Thiazole derivative compounds and their uses

Abstract

The present invention relates to a compound selected from a novel thiazole derivative compound, its pharma- ceutically acceptable salt, its solvate or its stereoisomer, and its medical use, and provides a TGFβR1 (ALK5) inhibitor that selectively inhibits only TGFβR1 without interfering with normal TGFβ signaling, and such a novel TGFβR1 inhibitor can be used for a variety of indications, including as an anticancer agent.

Description

[Technical Field]

[0001] The present invention relates to thiazole derivative compounds that are novel TGFβR1 (ALK5) inhibitors and their medical uses. [Background technology]

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

[0003] In association with ECM remodeling, TGFβ signaling increases fibroblast populations and ECM deposition, and in the immune system, TGFβ ligands can regulate T regulatory cell function and immune precursor cell growth and homeostasis.

[0004] In normal epithelial cells, TGFβ is a potent growth inhibitor and promoter of cell differentiation, but during tumor initiation and progression, TGFβ becomes a promoter of tumorigenesis by stimulating angiogenesis, altering the stromal environment, and inducing local and systemic immunosuppression.

[0005] Therefore, TGFβ is known as a therapeutic target for many clinical indications, and despite numerous efforts by many groups to develop TGFβ therapeutic agents, no safe and effective TGFβ therapeutic agents have been developed.

[0006] Therefore, among TGFβ therapeutic agents that are attracting attention as therapeutic targets for various clinical indications, it is necessary to develop therapeutic agents for various indications, such as immune anti-cancer agents, through the development of effective small molecule TGFβR1 (activin receptor-like kinase 5 (ALK5)) selective inhibitors with few side effects. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Republic of Korea Patent Publication No. 10-2019-0098255 (2019.08.21) Summary of the Invention [Problem to be solved by the invention]

[0008] An object of the present invention is to provide a compound selected from novel thiazole derivative compounds, pharmaceutically acceptable salts thereof, solvates thereof or stereoisomers thereof.

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

[0010] Yet another object of the present invention is to provide a health functional food composition for improving or preventing cancer diseases, which contains, as an active ingredient, a compound selected from the thiazole derivative compound, its pharmaceutically acceptable salt, its solvate, or its stereoisomer.

[0011] Yet another object of the present invention is to provide a reagent composition for inhibiting the expression of TGFβ (Transforming growth factor beta), which comprises, as an active ingredient, a compound selected from a thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof. [Means for solving the problem]

[0012] To achieve the above object, the present invention 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. [ka]

[0013] In the above Chemical Formula 1, A 1 is O or S, and A 2 is CH or N, and R 1 and R 2 are the same or different and are (C1-C4) alkyl, (C1-C4) alkylene, (C1-C4) alkoxy, trifluoromethyl (CF3), halo, NR 11 R 12 , unsubstituted or substituted (C3-C8)cycloalkyl, unsubstituted or substituted (C5-C10)aryl, and unsubstituted or substituted heteroaryl of 5 to 10 atoms containing one or more heteroatoms selected from the group consisting of N, O, and S, wherein R 11 and R 12 are the same or different and are any one of hydrogen, (C1-C5) alkyl and (C3-C8) cycloalkyl, and the substituted (C3-C8) cycloalkyl, substituted (C5-C10) aryl or substituted heteroaryl having 5 to 10 atoms is substituted with (C1-C5) alkyl; n is one of 0 to 3; Ar is unsubstituted or substituted (C5-C10) aryl or unsubstituted or substituted heteroaryl having 5 to 10 atoms containing one or more heteroatoms selected from the group consisting of N, O and S, and the substituted (C5-C10) aryl or substituted heteroaryl having 5 to 10 atoms is R 3 is substituted, and the R 3 -R 3-1 or -(C1-C5)alkyl-R 3-1 and R 3-1 is hydrogen, halogen, hydroxy, 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 , [ka] and wherein 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 hydrogen, hydroxy, trifluoromethyl, (C1-C5) alkyl, (C3-C8) cycloalkyl, -SO2-(C1-C3) alkyl, -(C1-C3) alkyl-R 301 and [ka] and R 301 is (C1-C4) alkylamino, di[(C1-C4) alkyl]amino, (C3-C8) cycloalkyl, [ka] and wherein R 3001 is hydrogen or (C1-C5) alkyl, and 302 is a halogen,

[0014] R 303 and R 304 are the same or different and are each hydrogen or (C-C) alkyl, 36 and R 37 are the same or different, [ka] and R 305 is hydrogen or (C1-C5) alkyl, and 306 is any one of hydrogen, amino, (C1-C4) alkylamino, and di[(C1-C4) alkyl]amino, and the R 38 and R 39 are the same or different and each is any one of hydrogen, (C1-C3) alkyl, and —(C1-C3) alkyl-(C1-C3) alkoxy.

[0015] The present invention also provides a pharmaceutical composition for treating or preventing cancer disease, comprising, as an active ingredient, a compound selected from the thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0016] The present invention also provides a functional health food composition for improving or preventing cancer diseases, which contains, as an active ingredient, a compound selected from the thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0017] The present invention also provides a reagent composition for inhibiting TGFβ expression, which comprises, as an active ingredient, a compound selected from the thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof. [Effects of the Invention]

[0018] The present invention relates to a compound selected from novel thiazole derivative compounds, their pharmaceutically acceptable salts, solvates or stereoisomers thereof, and their uses. The compound selectively inhibits only TGFβR1 without interfering with normal TGFβ signaling, and is effective in treating various related cancer diseases. The compound is therefore widely used as a treatment method in hospitals and other medical institutions. DETAILED DESCRIPTION OF THE INVENTION

[0019] The present invention will now be described in more detail.

[0020] The present invention 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:

[0021] [ka]

[0022] In the above Chemical Formula 1, A 1 is O or S, and A 2 is CH or N, and R1 and R 2 are the same or different and are (C1-C4) alkyl, (C1-C4) alkylene, (C1-C4) alkoxy, trifluoromethyl (CF3), halo, NR 11 R 12 , unsubstituted or substituted (C3-C8)cycloalkyl, unsubstituted or substituted (C5-C10)aryl, and unsubstituted or substituted heteroaryl of 5 to 10 atoms containing one or more heteroatoms selected from the group consisting of N, O, and S, wherein R 11 and R 12 are the same or different and are any one of hydrogen, (C1-C5) alkyl and (C3-C8) cycloalkyl, and the substituted (C3-C8) cycloalkyl, substituted (C5-C10) aryl or substituted heteroaryl having 5 to 10 atoms is substituted with (C1-C5) alkyl; n is one of 0 to 3; Ar is unsubstituted or substituted (C5-C10) aryl or unsubstituted or substituted heteroaryl having 5 to 10 atoms containing one or more heteroatoms selected from the group consisting of N, O and S, and the substituted (C5-C10) aryl or substituted heteroaryl having 5 to 10 atoms is R 3 is substituted, and the R 3 -R 3-1 or -(C1-C5)alkyl-R 3-1 and R 3-1 is hydrogen, halogen, hydroxy, 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 , [ka] and wherein R 31-1, R 31-2 , R 32 , R33 , R 34 , R 35-1 and R 35-2 are the same or different and are hydrogen, hydroxy, trifluoromethyl, (C1-C5) alkyl, (C3-C8) cycloalkyl, -SO2-(C1-C3) alkyl, -(C1-C3) alkyl-R 301 and [ka] and R 301 is (C1-C4) alkylamino, di[(C1-C4) alkyl]amino, (C3-C8) cycloalkyl, [ka] and wherein R 3001 is hydrogen or (C1-C5) alkyl, and 302 is a halogen,

[0023] R 303 and R 304 are the same or different and are each hydrogen or (C-C) alkyl, 36 and R 37 are the same or different, [ka] and R 305 is hydrogen or (C1-C5) alkyl, and 306 is any one of hydrogen, amino, (C1-C4) alkylamino, and di[(C1-C4) alkyl]amino, and the R 38 and R 39 are the same or different and each is any one of hydrogen, (C1-C3) alkyl, and —(C1-C3) alkyl-(C1-C3) alkoxy.

[0024] In the above formula 1, R 1is (C1-C3) alkyl, (C1-C3) alkylene, methoxy, trifluoromethyl (CF3), bromine (Br), (C3-C6) cycloalkyl and NR 11 R 12 and wherein R 11 and R 12 are the same or different and are one of hydrogen, (C1-C3) alkyl, and cyclopropyl; R 2 teeth, [ka] or naphthyl, 3 is CH or N, and R 21 is hydrogen or methyl, n is one of 0 to 2, and Ar is [ka] and wherein R 3 -R 3-1 or -(C1-C3)alkyl-R 3-1 and R 3-1 is hydrogen, fluorine, chlorine, hydroxy, 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 , [ka] and wherein R 31-1, R 31-2 , R 32 , R 33 , R 34 , R 35-1 and R 35-2are the same or different and are hydrogen, hydroxy, trifluoromethyl, (C1-C3) alkyl, (C3-C6) cycloalkyl, -SO2CH3, -(C1-C3) alkyl-R 301 and [ka] and R 301 is methylamino, dimethylamino, cyclopropyl, [ka] and wherein R 3001 is hydrogen or (C-C) alkyl, and 302 is fluorine, and the R 303 and R 304 are the same or different and each is hydrogen or methyl, 36 and R 37 are the same or different, [ka] and R 305 is (C1-C3) alkyl, and the R 306 is any one of hydrogen, amino, and methylamino, and the R 38 and R 39 are the same or different and each is any one of hydrogen, (C1-C3) alkyl, and -(C1-C3) alkyl-methoxy.

[0025] In the above formula 1, R 1 is methyl, ethyl, isopropyl, methoxy, ethylene, trifluoromethyl (CF3), bromine (Br), cyclopropyl, cyclopentyl, cyclohexyl and NR 11 R 12 and wherein R 11 and R 12 are the same or different and are any one of hydrogen, methyl, and cyclopropyl; R 2 teeth, [ka] n is one of 0 to 2, and Ar is [ka] and wherein R 3 -R 3-1 or -(C1-C3)alkyl-R 3-1 and R 3-1 is hydrogen, fluorine, chlorine, hydroxy, 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-C3)alkyl-R 37 , [ka] and wherein R 31-1 and R 31-2 are the same or different and are hydrogen, methyl, isopropyl, hydroxy, -SO2CH3, -(C1-C2)alkyl-R 301 and [ka] and R 301 is dimethylamino, cyclopropyl, [ka] and wherein R 3001 is one of methyl, ethyl, and isopropyl, and said R 302 is fluorine, and the R 303 and R 304 is methyl, and the R 32 is one of hydrogen, methyl, and -(C-C)alkyl-dimethylamino, and 33is one of methyl, ethyl, cyclopropyl, and trifluoromethyl, and said R 34 is one of hydroxy, methyl, ethyl, cyclopropyl, and trifluoromethyl, and said R 35-1 and R 35-2 are the same or different and are one of hydrogen, methyl, and cyclopropyl; 36 teeth, [ka] and R 305 is methyl, and the R 306 is amino or methylamino, and 37 teeth, [ka] and R 38 is methyl or -CH2CH2OCH3, and said R 39 is hydrogen or methyl.

[0026] The compound represented by Chemical Formula 1 may be selected from the following compound group:

[0027] (1) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0028] (2) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0029] (3) Methyl 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate

[0030] (4) 4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0031] (5) 4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0032] (6) 4-phenyl-5-((2-(pyridin-3-ylamino)pyridin-4-yl)oxy)thiazol-2-amine

[0033] (7) 5-((2-((6-fluoropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0034] (8) 4-phenyl-5-((2-(pyridin-4-ylamino)pyridin-4-yl)oxy)thiazol-2-amine

[0035] (9) 6-(4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0036] (10) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylbenzamide

[0037] (11) 5-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0038] (12) 3-(4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzenesulfonamide

[0039] (13) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylbenzenesulfonamide

[0040] (14) N-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0041] (15) 5-(2-((3-(methylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0042] (16) N-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopropanesulfonamide

[0043] (17) 4-phenyl-5-(2-((3-((trifluoromethyl)sulfonyl)phenyl)amino)pyridin-4-yl)oxy)thiazol-2-amine

[0044] (18) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid

[0045] (19) 5-(2-((3-((methylsulfonyl)methyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0046] (20) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-cyclopropylbenzenesulfonamide

[0047] (21) 5-((2-((3-fluorobenzyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0048] (22) 2-(4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide

[0049] (23) 3-(4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0050] (24) 5-((2-((2-methoxypyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0051] (25) 5-((2-(benzylamino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0052] (26) 4-phenyl-5-((2-((pyridin-4-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine

[0053] (27) 5-(2-((2-chloropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0054] (28) 4-phenyl-5-((2-((pyridin-3-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine

[0055] (29) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0056] (30) 5-((2-((2-fluoropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0057] (31) 5-((2-((6-methoxypyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0058] (32) 5-(4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0059] (33) 6-(4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0060] (34) 5-(2-((3-(ethylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0061] (35) 5-(2-((6-chloropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0062] (36) N-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide

[0063] (37) 5-((2-((1-methyl-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0064] (38) 5-((2-((1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0065] (39) 4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0066] (40) 3-(4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0067] (41) 2-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0068] (42) 2-(4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0069] (43) 2-(5-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0070] (44) 2-(3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0071] (45) 3-(4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0072] (46) 3-(4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0073] (47) 4-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0074] (48) 3-(4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0075] (49) 4-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0076] (50) 2-(3-(4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0077] (51) 3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0078] (52) 3-(4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0079] (53) 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0080] (54) 2-(4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)propan-2-ol

[0081] (55) 2-(5-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0082] (56) 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0083] (57) 3-(4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0084] (58) 3-(4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0085] (59) 2-(4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)propan-2-ol

[0086] (60) 3-(4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0087] (61) 2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0088] (62) 5-(2-(((1-(methylsulfonyl)-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0089] (63) 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0090] (64) 4-(4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0091] (65) 2-(5-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)propan-2-ol

[0092] (66) 2-methyl-2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoic acid

[0093] (67) N,N-Dimethyl-3-(4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0094] (68) 3-(4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid

[0095] (69) N-methyl-3-(4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0096] (70) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(3-(methylsulfonyl)phenyl)pyridin-2-amine

[0097] (71) N-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0098] (72) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((trifluoromethyl)sulfonyl)phenyl)pyridin-2-amine

[0099] (73) N-methyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0100] (74) N,N-Dimethyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0101] (75) N-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopropanesulfonamide

[0102] (76) N-Cyclopropyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0103] (77) N-(3-(ethylsulfonyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0104] (78) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0105] (79) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((methylsulfonyl)methyl)phenyl)pyridin-2-amine

[0106] (80) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-ylmethyl)pyridin-2-amine

[0107] (81) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-ylmethyl)pyridin-2-amine

[0108] (82) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-yl)pyridin-2-amine

[0109] (83) N-(6-fluoropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0110] (84) N-(6-chloropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0111] (85) N-(6-Methoxypyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0112] (86) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-yl)pyridin-2-amine

[0113] (87) N-(2-fluoropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0114] (88) N-(2-Methoxypyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0115] (89) N-(2-chloropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0116] (90) 6-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0117] (91) 5-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0118] (92) 5-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0119] (93) 2-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide

[0120] (94) N-Benzyl-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0121] (95) N-(4-Fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0122] (96) N-(3-Fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0123] (97) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(1-(methylsulfonyl)-1H-pyrazol-4-yl)pyridin-2-amine

[0124] (98) N-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0125] (99) N-(1-methyl-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0126] (100) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(1H-pyrazol-4-yl)pyridin-2-amine

[0127] (101) 6-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0128] (102) 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0129] (103) N-(4-Methoxyphenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0130] (104) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(piperazin-1-yl)phenyl)pyridin-2-amine

[0131] (105) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(2-(piperidin-1-yl)ethoxy)phenyl)pyridin-2-amine

[0132] (106) N-(3-Methoxy-4-(4-methylpiperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0133] (107) 1,1,1-trifluoro-N-(3-(4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0134] (108) N-(4-(4-(2-methoxyethyl)piperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0135] (109) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0136] (110) 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0137] (111) 2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)acetonitrile

[0138] (112) N-(3-((1H-tetrazol-5-yl)methyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0139] (113) 3-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanenitrile

[0140] (114) N-(3-(2-(2H-tetrazol-5-yl)ethyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0141] (115) 2-(3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0142] (116) 3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0143] (117) 3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0144] (118) 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0145] (119) 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0146] (120) 2-(4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0147] (121) 2-(5-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0148] (122) N-(3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)ethanesulfonamide

[0149] (123) N-(3-(4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide

[0150] (124) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0151] (125) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0152] (126) 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0153] (127) N-(6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)methanesulfonamide

[0154] (128) N-(4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0155] (129) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0156] (130) Methyl 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate

[0157] (131) Methyl 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate

[0158] (132) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0159] (133) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0160] (134) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0161] (135) 3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0162] (136) 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0163] (137) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0164] (138) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-hydroxynicotinamide

[0165] (139) 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-hydroxybenzamide

[0166] (140) 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(methylsulfonyl)nicotinamide

[0167] (141) 2-(3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0168] (142) 3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0169] (143) 3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0170] (144) 3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0171] (145) 3-(4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0172] (146) 6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0173] (147) 4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0174] (148) N-Methyl-4-(4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0175] (149) 6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0176] (150) N-methyl-6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0177] (151) 3-(4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0178] (152) 4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0179] (153) 2-(3-(4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0180] (154) 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0181] (155) 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0182] (156) 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0183] (157) 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0184] (158) 2-(4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0185] (159) 2-(5-(4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0186] (160) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0187] (161) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0188] (162) Methyl 6-(4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate

[0189] (163) 6-(4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0190] (164) 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0191] (165) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0192] (166) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0193] (167) 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0194] (168) 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0195] (169) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0196] (170) Methyl 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate

[0197] (171) 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0198] (172) 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0199] (173) 6-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0200] (174) 6-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0201] (175) 4-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0202] (176) 6-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0203] (177) 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0204] (178) 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0205] (179) 4-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0206] (180) 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0207] (181) 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0208] (182) 2-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0209] (183) 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0210] (184) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0211] (185) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0212] (186) 2-(4-(((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0213] (187) 2-(5-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0214] (188) N-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)ethanesulfonamide

[0215] (189) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0216] (190) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0217] (191) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate

[0218] (192) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0219] (193) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0220] (194) 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0221] (195) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0222] (196) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-isopropylnicotinamide

[0223] (197) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(4-methylpiperazin-1-yl)methanone

[0224] (198) 3-aminopyrrolidin-1-yl)(6-(4-(2-ethyl-4-phenylthiazol-5-yloxy)pyridin-2-ylamino)pyridin-3-yl)methanone

[0225] (199) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(pyrrolidin-1-yl)ethyl)nicotinamide

[0226] (200) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(3-(methylamino)pyrrolidin-1-yl)methanone

[0227] (201) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-methylpiperazin-1-yl)ethyl)nicotinamide

[0228] (202) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-isopropylpiperazin-1-yl)ethyl)nicotinamide

[0229] (203) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-ethylpiperazin-1-yl)ethyl)nicotinamide

[0230] (204) 5-(3-aminopyrrolidin-1-yl)-N-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)pyridin-2-amine

[0231] (205) N1-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N4-(2-(4-isopropylpiperazin-1-yl)ethyl)benzene-1,4-diamine

[0232] (206) N1-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N4-(2-(4-methylpiperazin-1-yl)ethyl)benzene-1,4-diamine

[0233] (207) N1-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N4-(2-(4-methylpiperazin-1-yl)ethyl)benzene-1,4-diamine

[0234] (208) N1-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N4-(2-(pyrrolidin-1-yl)ethyl)benzene-1,4-diamine

[0235] (209) N2-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N5-(2-(4-methylpiperazin-1-yl)ethyl)pyridine-2,5-diamine

[0236] (210) N2-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N5-(2-(pyrrolidin-1-yl)ethyl)pyridine-2,5-diamine

[0237] (211) N2-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N5-(2-(4-ethylpiperazin-1-yl)ethyl)pyridine-2,5-diamine

[0238] (212) N2-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N5-(2-(4-isopropylpiperazin-1-yl)ethyl)pyridine-2,5-diamine

[0239] (213) N,N-(5-(1H-pyrazol-4-yl)pyridin-2-yl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0240] (214) N-(4-(3-aminopyrrolidin-1-yl)phenyl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0241] (215) 4-((2-ethyl-4-phenylthiazol-5-yl)oxy)-N-(4-(3-(methylamino)pyrrolidin-1-yl)phenyl)pyridin-2-amine

[0242] (216) Methyl 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate

[0243] (217) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0244] (218) 3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0245] (219) 2-(3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0246] (220) 3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0247] (221) 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0248] (222) 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0249] (223) 2-(4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0250] (224) 2-(5-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0251] (225) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0252] (226) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0253] (227) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0254] (228) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0255] (229) 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0256] (230) 3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0257] (231) 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0258] (232) 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0259] (233) 3-((4-((2-(methylamino)-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0260] (234) 3-((4-((2-amino-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0261] (235) 3-((4-((2-(dimethylamino)-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0262] (236) 3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide

[0263] (237) 3-((6-((2-methyl-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide

[0264] (238) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzenesulfonamide

[0265] (239) 3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide

[0266] (240) 3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide

[0267] (241) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)picolinamide

[0268] (242) 2-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)isonicotinamide

[0269] (243) 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzamide

[0270] (244) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)nicotinic acid

[0271] (245) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)nicotinamide

[0272] (246) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzoic acid

[0273] (247) 3-((4-((2-amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0274] (248) 4-((4-((2-amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0275] (249) 3-((4-((2-amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0276] (250) 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0277] (251) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0278] (252) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0279] (253) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0280] (254) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0281] (255) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0282] (256) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0283] (257) 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0284] (258) 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0285] (259) 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0286] (260) 5-(4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0287] (261) 5-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0288] (262) 5-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0289] (263) 4-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0290] (264) 4-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0291] (265) 4-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0292] (266) 2-(4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinic acid

[0293] (267) 2-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide

[0294] (268) 2-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylisonicotinamide

[0295] (269) N-(2-(dimethylamino)ethyl)-6-(4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0296] (270) N-(cyclopropylmethyl)-6-(4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0297] (271) 2-(Dimethylamino)ethyl 6-(4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate

[0298] (272) N-(3-(4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0299] (273) 2-(Dimethylamino)ethyl 3-(6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide)-5-fluorobenzoate

[0300] (274) 3-(4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0301] (275) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0302] (276) 2-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide

[0303] (277) 3-(4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0304] (278) 6-(4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0305] (279) 6-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0306] (280) 2-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylisonicotinamide

[0307] (281) 3-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0308] (282) 6-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0309] (283) 3-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0310] (284) 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0311] (285) 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0312] (286) 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0313] (287) 3-(4-((2-isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0314] (288) 6-((4-((2-isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0315] (289) 3-(4-((4-(6-methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0316] (290) 6-(4-((2-isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0317] (291) 3-((4-((6-methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0318] (292) 3-(4-((2-(methylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0319] (293) 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0320] (294) 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0321] (295) 4-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0322] (296) 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0323] (297) 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0324] (298) 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0325] (299) 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0326] (300) 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0327] (301) 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0328] (302) 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0329] (303) 3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0330] (304) 2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)acetonitrile

[0331] (305) N-(3-((1H-tetrazol-5-yl)methyl)phenyl)-4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-amine

[0332] (306) 3-(4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanenitrile

[0333] (307) N-(3-(2-(2H-tetrazol-5-yl)ethyl)phenyl)-4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-amine

[0334] (308) Methyl 2-methyl-2-(3-(4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoate

[0335] (309) 2-methyl-2-(3-(4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoic acid

[0336] (310) 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0337] (311) N-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide

[0338] (312) 4-((2-ethyl-4-phenylthiazol-5-yl)oxy)-N-(5-(3-(methylamino)pyrrolidin-1-yl)pyridin-2-yl)pyridin-2-amine

[0339] The present invention also provides a pharmaceutical composition for treating or preventing cancer disease, comprising, as an active ingredient, a compound selected from the thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0340] The cancer disease may be selected from the group consisting of lung cancer, breast cancer, ovarian cancer, uterine cancer, pancreatic cancer, stomach cancer, liver cancer, colon cancer, skin cancer, head or neck cancer, brain cancer, laryngeal cancer, prostate cancer, bladder cancer, esophageal cancer, thyroid cancer, kidney cancer and rectal cancer, but is not limited thereto.

