to the wells (low volume, white 384-well plate (Greiner Cat. #784207)). The plate was shaken for 30 seconds, centrifuged at 1000 rpm for 10 seconds, and incubated at room temperature for 30 minutes. Then, 4 μL of 4X Eu-anti-GST antibody and 4 μL of 4X kinase tracer 178 were added to the wells. The plate was shaken for 30 seconds, centrifuged at 1000 rpm for 10 seconds, and incubated at room temperature for 60 minutes. Fluorescence was measured by a microplate reader Biotek Synergy H1 (Vermont, USA) under the following conditions.

[1445] Excitation: 340nm (30nm bandpass)

[1446] Kinase tracer emission: 665nm (10nm bandpass)

[1447] Eu Ab emission: 615nm (10nm bandpass)

[1448] Emission ratio = 665nm (tracer) / 615nm (Eu Ab)

[1449] *The higher the binding affinity of the compound to ALK5 kinase, the lower the emission ratio.

[1450] [Table 1]

[1451]

[1452] [Example 2] Assay for evaluating cellular inhibition of TGF-β signaling

[1453] Transient pools of 4T1 (SBE-luc2P) or HEK293 (SBE reporter cells) stable cells (BPS bioscience) containing SBE-luc2P (hygro) expression plasmid were cultured at 6×10 3 cells / well or 2.5x10 4 Cells were seeded in 96-well plates at 37°C and 5% CO.2 In the experiment, a transient pool of 4T1 (SBE-luc2P) cells at about 60% confluence was pretreated with the novel compound synthesized in the above synthesis example in 0.2% FBS. In addition, the cells were incubated at 37°C with 5% CO 2 HEK293 (SBE reporter cells) stable cells were pre-treated with various test compounds at about 80% confluence in 0.5% FBS. After 2 hours, the cells were incubated at 37°C with 5% CO 2 Cells were treated with TGF-β1 (2 ng / mL) for 24 hours. Cell lysates were prepared using luciferase assay (Promega) according to the manufacturer's instructions, and luminescence was measured by microplate reader Biotek Synergy H1 (Vermont, USA). The results are shown in Table 2.

[1454] [Table 2]

[1455]

[1456] The above description of the present disclosure is for illustrative purposes only, and those skilled in the art will understand that the present disclosure can be easily modified into other specific forms without changing the technical spirit or basic features of the present disclosure. Therefore, it should be understood that the exemplary embodiments described above are illustrative in all aspects and not restrictive.

[1457] The scope of the present disclosure is indicated by the appended claims, and all modifications or variations derived from the meaning and scope of the claims and their equivalents should be construed as being included in the scope of the present disclosure.

Claims

1. A compound selected from the group consisting of a thiazole derivative compound represented by the following Chemical Formula 1, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof: [Chemical formula 1] in, In Chemical Formula 1, A 1 is O or S, A 2 is CH or N, R 1 and R 2 The same or different and each is one of the following: (C1-C4) alkyl, (C1-C4) alkylene, (C1-C4) alkoxy, trifluoromethyl (CF3), halogen, NR 11 R 12 , unsubstituted or substituted (C3-C8)cycloalkyl, unsubstituted or substituted (C5-C10)aryl, and unsubstituted or substituted heteroaryl containing 5 to 10 atoms of one or more heteroatoms selected from the group consisting of N, O and S; R 11 and R 12 are the same or different and are each any one of the following: hydrogen, (C1-C5) alkyl, and (C3-C8) cycloalkyl; the substituted (C3-C8) cycloalkyl, substituted (C5-C10) aryl, or substituted heteroaryl of 5 to 10 atoms is substituted by (C1-C5) alkyl, n is one of 0 to 3, Ar is an unsubstituted or substituted (C5-C10) aryl group or an unsubstituted or substituted heteroaryl group of 5 to 10 atoms containing one or more heteroatoms selected from the group consisting of N, O and S, wherein the substituted (C5-C10) aryl group or the substituted heteroaryl group of 5 to 10 atoms is replaced by R 3 replace, R 3 For-R 3-1 or -(C1-C5)alkyl-R 3-1 , R 3-1 is hydrogen, halogen, hydroxyl, cyano, (C1-C5) alkyl, (C1-C5) alkoxy, -CONR 31-1 R 31-2 、-COOR 32 、-NHSO2R 33 、-SO2R 34 、-SO2NR 35-1 R 35-2 、-COR 36 、-NH-(C1-C3)alkyl-R 37 , as well as Any of R 31-1 , R 31-2 , R 32 , R 33 , R 34 , R 35-1 and R 35-2 are the same or different and are each hydrogen, hydroxy, trifluoromethyl, (C1-C5) alkyl, (C3-C8) cycloalkyl, -SO2-(C1-C3) alkyl, -(C1-C3) alkyl-R 301 as well as R 301 is (C1-C4) alkylamino, di[(C1-C4) alkyl]amino, (C3-C8) cycloalkyl, as well as Any of R 3001 is hydrogen or (C1-C5) alkyl, R 302 For halogen, R 303 and R 304 are the same or different and are each hydrogen or (C1-C3) alkyl, R 36 and R 37 The same or different and each R 305 is hydrogen or (C1-C5) alkyl, R 306 is any one of hydrogen, amino, (C1-C4) alkylamino and di[(C1-C4) alkyl]amino, R 38 and R 39 are the same or different and are each any one of hydrogen, (C1-C3) alkyl and -(C1-C3) alkyl-(C1-C3) alkoxy.