[0341] The cancer disease is a TGFβ-associated cancer disease.

[0342] The pharmaceutical composition can selectively inhibit transforming growth factor beta receptor 1 (TGFβR1).

[0343] In another embodiment of the present invention, the pharmaceutical composition may further comprise one or more additives selected from the group consisting of suitable carriers, excipients, disintegrants, sweeteners, coating agents, swelling agents, lubricants, glidants, flavoring agents, antioxidants, buffers, bacteriostats, diluents, dispersants, surfactants, binders, and lubricants commonly used in the manufacture of pharmaceutical compositions.

[0344] Specifically, carriers, excipients, and diluents that can be used include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginic acid, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, amorphous cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid formulations can be prepared by mixing the composition with at least one or more excipients, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc can also be used. Oral liquid formulations include suspensions, oral solutions, emulsions, syrups, etc., and contain various excipients, such as wetting agents, sweeteners, flavorings, and preservatives, in addition to the commonly used simple diluents of water and liquid paraffin. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Examples of non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Examples of suppository bases include witepsol, macrogol, Tween 61, cocoa butter, lauric butter, and glycerogelatin.

[0345] According to one embodiment of the present invention, the pharmaceutical composition may be administered to a subject in a conventional manner via intravenous, intraarterial, intraperitoneal, intramuscular, intraperitoneal, intrasternal, transdermal, intranasal, inhalation, topical, rectal, oral, intraocular or intradermal routes.

[0346] The dosage of the active ingredient according to the present invention varies depending on the condition and weight of the subject, the type and severity of the disease, the drug form, the route and duration of administration, and can be appropriately selected by those skilled in the art. The daily dosage is 0.01 to 200 mg / kg, preferably 0.1 to 200 mg / kg, and more preferably 0.1 to 100 mg / kg. The dosage may be administered once a day or in several divided doses, and the scope of the present invention is not limited thereby.

[0347] The present invention also provides a functional health food composition for improving or preventing cancer diseases, which contains, as an active ingredient, a compound selected from the thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0348] The cancer disease may be selected from the group consisting of lung cancer, breast cancer, ovarian cancer, uterine cancer, pancreatic cancer, stomach cancer, liver cancer, colon cancer, skin cancer, head or neck cancer, brain cancer, laryngeal cancer, prostate cancer, bladder cancer, esophageal cancer, thyroid cancer, kidney cancer and rectal cancer, but is not limited thereto.

[0349] The health functional foods may contain various nutrients, vitamins, minerals (electrolytes), flavorings such as synthetic flavorings and natural flavorings, coloring agents and fillers (cheese, chocolate, etc.), pectinic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated drinks, etc.

[0350] In addition, fruit pulp for producing natural fruit juice, synthetic fruit juice, and vegetable drinks may be included. These ingredients may be used independently or in combination. The functional health food composition may be in the form of any one of meat, sausage, bread, chocolate, candy, snacks, sweets, pizza, ramen, gum, ice cream, soup, drinking water, tea, functional water, health drinks, alcohol, and vitamin complexes.

[0351] In addition, the health functional food may further contain food additives, and unless otherwise specified, the suitability of a substance as a "food additive" shall be determined in accordance with the specifications and standards for the item in question, such as the general provisions and general test methods of the Food Additives Code approved by the Ministry of Food and Drug Safety.

[0352] Examples of items listed in the "Food Additives Code" include chemically synthesized products such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid; natural additives such as navy blue color, licorice extract, crystalline cellulose, sorghum color, and guar gum; and mixed preparations such as monosodium L-glutamate preparations, alkaline agents added to noodles, preservative preparations, and tar color preparations.

[0353] In this case, the content of the active ingredient added to the food during the process of producing the health functional food can be appropriately adjusted as needed, and preferably, it is added so that it is contained in an amount of 1 to 90 parts by weight per 100 parts by weight of the food.

[0354] The present invention also provides a reagent composition for inhibiting TGFβ expression, which comprises, as an active ingredient, a compound selected from the thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0355] The reagent composition can selectively inhibit TGFβR1.

[0356] Hereinafter, the present invention will be described in detail with reference to examples to aid in understanding the present invention. However, the following examples are merely illustrative of the contents of the present invention, and the scope of the present invention is not limited to the following examples. The examples of the present invention are provided to more completely explain the present invention to those skilled in the art.

[0357] [Synthesis Example 1] NMR data of novel thiazole derivative compounds

[0358] (1) A-1: ​​3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0359] 1H-NMR (400 MHz, MeOD-d4): δ 8.20-8.21 (1H, m), 8.07 (1H, d, J = 5.6 Hz), 7.70-7.72 (2H, m), 7.60-7.64 (1H, m), 7.36-7.44 (2H, m), 7.31 (2H, t, J = 7.8 Hz), 7.23-7.24 (1H, m), 6.60 (1H, dd, J = 6.0 and 2.4 Hz), 6.49 (1H, d, J = 2.4 Hz), 6.54 (1H, d, J = 2.0 Hz). *Five protons from NH and two NH2 were not observed. MS calculated: 439.51; MS found: 440.1 (M+H+)

[0360] (2) A-2: 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0361] 1H-NMR (400 MHz, DMSO-d6):δ 9.26 (1H, s), 8.11 (1H, d, J = 6.0 Hz), 8.03 (1H, s), 7.85-7.83 (2H, m), 7.72 (2H, d, J = 8.0 Hz), 7.37-7.35 (3H, m), 7.33-7.22 (3H, m), 7.17 (2H, s), 6.63 (1H, dd, J = 6.0, 2.4 Hz), 6.52 (1H, d, J = 2.4 Hz). MS calculated: 403.46; MS detected: 404.1 (M+H+)

[0362] (3) A-3: Methyl 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate

[0363] 1H-NMR (400 MHz, MeOD-d4): δ 8.16 (1H, t, J = 1.8 Hz), 8.04 (1H, d, J = 6.0 Hz), 7.72-7.69 (3H, m), 7.58 (1H, d, J = 7.6 Hz), 7.35-7.29 (3H, m), 7.25-7.23 (1H, m), 6.58 (1H, dd, J = 6.2, 2.2 Hz), 6.48 (1H, d, J = 2.4 Hz), 3.88 (3H, s). * Three protons from NH and NH2 were not observed. MS calculated: 418.47; MS found: 419.1 (M+H+).

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

[0365] 1H-NMR (400 MHz, DMSO-d6):δ 9.53 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 7.77 (2H, d, J = 8.4 Hz), 7.70-7.64 (4H, m), 7.32 (2H, t, J = 7.6 MS calculated: 439.51; MS detected: 440.1 (M+H+)

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

[0367] 1H-NMR (400 MHz, DMSO-d6):δ 9.41 (1H, s), 8.15 (1H, d, J = 6.0 Hz), 7.77-7.67 (7H, m), 7.34 (2H, t, J = 7.6 Hz), 7.23 (1H, t, J = 7.2 MS calculated: 403.46; MS detected: 404.1 (M+H+)

[0368] (6) A-6: 4-phenyl-5-((2-(pyridin-3-ylamino)pyridin-4-yl)oxy)thiazol-2-amine

[0369] 1H-NMR (400 MHz, DMSO-d6):δ 9.30 (1H, s), 8.69 (1H, d, J = 2.8 Hz), 8.23 ​​(1H, d, J = 9.2 Hz), 8.10 (1H, d, J =2.0 Hz), 8.06 (1H, d, J =3.6 Hz), 7.70 (2H, d, J = 7.6 Hz), 7.34 (2H, t, J = 8.0 Hz), 7.24-7.21 (2H, m), 7.15 (2H, s) 6.66 (1H, dd, J = 6.0, 2.4 Hz), 6.51 (1H, d, J = 2.4 Hz). MS calculated: 361.42 Detected: 362.1 (M+H+)

[0370] (7) A-7: 5-((2-((6-fluoropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0371] 1H-NMR (400 MHz, DMSO-d6):δ 9.37 (1H, s), 8.41 (1H, s), 8.26 (1H, t, J = 8.8 Hz), 8.11 (1H, d, J = 6.0 Hz), 7.71 (2H, d, J = 7.6 Hz), 7.36 (2H, t, J = 7.6 Hz), 7.26 (1H, m), 7.22 (2H, s), 7.07 (1H, dd, J = 4.4 Hz), 6.68 (1H, dd, J = 2.0 Hz), 6.28 (1H, d, J = 2.0 Hz). MS calculated: 379.41 Detected: 380.1 (M+H+)

[0372] (8) A-8 4-phenyl-5-((2-(pyridin-4-ylamino)pyridin-4-yl)oxy)thiazol-2-amine

[0373] 1H-NMR (400 MHz, DMSO-d6): δ 9.57 (1H, s), 8.26 (2H, d, J = 6.4 Hz), 8.18 (1H, d, J = 6.0 Hz ), 7.69 (2H, d, J = 7.2 Hz), 7.59 (2H, d, J = 6.4 Hz), 7.34 (2H, t, J = 8.0 Hz ), 7.23-7.19 (1H, t, J = 7.2 Hz), 7.17(s, 2H), 6.75 (1H, dd, J = 6.0, 3.6 Hz), 6.58 (1H, d, J = 3.6 Hz). MS Calculated: 361.42 Found: 362.1 (M+H+)

[0374] (9) A-9: 6-(4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0375] 1H-NMR (400 MHz, DMSO-d6):δ 10.1 (1H, s), 8.66 (1H, d, J = 2.4 Hz), 8.17 (1H, d, J = 6.0 Hz), 8.07 (1H, dd, J = 8.8. 2.4 Hz), 7.88 (1H, brs), 7.75 (1H, d, J = 8.8 Hz), 7.69 (2H, d, J = 7.2 Hz), 7.59 (1H, s), 7.33-7.29 (3H, m), 7.22 (1H, t, J = 7.6 Hz), 7.13 (2H, s), 6.71 (1H, dd, J = 6.0, 2.4 Hz).MS Calculated: 404.45 Found: 405.1 (M+H+)

[0376] (10) A-10: 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylbenzamide

[0377] 1H-NMR (400 MHz, MeOH-D4): δ 8.04 (1H, d, J = 6.0 Hz), 7.70 (3H, d, J = 7.6 Hz), 7.63 (1H, s), 7.50 (1H, d, J = 8.0 Hz), 7.32 (4H, t, J = 8.4 Hz), 7.24 (1H, d, J = 7.2 Hz), 6.95 (1H, d, J = 7.6 Hz), 6.57 (1H, dd, J = 10.0, 2.4 Hz), 6.47 (1H, d, J = 2, 0 Hz), 3.08 (3H, s), 3.00 (3H, s). * Protons from NH were not observed. MS calculated: 431.51 Found: 432.2 (M+H+)

[0378] (11) A-11: 5-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0379] 1H-NMR (400 MHz, DMSO-d6):δ 9.66 (1H, s), 8.71 (1H, d, J = 2.0 Hz), 8.36 (1H, d, J = 8.8 Hz), 8.17 (1H, d, J = 5.6 Hz), 7.91 (1H, d, J = 8.8 Hz), 7.85 (1H, s), 7.69 (2H, d, J = 7.6 Hz), 7.37 (1H, s), 7.34 (2H, t, J = 7.2 Hz), 7.23 (1H, d, J = 7.2 Hz), 7.17 (2H, s), 7.74 (1H, d, J = 8.0 Hz), 6.57 (1H, s). MS calculated: 404.45 Found: 405.1 (M+H+)

[0380] (12) A-12: 3-(4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzenesulfonamide

[0381] 1H-NMR (400 MHz, DMSO-d6):δ 9.48 (1H, s), 8.14 (1H, s), 8.12 (1H, d, J = 5.6 Hz), 7.85 (1H, d, J = 7.6 Hz), 7.69 (2H, d, J = 8.0 Hz), 7.44 (1H, t, J = 8.0 Hz), 7.36-7.30 (3H, m), 7.23 (2H, d, J = 7.2 Hz), 7.16 (2H, s), 6.68(1H, dd, J = 5.6, 2.0 Hz), 6.51 (1H, d, J = 2.0 Hz), 2.39 (3H, d, J = 5.2 Hz).MS Calculated: 453.54 Found: 454.1 (M+H+)

[0382] (13) A-13: 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylbenzenesulfonamide

[0383] 1H-NMR (400 MHz, DMSO-d6):δ 9.52 (1H, s), 8.12-8.10 (2H, m), 7.93 (1H, d, J = 10.0 Hz), 7.69 (2H, d, J = 7.2 Hz), 7.48 (1H, t, J = 8.0 Hz), 7.34 (2H, t, J = 7.2 Hz), 7.23 (2H, t, J = 7.6 Hz), 7.16 (2H, s), 6.68 (1H, dd, J = 5.6, 2.0 Hz), 6.50 (1H, d, J = 2.4 Hz), 2, 58 (6H, s). MS calculated: 467.56 Found: 468.1 (M+H+)

[0384] (14) A-14: N-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0385] 1H-NMR (400 MHz, DMSO-d6):δ 9.63 (1H, s), 9.18 (1H, s), 8.06 (1H, d, J = 6.0 Hz), 7.69 (2H, d, J = 7.2 Hz), 7.46-7.44 (2H, m), 7.34 (2H, t, J =7.2 Hz ), 7.23 (1H, t, J = 7.6 Hz), 7.15-7.11 (3H, m), 6.70 (1H, d, J = 9.2 Hz), 6.61 (1H, dd, J = 6.0, 2.4 Hz), 6.50 (1H, d, J = 1.6 Hz), 2.94 (3H, s). MS calculated: 453.54 Detected: 454.1 (M+H+)

[0386] (15) A-15: 5-(2-((3-(methylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0387] 1H-NMR (400 MHz, DMSO-d6):δ 9.55 (1H, s), 8.27 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 7.91 (1H, d, J = 9.2 Hz), 7.69 (2H, d, J = 7.2 Hz), 7.50 (1H, t, J = 8.0 Hz), 7.38-7.30 (3H, m), 7.23 (1H, t, J = 7.6 Hz), 7.16 (2H, s), 6.69 (1H, dd, J = 6.0, 2.4 Hz), 6.52 (1H, d, J = 2.0 Hz), 3.14 (3H, s). MS calculated: 438.52 Detected: 439.1 (M+H+)

[0388] (16) A-16: N-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopropanesulfonamide

[0389] 1H-NMR (400 MHz, DMSO-d6):δ 9.60 (1H, s), 9.17 (1H, s ), 8.06 (1H, d, J = 5.6 Hz), 7.69 (2H, d, J = 7.2 Hz), 7.52 (1H, s), 7.44 (1H, d, J = 8.4 Hz), 7.34 (2H, t, J = 7.2 Hz), 7.23 (1H, t, J = 7.6 Hz), 7.14-7.10 (3H, m), 6.72 (1H, d, J = 9.2 Hz), 6.60 (1H, dd, J = 5.6, 2.0 Hz), 6.50 (1H, d, J = 1.6 Hz), 2.57 (1H, q, J = 4.8 Hz), 0.93-0.83 (4H, m). MS calculated: 479.57 found: 480.1 (M+H+)

[0390] (17) A-17: 4-phenyl-5-(2-((3-((trifluoromethyl)sulfonyl)phenyl)amino)pyridin-4-yl)oxy)thiazol-2-amine

[0391] 1H-NMR (400 MHz, DMSO-d6):δ 9.79 (1H, s), 8.64 (1H, s), 8.18 (1H, d, J = 6.0 Hz), 8.07 (1H, d, J = 7.2 Hz), 7.69-7.65 (3H, m), 7.55 (1H, d, J = 7.2 Hz), 7.34 (2H, t, J =7.6 Hz), 7.23 (1H, d, J = 7.2 Hz), 7.18 (2H, s), 6.74 (1H, dd, J =6.0, 4.0 Hz), 6.53 (1H, d, J = 5.6 Hz). MS Calculated: 492.49 Found: 493.0 (M+H+)

[0392] (18) A-18: 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid

[0393] 1H-NMR (400 MHz, DMSO-d6): δ 9.56 (1H, brs), 8.03 (1H, d, J = 6.0 Hz), 7.68 (3H, d, J = 6.8 Hz), 7.54 (1H, brs), 7.36 (2H, t, J = 7.6 Hz), 7.25-7.23 (4H, m), 6.70 (1H, d, J = 4.8 Hz), 6.56 (1H, s). *Two protons from OH and NH were not observed. MS calculated: 440.50 Found: 441.1 (M+H+)

[0394] (19) A-19: 5-(2-((3-((methylsulfonyl)methyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0395] 1H-NMR (400 MHz, DMSO-d6):δ 9.21 (1H, s), 8.07 (1H, d, J = 5.2 Hz), 7.69 (3H, d, J = 7.6 Hz), 7.57 (1H, s), 7.34 (2H, t, J = 7.2 Hz), 7.21-7.25 (2H, m), 7.14 (2H, s), 6.90 (1H, d, J = 8.0 Hz), 6.61 (1H, dd, J = 6.0, 3.6 Hz), 4.38 (2H, s), 2.88 (3H, s). MS calculated: 452.5 Detection: 453.1 (M+H+)

[0396] (20) A-20: 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-cyclopropylbenzenesulfonamide

[0397] 1H-NMR (400 MHz, DMSO-d6):δ 9.48 (1H, s), 8.19 (1H, s), 8.12 (1H, d, J = 5.6 Hz), 7.84 (2H, m), 7.69 (2H, d, J = 7.6 Hz), 7.42 (1H, t, J = 7.6 Hz), 7.34 (2H, t, J = 7.6 Hz), 7.27-7.21 (2H, m), 7.16 (2H, s), 6.67 (1H, d, J = 3.6 Hz), 6.51 (1H, s), 2.06 (1H, m), 0.45-0, 44 (2H, m), 0.37 (2H, m). MS calculated: 479.11 Detected: 480.1 (M+H+)

[0398] (21) A-21: 5-((2-((3-fluorobenzyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0399] 1H-NMR (400 MHz, DMSO-d6): δ 7.84 (1H, d, J = 6.0 Hz), 7.62 (2H, d, J = 7.2 Hz), 7.30-7.22 (4H, m), 7.07 (1H, d, J = 7.6 Hz), 7.00 (1H, d, J = 9.6 Hz), 6.92 (1H, t, J = 7.6 Hz), 6.39 (1H, dd, J = 6.0, 2.0 Hz), 6.12 (1H, d, J = 2.0 Hz), 4.15 (2H, s). * Three protons from NH and NH2 were not observed. MS calculated: 392.45 found: 393.1 (M+H+).

[0400] (22) A-22: 2-(4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide

[0401] 1H-NMR (400 MHz, DMSO-d6):δ 9.92 (1H, s), 8.24 (1H, d, J = 5.2 Hz), 8.15 (1H, d, J = 5.6 Hz), 8.06 (2H, d, J = 6.4Hz), 7.69 (2H, d, J = MS Calculated: 404.45 Found: 405.1 (M+H+)

[0402] (23) A-23: 3-(4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0403] 1H-NMR (400 MHz, DMSO-d6):δ 9.25 (1H, s), 8.31-8.28 (1H, m), 8.09 (1H, d, J = 6.0 Hz), 7.98 (1H, s), 7.81 (1H, s), 7.69 (2H, d, J = 7.2 Hz), 7.32 (2H, t, J = 7.6 Hz), 7.27 (2H, d, J = 5.2 Hz), 7.22 (1H, t, J = 7.4 Hz), 7.15 (2H, s), 6.61 (1H, dd, J = 6.0, 2.4 Hz), 6.50 (1H, d, J = 2.0 Hz), 2.73 (3H, d, J = 4.4 Hz). MS calculated: 417.48; MS found: 418.1 (M+H+)

[0404] (24) A-24: 5-((2-((2-methoxypyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0405] 1H-NMR (400 MHz, DMSO-d6):δ 9.53 (1H, s), 8.17 (1H, d, J = 6.0 Hz), 7.86 (1H, d, J = 5.6 Hz), 7.68 (2H, d, J = 7.6 Hz), 7.32 (3H, t, J = 7.6 Hz), 7.22 (1H, t, J = 7.4 Hz), 7.17 (2H, s), 6.98 (1H, dd, J = 5.2, 2.0 Hz), 6.74 (1H, dd, J = 6.0, 2.0 Hz), 6.56 (1H, d, J = 2.4 Hz). 3.76 (3H, s). MS calculated: 391.45; MS detected: 392.1 (M+H+)

[0406] (25) A-25: 5-((2-(benzylamino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0407] 1H-NMR (400 MHz, MeOD): δ 7.83 (1H, d, J = 6.0 Hz), 7.64 (2H, d, J = 7.2 Hz), 7.34 (1H, d, J = 4.4 Hz), 7.28-7.23 (5H, m), 7.21-7.20 (2H, m), 6.36 (1H, d, J = 6.4 Hz), 6.14 (1H, d, J = 2.0 Hz), 4.39 (2H, d, J = 8.0 Hz). * Three protons from NH and NHBoc were not observed. MS calculated: 374.46 found: 375.1 (M+H+).

[0408] (26) A-26: 4-phenyl-5-((2-((pyridin-4-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine

[0409] 1H-NMR (400 MHz, DMSO-d6):δ 8.43 (2H, d, J = 5.6 Hz), 7.85 (1H, d, J = 5.6 Hz), 7.67 (2H, d, J = 7.2 Hz), 7.33-7.29 (3H, m), 7.23-7.21 (3H, m), 7.09 (2H, s), 6.34 (1H, dd, J = 5.6 2.0 Hz), 6.22 (1H, d, J = 2.0 Hz), 4.44 (2H, d, J = 6.0 Hz). MS calculated: 375.45 detected: 376.1 (M+H+)

[0410] (27) A-27: 5-(2-((2-chloropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0411] H-NMR (400 MHz, MeOH-d): δ 8.20 (1H, d, J = 5.6 Hz), 8.00 (1H, d, J = 6.0 Hz), 7.94 (1H, d, J = 1.6 Hz), 7.70 (2H, d, J = 8.0 Hz), 7.43 (1H, dd, J = 6.0, 2.0 Hz), 7.30 (2H, t, J = 7.6 Hz), 7.22 (1H, t, J = 7.6 Hz), 6.74 (1H, dd, J = 6.2, 2.2 Hz), 6.56 (1H, d, J = 2.0 Hz). * Three protons from NH and NH were not observed. MS calculated: 395.87; MS found: 396.1 (M+H+)

[0412] (28) A-28: 4-phenyl-5-((2-((pyridin-3-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine

[0413] 1H-NMR (400 MHz, MeOH-d4):δ 8.46 (1H, s), 8.38 (1H, d, J = 4.4 Hz), 7.85 (1H, d, J = 5.6 Hz), 7.75 (1H, d, J = 7.6 Hz), 7.65 (2H, d, J = 7.6 Hz), 7.35 (1H, dd, J = 8.0, 5.2 Hz), 7.31 (2H, t, J = 8.8 Hz), 7.24 (1H, t, J = 10.0 Hz), 6.38 (1H, dd, J = 6.0, 2.4 Hz), 6.17 (1H, d, J = 2.4 Hz), 4.50 (2H, s). * The three protons from NH and NH2 were not observed. MS calculated: 375.45; MS found: 376.1 (M+H+).

[0414] (29) A-29: 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0415] 1H-NMR (400 MHz, DMSO-d6):δ 9.21 (1H, brs), 8.06 (1H, d, J = 6.0 Hz), 7.69 (3H, d, J = 7.6 Hz), 7.51 (1H, s), 7.34 (2H, t, J = 7.2 Hz), 7.23-7.19 (2H, m), 7.14 (2H, brs), 6.87 (1H, d, J = 7.6 Hz), 6.80 (2H, s), 6.60 (1H, d, J = 6.0 Hz), 6.52 (1H, d, J = 2.0 Hz), 4.16 (2H, s). MS calculated: 453.54 Found: 454.1 (M+H+)

[0416] (30) A-30: 5-((2-((2-fluoropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0417] 1H-NMR (400 MHz, DMSO-d6):δ 9.91 (1H, s), 8.23 ​​(1H, d, J = 6.0 Hz), 7.91 (1H, d, J = 5.6 Hz), 7.68 (2H, d, J = 7.6 Hz), 7.61 (1H, s), 7.33 (2H, t, J = 7.2 Hz), 7.23 (2H, d, J = 7.2 Hz), 7.17 (2H, s), 6.80 (1H, d, J = 6.0 Hz), 6.60 (1H, d, J = 2.4 Hz). MS Calculated: 379.41 Detected: 380.1 (M+H+)

[0418] (31) A-31: 5-((2-((6-methoxypyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0419] 1H-NMR (400 MHz, DMSO-d6):δ 9.01 (1H, s), 8.31 (1H, d, J = 2.8 Hz), 8.02 (1H, d, J = 6.0 Hz), 7.94 (1H, dd, J = 8.8. 2.4 Hz), 7.69 (2H, d, J = 7.2 Hz), 7.34 (2H, t, J = 7.2 Hz), 7.21 (1H, t, J = 7.2 Hz), 7.13 (2H, s), 6.72 (1H, d, J = 8.8 Hz), 6.56 (1H, d, J = 6.0 Hz), 6.39 (1H, s), 3.76 (3H, s). MS calculated: 391.45 Detected: 392.1 (M+H+)

[0420] (32) A-32: 5-(4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0421] 1H-NMR (400 MHz, DMSO-d6):δ 9.46 (1H, s), 8.82 (1H, d, J = 2.4 Hz), 8.53 (2H, d, J = 9.2 Hz), 8.14 (1H, d, J = 6.0 Hz), 8.04 (1H, s), 7.70 (2H, d, J = 8.0 Hz), 7.51 (1H, s), 7.34 (2H, t, J = 7.2 Hz), 7.23 (1H, t, J = 7.6 Hz), 7.17 (2H, s), 6.69 (1H, dd, J =6.0, 2.4 Hz), 6.53 (1H, d, J = 2.0 Hz). MS calculated: 404.45 Detected: 405.1 (M+H+)

[0422] (33) A-33: 6-(4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0423] 1H-NMR (400 MHz, DMSO-d6):δ 9.89 (1H, s), 8.16 (1H, d, J = 5.6 Hz), 7.96 (1H, d, J = 8.4 Hz), 7.82 (1H, t, J = 7.2 Hz), 7.69 (2H, d, J = MS Calculated: 404.45 Detected: 405.1 (M+H+)

[0424] (34) A-34: 5-(2-((3-(ethylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0425] 1H-NMR (400 MHz, DMSO-d6):δ 9.55 (1H, s), 8.22 (1H, s), 8.14 (1H, d, J = 6.4 Hz), 7.93 (1H, d, J = 8.0 Hz), 7.69 (2H, d, J = 7.2 Hz), 7.50 (1H, t, J = 8.0 Hz), 7.34 (3H, t, J = 7.6 Hz), 7.23 (1H, t, J = 7.6 Hz), 7.15 (2H, s), 6.69 (1H, dd, J = 5.6, 2.4 Hz), 6.52 (1H, d, J = 2.0 Hz), 3.22 (2H, q, J = 7.6 Hz), 1.90 (3H, t, J = 7.2 Hz). MS Calculated: 425.55 Detected: 453.1 (M+H+)

[0426] (35) A-35: 5-(2-((6-chloropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0427] 1H-NMR (400 MHz, DMSO-d6):δ 9.46 (1H, s), 8.57 (1H, d, J = 2.8 Hz), 8.22 (1H, d, J = 8.4 Hz), 8.12(1H, d, J = 5.6 Hz), 7.69 (2H, d, J = 7.2 Hz), 7.36-7.30 (3H, m), 7.21 (1H, m), 7.16 (2H, s), 6.70 (1H, dd, J = 8.4, 2.4 Hz), 6.50 (1H, d, J = 1.6 Hz). MS calculated: 395.87 detected: 396.0 (M+H+)

[0428] (36) A-36: N-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide

[0429] 1H-NMR (400 MHz, DMSO-d6): δ 9.35 (1H, brs), 8.08 (1H, d, J = 5.6 Hz), 7.68 (2H, d, J = 7.2 Hz), 7.63 (1H, s), 7.54 (1H, d, J = 8.0 Hz), 7.33 (2H, t, J = 7.8 Hz), 7.22-7.26 (3H, m), 6.76 (1H, d, J = 8.0 Hz), 6.65 (1H, d, J = 6.0 Hz), 6.52 (1H, s). *Two protons from NH were not observed. MS calculated: 507.51; MS found: 508.1 (M+H+).

[0430] (37) A-37: 5-((2-((1-methyl-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0431] 1H-NMR (400 MHz, DMSO-d6):δ 8.85 (1H, s), 8.01 (1H, d, J = 6.0 Hz), 7.84 (1H, s), 7.68 (2H, d, J = 7.2 Hz), 7.33-7.28 (3H, m), 7.22 (1H, t, J = 7.2 Hz), 7.12 (2H, s), 6.45 (1H, dd, J = 5.6, 2.0 Hz), 6.28 (1H, d, J = 2.4 Hz), 3.74 (3H, s). MS Calculated: 364.42 Detected: 365.1 (M+H+)

[0432] (38) A-38: 5-((2-((1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0433] 1H-NMR (400 MHz, DMSO-d6):δ 12.4 (1H, brs), 8.94 (1H, s), 8.00 (1H, d, J = 6.0 Hz), 7.68 (3H, d, J = 7.2 Hz), 7.32 (3H, t, J = 7.6 Hz), 7.21 (1H, t, J = 7.2 Hz), 7.12 (2H, s), 6.44 (1H, dd, J = 6.0, 2.0 Hz), 6.28 (1H, d, J = 1.6 Hz). MS calculated: 350.40; MS detected: 351.1 (M+H+)

[0434] (39) A-39: 4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0435] 1H-NMR (400 MHz, DMSO-d6):δ 12.4 (1H, brs), 9.55 (1H, s), 8.17 (1H, d, J = 5.6 Hz), 7.82 (2H, d, J = 8.4 Hz), 7.76-7.70 (4H, m), 7.35 (2H, t, J = 7.6 Hz), 7.26-7.22 (1H, m), 7.18 (2H, s), 6.72 (1H, dd, J = 6.0, 2.4 Hz), 6.59 (1H, d, J = 2.4 Hz). MS calculated: 404.44; MS detected: 405.1 (M+H+)

[0436] (40) A-40: 3-(4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0437] 1H-NMR (400 MHz, MeOD-d4): δ 9.14 (1H, s), 8.09 (1H, d, J = 5.6 Hz), 7.78 (1H, d, J = 8.8 Hz), 7.71 (2H, d, J = 8.0 Hz), 7.40-7.33 (3H, m), 7.24 (2H, t, J = 7.6 Hz), 7.16 (2H, s), 6.59 (1H, d, J = 4.0 Hz), 6.51 (1H, d, J = 2.4 Hz). *Two protons from NH and OH were not observed. MS calculated: 404.44; MS found: 405.1 (M+H+).

[0438] (41) A-41: 2-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0439] 1H-NMR (400 MHz, CDCl3): δ 8.08 (1H, d, J = 6.0 Hz), 7.74 (2H, d, J = 8.0 Hz), 7.38 (1H, s), 7.34-7.29 (3H, m), 7.26-7.25 (1H, m), 7.13 (1H, d, J = 8.0 Hz), 7.09 (1H, d, J = 8.0 Hz), 6.70 (1H, s), 6.59 (1H, d, J = 1.6 Hz), 6.54 (1H, dd, J = 5.4, 2.2 Hz), 4.83 (1H, s), 1.55 (6H, s). * Protons from OH were not observed. MS calculated: 418.51; MS found: 419.2 (M+H+)

[0440] (42) A-42: 2-(4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0441] 1H-NMR (400 MHz, DMSO-d6):δ 9.59 (1H, s), 8.21-8.19 (2H, m), 7.71-7.67 (4H, m), 7.34 (2H, t, J = 7.6 Hz), 7.24 (1H, t, J = 7.6 Hz), 7.18 (2H, s), 6.74 (1H, dd, J = 5.6, 2.0 Hz), 6.62 (1H, d, J = 2.4 Hz), 5.10 (1H, s), 1.40 (6H, s). MS calculated: 419.50; MS detected: 420.2(M+H+)

[0442] (43) A-43: 2-(5-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0443] 1H-NMR (400 MHz, DMSO-d6):δ 9.21 (1H, s), 8.58 (1H, d, J = 2.0 Hz), 8.07 (2H, dd, J = 8.4, 2.8 Hz), 7.69 (2H, d, J = 8.4 Hz), 7.49 (1H, d, J = 8.8 Hz), 7.33 (2H, t, J = 7.6 Hz), 7.22 (1H, t, J = 7.4 Hz), 7.14 (2H, s), 6.62 (1H, dd, J = 6.0, 2.4 Hz), 6.48 (1H, dd, J = 2.0 Hz), 5.04 (1H, s), 1.38 (6H, s). MS calculated: 419.50; MS found: 420.2 (M+H+)

[0444] (44) A-44: 2-(3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0445] 1H-NMR (400 MHz, DMSO-d6):δ 9.06 (1H, s), 8.17 (1H, d, J = 1.2 Hz), 8.08 (1H, d, J = 5.6 Hz), 7.73 (2H, dd, J = 8.4, 1.2 Hz), 7.64-7.62 (1H, m), 7.51 (1H, t, J = 2.0 Hz), 7.36 (2H, t, J = 7.6 Hz), 7.27-7.22 (1H, m), 7.15 (1H, t, J = 8.0 Hz), 6.97 (1H, d, J = 8.4 Hz), 6.59 (1H, dd, J = 5.8. 2.2 Hz), 6.51 (1H, d, J = 2.4 Hz), 4.92 (1H, s), 2.60-2.52 (1H, m), 0.75-0.73 (2H, m), 0.57-0.55 (2H, m). MS calculated: 458.58; MS detected: 459.2 (M+H+)

[0446] (45) A-45: 3-(4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0447] 1H-NMR (400 MHz, CDCl3):δ 9.14 (1H, d, J = 5.6 Hz), 7.93 (1H, t, J = 1.6 Hz), 7.72 (2H, d, J = 8.0 Hz), 7.52-7.43 (1H, m), 7.42-7.39 (2H, m), 7.33-7.29 (2H, m), 7.26-7.23 (1H, m), 6.78 (1H, brs), 6.66 (1H, dd, J = 6.0, 2.0 Hz), 6.53 (1H, d, J = 2.0 Hz), 5.66 (1H, s), 4.94 (2H, s), 2.68-2.61 (1H, m), 0.82-0.73 (2H, m), 0.74-0.71 (2H, m). MS calculated: 479.57; MS detected: 480.1 (M+H+)

[0448] (46) A-46: 3-(4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0449] 1H-NMR (400 MHz, DMSO-d6):δ 9.24 (1H, s), 8.18 (1H, s), 8.12 (1H, d, J = 6.0 Hz), 8.02 (1H, s), 7.84-7.82 (2H, m), 7.73 (2H, d, J = 7.2 Hz), 7.38-7.34 (3H, m), 7.31-7.25 (3H, m), 6.64 (1H, dd, J = 5.6, 2.4 Hz), 6.52 (1H, d, J = 2.0 Hz), 2.60-2.52 (1H, m), 0.77-0.73 (2H, m), 0.58-0.54 (2H, m). MS calculated: 443.52; MS detected: 444.2 (M+H+)

[0450] (47) A-47: 4-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0451] 1H-NMR (400 MHz, DMSO-d6):δ 9.40 (1H, s), 8.19 (1H, d, J = 1.6 Hz), 8.16 (1H, d, J = 6.0 Hz), 7.80-7.73 (5H, m), 7.69 (2H, d, J = 8.4 Hz), 7.36 (2H, t, J = 7.4 Hz), 7.28-7.24 (1H, m), 7.11 (1H, brs), 6.70 (1H, dd, J = 5.8. 2.2 Hz), 6.56 (1H, d, J = 2.4 Hz), 2.60-2.55 (1H, m), 0.77-0.72 (2H, m), 0.58-0.55 (2H, m). MS calculated: 443.52; MS found: 444.2 (M+H+)

[0452] (48) A-48: 3-(4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0453] 1H-NMR (400 MHz, DMSO-d6):δ 9.33 (1H, s), 8.24 (1H, s), 8.18 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 7.89 (1H, d, J = 9.2 Hz), 7.73 (1H, d, J = 8.0 Hz), 7.45 (1H, d, J = 8.0 Hz), 7.38-7.33 (2H, m), 7.28-7.24 (1H, m), 6.67 (1H, dd, J = 7.8. 1.0 Hz), 6.52 (1H, d, J = 1.6 Hz), 2.69-2.64 (1H, m), 0.77-0.71 (2H, m), 0.58-0.54 (2H, m). * Three protons from NH and OH were not observed. MS calculated: 444.51; MS found: 445.1 (M+H+).

[0454] (49) A-49: 4-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0455] 1H-NMR (400 MHz, MeOH-d4): δ 7.96 (1H, d, J = 5.6 Hz), 7.78-7.75 (3H, m), 7.63 (1H, d, J = 8.4 Hz), 7.36 (2H, d, J = 8.8 Hz), 7.22 (2H, t, J = 7.4 Hz), 7.16-7.14 (1H, m), 6.49 (1H, dd, J = 6.0, 2.4 Hz), 6.41 (1H, d, J = 2.4 Hz), 2.53-2.47 (1H, m), 0.71-0.69 (2H, m), 0.57-0.54 (2H, m). * The four protons from NH2 and OH were not observed. MS calculated: 444.51; MS found: 445.2 (M+H+).

[0456] (50) A-50: 2-(3-(4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0457] 1H-NMR (400 MHz, CDCl3): δ 8.08 (1H, d, J = 5.2 Hz), 7.76 (2H, d, J = 8.0 Hz), 7.37-7.36 (1H, m), 7.34-7.28 (2H, m), 7.25-7.21 (1H, m), 7.14-7.10 (2H, m), 6.56 (1H, s), 6.58 (1H, d, J = 2.0 Hz), 6.56-6.54 (1H, m), 5.04 (1H, d, J = 4.4 Hz), 2.98 (3H, d, J = 4.4 Hz), 1.54 (6H, s). *Two protons from the OH and NH peaks were not observed. MS calculated: 432.54; MS found: 433.2 (M+H+)

[0458] (51) A-51: 3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0459] 1H-NMR (400 MHz, DMSO-d6): δ 9.45 (1H, s), 8.20 (1H, t, J = 2.0 Hz), 8.13 (1H, d, J = 6.0 Hz), 7.81 (1H, d, J = 8.0 Hz), 7.77-7.74 (2H, m), 7.69 (1H, d, J = 4.4 Hz), 7.43-7.36 (4H, m), 7.34-7.25 (2H, m), 6.69-6.67 (1H, m), 6.53 (1H, d, J = 2.4 Hz), 2.89 (3H, d, J = 4.8 Hz). * Protonated NH was not observed. MS calculated: 453.54; MS found: 454.1 (M+H+)

[0460] (52) A-52: 3-(4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0461] 1H-NMR (400 MHz, DMSO-d6):δ 9.24 (s, 1H), 8.11 (d, J = 6.0 Hz, 1H), 8.02 (s, 1H), 7.83-7.81 (m, 2H), 7.76 (d, J = 7.2 Hz, 2H), 7.68-7.67 (m, 1H), 7.37-7.32 (m, 3H), 7.28-7.25 (m, 3H), 6.63 (dd, J = 1.6 Hz,5.6 Hz, 1H), 6.51 (d, J = 2.0 Hz, 1H), 2.88 (d, J = 5.2 Hz,3H). MS calculated: 417.48; MS detected: 418.2 (M+H+)

[0462] (53) A-53: 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0463] 1H-NMR (400 MHz, DMSO-d6):δ 9.53 (1H, s), 8.16 (1H, d, J = 5.6 Hz), 7.80-7.74 (4H, m), 7.69-7.65 (3H, s), 7.36 (2H, t, J = 7.2 Hz), 7.26-7.24 (1H, m), 7.12 (2H, m), 6.73-6.72 (1H, m), 6.57 (1H, s), 2.89 (3H, d, J = 4.8 Hz). MS calculated: 453.54; MS detected: 454.1 (M+H+)

[0464] (54) A-54: 2-(4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)propan-2-ol

[0465] 1H-NMR (400 MHz, DMSO-d6):δ 9.53 (1H, s), 8.17 (2H, dd, J = 1.6 Hz,5.8 Hz), 7.72 (2H, d, J = 6.8 Hz), 7.68-7.62 (3H, m), 7.33 (2H, t, J = 7.6 Hz), 7.22 (1H, t, J = 7.2 Hz), 6.71 (1H, dd, J = 2.4 Hz,5.6 Hz), 6.59 (1H, d, J = 2.0 Hz), 5.06 (1H, s), 2.86 (3H, d, J = 4.8 Hz), 1.36 (6H, s). MS calculated: 433.53; MS Detected: 434.2 (M+H+)

[0466] (55) A-55: 2-(5-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0467] 1H-NMR (400 MHz, DMSO-d6):δ 9.19 (1H, s), 8.57 (1H, d, J = 2.8 Hz), 8.07-8.05 (2H, m), 7.73 (2H, d, J = 7.6 Hz), 7.65-7.64 (1H, m), 7.47 (1H, d, J = 8.8 Hz), 7.33 (2H, t, J = 8.0 Hz), 7.23 (1H, d, J = 7.2 Hz), 6.61 (1H, dd, J = 2.4 Hz,7.2 Hz), 6.47 (1H, S), 5.08 (1H, s), 2.86 (3H, d, J = 4.8 Hz), 1.37 (6H, s). MS calculated: 433.53; MS found: 434.1 (M+H+)

[0468] (56) A-56: 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0469] 1H-NMR (400 MHz, DMSO-d6):δ 12.43 (1H, s), 9.51 (1H, s), 8.17 (1H, d, J = 5.6 Hz), 7.80 (2H, d, J = 8.8 Hz), 7.76-7.70 (4H, m), 7.69-7.67 (1H, m), 7.35 (2H, t, J = 7.6 Hz), 7.25 (1H, t, J = 7.6 Hz), 6.72 (1H, dd, J = 2.4 Hz,5.8 Hz), 6.58 (1H, d, J = 2.4 Hz), 2.89 (3H, d, J = 4.8 Hz). MS calculated: 418.47; MS Detected: 419.1 (M+H+)