2. The compound according to claim 1, wherein In Chemical Formula 1, R 1 is (C1-C3) alkyl, (C1-C3) alkylene, methoxy, trifluoromethyl (CF3), bromine (Br), (C3-C6) cycloalkyl and NR 11 R 12 Any of the R 11 and R 12 are the same or different and are each any one of hydrogen, (C1-C3) alkyl and cyclopropyl, R 2 for or naphthyl, A 3 CH or N, R 21 is hydrogen or methyl, n is one of 0 to 2, Ar as well as Any of the R 3 For-R 3-1 or -(C1-C3)alkyl-R 3-1 , R 3-1 is hydrogen, fluorine, chlorine, hydroxyl, cyano, (C1-C3) alkyl, (C1-C3) alkoxy, -CONR 31-1 R 31-2 、-COOR 32 、-NHSO2R 33 、-SO2R 34 、-SO2NR 35-1 R 35-2 、-COR 36 、-NH-(C1-C3)alkyl-R 37 , as well as Any of the R 31-1 , R 31-2 , R 32 , R 33 , R 34 , R 35-1 and R 35-2 the same or different and each is hydrogen, hydroxy, trifluoromethyl, (C1-C3) alkyl, (C3-C6) cycloalkyl, -SO2CH3, -(C1-C3) alkyl-R 301 as well as R 301 Methylamino, dimethylamino, cyclopropyl, as well as Any of the R 3001 is hydrogen or (C1-C3) alkyl, R 302 is fluorine, R 303 and R 304 are the same or different and are each hydrogen or methyl, R 36 and R 37 The same or different and each R 305 is (C1-C3) alkyl, R 306 is any one of hydrogen, amino and methylamino, R 38 and R 39 are the same or different and are each any one of hydrogen, (C1-C3) alkyl and -(C1-C3) alkyl-methoxy.

3. The compound according to claim 1, wherein In Chemical Formula 1, R 1 Methyl, ethyl, isopropyl, methoxy, ethylene, trifluoromethyl (CF3), bromine (Br), cyclopropyl, cyclopentyl, cyclohexyl and NR 11 R 12 Any of the R 11 and R 12 are the same or different and are each any one of hydrogen, methyl and cyclopropyl, R 2 for as well as One of n is one of 0 to 2, Ar as well as Any of the R 3 For-R 3-1 or -(C1-C3)alkyl-R 3-1 , R 3-1 is hydrogen, fluorine, chlorine, hydroxyl, cyano, methyl, methoxy, -CONR 31-1 R 31-2 、-COOR 32 、-NHSO2R 33 、-SO2R 34 、-SO2NR 35- 1 R 35-2 、-COR 36 、-NH-(C1-C2)alkyl-R 37 , as well as Any of R 31-1 and R 31-2 are the same or different and are each hydrogen, methyl, isopropyl, hydroxy, -SO2CH3, -(C1-C2)alkyl-R 301 as well as Any of the R 301 For dimethylamino, cyclopropyl, as well as Any of the R 3001 is one of methyl, ethyl and isopropyl, R 302 is fluorine, R 303 and R 304 Methyl, R 32 is one of hydrogen, methyl and -(C1-C2)alkyl-dimethylamino, R 33 is one of methyl, ethyl, cyclopropyl and trifluoromethyl, R 34 is one of hydroxyl, methyl, ethyl, cyclopropyl and trifluoromethyl, R 35-1 and R 35-2 are the same or different and are each one of hydrogen, methyl and cyclopropyl, R 36 for R 305 is methyl, R 306 is amino or methylamino, R 37 for R 38 is methyl or -CH2CH2OCH3, and R 39 It is hydrogen or methyl.

4. The thiazole derivative compound, its stereoisomer, its hydrate or its salt according to claim 1, wherein the compound represented by Chemical Formula 1 is any one selected from the group consisting of the following compounds: (1) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (2) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (3) Methyl 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate (4) 4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (5) 4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (6) 4-phenyl-5-((2-(pyridin-3-ylamino)pyridin-4-yl)oxy)thiazol-2-amine (7) 5-((2-((6-fluoropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (8) 4-phenyl-5-((2-(pyridin-4-ylamino)pyridin-4-yl)oxy)thiazol-2-amine (9) 6-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (10) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylbenzamide (11) 5-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (12) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzenesulfonamide (13) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylbenzenesulfonamide (14) N-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide (15) 5-((2-((3-(methylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (16) N-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopropanesulfonamide (17) 4-phenyl-5-((2-((3-((trifluoromethyl)sulfonyl)phenyl)amino)pyridin-4-yl)oxy)thiazol-2-amine (18) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid (19) 5-((2-((3-((methylsulfonyl)methyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (20) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-cyclopropylbenzenesulfonamide (21) 5-((2-((3-fluorobenzyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (22) 2-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide (23) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide (24) 5-((2-((2-methoxypyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (25) 5-((2-(Benzylamino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (26) 4-phenyl-5-((2-((pyridin-4-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine (27) 5-((2-((2-chloropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (28) 4-phenyl-5-((2-(pyridin-3-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine (29) (3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide (30) 5-((2-((2-fluoropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (31) 5-((2-((6-methoxypyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (32) 5-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (33) 6-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (34) 5-((2-((3-(ethylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (35) 5-((2-((6-chloropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (36) N-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide (37) 5-((2-((1-methyl-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (38) 5-((2-((1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (39) 4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (40) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (41) 2-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (42) 2-(4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (43) 2-(5-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (44) 2-(3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (45) 3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (46) 3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (47) 4-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (48) 3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (49) 4-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (50) 2-(3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (51) 3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (52) 3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (53) 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (54) 2-(4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (55) 2-(5-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (56) 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (57) 3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (58) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (59) 2-(4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (60) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (61) 2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (62) 5-((2-((1-(methylsulfonyl)-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (63) 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (64) 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (65) 2-(5-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (66) 2-methyl-2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoic acid (67) N,N-Dimethyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (68) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid (69) N-methyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (70) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(3-(methylsulfonyl)phenyl)pyridin-2-amine (71) N-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide (72) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((trifluoromethyl)sulfonyl)phenyl)pyridin-2-amine (73) N-methyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (74) N,N-Dimethyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (75) N-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopropanesulfonamide (76) N-cyclopropyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (77) N-(3-(ethylsulfonyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (78) (3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide (79) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((methylsulfonyl)methyl)phenyl)pyridin-2-amine (80) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-ylmethyl)pyridin-2-amine (81) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-ylmethyl)pyridin-2-amine (82) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-yl)pyridin-2-amine (83) N-(6-fluoropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (84) N-(6-chloropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (85) N-(6-methoxypyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (86) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-yl)pyridin-2-amine (87) N-(2-fluoropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (88) N-(2-methoxypyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (89) N-(2-chloropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (90) 6-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (91) 5-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (92) 5-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (93) 2-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide (94) N-Benzyl-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (95) N-(4-fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (96) N-(3-fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (97) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(1-(methylsulfonyl)-1H-pyrazol-4-yl)pyridin-2-amine (98) N-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (99) N-(1-methyl-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (100) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(1H-pyrazol-4-yl)pyridin-2-amine (101) 6-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (102) 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (103) N-(4-methoxyphenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (104) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(piperazin-1-yl)phenyl)pyridin-2-amine (105) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(2-(piperidin-1-yl)ethoxy)phenyl)pyridin-2-amine (106) N-(3-methoxy-4-(4-methylpiperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (107) 1,1,1-trifluoro-N-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide (108) N-(4-(4-(2-methoxyethyl)piperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (109) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (110) 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (111) 2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)acetonitrile (112) N-(3-((1H-tetrazolyl-5-yl)methyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (113) 3-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propionitrile (114) N-(3-(2-(2H-tetrazolyl-5-yl)ethyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (115) 2-(3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (116) 3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (117) 3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (118) 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (119) 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (120) 2-(4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (121) 2-(5-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (122) N-(3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)ethanesulfonamide (123) N-(3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide (124) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (125) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide (126) 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide (127) N-(6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)methanesulfonamide (128) N-(4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide (129) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (130) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate (131) Methyl 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate (132) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (133) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (134) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid (135) 3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (136) 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (137) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid (138) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-hydroxynicotinamide (139) 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-hydroxybenzamide (140) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(methylsulfonyl)nicotinamide (141) 2-(3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (142) 3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (143) 3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (144) 3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (145) 3-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (146) 6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (147) 4-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (148) N-methyl-4-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (149) 6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (150) N-methyl-6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (151) 3-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (152) 4-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (153) 2-(3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (154) 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (155) 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (156) 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (157) 