[0470] (57) A-57: 3-(4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0471] 1H-NMR (400 MHz, DMSO-d6):δ 9.32 (1H, s), 8.25 (1H, s), 8.13 (1H, d, J = 5.2 Hz), 7.88 (1H, d, J = 8.4 Hz), 7.75 (2H, d, J = 7.6 Hz), 7.68 (1H, d, J = 4.8 Hz), 7.44 (1H, d, J = 8.0 Hz), 7.37-7.26 (3H, m), 7.25 (1H, t, J = 7.4 Hz), 6.66 (1H, dd, J = 2.4 Hz,6.0 Hz), 6.51 (1H, d, J = 2.0 Hz), 2.89 (3H, d, J = 4.8 Hz). *No protonated OH was observed. MS calculated: 418.47; MS found: 419.1 (M+H+)

[0472] (58) A-58: 3-(4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0473] 1H-NMR (400 MHz, DMSO-d6):δ 9.45 (1H, s), 8.18 (1H, s), 8.16 (1H, d, J = 6.0 Hz), 7.84-7.79 (3H, m), 7.42 (3H, t, J = 7.8 Hz), 7.33 (2H, d, J = 7.6 Hz), 7.30 (2H, s), 6.70 (1H, dd, J = 6.0, 2.4 Hz), 6.47 (1H, d, J = 1.6 Hz), 2.71 (3H, s). MS calculated: 438.52; MS detected: 439.1 (M+H+)

[0474] (59) A-59: 2-(4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)propan-2-ol

[0475] 1H-NMR (400 MHz, CDCl3): δ 8.29 (1H, d, J = 5.6 Hz), 8.21 (1H, d, J = 6.0 Hz), 7.85 (2H, d, J = 7.6 Hz), 7.36 (2H, t, J = 7.6 Hz), 7.30-7.29 (2H, m), 7.17-7.16 (1H, m), 6.81 (1H, brs), 6.68 (1H, dd, J = 5.6, 2.0 Hz), 6.52 (1H, s), 2.70 (3H, s), 1.49 (6H, s). * Protons from OH were not observed. MS calculated: 418.51; MS found: 419.2 (M+H+)

[0476] (60) A-60: 3-(4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0477] 1H-NMR (400 MHz, DMSO-d6): δ 9.23 (1H, s), 8.13 (1H, d, J = 5.2 Hz), 8.02 (1H, s), 7.85-7.79 (4H, m), 7.42 (2H, t, J = 7.6 Hz), 7.35 (1H, t, J = 7.8 Hz), 7.33-7.27 (3H, m), 6.65 (1H, dd, J = 5.8. 2.2 Hz), 6.45 (1H, d, J = 2.0 Hz), 2.70 (3H, s). MS calculated: 402.47; MS detected: 403.1 (M+H+)

[0478] (61) A-61: 2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0479] 1H-NMR (400 MHz, DMSO-d6): δ 9.05 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.82 (2H, d, J = 8.0 Hz), 7.59 (1H, d, J = 8.4 Hz), 7.50 (1H, s), 7.41 (2H, t, J = 7.6 Hz), 7.31 (1H, t, J = 7.4 Hz), 7.15 (1H, t, J = 7.8 Hz), 6.98 (1H, d, J = 8.0 Hz), 6.60 (1H, dd, J = 5.8. 2.2 Hz), 6.44 (1H, d, J = 2.4 Hz), 4.92 (1H, s), 2.69 (3H, s), 1.38 (6H, s). MS calculated: 418.2; MS found: 439.1 (M+H+)

[0480] (62) A-62: 5-(2-(((1-(methylsulfonyl)-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0481] 1H-NMR (400 MHz, MeOH-d4): δ 8.46 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.82 (1H, s), 7.70 (2H, d, J = 7.6 Hz), 7.30 (2H, t, J = 8.0 Hz), 7.22, 7.20 (1H, m), 6.55 (1H, dd, J = 5.6, 2.0 Hz), 6.36 (1H, d, J = 2.0 Hz), 3.28 (3H, s). * Three protons from NH and NHBoc were not observed. MS calculated: 428.49 found: 429.1 (M+H+).

[0482] (63) A-63: 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0483] 1H-NMR (400 MHz, CDCl3): δ 9.38 (1H, s), 8.17 (1H, d, J = 5.6 Hz), 7.82 (2H, d, J = 6.8 Hz), 7.77-7.75 (3H, m), 7.67 (2H, d, J = 8.8 Hz), MS Calculated: 402.47; MS Detected: 403.1 (M+H+)

[0484] (64) A-64: 4-(4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0485] 1H-NMR (400 MHz, DMSO-d6): δ 9.52 (1H, s), 8.19 (1H, d, J = 6.0 Hz), 7.82 (2H, d, J = 6.8 Hz), 7.77 (2H, d, J = 8.8 Hz), 7.67 (2H, d, J = 9.2 Hz), 7.41 (2H, t, J = 7.2 Hz), 7.33-7.31 (1H, m), 7.13 (2H, s), 6.74 (1H, dd, J = 2.4 Hz,6.0 Hz), 6.50 (1H, d, J = 2.4 Hz), 2.70 (3H, s). MS calculated: 438.52; MS detected: 439.1 (M+H+)

[0486] (65) A-65: 2-(5-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)propan-2-ol

[0487] 1H-NMR (400 MHz, DMSO-d6): δ 9.21 (1H, s), 8.59 (1H, d, J = 2.4 Hz), 8.11 (1H, d, J = 6.0 Hz), 8.08 (1H, dd, J = 8.6, 2.6 Hz), 7.83 (2H, d, J = 8.4 Hz), 7.51 (1H, d, J = 8.8 Hz), 7.42 (2H, t, J = 7.6 Hz), 7.32 (1H, t, J = 7.2 Hz), 6.66 (1H, dd, J = 5.8. 2.2 Hz), 6.43 (1H, d, J = 2.4 Hz), 5.07 (1H, s), 2.70 (3H, s), 1.40 (6H, s). MS calculated: 418.51; MS found: 419.2 (M+H+)

[0488] (66) A-66: 2-methyl-2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoic acid

[0489] 1H-NMR (400 MHz, DMSO-d6): δ 9.14 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.81 (2H, d, J = 7.2 Hz), 7.65 (1H, d, J = 7.2 Hz), 7.42-7.39 (3H, m), 7.33-7.31 (1H, m), 7.18 (1H, t, J = 12.0 Hz), 6.87 (1H, d, J = 8.0 Hz), 6.63 (1H, dd, J = 2.4 Hz,6.0 Hz), 6.43 (1H, d, J = 2.4 Hz), 2.69 (3H, s), 1.43 (6H, s). No protons from OH were observed. MS calculated: 445.53; MS found: 446.2 (M+H+).

[0490] (67) A-67: N,N-dimethyl-3-(4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0491] 1H-NMR (400 MHz, DMSO-d6): δ 9.22 (1H, s), 8.12 (1H, d, J = 5.6 Hz), 7.80 (2H, d, J = 6.8 Hz), 7.74 (1H, s), 7.54 (1H, d, J = 7.6 Hz), 7.39 (2H, t, J = 7.8 Hz), 7.31-7.24 (2H, m), 6.85 (1H, d, J = 7.2 Hz), 6.65 (1H, dd, J = 6.2,2.2 Hz), 6.41 (1H, d, J = 2.0 Hz), 2.94 (3H, s), 2.88 (3H, s), 2.68 (3H, s). MS calculated: 430.52; MS found: 431.1 (M+H+)

[0492] (68) 3-(4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid

[0493] 1H-NMR (400 MHz, DMSO-d6): δ 9.15 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.81-7.78 (3H, m), 7.63 (1H, d, J = 8.4 Hz), 7.40 (2H, t, J = 7.8 Hz), 7.29 (1H, t, J = 7.4 Hz), 7.17-7.09 (2H, m), 6.60 (1H, dd, J = 6.0, 2.4 Hz), 6.42 (1H, d, J = 2.4 Hz), 2.68 (3H, s). * Protons from OH were not observed. MS calculated: 439.51; MS found: 440.1 (M+H+)

[0494] (69) A-69: N-methyl-3-(4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0495] 1H-NMR (400 MHz, DMSO-d6): δ 9.24 (1H, s), 8.32-8.28 (1H, m), 8.11 (1H, d, J = 5.2 Hz), 7.98 (1H, s), 7.81-7.78 (3H, m), 7.39 (2H, t, MS Calculated: 416.50; MS detection: 417.1 (M+H+)

[0496] (70) A-70: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(3-(methylsulfonyl)phenyl)pyridin-2-amine

[0497] 1H-NMR (400 MHz, DMSO-d6): δ 9.53 (1H, s), 8.26 (1H, s), 8.17 (1H, d, J = 6.0 Hz), 7.88 (1H, d, J = 9.2 Hz), 7.80 (2H, d, J = 7.2 Hz), 7.49 (1H, d, J = 8.0 Hz), 7.41-7.37 (3H, m), 7.30 (1H, t, J = 7.4 Hz), 6.71 (1H, dd, J = 5.6, 2.0 Hz), 6.45 (1H, d, J = 2.4 Hz), 3.14 (3H, s), 2.69 (3H, s). MS calculated: 437.53; MS detected: 438.0 (M+H+)

[0498] (71) A-71: N-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0499] 1H-NMR (400 MHz, DMSO-d6): δ 9.64 (1H, s), 9.16 (1H, s), 8.09 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.2 Hz), 7.45-7.41 (2H, m), 7.39 (2H, t, J = 7.8 Hz), 7.30 (1H, t, J = 5.2 Hz), 7.14 (1H, t, J = 8.4 Hz), 6.70 (1H, d, J = 8.0 Hz), 6.62 (1H, dd, J = 3.8. 1.8 Hz), 6.43 (1H, d, J = 2.4 Hz), 2.94 (3H, s), 2.68 (3H, s). MS calculated: 452.55; MS found: 453.1 (M+H+)

[0500] (72) A-72: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((trifluoromethyl)sulfonyl)phenyl)pyridin-2-amine

[0501] 1H-NMR (400 MHz, DMSO-d6): δ 9.97 (1H, s), 8.83 (1H, s), 8.20 (1H, d, J = 5.6 Hz), 8.04 (1H, d, J = 8.8 Hz), 7.80 (2H, d, J = 8.0 Hz), 7.68 (1H, t, J = 8.0 Hz), 7.56 (1H, d, J = 7.6 Hz), 7.39 (2H, t, J = 7.8 Hz), 7.17 (1H, t, J = 7.8 Hz), 6.77 (1H, dd, J = 5.6, 2.4 Hz), 6.46 (1H, d, J = 2.0 Hz), 2.69 (3H, s). MS calculated: 491.51; MS found: 492.0 (M+H+)

[0502] (73) A-73: N-methyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0503] 1H-NMR (400 MHz, DMSO-d6): δ 9.46 (1H, s), 8.15-8.14 (2H, m), 7.83-7.79 (3H, m), 7.45-7.35 (4H, m), 7.31 (1H, t, J = 3.8 Hz), 7.23 (1H, d, J = 8.4 Hz), 6.69 (1H, d, J = 6.0 Hz), 6.44 (1H, d, J = 2.4 Hz), 2.68 (3H, s), 2.39 (3H, d, J = 4.8 Hz). MS calculated: 452.55; MS detected: 453.1 (M+H+)

[0504] (74) A-74: N,N-dimethyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0505] 1H-NMR (400 MHz, DMSO-d6): δ 9.50 (1H, s), 8.15 (1H, d, J = 5.6 Hz), 8.09 (1H, s), 7.90 (1H, d, J = 7.6 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.47 (1H, t, J = 8.0 Hz), 7.39 (2H, t, J = 7.8 Hz), 7.30 (1H, t, J = 5.8 Hz), 7.19 (1H, d, J = 8.0 Hz), 6.70 (1H, dd, J = 8.2,2.2 Hz), 6.43 (1H, s), 2.68 (3H, s), 2.58 (6H, s). MS calculated: 466.58; MS found: 467.1 (M+H+)

[0506] (75) A-75: N-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopropanesulfonamide

[0507] 1H-NMR (400 MHz, DMSO-d6): δ 9.61 (1H, s), 9.15 (1H, s), 8.09 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.50 (1H, s), 7.44-7.37 (3H, m), 7.29 (1H, t, J = 7.4 Hz), 7.13 (1H, t, J = 8.2 Hz), 6.72 (1H, d, J = 8.4 Hz), 6.62 (1H, dd, J = 5.8. 2.2 Hz), 6.43 (1H, d, J = 2.4 Hz), 2.68 (3H, s), 2.58-2.54 (1H, m), 0.93-0.89 (4H, m). MS calculated: 478.59; MS found: 479.1 (M+H+)

[0508] (76) A-76: N-cyclopropyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0509] 1H-NMR (400 MHz, DMSO-d6): δ 9.47 (1H, s), 8.18 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 7.84-7.79 (3H, m), 7.45-7.37 (3H, m), 7.31-7.26 (2H, m), 6.69 (1H, dd, J = 6.2, 2.2 Hz), 6.44 (1H, d, J = 2.0 Hz), 2.68 (3H, s), 2.10-2.06 (1H, m), 0.46-2.43 (2H, m), 0.39-0.37 (2H, m). * Protons from NH were not observed. MS calculated: 478.59; MS found: 479.1 (M+H+)

[0510] (77) A-77: N-(3-(ethylsulfonyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0511] 1H-NMR (400 MHz, DMSO-d6): δ 9.60 (1H, s), 8.38 (1H, s), 8.16 (1H, d, J = 5.2 Hz), 7.90 (1H, d, J = 9.6 Hz), 7.80 (2H, d, J = 7.2 Hz), 7.49 (1H, t, J = 8.0 Hz), 7.39 (2H, t, J = 7.4 Hz), 7.32 (2H, t, J = 9.2 Hz), 6.71 (1H, d, J = 5.6 Hz), 6.45 (1H, s), 3.22 (2H, q, J = 5.9 Hz), 2.69 (3H, s), 1.08 (3H, t, J = 7.4 Hz). MS calculated: 438.52 Found: 439.1 (M+H+)

[0512] (78) A-78: 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0513] 1H-NMR (400 MHz, DMSO-d6): δ 9.16 (1H, s), 8.09 (1H, d, J = 7.6 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.68 (1H, d, J = 8.4 Hz), 7.55 (1H, s), 7.39 (2H, t, J = 7.8 Hz), 7.30 (1H, t, J = 6.0 Hz), 7.21 (1H, t, J = 7.8 Hz), 6.90 (1H, d, J = 7.6 Hz), 6.62 (1H, dd, J = 6.0, 2.4 Hz), 6.44 (1H, d, J = 2.4 Hz), 4.17 (2H, s), 2.68 (3H, s). *Two protons from NH2 were not observed. MS calculated: 452.55; MS found: 453.1 (M+H+)

[0514] (79) A-79: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((methylsulfonyl)methyl)phenyl)pyridin-2-amine

[0515] 1H-NMR (400 MHz, DMSO-d6): δ 9.19 (1H, s), 8.09 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.67 (1H, d, J = 8.0 Hz), 7.59 (1H, s), 7.39 (2H, t, J = 7.8 Hz), 7.29 (1H, t, J = 7.8 Hz), 7.23 (1H, t, J = 7.8 Hz), 6.90 (1H, d, J = 7.6 Hz), 6.62 (1H, dd, J = 6.0, 2.4 Hz), 6.44 (1H, d, J = 2.4 Hz), 4.39 (2H, s), 2.89 (3H, s), 2.68 (3H, s). MS calculated: 451.56; MS found: 452.1 (M+H+)

[0516] (80) A-80: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-ylmethyl)pyridin-2-amine

[0517] 1H-NMR (400 MHz, DMSO-d6): δ 8.43 (2H, d, J = 5.6 Hz), 7.87 (1H, d, J = 6.0 Hz), 7.78 (2H, d, J = 7.2 Hz), 7.38 (2H, t, J = 7.4 Hz), 7.32-7.28 (2H, m), 7.22 (2H, d, J = 5.6 Hz), 6.35 (1H, dd, J = 6.0, 2.4 Hz), 6.16 (1H, d, J = 2.0 Hz), 4.44 (2H, d, J = 6.0 Hz), 2.65 (3H, s). MS calculated: 374.46; MS found: 375.1 (M+H+)

[0518] (81) A-81: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-ylmethyl)pyridin-2-amine

[0519] 1H-NMR (400 MHz, DMSO-d6): δ 8.47 (1H, s), 8.40 (1H, d, J = 3.2 Hz), 7.91 (1H, d, J = 5.6 Hz), 7.78 (2H, d, J = 7.2 Hz), 7.64 (1H, d, J = 7.6 Hz), 7.38 (2H, t, J = 7.4 Hz), 7.29 (2H, t, J = 6.6 Hz), 7.24 (1H, t, J = 5.8 Hz), 6.35 (1H, dd, J = 6.0, 2.4 Hz), 6.14 (1H, d, J = 2.4 Hz), 4.43 (2H, d, J = 6.0 Hz), 2.65 (3H, s). MS calculated: 374.46; MS found: 375.1 (M+H+)

[0520] (82) A-82: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-yl)pyridin-2-amine

[0521] 1H-NMR (400 MHz, DMSO-d6): δ 9.28 (1H, s), 8.69 (1H, s), 8.15-7.12 (2H, m), 8.07 (1H, s), 7.80 (2H, d, J = 7.2 Hz), 7.39 (2H, t, J = 7.8 Hz), 7.30 (1H, t, J = 7.4 Hz), 6.64 (1H, dd, J = 5.6, 2.0 Hz), 6.68 (1H, dd, J = 5.6, 2.0 Hz), 6.43 (1H, d, J = 2.4 Hz), 2.68 (3H, s). MS calculated: 360.43; MS found: 361.1 (M+H+)

[0522] (83) A-83: N-(6-fluoropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0523] 1H-NMR (400 MHz, DMSO-d6): δ 9.33 (1H, s), 8.39 (1H, s), 8.21 (1H, t, J = 6.6 Hz), 8.11 (1H, d, J = 5.2 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.39 (2H, t, J = 7.8 Hz), 7.30 (1H, t, J = 7.8 Hz), 7.06 (1H, dd, J = 9.2, 3.2 Hz), 6.68 (1H, dd, J = 5.8. 2.2 Hz), 6.39 (1H, d, J = 2.0 Hz), 2.68 (3H, s). MS calculated: 378.42; MS detected: 379.1 (M+H+)

[0524] (84) A-84: N-(6-chloropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0525] 1H-NMR (400 MHz, DMSO-d6): δ 9.45 (1H, s), 8.57 (1H, d, J = 3.2 Hz), 8.19 (1H, dd, J = 8.6, 2.6 Hz), 8.14 (1H, d, J = 6.0 Hz), 7.80 (2H, MS Calculated: 394.88; MS detection: 395.1 (M+H+)

[0526] (85) A-85: N-(6-methoxypyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0527] 1H-NMR (400 MHz, DMSO-d6): δ 9.00 (1H, s), 8.30 (1H, d, J = 2.4 Hz), 8.04 (1H, d, J = 6.4 Hz), 7.93 (1H, dd, J = 9.0, 2.2 Hz), 7.80 (2H, d, J = 8.0 Hz), 7.40 (2H, t, J = 7.8 Hz), 7.30 (1H, t, J = 7.4 Hz), 6.72 (1H, d, J = 8.8 Hz), 6.58 (1H, d, J = 5.6 Hz), 6.32 (1H, d, J = 1.6 Hz), 3.77 (3H, s), 2.67 (3H, s). MS calculated: 390.46; MS found: 391.1 (M+H+)

[0528] (86) A-86: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-yl)pyridin-2-amine

[0529] 1H-NMR (400 MHz, DMSO-d6):δ 9.56 (1H, s), 8.26 (2H, brs), 8.21 (1H, d, J = 5.6 Hz), 7.79 (2H, d, J = 7.6 Hz), 7.59 (2H, s), 7.39 (2H, MS calculated: 360.43; MS detected: 361.1 (M+H+)

[0530] (87) A-87: N-(2-fluoropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0531] 1H-NMR (400 MHz, DMSO-d6):δ 9.89 (1H, s), 8.25 (1H, d, J = 5.6 Hz), 7.92 (1H, d, J = 6.0 Hz), 7.79 (2H, d, J = 8.0 Hz), 7.61 (1H, d, J = 1.6 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.30 (1H, t, J = 8.0 Hz), 7.22 (1H, d, J = 6.0 Hz), 6.84 (1H, dd, J = 5.8. 2.2 Hz), 6.52 (1H, d, J = 2.0 Hz), 2.69 (3H, s). MS calculated: 378.42; MS detected: 379.1 (M+H+)

[0532] (88) A-88: ​​N-(2-methoxypyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0533] 1H-NMR (400 MHz, DMSO-d6):δ 9.51 (1H, s), 8.20 (1H, d, J = 5.6 Hz), 7.86 (1H, d, J = 6.0 Hz), 7.79 (2H, d, J = 7.6 Hz), 7.39 (2H, t, J MS Calculated: 390.46; MS Detected: 391.1 (M+H+)

[0534] (89)A-89: N-(2-chloropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0535] 1H-NMR (400 MHz, DMSO-d6):δ 9.83 (1H, s), 8.26 (1H, d, J = 6.0 Hz), 8.07 (1H, d, J = 5.2 Hz), 7.94 (1H, d, J = 1.6 Hz), 7.79 (2H, d, J = MS Calculated: 394.88; MS detection: 395.1 (M+H+)

[0536] (90) A-90: 6-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0537] 1H-NMR (400 MHz, DMSO-d6):δ 10.1 (1H, s), 8.65 (1H, d, J = 2.4 Hz), 8.19 (1H, d, J = 6.0 Hz), 8.06 (1H, dd, J = 9.0, 2.2 Hz), 7.89 (1H, s), 7.80 (2H, d, J = 7.2 Hz), 7.69 (1H, d, J = 8.8 Hz), 7.62 (1H, d, J = 2.4 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.30-7.29 (2H, m), 6.71 (1H, dd, J = 5.8. 2.2 Hz), 2.69 (3H, s). MS calculated: 403.46; MS found: 404.1 (M+H+)

[0538] (91) A-91: 5-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0539] 1H-NMR (400 MHz, DMSO-d6):δ 9.64 (1H, s), 7.70 (1H, d, J = 2.8 Hz), 8.35 (1H, dd, J = 8.8. 2.4 Hz), 8.19 (1H, d, J = 6.0 Hz), 7.90 (1H, d, J = 8.8 Hz), 7.86 (1H, s), 7.80 (2H, d, J = 7.2 Hz), 7.41-7.38 (3H, m), 7.31 (1H, d, J = 7.2 Hz), 6.76 (1H, dd, J = 7.4, 1.8 Hz), 6.49 (1H, d, J = 2.4 Hz), 2.69 (3H, s). MS calculated: 403.46; MS found: 404.1 (M+H+)

[0540] (92) A-92: 5-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0541] 1H-NMR (400 MHz, DMSO-d6):δ 9.56 (1H, s), 8.80 (1H, d, J = 1.6 Hz), 8.52 (2H, s), 8.16 (1H, d, J = 5.2 Hz), 8.05 (1H, s), 7.80 (2H, d, J = 7.2 Hz), 7.52 (1H, s), 7.39 (2H, t, J = 7.8 Hz), 7.30 (1H, t, J = 7.2 Hz), 6.71 (1H, dd, J = 5.6, 2.0 Hz), 6.46 (1H, d, J = 1.6 Hz), 2.69 (3H, s). MS calculated: 403.46; MS Detection: 404.1 (M+H+)

[0542] (93) A-93: 2-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide

[0543] 1H-NMR (400 MHz, DMSO-d6):δ 9.94 (1H, s), 8.24 (1H, d, J = 4.8 Hz), 8.17 (1H, d, J = 6.0 Hz), 8.08 (1H, s), 8.01 (1H, s), 7.80 (2H, d, J = 6.8 Hz), 7.61-7.59 (2H, m), 7.39 (2H, t, J = 7.6 Hz), 7.28 (1H, t, J = 7.4 Hz), 7.20 (1H, d, J = 5.2 Hz), 6.67 (1H, dd, J = 5.6, 2.4 Hz), 2.68 (3H, s). MS calculated: 403.46; MS detected: 404.1 (M+H+)

[0544] (94) A-94: N-benzyl-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0545] 1H-NMR (400 MHz, DMSO-d6):δ 7.89 (1H, d, J = 5.6 Hz), 7.77 (2H, d, J = 7.2 Hz), 7.38 (2H, t, J = 7.6 Hz), 7.31-7.23 (5H, m), 7.20-7.17 (2H, m), 6.32 (1H, dd, J = 5.6, 2.0 Hz), 6.12 (1H, d, J = 2.4 Hz), 4.40 (2H, d, J = 6.0 Hz), 2.64 (3H, s). MS calculated: 373.47; MS detected: 374.1 (M+H+)

[0546] (95) A-95: N-(4-fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0547] 1H-NMR (400 MHz, DMSO-d6):δ 7.24 (1H, d, J = 5.6 Hz), 7.77 (2H, d, J = 7.6 Hz), 7.38 (2H, t, J = 7.6 Hz), 7.31-7.26 (3H, m), 7.19 (1H, t, MS Calculated: 391.46; MS Found: 392.1 (M+H+)

[0548] (96) A-96: N-(3-fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0549] 1H-NMR (400 MHz, DMSO-d6):δ 8.00 (1H, d, J = 8.0 Hz), 7.90 (2H, d, J = 5.6 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.33-7.27 (3H, m), 7.09-6.99 (3H, m), 6.35 (1H, d, J = 4.8 Hz), 6.14 (1H, s), 4.42 (2H, d, J = 6.0 Hz), 2.69 (3H, s). MS calculated: 394.46; MS detected: 392.1 (M+H+)

[0550] (97) A-97: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(1-(methylsulfonyl)-1H-pyrazol-4-yl)pyridin-2-amine

[0551] 1H-NMR (400 MHz, DMSO-d6):δ 9.40 (1H, s), 8.43 (1H, s), 8.16 (1H, d, J = 5.6 Hz), 7.84 (1H, s), 7.79 (2H, d, J = 8.0 Hz), 7.39 (2H, t, MS calculated: 427.50; MS detection: 428.1 (M+H+)

[0552] (98) A-98: N-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0553] 1H-NMR (400 MHz, DMSO-d6):δ 9.40 (1H, s), 8.42 (1H, s), 8.16 (1H, d, J = 6.0 Hz), 7.85 (1H, s), 7.79 (2H, d, J = 7.6 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.29 (1H, d, J = 7.4 Hz), 6.62 (1H, dd, J = 6.0, 2.0 Hz), 6.33 (1H, d, J = 2.0 Hz), 3.03-2.99 (1H, m), 2.68 (3H, s), 1.17-1.14 (2H, m), 1.12-1.10 (2H, m). MS calculated: 453.54; MS found: 454.1 (M+H+)

[0554] (99) A-99: N-(1-methyl-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0555] 1H-NMR (400 MHz, DMSO-d6):δ 8.85 (1H, s), 8.03 (1H, d, J = 5.2 Hz), 7.85 (1H, s), 7.79 (2H, d, J = 7.6 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.31-7.27 (2H, m), 6.46 (1H, dd, J = 5.6, 2.0 Hz), 6.22 (1H, d, J = 2.4 Hz), 3.75 (3H, s), 2.66 (3H, s). MS calculated: 363.44; MS detected: 364.1 (M+H+)

[0556] (100) A-100: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(1H-pyrazol-4-yl)pyridin-2-amine

[0557] 1H-NMR (400 MHz, DMSO-d6):δ 12.4 (1H, brs), 8.82 (1H, s), 8.02 (1H, d, J = 5.6 Hz), 7.83 (1H, s), 7.79 (2H, d, J = 7.6 Hz), 7.39 (3H, MS calculated: 349.41; MS detected: 350.1 (M+H+)

[0558] (101) A-101: 6-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0559] 1H-NMR (400 MHz, DMSO-d6):δ 9.89 (1H, s), 8.18 (1H, d, J = 5.6 Hz), 7.91 (1H, d, J = 8.8 Hz), 7.83-7.79 (3H, m), 7.63 (1H, s), 7.49 (1H, d, J = 6.8 Hz), 7.40 (1H, s), 7.38 (2H, t, J = 7.4 Hz), 7.30-7.28 (2H, m), 6.71 (1H, dd, J = 6.4, 3.4 Hz), 2.68 (3H, s). MS calculated: 403.46; MS detection: 404.1 (M+H+)

[0560] (102) A-102: 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0561] 1H-NMR (400 MHz, DMSO-d6):δ 9.79 (1H, s), 8.31 (1H, d, J = 5.2 Hz), 8.24-8.22 (2H, m), 7.99 (1H, s), 7.81-7.79 (3H, m), 7.54 (1H, s), 7.38 (2H, t, J = 6.8 Hz), 7.30 (1H, d, J = 6.8 Hz), 6.81 (1H, s), 6.53 (1H, d, J = 2.4 Hz), 2.69 (3H, s). MS calculated: 403.46; MS detected: 404.1 (M+H+)

[0562] (103) A-103: N-(4-methoxyphenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0563] 1H-NMR (400 MHz, DMSO-d6):δ 8.86 (1H, s), 8.03 (1H, d, J = 5.6 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.44 (2H, d, J = 9.6 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.29 (1H, t, J = 7.4 Hz), 6.81 (2H, d, J = 8.8 Hz), 6.53 (1H, dd, J = 5.8. 2.2 Hz), 6.31 (1H, d, J = 2.4 Hz), 3.67 (3H, s), 2.67 (3H, s). MS calculated: 389.47; MS detected: 390.1 (M+H+)

[0564] (104) A-104: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(piperazin-1-yl)phenyl)pyridin-2-amine

[0565] 1H-NMR (400 MHz, DMSO-d6): δ 8.80 (1H, s), 8.01 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.2 Hz), 7.41-7.37 (4H, m), 7.30 (1H, d, J = 7.6 Hz), 6.81 (2H, d, J = 8.8 Hz), 6.50 (1H, dd, J = 5.6, 2.4 Hz), 6.30 (1H, d, J = 2.4 Hz), 2.98-2.93 (4H, m), 2.87-2.83 (4H, m), 2.67 (3H, s). * Protons from NH were not observed. MS calculated: 443.56; MS found: 444.2 (M+H+)

[0566] (105) A-105: 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(2-(piperidin-1-yl)ethoxy)phenyl)pyridin-2-amine

[0567] 1H-NMR (400 MHz, DMSO-d6):δ 8.86 (1H, s), 8.03 (1H, d, J = 5.6 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.44-7.37 (4H, m), 7.30 (1H, d, J= 7.2 Hz), 6.81 (2H, d, J = 9.2 Hz), 6.53 (1H, dd, J = 5.8. 2.2 Hz), 6.31 (1H, d, J = 2.4 Hz), 3.97 (2H, t, J = 5.8 Hz), 2.67 (3H, s), 2.62-2.58 (2H, m), 2.39 (4H, s), 1.49-1.44 (4H, m), 1.38-1.32 (2H, m). MS calculated: 486.63; MS found: 487.2 (M+H+)

[0568] (106) A-106: N-(3-methoxy-4-(4-methylpiperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0569] 1H-NMR (400 MHz, DMSO-d6):δ 8.90 (1H, s), 8.05 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.29 (1H, t, J = 7.4 Hz), 7.18 (1H, d, J = 2.4 Hz), 7.06 (1H, dd, J = 8.6, 2.2 Hz), 6.74 (1H, d, J = 8.8 Hz), 6.54 (1H, dd, J = 5.8. 2.2 Hz), 6.34 (1H, d, J = 2.0 Hz), 3.69 (3H, s), 2.85 (4H, brs), 2.67 (3H, s), 2.40 (4H, brs), 2.18 (3H, s). MS calculated: 487.62; MS detected: 488.2 (M+H+)

[0570] (107) A-107: 1,1,1-trifluoro-N-(3-(4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0571] 1H-NMR (400 MHz, DMSO-d6): δ 9.25 (1H, brs), 8.11 (1H, d, J = 5.6 Hz), 7.80 (2H, d, J = 8.0 Hz), 7.62 (1H, brs), 7.53 (1H, d, J = 8.4 Hz), 7.40 (2H, t, J = 7.6 Hz), 7.29-7.31 (1H, m), 7.22 (1H, t, J = 8.8 Hz), 6.74 (1H, d, J = 8.4 Hz), 6.45 (1H, d, J = 6.4 Hz), 6.43 (1H, s), 2.68 (3H, s). * Protons from NH were not observed. MS calculated: 506.07; MS found: 507.1 (M+H+)

[0572] (108) A-108: N-(4-(4-(2-methoxyethyl)piperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0573] 1H-NMR (400 MHz, DMSO-d6):δ 8.79 (1H, s), 8.01 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.41-7.36 (4H, m), 7.29 (1H, t, J = 7.2 Hz), 6.81 (2H, d, J = 8.8 Hz), 6.48 (1H, dd, J = 8.4, 2.4 Hz), 6.30 (1H, d, J = 2.0 Hz), 3.44 (2H, t, J = 5.6 Hz), 3.22 (3H, s), 3.32-2.98 (4H, m), 2.67 (3H, s), 2.56-2.48 (6H, m). MS calculated: 501.64; MS found: 502.2 (M+H+)

[0574] (109) A-109: 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0575] 1H-NMR (400 MHz, DMSO-d6):δ 12.8 (1H, brs), 9.31 (1H, s), 8.24 (1H, s), 8.16 (1H, d, J = 6.0 Hz), 7.87 (1H, d, J = 7.6 Hz), 7.83 (2H, MS Calculated: 403.45; MS detection: 404.1 (M+H+)

[0576] (110) A-110: 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0577] 1H-NMR (400 MHz, DMSO-d6): δ 9.50 (1H, s), 8.19 (1H, d, J = 6.0 Hz), 7.83-7.82 (4H, m), 7.72 (2H, d, J = 8.8 Hz), 7.41 (2H, t, J = 6.8 Hz), 7.33-7.29 (1H, m), 6.74 (1H, dd, J = 1.6 Hz, 5.4 Hz), 6.51 (1H, d, J = 1.6 Hz), 2.70 (3H, s). *No protons from OH were observed. MS calculated: 403.65; MS found: 404.1 (M+H+).

[0578] (111) A-111: 2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)acetonitrile

[0579] 1H-NMR (400 MHz, CDCl3):δ 8.11 (1H, d, J = 8.0 Hz), 7.85 (2H, d, J = 8.0 Hz), 7.49-7.13 (3H, m), 7.32-7.27 (2H, m), 7.20 (1H, d, J = 16.0 Hz), 6.98 (1H, d, J = 8.0 Hz), 6.57 (1H, s), 6.55 (1H, dd, J = 8.4, 4.4 Hz), 6.45 (1H, d, J = 4.0 Hz), 3.70 (2H, s), 2.70 (3H, s).

[0580] (112) A-112: N-(3-((1H-tetrazol-5-yl)methyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0581] 1H-NMR (400 MHz, DMSO-d6): δ9.09(1H, s),8.08(1H,d,J = 5.6 Hz), 7.79 (2H, d, J = 7.6 Hz), 7.57 (1H, d, J = 8.8 Hz), 7.41-7.37 (3H, m), 7.29 (1H, t, J = 7.6 Hz), 7.17 (1H, t, J = 8.0 Hz), 6.75 (1H, d, J = 7.6 Hz), 6.61 (1H, dd, J = 6.0, 2.4 Hz), 6.40 (1H, d, J = 2.0 Hz), 4.20 (2H, s), 2.67 (3H, s). * No proton from NH was observed. MS calculated: 441.51 Found: 442.2 (M+H+)

[0582] (113) A-113: 3-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanenitrile

[0583] 1H-NMR (400 MHz, DMSO-d6):δ 9.08 (1H, s), 8.09 (1H, d, J = 5.6 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.51 (1H, d, J = 8.0 Hz), 7.43-7.37 (3H, m), 7.30 (1H, t, J = 4.8 Hz), 7.17 (1H, t, J = 7.8 Hz), 6.80 (1H, d, J = 8.0 Hz), 6.61 (1H, dd, J = 6.0, 2.4 Hz), 6.43 (1H, d, J = 2.4 Hz), 2.79-2.74 (4H, m), 2.68 (3H, s). MS calculated: 412.5 Found: 413.2 (M+H+)

[0584] (114) A-114: N-(3-(2-(2H-tetrazol-5-yl)ethyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0585] 1H-NMR (400 MHz, DMSO-d6): δ 9.03 (1H, s), 8.09 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.44-7.37 (4H, m), 7.30 (1H, t, J = 6.0 Hz), 7.11 (1H, t, J = 7.4 Hz), 6.72 (1H, d, J = 8.4 Hz), 6.60 (1H, dd, J = 6.0, 2.4 Hz), 6.41 (1H, s), 3.18-3.07 (2H, m), 2.96-2.91 (2H, m), 2.67 (3H, s). * Protons from NH were not observed. MS calculated: 455.53 Found: 456.2 (M+H+)

[0586] (115) A-115: 2-(3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0587] 1H-NMR (400 MHz, CDCl3): δ 8.09 (1H, dd, J = 5.0, 1.0 Hz), 7.83 (2H, dd, J = 8.2, 1.4 Hz), 7.37-7.33 (3H, m), 7.30-7.25 (2H, m), 7.17-7.11 (2H, m), 6.59 (1H, brs), 6.51-6.49 (2H, m), 2.24-2.20 (1H, m), 1.55 (6H, s), 1.14-1.10 (4H, m). No protons from NH were observed. MS calculated: 443.56; MS found: 444.2 (M+H+).

[0588] (116) A-116: 3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0589] 1H-NMR (400 MHz, CDCl3):δ 8.12 (1H, d, J = 4.0 Hz), 7.95 (1H, s), 7.83 (2H, d, J = 8.8 Hz), 7.52-7.47 (2H, m), 7.41-7.31 (3H, m), 7.28-7.27 (1H, m), 6.80 (1H, brs), 6.59 (1H, dd, J = 2.4 Hz,5.4 Hz), 6.42-6.40 (1H, m), 4.89 (2H, brs), 2.29-2.22 (1H, m), 1.17-1.12 (4H, m). MS calculated: 464.56; MS found: 465.1 (M+H+)

[0590] (117) A-117: 3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0591] 1H-NMR (400 MHz, CDCl3): δ 8.12 (1H, s), 7.86-7.84 (3H, m), 7.49-7.47 (1H, m), 7.43-7.41 (1H, m), 7.39-7.34 (3H, m), 7.29-7.26 (2H, m), 6.54-6.60 (2H, m), 6.45 (1H, s), 2.21-2.30 (1H, m), 1.56-1.13 (4H, m). *No protons from NH were observed. MS calculated: 428.51; MS found: 429.2 (M+H+).

[0592] (118) A-118: 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0593] 1H-NMR (400 MHz, DMSO-d6):δ 9.53 (1H, s), 8.19 (1H, d, J = 5.6 Hz), 7.81-7.77 (4H, m), 7.67 (2H, d, J = 9.2 Hz), 7.41 (2H, t, J = 8.0 Hz), 7.33-7.30 (1H, m), 7.14 (2H, s), 6.75 (1H, dd, J = 5.8. 2.2 Hz), 6.49 (1H, d, J = 2.4 Hz), 2.48-2.42 (1H, m), 1.18-1.15 (2H, m), 1.10-1.07 (2H, m). MS calculated: 464.56; MS detected: 465.1 (M+H+)

[0594] (119) A-119: 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0595] 1H-NMR (400 MHz, DMSO-d6):δ 9.39 (1H, s), 8.17 (1H, d, J = 5.6 Hz), 7.81-7.75 (5H, m), 7.68 (2H, d, J = 8.8 Hz), 7.41 (2H, t, J = 7.6 Hz), 7.31 (1H, t, J = 7.4 Hz), 7.12 (1H, brs), 6.71 (1H, dd, J = 6.0, 2.4 Hz), 6.48 (1H, d, J = 2.0 Hz), 2.50-2.42 (1H, m), 1.20-1.15 (2H, m), 1.10-1.07 (2H, m). MS calculated: 428.51; MS detected: 429.2 (M+H+)

[0596] (120) A-120: 2-(4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0597] 1H-NMR (400 MHz, DMSO-d6):δ 9.52 (1H, s), 8.20-8.18 (2H, m), 7.77 (2H, d, J = 7.6 Hz), 7.67-7.63 (2H, m), 7.38 (2H, t, J = 7.6 Hz), 7.29 (1H, t, J = 7.4 Hz), 6.74 (1H, dd, J = 6.0, 2.4 Hz), 6.52 (1H, dd, J = 2.4 Hz), 5.07 (1H, s), 2.43-7.40 (1H, m), 1.39 (6H, s), 1.17-1.12 (2H, m), 1.08-1.05 (2H, m). MS calculated: 444.55; MS found: 445.2 (M+H+)

[0598] (121) A-121: 2-(5-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0599] 1H-NMR (400 MHz, DMSO-d6):δ 9.19 (1H, s), 8.56 (1H, dd, J = 2.8 Hz), 8.09 (1H, d, J = 6.0 Hz), 8.06 (1H, dd, J = 8.8. 2.8 Hz), 7.78 (2H, d, J = 7.2 Hz), 7.48 (1H, d, J = 8.8 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.29 (1H, t, J = 7.4 Hz), 6.64 (1H, dd, J = 5.8, 2.2 Hz), 6.39 (1H, d, J = 2.4 Hz), 5.05 (1H, s), 2.44-2.38 (1H, m), 1.38 (6H, s), 1.17-1.12 (2H, m), 1.07-1.03 (2H, m). MS calculated: 444.55; MS found: 445.2 (M+H+)

[0600] (122) A-122: N-(3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)ethanesulfonamide

[0601] 1H-NMR (400 MHz, DMSO-d6):δ 9.67 (1H, bs), 9.14 (1H, s), 8.08 (1H, d, J = 5.6 Hz), 7.77 (2H, d, J = 8.0 Hz), 7.44-7.45 (2H, m), 7.38 (2H, t, J = 7.4 Hz), 7.26-7.30 (1H, m), 7.13 (1H, t, J = 8.2 Hz), 6.70 (1H, d, J = 8.8 Hz), 6.61 (1H, dd, J = 8.5 and 2.2 Hz), 6.42 (1H, s), 3.04 (2H, q, J = 7.1 Hz), 2.37-2.42 (1H, m), 1.15-1.18 (3H, m), 1.12-1.14 (2H, m), 1.04-1.06 (2H, m). MS calculated: 492.13; MS found: 493.2 (M+H+)

[0602] (123) A-123: N-(3-(4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide

[0603] 1H-NMR (400 MHz, DMSO-d6):δ 11.7 (1H, bs), 9.25 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.77 (2H, d, J = 7.6 Hz), 7.61 (1H, s), 7.53 (1H, d, J = 8.4 Hz), 7.38 (2H, t, J = 7.6 Hz), 7.29 (1H, t, J = 7.0 Hz), 7.21 (1H, t, J = 8.2 Hz), 6.73 (1H, d, J = 8.0 Hz), 6.34-6.66 (1H, m), 6.42 (1H, s), 2.39-2.45 (1H, m), 1.04-1.24 (4H, m). MS calculated: 532.09; MS found: 533.1 (M+H+)

[0604] (124) A-124: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0605] 1H-NMR (400 MHz, DMSO-d6):δ 9.86 (1H, s), 8.18 (1H, d, J = 6.0 Hz), 7.98 (1H, d, J = 8.0 Hz), 7.83-7.77 (3H, m), 7.59 (1H, s), 7.50 (1H, d, J = 7.6 Hz), 7.46 (1H, s), 7.39 (2H, t, J = 7.2 Hz), 7.29 (1H, t, J = 6.8 Hz), 7.21 (1H, d, J = 2.0 Hz), 6.71 (1H, dd, J = 6.0, 4.0 Hz), 2.40 (1H, m), 1.13-1.11 (2H, m), 1.06-1.05 (2H, m). MS calculated: 429.49 Found: 430.1 (M+H+)