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (158) 2-(4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (159) 2-(5-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (160) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (161) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide (162) Methyl 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate (163) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (164) 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide (165) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (166) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (167) 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (168) 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (169) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid (170) Methyl 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate (171) 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (172) 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (173) 6-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (174) 6-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (175) 4-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (176) 6-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (177) 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (178) 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (179) 4-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (180) 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (181) 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (182) 2-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (183) 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (184) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (185) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (186) 2-(4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (187) 2-(5-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (188) N-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)ethanesulfonamide (189) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide (190) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (191) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate (192) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (193) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (194) 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (195) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (196) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-isopropylnicotinamide (197) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(4-methylpiperazin-1-yl)methanone (198) (3-aminopyrrolidin-1-yl)(6-(4-(2-ethyl-4-phenylthiazol-5-yloxy)pyridin-2-ylamino)pyridin-3-yl)methanone (199) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(pyrrolidin-1-yl)ethyl)nicotinamide (200)(6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(3-(methylamino)pyrrolidin-1-yl)methanone (201) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-methylpiperazin-1-yl)ethyl)nicotinamide (202) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-isopropylpiperazin-1-yl)ethyl)nicotinamide (203) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-ethylpiperazin-1-yl)ethyl)nicotinamide (204) 5-(3-aminopyrrolidin-1-yl)-N-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)pyridin-2-amine (205)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-isopropylpiperazin-1-yl)ethyl)benzene-1,4-diamine (206)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-methylpiperazin-1-yl)ethyl)benzene-1,4-diamine (207)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-ethylpiperazin-1-yl)ethyl)benzene-1,4-diamine (208)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(Pyrrolidin-1-yl)ethyl)benzene-1,4-diamine (209)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-methylpiperazin-1-yl)ethyl)pyridine-2,5-diamine (210)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(Pyrrolidin-1-yl)ethyl)pyridine-2,5-diamine (211)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-ethylpiperazin-1-yl)ethyl)pyridine-2,5-diamine (212)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-isopropylpiperazin-1-yl)ethyl)pyridine-2,5-diamine (213) N-(5-(1H-pyrazol-4-yl)pyridin-2-yl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (214) N-(4-(3-aminopyrrolidin-1-yl)phenyl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (215) 4-((2-ethyl-4-phenylthiazol-5-yl)oxy)-N-(4-(3-(methylamino)pyrrolidin-1-yl)phenyl)pyridin-2-amine (216) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid methyl ester (217) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid (218) 3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (219) 2-(3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (220) 3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (221) 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (222) 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (223) 2-(4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (224) 2-(5-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (225) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide (226) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (227) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (228) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (229) 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide (230) 3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (231) 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (232) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (233) 3-((4-((2-(methylamino)-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (234) 3-((4-((2-amino-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (235) 3-((4-((2-(dimethylamino)-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (236) 3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide (237) 3-((6-((2-methyl-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide (238) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzenesulfonamide (239) 3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide (240) 3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide (241) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)picolinamide (242) 2-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)isonicotinamide (243) 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzamide (244) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)nicotinic acid (245) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)nicotinamide (246) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzoic acid (247) 3-((4-((2-amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (248) 4-((4-((2-amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (249) 3-((4-((2-amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (250) 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (251) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (252) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (253) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (254) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid (255) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (256) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide (257) 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (258) 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (259) 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide (260) 5-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (261) 5-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (262) 5-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (263) 4-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid (264) 4-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (265) 4-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide (266) 2-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinic acid (267) 2-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide (268) 2-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylisonicotinamide (269) N-(2-(dimethylamino)ethyl)-6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (270) N-(Cyclopropylmethyl)-6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (271) 2-(dimethylamino)ethyl 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (272) N-(3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide (273) 2-(Dimethylamino)ethyl 3-(6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamido)-5-fluorobenzoate (274) 3-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (275) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (276) 2-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide (277) 3-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (278) 6-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (279) 6-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide (280) 2-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylisonicotinamide (281) 3-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide (282) 6-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (283) 3-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (284) 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (285) 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (286) 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (287) 3-((4-((2-isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (288) 6-((4-((2-isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (289) 3-((4-((4-(6-methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (290) 6-((4-((2-isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (291) 3-((4-((4-(6-methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (292) 3-((4-((2-(methylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (293) 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (294) 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (295) 4-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (296) 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (297) 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide (298) 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (299) 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (300) 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (301) 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid (302) 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide (303) 3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (304) 2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)acetonitrile (305) N-(3-((1H-tetrazolyl-5-yl)methyl)phenyl)-4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-amine (306) 3-(3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propionitrile (307) N-(3-(2-(2H-tetrazolyl-5-yl)ethyl)phenyl)-4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-amine (308) Methyl 2-methyl-2-(3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoate (309) 2-Methyl-2-(3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoic acid (310) 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (311) N-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide (312) 4-((2-ethyl-4-phenylthiazol-5-yl)oxy)-N-(5-(3-(methylamino)pyrrolidin-1-yl)pyridin-2-yl)pyridin-2-amine.