[0606] (125) A-125: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0607] 1H-NMR (400 MHz, DMSO-d6):δ 9.85 (1H, s), 8.18 (1H, d, J = 5.6 Hz), 8.02 (1H, d, J = 4.2 Hz), 7.95 (1H, d, J = 8.0 Hz), 7.82-7.77 (3H, m), 7.47 (1H, d, J = 7.2 Hz), 7.39 (2H, t, J = 7. 6 Hz), 7.30-7.25 (2H, m), 6.74 (1H, dd, J = 6.0, 2.4 Hz), 2.86 (3H, d, J = 5.2 Hz), 2.38-2.37 (1H, m), 1.14-1.10 (2H, m), 1.05-1.02 (2H, m). MS calculated: 443.52 Found: 444.2 (M+H+)

[0608] (126) A-126: 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0609] 1H-NMR (400 MHz, DMSO-d6):δ 9.34 (1H, s), 8.15 (2H, d, J = 6.0 Hz), 7.78 (2H, d, J = 8.0 Hz), 7.71 (4H, q, , J = 9.2 Hz), 7.40 (2H, t, J = 7.6 Hz), 7.30 (1H, t, J = 7.6 Hz), 6.68 (1H, d, J = 6.0 Hz), 6.45 (1H, s), 2.73 (3H, d, J = 4.0), 2.40 (1H, m), 1.15-1.13 (2H, m), 1.05 (2H, m). MS Calculated: 442.53 Detected: 443.2 (M+H+)

[0610] (127) A-127: N-(6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)methanesulfonamide

[0611] 1H-NMR (400 MHz, DMSO-d6):δ 9.79 (1H, s), 9.46 (1H, s), 8.13 (1H, d, J = 6.0 Hz), 8.02 (1H, d, J = 2.4 Hz), 7.77 (2H, d, J = 7.2 Hz), 7.67 (1H, d, J = 9.2 Hz), 7.53-7.49 (2H, m), 7.37 (2H, t, J = 7.6 Hz), 7.28 (1H, t, J = 7.2 Hz), 6.64 (1H, dd, J = 6.0, 2.4 Hz), 2.93 (3H, s), 2.41-2.27 (1H, m), 1.15-1.13 (2H, m), 1.06-1.04 (2H, m). MS calculated: 479.57; MS found: 480.2 (M+H+)

[0612] (128) A-128: N-(4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0613] 1H-NMR (400 MHz, DMSO-d6):δ 9.33 (1H, s), 9.07 (1H, s), 8.07 (1H, d, J = 5.6 Hz), 7.78 (2H, d, J = 7.6 Hz), 7.54 (2H, d, J = 8.8 Hz), 7.40 (2H, t, J = 7.2 Hz), 7.30 (1H, t, J = 7.6 Hz), 7.08 (2H, d, J = 8.8 Hz), 6.60 (1H, dd, J = 6.0, 2.4 Hz), 6.36 (1H, d, J = 2.0 Hz), 2.86 (3H, s), 2.40 (1H, m), 1.14-1.12 (2H, m), 1.14 (2H, m). MS Calculated: 478.59 Found: 479.2 (M+H+)

[0614] (129) A-129: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0615] 1H-NMR (400 MHz, DMSO-d6):δ 10.09 (1H, s), 8.65 (1H, s), 8.19 (1H, d, J = 5.6 Hz), 8.07 (1H, d, J = 9.2 Hz), 7.78 (1H, brs), 7.76 (2H, d, J = 3.2 Hz), 7.73 (1H, d, J = 8.4 Hz), 7.56 (1H, s), 7.39 (2H, t, J = 7.6 Hz), 7.92 (2H, t, J = 7.2 Hz), 6.71 (1H, dd, J = 5.6, 2.4 Hz), 2.42 (1H, m), 1.15-1.11 (2H, m), 1.05-1.04 (2H, m). MS calculated: 429.49 Found: 430.2 (M+H+)

[0616] (130) A-130: Methyl 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate

[0617] 1H-NMR (400 MHz, DMSO-d6):δ 10.32 (1H, brs), 8.69 (1H, s), 8.21 (1H, d, J = 5.6 Hz), 8.10-8.11 (1H, m), 7.78 (3H, t, J = 8.2 Hz), 7.58 (1H, s), 7.37 (2H, t, J = 7.6 Hz), 7.28 (1H, t, J = 7.2 Hz), 6.75-6.77 (1H, m), 3.81 (3H, s), 2.38-2.43 (1H, m), 1.15-1.21 (2H, m), 1.05-1.11 (2H, m). MS calculated: 444.13 MS detection: 445.1 (M+H+)

[0618] (131) A-131: Methyl 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate

[0619] 1H-NMR (400 MHz, DMSO-d6):δ 10.16 (1H, s), 8.18 (1H, d, J = 5.6 Hz), 7.91 (1H, d, J = 8.8 Hz), 7.84-7.77 (3H, m), 7.72 (1H, s), 7.55 (1H, d, J = 7.2 Hz), 7.39 (2H, J = 7.6 Hz), 7.30 (1H, t, J = 7.2 Hz), 6.71 (1H, d, J = 5.6 Hz), 3.79 (3H, s), 2.39-2.38 (1H, m), 1.14-1.11 (2H, m), 1.10-1.03 (2H, m). MS Calculated: 444.51 Found: 445.2 (M+H+)

[0620] (132) A-132: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0621] 1H-NMR (400 MHz, DMSO-d6): δ 10.65 (1H, brs), 8.71 (1H, s), 8.25 (1H, d, J = 6.0 Hz), 8.14 (1H, d, J = 8.4 Hz), 7.76 (2H, d, J = 6.8 Hz), 7.61-7.63 (1H, m), 7.44 (1H, brs), 7.38 (2H, t, J = 7.6 Hz), 7.27-7.31 (1H, m), 6.87 (1H, brs), 2.34-2.44 (1H, m), 1.14-1.16 (2H, m), 1.06-1.14 (2H, m). * Protons from NH were not observed. MS calculated: 430.48; MS found: 431.1 (M+H+)

[0622] (133) A-133: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0623] 1H-NMR (400 MHz, DMSO-d6):δ 10.08 (1H, s), 8.60 (1H, s), 8.32-8.33 (1H, m), 8.17 (1H, d, J = 6.0 Hz), 8.00-8.02 (1H, m), 7.71-7.77 (3H, m), 7.54 (1H, s), 7.36 (2H, t, J = 7.6 Hz), 7.26 (1H, t, J = 7.0 Hz), 6.70 (1H, dd, J = 6.0 and 2.4 Hz), 2.74 (3H, d, J = 6.0 Hz), 2.30-2.46 (1H, m), 1.12-1.14 (2H, m), 1.03-1.04 (2H, m). MS calculated: 443.53; MS found: 444.1 (M+H+)

[0624] (134) A-134: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0625] 1H-NMR (400 MHz, DMSO-d6): δ 10.06 (1H, s), 8.16 (1H, d, J = 5.6 Hz), 7.89 (1H, d, J = 8.0 Hz), 7.81-7.74 (4H, m), 7.53 (1H, d, J = 7.6 Hz), 7.39 (2H, t, J = 7.2 Hz), 7.29 (1H, t, J = 7.2 Hz), 6.64 (1H, d, J = 3.6 Hz), 2.39-2.37 (1H, m), 1.13-1.10 (2H, m), 1.05-1.04 (2H, m). * Protons from OH were not observed. MS calculated: 430.48 Found: 431.1 (M+H+)

[0626] (135) A-135: 3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0627] 1H-NMR (400 MHz, DMSO-d6):δ 12.9 (1H, brs), 9.35 (1H, s), 8.23 ​​(1H, t, J = 1.8 Hz), 8.15 (1H, d, J = 6.0 Hz), 7.87 (1H, dd, J = 7.6, 1.6 Hz), 7.80 (2H, d, J = 5.6 Hz), 4.47 (1H, d, J = 8.0 Hz), 7.43-7.31 (4H, m), 6.69 (1H, dd, J = 5.8. 2.2 Hz), 6.44 (1H, d, J = 2.4 Hz), 2.47-2.41 (1H, m), 1.17-1.13 (2H, m), 1.10-1.17 (2H, m). MS calculated: 429.49 MS found: 430.2 (M+H+)

[0628] (136) A-136: 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0629] 1H-NMR (400 MHz, DMSO-d6): δ 9.52 (1H, s), 8.19 (1H, d, J = 6.0 Hz), 7.81 (3H, t, J = 9.0 Hz), 7.74 (2H, d, J = 8.4 Hz), 7.41 (2H, t, J = 7.6 Hz), 7.31 (1H, t, J = 8.6 Hz), 6.85 (1H, dd, J = 7.6, 2.4 Hz), 6.51 (1H, d, J = 2.4 Hz), 2.49-2.42 (1H, m), 1.19-1.14 (2H, m), 1.09-1.05 (2H, m). *Two protons from NH and OH were not observed. MS calculated: 429.49; MS found: 430.2 (M+H+)

[0630] (137) A-137: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0631] 1H-NMR (400 MHz, DMSO-d6):δ 9.40 (1H, s), 8.41 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 7.83 (1H, s), 7.68 (2H, d, J = 7.6 Hz), 7.33 (2H, t, J = 7.2 Hz), 7.23 (1H, t, J = 8.0 Hz), 7.14 (2H, s), 6.61 (1H, dd, J = 6.0, 2.4 Hz), 6.40 (1H, d, J = 2.4 Hz), 3.01 (1H, q, J = 3.6 Hz), 1.17-1.10 (4H, m). MS calculated: 454.53 Detected: 455.1 (M+H+)

[0632] (138) A-138: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-hydroxynicotinamide

[0633] 1H-NMR (400 MHz, DMSO-d6):δ 11.1 (1H, s), 10.2 (1H, brs), 9.01 (1H, brs), 8.53 (1H, s), 8.19 (1H, d, J = 6.4 Hz), 7.97 (1H, d, J = 9.2 Hz), 7.77 (2H, d, J = 7.2 Hz), 7.70 (1H, d, J = 8.0 Hz), 7.54 (1H, s), 7.38 (2H, t, J = 7.4 Hz), 7.28 (1H, t, J = 8.0 Hz), 6.74 (1H, s), 2.48-2.38 (1H, m), 1.18-1.11 (2H, m), 1.09-1.02 (2H, m). MS calculated: 445.49; MS found: 446.2 (M+H+)

[0634] (139) A-139: 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-hydroxybenzamide

[0635] 1H-NMR (400 MHz, DMSO-d6):δ 11.0 (1H, s), 9.36 (1H, s), 8.82 (1H, s), 8.15 (1H, d, J = 6.0 Hz), 7.77 (2H, d, J = 7.6 Hz), 7.64 (3H, q, J = 8.1 Hz), 7.38 (2H, t, J = 7.6 Hz), 7.29 (1H, t, J = 7.4 Hz), 6.69 (1H, dd, J = 8.4, 2.4 Hz), 6.45 (1H, d, J = 2.4 Hz), 2.44-2.38 (1H, m), 1.18-1.12 (2H, m), 1.08-1.03 (2H, m). * No protons from OH were observed. MS calculated: 444.51 MS found: 445.2 (M+H+)

[0636] (140) A-140: 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(methylsulfonyl)nicotinamide

[0637] 1H-NMR (400 MHz, DMSO-d6):δ 9.97 (1H, s), 8.45 (1H, s), 8.16 (1H, d, J = 5.2 Hz), 8.05 (1H, dd, J = 8.8. 2.0 Hz), 7.78 (2H, d, J = 7.6 Hz), 7.62 (1H, d, J = 8.8 Hz), 7.58 (1H, s), 7.38 (2H, t, J = 7.6 Hz), 7.27 (1H, t, J = 7.4 Hz), 6.84 (1H, d, J = 8.4 Hz), 6.68 (1H, d, J = 3.2 Hz), 2.86 (3H, s), 2.46-2.37 (1H, m), 1.18-1.12 (2H, m), 1.09-1.02 (2H, m). MS calculated: 507.58 MS found: 508.1 (M+H+)

[0638] (141) A-141: 2-(3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0639] 1H-NMR (400 MHz, CDCl3): δ 8.10 (1H, d, J = 6.0 Hz), 7.82-7.80 (2H, m), 7.36-7.33 (3H, m), 7.30-7.26 (2H, m), 7.16 (1H, dd, J = 8.4, 1.2 Hz), 7.11 (1H, dd, J = 8.4, 1.2 Hz), 6.68 (1H, brs), 6.57 (1H, d, J = 2.4 Hz), 6.55 (1H, dd, J = 5.8, 2.2 Hz), 4.12 (3H, s), 1.55 (6H, s). * Protons from NH were not observed. MS calculated: 433.52 MS found: 434.1 (M+H+)

[0640] (142) A-142: 3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0641] 1H-NMR (400 MHz, CDCl3):δ 8.16 (1H, d, J = 6.0 Hz), 8.02-7.98 (1H, m), 7.82 (2H, d, J = 7.6 Hz), 7.55-7.52 (1H, m), 7.49-7.40 (2H, m), 7.37-7.34 (2H, m), 7.29-7.26 (1H, m), 6.64 (2H, dd, J = 5.6, 2.0 Hz), 6.49 (1H, d, J = 2.0 Hz), 4.75 (2H, s), 4.15 (3H, s). MS calculated: 454.52; MS detection: 455.1 (M+H+)

[0642] (143) A-143: 3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0643] 1H-NMR (400 MHz, DMSO-d6):δ 9.25 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 8.02 (1H, t, J = 2.0 Hz), 7.86-7.77 (4H, m), 7.43-7.27 (6H, m), 6.67 (1H, dd, J = 6.0, 2.4 Hz), 6.52 (1H, d, J = 2.4 Hz), 4.13 (3H, s). MS calculated: 418.47; MS found: 419.1 (M+H+)

[0644] (144) A-144: 3-((4-((2-methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0645] 1H-NMR (400 MHz, DMSO-d6):δ 12.8 (1H, brs), 9.39 (1H, s), 8.23 ​​(1H, s), 8.16 (1H, d, J = 6.0 Hz), 7.87 (1H, d, J = 6.8 Hz), 7.78 (2H, MS calculated: 419.45; MS detected: 420.1 (M+H+)

[0646] (145) A-145: 3-(4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0647] 1H-NMR (400 MHz, DMSO-d6):δ 9.46 (1H, s), 8.20 (1H, d, J = 6.0 Hz), 8.17 (1H, s), 7.87 (2H, d, J = 7.2 Hz), 7.81 (1H, d, J = 8.4 Hz), 7.49 (2H, t, J = 7.4 Hz), 7.45-7.41 (2H, m), 7.34 (1H, d, J = 7.6 Hz), 7.30 (2H, s), 6.80 (1H, dd, J = 5.8, 2.2 Hz), 6.52 (1H, d, J = 2.4 Hz). MS calculated: 492.49; MS detected: 493.1 (M+H+)

[0648] (146) A-146: 6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0649] 1H-NMR (400 MHz, DMSO-d6):δ 10.15 (s, 1H), 8.66 (d, J = 2.1 Hz, 1H), 8.23 ​​(d, J = 6.0 Hz, 1H), 8.07 (dd, J = 8.8. 2.4 Hz, 1H), 7.88-7.83 (m, 3H), 7.71 (d, J = 8.8 Hz, 1H), 7.64 (d, J = 2.4 Hz, 1H), 7.46 (t, J = 7.2 Hz, 2H), 7.39 (t, J = 7.6 Hz, 1H), 7.29 (s, 1H), 6.85 (dd, J = 5.2, 1.6 Hz, 1H). MS calculated: 457.43; Detected: 458.15.(M+H+)

[0650] (147) A-147: 4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0651] 1H-NMR (400 MHz, DMSO-d6):δ 9.37 (s, 1H), 8.19 (d, J = 5.6 Hz, 1H), 7.84 (d, J = 7.2 Hz, 2H), 7.77-7.75 (m, 3H), 7.66 (d, J = 9.2 Hz, [M+H]+ calcd for 456.44, detection 457.22 (M+H+)

[0652] (148) A-148: N-methyl-4-(4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0653] 1H-NMR (400 MHz, DMSO-d6):δ 9.36 (s, 1H), 8.20-8.17 (m, 2H), 7.84 (d, J = 7.6 Hz, 2H), 7.71 (d, J = 8.0, 4.0 Hz, 2H), 7.66 (d, J = 9.2 Hz, 2H), 7.47 (t, J = 7.6 Hz, 2H), 7.40 (t, J = 6.8 Hz, 1H), 6.78 (dd, J = 6.0, 2.4 Hz, 1H), 6.51 (d, J = 2.4 Hz, 1H), 2.73 (d, J = 4.8 Hz,3H). [M+H]+ Calculated for 470.47, detected 471.22 (M+H+)

[0654] (149) A-149: 6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0655] 1H-NMR (400 MHz, DMSO-d6):δ 11.50 (br s, 1H), 8.73 (s, 1H), 8.31 (d, J = 6.4 Hz, 1H), 8.19 (d, J = 8.8 Hz, 1H), 7.83 (d, J = 8.0 Hz, 2H), 7.58 (d, J = 8.8 Hz, 1H), 7.50-7.44 (m, 1H), 7.05 (d, J = 4.0 Hz, 1H). [M+H]+ calcdfor458.42, detection 459.20

[0656] (150) A-150: N-methyl-6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0657] 1H-NMR (400 MHz, DMSO-d6):δ 10.15 (s, 1H), 8.61 (s, 1H), 8.34 (br s, 1H), 8.23 ​​(d, J = 6.0 Hz, 1H), 8.03 (dd, J = 8.0, 1.6 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.62 (d, J = 2.0 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.40-7.39 (m, 1H), 6.85 (dd, J = 5.6, 2.8 Hz, 1H), 2.75 (d, J = 4.0 Hz, 3H). MS calculated: 471.46; detected: 472.21 (M+H+)

[0658] (151) A-151: 3-(4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0659] 1H-NMR (400 MHz, DMSO-d6): δ 9.34 (1H, s), 8.19 (2H, d, J = 6.0 Hz), 7.87 (2H, d, J = 6.8 Hz), 7.49-7.42 (4H, m), 7.36-7.30 (2H, m), 6.77 (1H, d, J = 4.8 Hz), 6.50 (1H, s). *No protons from OH were observed. MS calculated: 457.43; found: 458.1 (M+H+).

[0660] (152) A-152: 4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0661] 1H-NMR (400 MHz, DMSO-d6):δ 12.4 (1H, brs), 9.52 (1H, s), 8.24 (1H, d, J = 6.0 Hz), 7.87-7.82 (4H, m), 7.74 (2H, d, J = 8.4 Hz), 7.49 (2H, t, J = 7.4 Hz), 7.42 (1H, t, J = 7.4 Hz), 6.84 (1H, dd, J = 6.0, 2.4 Hz), 6.57 (1H, d, J = 2.0 Hz). MS calculated: 457.43; detected: 458.1 (M+H+)

[0662] (153) A-153: 2-(3-(4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0663] 1H-NMR (400 MHz, CDCl3): δ 8.07 (1H, d, J = 6.0 Hz), 7.83-7.80 (2H, m), 7.52-7.27 (3H, m), 7.25-7.21 (2H, m), 7.15-7.09 (2H, m), 6.72 (1H, brs), 6.58 (1H, d, J = 2.4 Hz), 6.56-6.54 (1H, m), 3.10 (6H, s), 1.55 (6H, s). *No proton from NH observed. MS calculated: 446.56; MS found: 447.2 (M+H+).