5. A pharmaceutical composition for treating or preventing cancer diseases, comprising a compound as an active ingredient, wherein the compound is selected from the thiazole derivative compound according to claim 1, a pharmaceutically acceptable salt thereof, a solvate thereof or a stereoisomer thereof.

6. The pharmaceutical composition according to claim 5, wherein the cancer disease is selected from the group consisting of lung cancer, breast cancer, ovarian cancer, uterine cancer, pancreatic cancer, lung cancer, stomach cancer, liver cancer, colorectal cancer, skin cancer, head and neck cancer, brain cancer, laryngeal cancer, prostate cancer, bladder cancer, esophageal cancer, thyroid cancer, kidney cancer and rectal cancer. 7 . The pharmaceutical composition according to claim 5 , wherein the cancer disease is a cancer disease associated with transforming growth factor β (TGFβ).

8. The pharmaceutical composition according to claim 5, wherein the pharmaceutical composition selectively inhibits transforming growth factor beta receptor 1 (TGFβR1).

9. A health functional food composition for improving or preventing cancer diseases, comprising a compound as an active ingredient, wherein the compound is selected from the thiazole derivative compound according to claim 1, a pharmaceutically acceptable salt thereof, a solvate thereof or a stereoisomer thereof.

10. The health functional food composition according to claim 9, wherein the cancer disease is selected from the group consisting of lung cancer, breast cancer, ovarian cancer, uterine cancer, pancreatic cancer, lung cancer, stomach cancer, liver cancer, colorectal cancer, skin cancer, head and neck cancer, brain cancer, laryngeal cancer, prostate cancer, bladder cancer, esophageal cancer, thyroid cancer, kidney cancer and rectal cancer.

11. A reagent composition for inhibiting the expression of transforming growth factor β (TGFβ), the reagent composition comprising a compound as an active ingredient, wherein the compound is selected from the thiazole derivative compound according to claim 1, a pharmaceutically acceptable salt thereof, a solvate thereof or a stereoisomer thereof. 12 . The reagent composition according to claim 11 , wherein the reagent composition selectively inhibits transforming growth factor β receptor 1 (TGFβR1).

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