[0664] (154) A-154: 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0665] 1H-NMR (400 MHz, DMSO-d6):δ 9.43 (1H, s), 8.20 (1H, t, J = 2.0 Hz), 8.14 (1H, d, J = 6.0 Hz), 7.81-7.77 (3H, m), 7.43-7.35 (3H, m), 7.32-7.25 (4H, m), 6.67 (1H, dd, J = 5.6 Hz,2.0 Hz), 6.52 (1H, d, J = 2.4 Hz), 3.08 (6H, s). MS calculated: 467.56; MS detected: 468.2 (M+H+)

[0666] (155) A-155: 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0667] 1H-NMR (400 MHz, DMSO-d6):δ 9.22 (1H, s), 8.11 (1H, d, J = 6.0 Hz), 8.02 (1H, s), 7.83 (1H, d, J =9.6 Hz), 7, 78 (3H, d, J = 7.2 Hz), 7.38-7.34 (3H, m), 7.30-7.24 (3H, m), 6.64 (1H, dd, J = 2.0 Hz,5.0 Hz), 6.51 (1H, dd, J =2.4 Hz), 3.08 (6H, s). MS calculated: 431.51; MS detected: 432.2 (M+H+)

[0668] (156) A-156: 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0669] 1H-NMR (400 MHz, DMSO-d6):δ 9.52 (1H, s), 8.17 (1H, d, J = 5.6 Hz), 7.80-7.77 (4H, m), 7.66 (2H, d, J = 9.2 Hz), 7.37 (2H, t, J = 7.2 MS Calculated: 467.56; MS Calculated: 467.56; Detection: 468.2 (M+H+)

[0670] (157) A-157: 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0671] 1H-NMR (400 MHz, DMSO-d6):δ 9.38 (1H, s), 8.16 (1H, d, J = 6.0 Hz), 7.79-7.75 (4H, m), 7.68 (2H, d, J = 8.4 Hz), 7.37 (2H, t, J = 8.0 MS calculated: 431.51; MS detected: 432.2 (M+H+)

[0672] (158) A-158: 2-(4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0673] 1H-NMR (400 MHz, DMSO-d6):δ 9.51 (1H, s), 8.17 (2H, d, J = 5.6 Hz), 7.75 (2H, d, J = 7.2 Hz), 7.68 (1H, d, J = 1.2 Hz), 7.63-7.61 (1H, m), 7.36-7.32 (2H, m), 7.26-7.22 (1H, m), 6.72 (1H, dd, J = 2.4 Hz,5.8 Hz), 6.58 (1H, d, J = 2.0 Hz), 5.06 (1H, s), 3.06 (6H, s), 1.36 (6H, s). MS calculated: 447.55; MS detected: 448.2 (M+H+)

[0674] (159) A-159: 2-(5-(4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0675] 1H-NMR (400 MHz, DMSO-d6):δ 9.18 (1H, s), 8.57 (1H, d, J = 2.8 Hz), 8.08-8.05 (2H, m), 7.76 (2H, d, J = 6.8 Hz), 7.48 (1H, d, J = 8.8 Hz), 7.35 (2H, t, J = 7.8 Hz), 7.25 (1H, t, J = 7.4 Hz), 6.63 (1H, dd, J = 5.4, 2.2 Hz), 6.46 (1H, d, J = 2.0 Hz), 5.04 (1H, s), 3.06 (6H, s), 1.38 (6H, s). MS calculated: 447.55; MS detected: 448.2 (M+H+)

[0676] (160) A-160: 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0677] 1H-NMR (400 MHz, DMSO-d6):δ 9.84 (1H, s), 8.16 (1H, d, J = 5.6 Hz), 8.00 (1H, d, J = 8.8 Hz), 7.83-7.76 (3H, m), 7.56 (1H, s), 7.50-7.47 (2H, m), 7.34 (2H, t, J = 7.6 Hz), 7.27-7.25 (2H, m), 6.71 (1H, dd, J = 6.0, 2.4Hz), 3.06 (6H, s). MS calculated: 432.50; MS detected: 433.2 (M+H+)

[0678] (161) A-161: 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0679] 1H-NMR (400 MHz, DMSO-d6):δ 9.83 (1H, s), 8.17 (1H, d, J = 5.6), 8.02-7.95 (2H, m), 7.82-7.49 (3H, m), 7.47 (1H, d, J = 7.2 Hz), 7.35 (2H, t, J = 7.6 Hz), 7.26-7.22 (2H, m), 6.72 (1H, d, J = 5.6 Hz), 3.05 (6H, s), 2.77 (3H, d, J = 4.8 Hz). MS calculated: 446.52; MS detected: 447.2 (M+H+)

[0680] (162) A-162: Methyl 6-(4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate

[0681] 1H-NMR (400 MHz, DMSO-d6):δ 10.1 (1H, s), 8.15 (1H, d, J = 5.2 Hz), 7.92 (1H, d, J = 8.4 Hz), 7.83-7.75 (4H, m), 7.54 (1H, d, J = 7.2 MS calculated: 447.51; MS detected: 448.2 (M+H+)

[0682] (163) A-163: 6-(4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0683] 1H-NMR (400 MHz, DMSO-d6):δ 10.1 (1H, s), 8.66 (1H, d, J = 2.4 Hz), 8.17 (1H, d, J = 6.0 Hz), 8.06 (1H, dd, J = 8.8. 2.0 Hz), 7.89 (1H, s), 7.75 (3H, d, J = 8.8 Hz), 7.58 (1H, d, J = 2.0 Hz), 7.34 (2H, t, J = 7.6 Hz), 7.29 (1H, s), 7.24 (1H, t, J = 7.6 Hz), 6.70 (1H, dd, J = 6.0, 2.4 Hz), 3.06 (6H, s). MS calculated: 432.50; MS found: 433.2 (M+H+)

[0684] (164) A-164: 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0685] 1H-NMR (400 MHz, DMSO-d6):δ 9.35 (1H, s), 8.17-8.13 (2H, m), 7.76 (2H, d, J = 7.2 Hz), 7.68 (4H, q, J = 7.9 Hz), 7.35 (2H, t, J = 7.8 MS Calculated: 445.54; MS detection: 446.2 (M+H+)

[0686] (165) A-165: 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0687] 1H-NMR (400 MHz, DMSO-d6): δ 8.71 (1H, s), 8.23 ​​(1H, d, J = 6.0 Hz), 8.13 (1H, d, J = 8.0 Hz), 7.75 (2H, d, J = 7.6 Hz), 7.66 (1H, s), 7.48 (1H, s), 7.35 (2H, t, J = 7.6 Hz), 7.25 (1H, t, J = 7.4 Hz), 6.85 (1H, s), 3.06 (6H, s). *Two protons from NH and OH were not observed. MS calculated: 433.48; MS found: 434.1 (M+H+).

[0688] (166) A-166: 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0689] 1H-NMR (400 MHz, DMSO-d6):δ 10.1 (1H, s), 8.62 (1H, d, J = 2.4 Hz), 8.35 (1H, d, J = 4.8 Hz), 8.17 (1H, d, J = 5.6 Hz), 8.02 (1H, d, J = 8.4 Hz), 7.76 (3H, d, J = 8.4 Hz), 7.56 (1H, s), 7.34 (2H, t, J = 7.8 Hz), 7.24 (1H, t, J = 7.2 Hz), 6.70 (1H, dd, J = 6.0, 2.4 Hz), 3.06 (6H, s), 2.75 (3H, d, J = 4.0 Hz). MS calculated: 446.52; MS found: 447.2 (M+H+)

[0690] (167) A-167: 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0691] 1H-NMR (400 MHz, DMSO-d6): δ 9.38 (1H, s), 8.23 ​​(1H, s), 8.13 (1H, d, J = 5.6 Hz), 7.86 (1H, d, J = 8.0 Hz), 7.78 (2H, d, J = 8.4 Hz), 7.47 (1H, d, J = 7.2 Hz), 7.39-7.33 (3H, m), 7.29-7.27 (1H, m), 6.68 (1H, dd, J = 2.4 Hz, 5.6 Hz), 6.52 (1H, d, J = 2.0 Hz), 3.08 (6H, s). * Protons from OH were not observed. MS calculated: 432.49; MS found: 433.2 (M+H+)

[0692] (168) A-168: 4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0693] 1H-NMR (400 MHz, DMSO-d6): δ 9.49 (1H, s), 8.16 (1H, d, J = 6.0 Hz), 7.79 (4H, t, J = 7.6 Hz), 7.69 (2H, d, J = 8.4 Hz), 7.37 (2H, t, J = 7.6 Hz), 7.27 (1H, t, J = 7.2 Hz), 6.71 (1H, d, J = 3.2 Hz), 6.56 (1H, d, J = 2.0 Hz), 3.08 (6H, s). *No proton from NH was observed. MS calculated: 432.49; MS found: 433.2 (M+H+).

[0694] (169) A-169: 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0695] 1H-NMR (400 MHz, DMSO-d6): δ 10.1 (1H, s), 8.14 (1H, d, J = 5.6 Hz), 7.89 (1H, d, J = 8.8 Hz), 7.82-7.74 (4H, m), 7.53 (1H, d, J = 6.8 Hz), 7.34 (2H, t, J = 7.6 Hz), 7.23 (1H, t, J = 8.0 Hz), 6.64 (1H, m), 3.05 (6H, s). *No protons from OH were observed. MS calculated: 433.48; MS found: 434.1 (M+H+).

[0696] (170) A-170: 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid methyl ester

[0697] 1H-NMR (400 MHz, DMSO-d6): δ 9.38 (1H, s), 8.26 (1H, s), 8.18 (1H, d, J = 5.6 Hz), 7.92 (1H, d, J = 8.0 Hz), 7.79 (2H, d, J = 8.4 Hz), 7.49-7.35 (5H, m), 6.74 (1H, dd, J = 5.8. 2.2 Hz), 6.49 (1H, d, J = 2.4 Hz), 3.84 (3H, s). MS calculated: 482.35; MS detected: 484.0 (M+H+)

[0698] (171) A-171: 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0699] 1H-NMR (400 MHz, CDCl3): δ 9.85 (1H, s), 8.05-8.01 (2H, m), 7.85 (1H, d, J = 7.6 Hz), 7.78 (2H, d, J = 8.0 Hz), 7.52-7.29 (5H, m), 6.69 (1H, d, J = 2.0 Hz), 6.58 (1H, dd, J = 6.6, 2.2 Hz). * No protons from OH were observed. MS calculated: 468.32; MS found: 469.0 (M+H+).

[0700] (172) A-172: 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0701] 1H-NMR (400 MHz, MeOD-d4): δ 8.15 (1H, d, J = 6.0 Hz), 7.89 (1H, d, J = 8.0 Hz), 7.74 (2H, d, J = 7.2 Hz), 7.61 (1H, d, J = 2.0 Hz), 7.50 (1H, t, J = 8.0 Hz), 7.44 (1H, s), 7.30 (2H, t, J = 7.2 Hz), 7.28-7.24 (1H, m), 7.12 (1H, d, J = 8.0 Hz), 6.98 (1H, dd, J = 5.8-2.2 Hz). *The three protons from NH and NH2 were not observed. MS calculated: 467.34; MS found: 468.0 (M+H+)

[0702] (173) A-173: 6-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0703] 1H-NMR (400 MHz, DMSO-d6):δ 10.1 (1H, s), 8.64 (1H, d, J = 2.0 Hz), 8.19 (1H, d, J = 5.6 Hz), 8.60 (1H, dd, J = 9.0, 2.2 Hz), 7.88 (1H, s), 7.81 (2H, d, J = 7.2 Hz), 7.69 (1H, d, J = 8.8 Hz), 7.61 (1H, d, J = 2.0 Hz), 7.39 (2H, t, J = 7.4 Hz), 7.29 (2H, t, J = 7.4 Hz), 6.72 (1H, dd, J = 5.6, 2.4 Hz), 3.45 (1H, quint, J = 7.8 Hz), 2.20-2.09 (2H, m), 1.87-1.74 (4H, m), 1.71-1.65 (2H, m). MS calculated: 457.55; MS detected: 458.2 (M+H+)

[0704] (174) A-174: 6-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0705] 1H-NMR (400 MHz, DMSO-d6):δ 10.70 (1H, brs), 8.69 (1H, s), 8.25 (1H, d, J = 5.6 Hz), 8.13 (1H, d, J = 8.0 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.61 (1H, d, J = 7.6 Hz), 7.51 (1H, brs), 7.40 (2H, t, J = 7.6 Hz), 7.31 (1H, t, J = 7.2 Hz), 6.87 (1H, s), 3.37-3.44 (1H, t, J = 8.0 Hz), 2.15-2.13 (2H, m), 1.86-1.85 (2H, m), 1.86-1.83 (2H, m), 1.82-1.75 (2H, m), 1.68-1.67 (2H, m). *No protons from OH were observed. MS calculated: 458.53 Found: 459.2 (M+H+)

[0706] (175) A-175: 4-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0707] 1H-NMR (400 MHz, DMSO-d6):δ 9.52 (1H, s), 8.18 (1H, d, J = 6.0 Hz), 7.81-7.79 (4H, m), 7.22 (2H, d, J = 8.8 Hz), 7.41 (2H, t, J = 8.0 Hz), 7.31 (1H, t, J = 7.2 Hz), 6.73 (1H, dd, J = 5.6, 2.0 Hz), 6.50 (1H, d, J = 2.0 Hz), 3.46 (1H, t, J = 7.6 Hz), 2.14-2.12 (2H, m), 1.85-1.76 (4H, m), 1.68-1.66 (2H, m). * No protons from OH were observed. MS calculated: 457.54 Found: 458.2 (M+H+)

[0708] (176) A-176: 6-((4-((2-cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0709] 1H-NMR (400 MHz, DMSO-d6):δ 10.12 ( 1H, s), 8.59 (1H, s), 8.34 (1H, d, J = 4.0 Hz), 8.19 (1H, d, J = 5.6 Hz), 8.03 (1H, d, J = 10.8 Hz), 7.81 (2H, d, J = 7.6 Hz), 7.71 (1H, d, J = 9.6 Hz), 7.59 (1H, s), 7.40 (2H, t, J = 8.0 Hz), 7.30 (1H, t, J = 7.2 Hz), 6.73 (1H, dd, J = 5.6, 2.4 Hz), 3.44 (1H, t, J = MS calculated: 471.17; MS detected: 472.2 (M+H+)

[0710] (177) A-177: 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0711] 1H-NMR (400 MHz, CDCl3): δ 8.67 (1H, d, J = 2.0 Hz), 8.15 (1H, d, J = 6.0 Hz), 8.08 (1H, dd, J = 8.8. 2.4 Hz), 7.83 (2H, d, J = 7.6 Hz), 7.60 (1H, s), 7.56 (1H, d, J = 8.8 Hz), 7.36 (2H, t, J = 7.2 Hz), 7.28 (1H, t, J = 7.2 Hz), 6.68 (1H, dd, J = 5.2,2.0 Hz), 3.03-2.97 (1H, m), 2.21-2.20 (2H, m), 1.91-1.88 (2H, m), 1.78-1.75 (1H, m), 1.61-1.32 (5H, m). *Three protons from NH and NH2 were not observed. MS calculated: 471.57; MS found: 472.2 (M+H+).

[0712] (178) A-178: 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0713] 1H-NMR (400 MHz, DMSO-d6):δ 11.12 (1H, brs), 8.73 (1H, s), 8.30 (1H, d, J = 6.0 Hz), 8.20 (1H, d, J = 8.4 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.50 (1H, d, J = 8.4 Hz), 7.41-7.37 (3H, m), 7.32 (1H, t, J = 7.6 Hz), 6.97 (1H, s), 3.03 (1H, m), 2.12 (2H, m), 1.81-1.78 (2H, m), 1.69-1.66 (1H, m), 1.55-1.45 (2H, m), 1.42-1.36 (2H, m), 1.27-1.21 (1H, m).* No protons from OH were observed. MS calculated: 472.56 Found: 473.2 (M+H+)

[0714] (179) A-179: 4-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0715] 1H-NMR (400 MHz, DMSO-d6):δ 9.51 (1H, s), 8.18 (1H, d, , J = 5.6 Hz), 7.81-7.78 (4H, m), 7.72 (2H, d, J = 8.8 Hz), 7.41 (2H, t, J = 8.0 Hz), 7.31 (1H, t, J = 7.2 Hz), 6.71 (1H, d, J = 4.4 Hz), 6.48 (1H, s), 2.97-2.91 (1H, m), 2.11-2.09 (2H, m), 1.77-1.75 (2H, m), 1.66-1.65 (1H, m), 2.53-1.38 (4H, m), 1.26-1.23 (1H, m). * No protons from OH were observed. MS calculated: 471.57 Found: 472.2 (M+H+)

[0716] (180) A-180: 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0717] 1H-NMR (400 MHz, DMSO-d6):δ 10.13 (1H, s), 8.60 (1H, s), 8.33 (1H, s), 8.19 (1H, d, J = 5.6 Hz), 8.03 (1H, d, J = 8.8 Hz), 7.81 (2H, d, J = 8.0 Hz), 7.69 (1H, d, J = 9.6 Hz), 7.60 (1H, s), 7.40 (2H, t, J = 7.6 Hz), 7.30 (1H, t, J = 7.2 Hz), 6.72 (1H, d, J = 5.6 Hz), 2.98-2.91 (1H, m), 2.75 (3H, d, J = MS Calculated: 485.60; MS detection: 486.3 (M+H+)

[0718] (181) A-181: 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0719] 1H-NMR (400 MHz, DMSO-d6):δ 9.44 (1H, s), 8.18-8.16 (2H, m), 7.84-7.79 (3H, m), 7.42 (3H, t, J = 7.4 Hz), 7.33 (2H, d, J = 7.2 Hz), 7.19 (2H, s), 6.70 (1H, dd, J = 6.0, 2.4 Hz), 6.47 (1H, d, J = 2.8 Hz), 3.03 (2H, q, J = 7.6 Hz), 1.36 (3H, t, J = 7.6 Hz). MS calculated: 452.55; MS detection: 453.1 (M+H+)

[0720] (182) A-182: 2-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0721] 1H-NMR (400 MHz, DMSO-d6):δ 9.06 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.83 (2H, d, J = 8.0 Hz), 7.61 (1H, d, J = 9.2 Hz), 7.50 (1H, s), 7.42 (2H, t, J = 7.6 Hz), 7.32 (1H, t, J = 7.2 Hz), 7.15 (1H, t, J = 7.8 Hz), 6.98 (1H, d, J = 7.6 Hz), 6.60 (1H, dd, J = 5.4, 1.8 Hz), 6.44 (1H, d, J = 2.0 Hz), 4.92 (1H, s), 3.02 (2H, q, J = 7.5 Hz), 1.38 (6H, s), 1.35 (3H, t, J = 7.6 Hz). MS calculated: 431.55; MS detected: 432.2 (M+H+)

[0722] (183) A-183: 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0723] 1H-NMR (400 MHz, DMSO-d6):δ 9.24 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 8.02 (1H, s), 7.85-7.80 (4H, m), 7.42 (2H, t, J = 7.6 Hz), 7.36 (1H, t, J = 7.8 Hz), 7.32-7.27 (3H, m), 6.65 (1H, dd, J = 6.0, 1.6 Hz), 6.45 (1H, d, J = 2.0 Hz), 3.02 (2H, q, J = 7.5 Hz), 1.36 (3H, t, J = 7.4 Hz). MS detection: 417.2 (M+H+)

[0724] (184) A-184: 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0725] 1H-NMR (400 MHz, DMSO-d6):δ 9.53 (1H, s), 8.19 (1H, d, J = 6.0 Hz), 7.83 (2H, d, J = 7.2 Hz), 7.78 (2H, d, J = 8.8 Hz), 7.67 (2H, d, J = 8.8 Hz), 7.42 (2H, t, J = 7.6 Hz), 7.32 (1H, t, J = 8.0 Hz), 7.14 (2H, s), 6.75 (1H, dd, J = 5.8. 1.8 Hz), 6.50 (1H, d, J = 2.4 Hz), 3.03 (2H, q, J = 7.5 Hz), 1.36 (3H, t, J = 7.4 Hz). MS calculated: 452.55; MS detected: 453.1 (M+H+)

[0726] (185) A-185: 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0727] 1H-NMR (400 MHz, DMSO-d6):δ 9.39 (1H, s), 8.18 (1H, d, J = 5.6 Hz), 7.83 (2H, d, J = 7.2 Hz), 7.77 (3H, d, J = 8.8 Hz), 7.68 (2H, d, J = 8.8 Hz), 7.42 (2H, t, J = 7.6 Hz), 7.32 (1H, t, J = 7.8 Hz), 7.12 (1H, brs), 6.71 (1H, dd, J = 6.0, 2.4 Hz), 6.48 (1H, d, J = 2.0 Hz), 3.03 (2H, q, J = 7.6 Hz), 1.36 (3H, t, J = 7.4 Hz). MS calculated: 416.50; MS detected: 417.2 (M+H+)

[0728] (186) A-186: 2-(4-(((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0729] 1H-NMR (400 MHz, DMSO-d6):δ 9.55 (1H, s), 8.21 (2H, t, J = 5.4 Hz), 7.83 (2H, d, J = 8.0 Hz), 7.69 (1H, d, J = 1.6 Hz), 7.66 (1H, dd, J = 5.6, 2.0 Hz), 7.42 (2H, t, J = 7.6 Hz), 7.32 (1H, t, J = 7.4 Hz), 6.76 (1H, dd, J = 7.0, 3.4 Hz), 6.55 (1H, d, J = 2.4 Hz), 5.10 (1H, s), 3.03 (2H, q, J = 7.6 Hz), 1.39 (6H, s), 1.36 (3H, t, J = 7.2 Hz). MS calculated: 432.54; MS found: 433.2 (M+H+)

[0730] (187) A-187: 2-(5-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0731] 1H-NMR (400 MHz, DMSO-d6):δ 9.21 (1H, s), 8.59 (1H, d, J = 2.4 Hz), 8.12 (1H, d, J = 6.0 Hz), 8.08 (1H, dd, J = 8.8. 2.4 Hz), 7.84 (2H, d, J = 8.0 Hz), 7.51 (1H, d, J = 9.2 Hz), 7.42 (2H, t, J = 7.6 Hz), 7.32 (1H, t, J = 7.6 Hz), 6.66 (1H, dd, J = 6.0, 2.4 Hz), 6.42 (1H, d, J = 2.4 Hz), 5.07 (1H, s), 3.03 (2H, q, J = 7.5 Hz), 1.40 (6H, s), 1.36 (3H, t, J = 7.6 Hz). MS calculated: 432.54; MS detected: 433.2 (M+H+)

[0732] (188) A-188: N-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)ethanesulfonamide

[0733] 1H-NMR (400 MHz, DMSO-d6):δ 9.66 (1H, brs), 9.14 (1H, s), 8.08 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.2 Hz), 7.37-7.45 (4H, m), 7.29 (1H, t, J = 7.4 Hz), 7.13 (1H, t, J = 8.2 Hz), 6.70 (1H, d, J = 7.6 Hz), 6.62 (1H, dd, J = 6.0 and 2.4 Hz), 6.42 (1H, s), 2.97-3.07 (4H, m), 1.33 (3H, t, J = 7.8 Hz), 1.16 (3H, t, J = 7.4 Hz). MS calculated: 480.13; MS detected: 481.1 (M+H+)

[0734] (189) A-189: 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0735] 1H-NMR (400 MHz, DMSO-d6):δ 9.35 (1H, s), 8.16 (2H, d, J = 5.6 Hz), 7.82 (2H, d, J = 7.6 Hz), 7.71 (4H, q, J = 8.8 Hz), 7.41 (2H, t, J = 8.0 Hz), 7.31 (1H, t, J = 7.6 Hz), 6.69 (1H, dd, J = 5.6, 2.4 Hz), 6.46 (1H, d, J = 2.4 Hz), 3.03 (2H, q, J = 7.6 Hz), 2.73 (3H, d, J = 5.6 Hz), 1.35 (3H, t, J = 7.6 Hz). MS calculated: 430.52 Found: 431.2 (M+H+)

[0736] (190) A-190: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0737] 1H-NMR (400 MHz, DMSO-d6):δ 10.1 (1H, s), 8.65 (1H, d, J = 2.4 Hz), 8.19 (1H, d, J = 6.0 Hz), 8.06 (1H, d, J = 10.8 Hz), 7.88 (1H, s), 7.81 (2H, d, J = 7.6 Hz), 7.69 (1H, d, J = 8.4 Hz), 7.63 (1H, s), 7.39 (2H, t, J = 7.6 Hz), 7.29 (2H, t, J = 8.0 Hz), 6.72 (1H, d, J = 5.2 Hz), 3.00 (2H, q, J = 7.0 Hz), 1.34 (3H, t, J = 7.4 Hz). MS Calculated: 432.50 Found: 433.2 (M+H+)

[0738] (191) A-191: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid salt

[0739] 1H-NMR (400 MHz, DMSO-d6):δ 10.33 (1H, s), 8.69 (1H, s), 8.21 (1H, d, J = 6.0 Hz), 8.09-8.12 (1H, m), 7.76-7.81 (3H, m), 7.58 (1H, s), 7.62 (1H, s), 7.42 (1H, t, J = 5.0 Hz), 7.29 (1H, t, J = 7.2 Hz), 6.75-6.77 (1H, m), 3.81 (3H, s), 2.98-3.03 (2H, m), 1.34 (3H, t, J = 7.4 Hz). MS calculated: 432.13; MS detected: 433.1 (M+H+)

[0740] (192) A-192: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0741] 1H-NMR (400 MHz, DMSO-d6): δ 8.75 (1H, s), 8.30 (1H, d, J = 6.8 Hz), 8.21 (1H, d, J = 8.8 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.49-7.51 (1H, m), 7.39 (2H, t, J = 7.8 Hz), 7.29-7.34 (2H, m), 7.00 (1H, brs), 3.00-3.05 (2H, m), 1.35 (3H, t, J = 7.6 Hz m). *Two protons from NH and OH were not observed. MS calculated: 418.11; MS found: 419.1 (M+H+).

[0742] (193) A-193: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0743] 1H-NMR (400 MHz, DMSO-d6):δ 10.11 (1H, s), 8.60 (1H, s), 8.34 (1H, brs), 8.19 (1H, d, J = 6.0 Hz), 8.01-8.04 (1H, m), 7.81 (2H, d, J = 7.2 Hz), 7.70 (1H, d, J = 9.2 Hz), 7.60 (1H, s), 7.37-7.39 (2H, m), 7.29-7.30 (1H, m), 6.71-6.72 (1H, m), 2.98-3.04 (2H, m), 2.75 (3H, d, J = 4.4 Hz), 1.34 (3H, t, J = 7.4 Hz). MS calculated: 431.14; MS found: 432.1 (M+H+)

[0744] (194) A-194: 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0745] 1H-NMR (400 MHz, DMSO-d6): δ 9.36 (1H, s), 8.23 ​​(1H, s), 8.15 (1H, d, J = 6.0 Hz), 7.88-7.83 (3H, m), 7.48-7.40 (3H, m), 7.38-7.30 (2H, m), 6.69 (1H, dd, J = 5.8, 2.2 Hz), 6.45 (1H, d, J = 2.0 Hz), 3.03 (2H, q, J = 7.5 Hz), 1.36 (3H, t, J = 7.4 Hz). *No protons from OH were observed. MS calculated: 417.48; MS found: 418.2 (M+H+).

[0746] (195) A-195: 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0747] 1H-NMR (400 MHz, DMSO-d6): δ 9.54 (1H, s), 8.20 (1H, d, J = 6.0 Hz), 7.84-7.81 (4H, m), 7.74 (2H, d, J = 8.4 Hz), 7.42 (2H, t, J = 7.6 Hz), 7.32 (1H, t, J = 7.8 Hz), 6.75 (1H, dd, J = 6.0, 2.4 Hz), 6.52 (1H, d, J = 2.4 Hz), 3.03 (2H, q, J = 7.5 Hz), 1.36 (3H, t, J = 7.6 Hz). * Protons from OH were not observed. MS calculated: 417.48; MS found: 418.1 (M+H+)

[0748] (196) A-196: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-isopropylnicotinamide

[0749] 1H-NMR (400 MHz, DMSO-d6):δ 8.61 (1H, s), 8.15 (1H, d, J = 6.0 Hz), 8.03 (1H, d, J = 8.8 Hz), 7.83 (2H, d, J = 7.6 Hz), 7.62 (1H, s), 7.56 (1H, d, J = 8.8 Hz), 7.36 (2H, t, J = 7.6 Hz), 7.29 (1H, d, J = 6.8 Hz), 6.69 (1H, d, J = 5.2 Hz), 4.23-4.14 (1H, m), 3.05 (2H, q, J = 7.7 Hz), 1.43 (3H, t, J = 7.6 Hz), 1.24 (6H, d, J = 6.8 Hz). Two protons from NH and OH were not observed. MS calculated: 459.56; MS found: 460.3 (M+H+).

[0750] (197) A-197: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(4-methylpiperazin-1-yl)methanone

[0751] 1H-NMR (400 MHz, DMSO-d6): δ 10.1 (1H, s), 8.20-8.17 (2H, m), 7.81 (2H, d, J = 6.8 Hz), 7.68-7.64 (3H, m), 7.39-7.34 (2H, m), 7.30-7.23 (1H, m), 6.69 (1H, s), 3.48 (4H, s), 3.00 (2H, q, J = 8.0 Hz), 2.29 (4H, s), 2.06 (3H, s), 1.33 (3H, t, J = 7.0 Hz). MS calculated: 500.62; MS detection: 501.3 (M+H+)

[0752] (198) A-198: 3-aminopyrrolidin-1-yl)(6-(4-(2-ethyl-4-phenylthiazol-5-yloxy)pyridin-2-ylamino)pyridin-3-yl)methanone

[0753] 1H-NMR (400 MHz, DMSO-d6):δ 10.1 (1H, s), 8.34 (1H, s), 8.18 (1H, d, J = 6.0 Hz), 7.81 (3H, d, J = 7.6 Hz), 7.69 (1H, d, J = 8.4 Hz), 7.63 (1H, s), 7.39 (2H, t, J = 7.6 Hz), 7.29 (1H, t, J = 7.4 Hz), 6.70 (1H, d, J = 5.2 Hz), 3.70-3.52 (3H, m), 3.38-3.24 (2H, m), 3.00 (2H, q, J = 7.5 Hz), 1.98 (1H, brs), 1.88 (1H, brs), 1.33 (3H, t, J = 7.4 Hz). *Two protons from NH2 were not observed. MS calculated: 486.59; MS found: 487.2 (M+H+)

[0754] (199) A-199: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(pyrrolidin-1-yl)ethyl)nicotinamide

[0755] 1H-NMR (400 MHz, MeOH-d4):δ 8.64 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 8.04 (1H, dd, J = 8.8. 2.0 Hz), 7.82 (2H, d, J = 7.6 Hz), 7.61 (1H, s), 7.57 (1H, d, J = 9.2 Hz), 7.35 (2H, t, J = 7.8 Hz), 7.27 (1H, t, J = 9.0 Hz), 6.67 (1H, dd, J = 5.6, 2.0 Hz), 3.54 (2H, t, J = 6.8 Hz), 3.04 (2H, q, J = 7.5 Hz), 2.74 (2H, t, J = 6.6 Hz), 2.65 (4H, s), 1.84 (4H, s), 1.42 (3H, t, J = 7.8 Hz). *Two protons from NH were not observed. MS calculated: 514.64; MS found: 515.3 (M+H+).

[0756] (200) A-200: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(3-(methylamino)pyrrolidin-1-yl)methanone

[0757] 1H-NMR (400 MHz, MeOH-d4):δ 8.39 (1H, d, J = 3.2 Hz), 8.13 (1H, d, J = 6.0 Hz), 7.82 (3H, d, J = 8.0 Hz), 7.61 (1H, s), 7.57 (1H, d, J = 8.8 Hz), 7.35 (2H, t, J = 7.8 Hz), 7.27 (1H, t, J = 7.4 Hz), 6.66 (1H, dd, J = 6.0, 2.0 Hz), 3.78-3.71 (2H, m), 3.70-3.57 (2H, m), 3.50-3.45 (1H, m), 3.40-3.33 (1H, m), 3.03 (2H, q, J = 7.5 Hz), 2.42 (1.5H, s), 2.32 (1.5H, s), 1.91-1.80 (1H, m), 1.42 (3H, t, J = 7.6 Hz). * No proton from NH was observed. MS calculated: 500.62; MS found: 501.2 (M+H+).

[0758] (201) A-201: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-methylpiperazin-1-yl)ethyl)nicotinamide

[0759] 1H-NMR (400 MHz, DMSO-d6):δ 10.1 (1H, s), 8.60 (1H, d, J = 2.0 Hz), 8.34 (1H, t, J = 5.4 Hz), 8.19 (1H, d, J = 6.0 Hz), 8.02 (1H, dd, J = 8.6, 2.2 Hz), 7.81 (2H, d, J = 7.6 Hz), 7.70 (1H, d, J = 8.8 Hz), 7.61 (1H, d, J = 2.4 Hz), 7.41-7.37 (2H, m), 7.30-7.27 (1H, m), 6.72 (1H, dd, J = 5.6, 2.4 Hz), 3.34 (2H, s), 3.00 (2H, q, J = 7.5 Hz), 2.48-2.41 (3H, m), 2.39-2.11 (7H, m), 1.97 (3H, s), 1.33 (3H, t, J = 7.8 Hz). MS calculated: 543.68; MS detection: 544.3 (M+H+)

[0760] (202) A-202: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-isopropylpiperazin-1-yl)ethyl)nicotinamide

[0761] 1H-NMR (400 MHz, DMSO-d6): δ 10.15 (1H, s), 8.61 (1H, s), 8.34 (1H, s), 8.19 (1H, d, J = 5.6 Hz), 8.03 (1H, d, J = 8.8 Hz), 7.81 (2H, d, J = 7.6 Hz), 7.70 (1H, d, J = 8.8 Hz), 7.61 (1H, s), 7.38 (2H, t, J = 7.4 Hz), 7.28 (1H, t, J = 7.2 Hz), 6.71 (1H, d, J = 5.2 Hz), 3.32 (2H, s), 3.00 (2H, q, J = MS calculated: 571.74; MS detected: 572.3 (M+H+)

[0762] (203) A-203: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-ethylpiperazin-1-yl)ethyl)nicotinamide

[0763] 1H-NMR (400 MHz, DMSO-d6):δ 10.16 (1H, s), 8.60 (1H, d, J =1.6 Hz), 8.34 (1H, t, J =5.4 Hz), 8.19 (1H, d, J =5.6 Hz), 8.02 (1H, dd, J =8.4, 2.0 Hz), 7.81 (2H, d, J =7.6 Hz), 7.70 (1H, d, J =8.8 Hz), 7.61 (1H, d, J =2.0 Hz), 7.39 (2H, t, J =7.6 Hz), 7.29 (1H, d, J =6.8 Hz), 6.72 (1H, dd, J =5.4, 2.2 Hz), MS Calculated: 557.71; MS detected: 558.3 ​​(M+H+)

[0764] (204) A-204: 5-(3-aminopyrrolidin-1-yl)-N-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)pyridin-2-amine

[0765] 1H-NMR (400 MHz, CDCl3):δ 8.03(1H,d,J = 5.6 Hz), 7.87 (2H, d, J = 7.6 Hz), 7.59 (1H, s), 7.35 (2H, t, J = 7.6 Hz), 7.28-7.25 (3H, m), 6.88 (1H, d, J = 8.4 Hz), 6.47 (1H, d, J = 6.4 Hz), 3.80-3.73 (1H, m), 3.52-3.42 (2H, m), 3.29 (1H, q, J = 7.6 Hz), 3.01 (2H, q, J = 7.6 Hz), 2.29-2.20 (2H, m), 1.85-1.80 (1H, m), 1.42 (3H, t, J = 7.6 Hz). * Three protons from NH and NH2 were not observed. MS calculated: 458.58; MS found: 459.3 (M+H+).

[0766] (205) A-205: N1-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N4-(2-(4-isopropylpiperazin-1-yl)ethyl)benzene-1,4-diamine

[0767] 1H-NMR (400 MHz, MeOH-d4):δ 7.88 (1H, d, J =6.0 Hz), 7.78 (2H, d, J =8.0 Hz), 7.35 (2H, t, J =7.6 Hz), 7.28 (1H, d, J =7.2 Hz), 7.01 (2H, d, J =8.4 Hz), 6.60 (2H, d, J =8.8 Hz), 6.39-6.37 (1H, m), 6.17 (1H, s), 3.19 (2H, t, J =6.4 Hz), 2.97 (2H, dd, J =15.0, 7.8 Hz), 2.70-2.58 (11H, m), 1.37 (3H, t, J =7.4 Hz), 1.08 (6H, d, J =6.8 Hz). *Two protons from NH were not observed. MS calculated: 542.74; MS found: 543.4 (M+H+)

[0768] (206) A-206: N1-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N4-(2-(4-methylpiperazin-1-yl)ethyl)benzene-1,4-diamine

[0769] 1H-NMR (400 MHz, DMSO-d6):δ 8.58 (1H, s), 7.97 (1H, d, J =6.0 Hz), 7.8 (2H, d, J =7.2 Hz), 7.39-7.37 (2H, m), 7.31-7.29 (1H, m), 7.16 (2H, d, J =8.0 Hz), 6.49-6.43 (3H, m), 6.22 (1H, s), 5.04 (1H, s), 3.04-2.97 (4H, m), 2.46-2.30 (10H, m), 2.12 (3H, s), 1.32 (3H, t, J =7.2 Hz), MS calculated: 514.68; MS detected: 515.3 (M+H+)

[0770] (207) A-206: N1-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N4-(2-(4-methylpiperazin-1-yl)ethyl)benzene-1,4-diamine

[0771] 1H-NMR (400 MHz, MeOH-d4):δ7.87(1H,d,J =6.0 Hz), 7.77 (2H, d, J =7.6 Hz), 7.34 (2H, t, J =7.6 Hz), 7.28 (1H, d, J =7.6 Hz), 7.01 (2H, d, J =8.8 Hz), 6.59 (2H, d, J =8.4 Hz), 6.37 (1H, dd, J =5.6, 2.4 Hz), 6.17 (1H, d, J =2.0 Hz), 3.18 (2H, t, J =6.4 Hz), 2.96 (2H, q, J =7.6 Hz), 2.60-2.57 (6H, m), 2.46-2.40 (6H, m), 1.36 (3H, t, J =7.6 Hz), 1.09 (3H, t, J =7.0 Hz). *Two protons from NH were not observed. MS calculated: 528.71; MS found: 529.3 (M+H+).

[0772] (208) A-208: N1-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N4-(2-(pyrrolidin-1-yl)ethyl)benzene-1,4-diamine

[0773] 1H-NMR (400 MHz, DMSO-d6):δ 8.58 (1H, s), 7.97 (1H, d, J =6.0 Hz), 7.80 (2H, d, J =7.6 Hz), 7.39 (2H, t, J =7.6 Hz), 7.29 (1H, t, J =7.4 Hz), 7.16 (2H, d, J =8.4 Hz), 6.48 (2H, d, J =8.8 Hz), 6.43 (1H, dd, J =6.0, 2.0 Hz), 6.22 (1H, d, J =2.0 Hz), 5.12 (1H, t, J =5.4 Hz), 3.05 (2H, m), 2.97 (2H, q, J =7.5 MS calculated: 485.64; MS detected: 486.3 (M+H+)

[0774] (209) A-209: N2-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N5-(2-(4-methylpiperazin-1-yl)ethyl)pyridine-2,5-diamine

[0775] 1H-NMR (400 MHz, DMSO-d6):δ 9.30 (1H, s), 8.04 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 8.0 Hz), 7.56 (1H, s), 7.37-7.41 (4H, m), 7.28 (1H, t, J = 7.2 Hz), 6.99 (1H, d, J = 6.0 Hz), 6.50 (1H, d, J = 5.6 Hz), 5.15 (1H, t, J = 5.4 Hz), 3.02-3.06 (2H, m), 2.99 (2H, q, J = 6.4 Hz), 2.43-4.48 (2H, m), 2.00-2.42 (8H, m), 1.33 (3H, t, J = 7.6 Hz). MS calculated: 516.3; MS detected: 515.25 (M+H+)

[0776] (210) A-210: N2-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N5-(2-(pyrrolidin-1-yl)ethyl)pyridine-2,5-diamine

[0777] 1H-NMR (400 MHz, DMSO-d6):δ9.29(1H, s),8.04(1H,d,J = 6.0 Hz), 7.81 (2H, d, J = 7.2 Hz), 7.56 (1H, d, J = 2.4 Hz), 7.37-7.39 (4H, m), 7.28-7.30 (1H, m), 6.98 (1H, dd, J = 8.6 and 2.6 Hz), 6.50 (1H, dd, J = 5.6 and 2.4 Hz), 5.20-5.25 (1H, m), 3.06 (2H, q, J = 6.1 Hz), 2.99 (2H, q, J = 7.5 Hz), 2.56 (2H, t, MS calculated: 487.3; MS detected: 486.2 (M+H+)

[0778] (211) A-211: N2-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N5-(2-(4-ethylpiperazin-1-yl)ethyl)pyridine-2,5-diamine

[0779] 1H-NMR (400 MHz, DMSO-d6):δ 9.29 (1H, s), 8.04 (1H, d, J = 6.0 Hz), 7.81 (2H, d, J = 7.6 Hz), 7.56 (1H, d, J = 3.2 Hz), 7.37-7.41 (4H, m), 7.27-7.30 (1H, m), 6.98-7.00 (1H, m), 6.49-6.51 (1H, m), 5.10-5.20 (1H, m), 3.02-3.06 (2H, m), 2.99 (2H, q, J = 7.3 Hz), 2.38-2.48 (10H, m), 2.27 (2H, q, J = MS calculated: 529.2; MS detected: 530.3 (M+H+)

[0780] (212) A-212: N2-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N5-(2-(4-isopropylpiperazin-1-yl)ethyl)pyridine-2,5-diamine

[0781] 1H-NMR (400 MHz, DMSO-d6):δ 9.29 (1H, s), 8.04 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.56 (1H, d, J = 2.4 Hz), 7.37-7.41 (4H, m), 7.27-7.30 (1H, m), 6.99 (1H, d, J = 8.8 Hz), 6.50 (1H, d, J = 5.2 Hz), 5.10-5.15 (1H, m), 3.02-3.06 (2H, m), 2.99 (2H, q, J = 7.3 Hz), 2.30-2.49 (10H, m), 1.33 (3H, t, J = 7.6 Hz), 0.93 (6H, d, J = 6.8 Hz). MS calculated: 543.7; MS detected: 544.3 (M+H+)

[0782] (213) A-213: N,N-(5-(1H-pyrazol-4-yl)pyridin-2-yl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0783] 1H-NMR (400 MHz, DMSO-d6):δ 12.9 (1H, s), 9.80 (1H, s), 8.44 (1H, s), 8.14 (2H, d, J = 6.0 Hz), 7.88-7.81 (4H, m), 7.67 (1H, d, J = 8.8 Hz), 7.58 (1H, s), 7.39 (2H, t, J = 7.8 Hz), 7.29 (1H, t, J = 7.4 Hz), 6.63 (1H, dd, J = 5.6, 1.6 Hz), 3.00 (2H, q, J = 7.6 Hz), 1.34 (3H, t, J = 7.6 Hz). MS calculated: 440.52; MS detected: 441.2 (M+H+)

[0784] (214) A-214: N-(4-(3-aminopyrrolidin-1-yl)phenyl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine

[0785] 1H-NMR (400 MHz, CDCl3):δ 7.96 (1H, d, J = 6.0 Hz), 7.81 (2H, d, J = 7.2 Hz), 7.34 (2H, t, J = 7.6 Hz), 7.28-7.24 (1H, m), 7.02 (2H, d, J = 8.4 Hz), 6.75 (1H, brs), 6.47 (2H, d, J = 8.4 Hz), 6.34 (1H, d, J = 6.0 Hz), 6.26 (1H, s), 3.79 (1H, brs), 3.47-3.45 (2H, m), 3.20-3.28 (, 2H, m), 2.96 (2H, q, J = 7.6 Hz), 2.25-2.22 (1H, m), 2.04-1.90 (1H, m), 1.38 (3H, t, J = 8.0 Hz). *Two protons from NH2 were not observed. MS calculated: 457.19; MS found: 458.3 (M+H+).

[0786] (215) A-215: 4-((2-ethyl-4-phenylthiazol-5-yl)oxy)-N-(4-(3-(methylamino)pyrrolidin-1-yl)phenyl)pyridin-2-amine

[0787] 1H-NMR (400 MHz, DMSO-d6):δ 8.73 (1H, s), 7.99 (1H, d, J =6.0 Hz), 7.81 (2H, d, J =7.6 Hz), 7.41-7.27 (6H, m), 6.50 (2H, d, J =8.8 Hz), 6.46 (1H, dd, J =5.6, 2.0 Hz), 6.26 (1H, d, J =2.0 Hz), 3.74-3.71 (1H, m), 3.42-3.33 (2H, m), 3.28-3.25 (1H, m), 3.19-3.15 (1H, m), 3.00 (2H, q, J =7.6 Hz), 2.55 (3H, s), 2.29-2.24 (1H, m), 2.05-2.00 (1H, m), 1.32 (3H, t, J =7.4 Hz). MS calculated: 471.62; MS found: 472.3 (M+H+)

[0788] (216) A-216: Methyl 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate

[0789] 1H-NMR (400 MHz, DMSO-d6):δ 10.15 (1H, s), 8.18 (1H, d, J = 6.0 Hz), 7.93 (1H, d, J = 8.8 Hz), 7.83-7.79 (3H, m), 7.75 (1H, d, J = 2.0 Hz), 7.54 (1H, d, J = 6.8 Hz), 7.41 (2H, t, J = 7.6 Hz), 7.30 (1H, t, J = 7.6 Hz), 6.71 (1H, dd, J = 5.6, 2.0 Hz), 3.78 (3H, s), 3.28-3.24 (1H, m), 1.36 (6H, d, J = 6.4 Hz). MS calculated: 446.52 Found: 447.2 (M+H+)

[0790] (217) A-217: 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0791] 1H-NMR (400 MHz, DMSO-d6): δ 10.31 (1H, brs), 8.17 (1H, d, J = 6.0 Hz), 7.83-7.76 (4H, m), 7.52 (1H, d, J = 7.6 Hz), 7.41 (2H, t, J = 7.6 Hz), 7.30 (2H, t, J = 7.2 Hz), 6.62 (1H, s), 3.28-3.23 (1H, m), 1.37 (6H, d, J = 7.2 Hz). *No protons from OH were observed. MS calculated: 432.49 found: 433.2 (M+H+).

[0792] (218) A-218: 3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0793] 1H-NMR (400 MHz, DMSO-d6):δ 9.44 (1H, s), 8.16 (2H, d, J = 6.0 Hz), 7.85-7.80 (3H, m), 7.44-7.39 (3H, m), 7.33-7.29 (4H, m), 6.69 (1H, MS calculated: 466.58; MS detected: 467.1 (M+H+)

[0794] (219) A-219: 2-(3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol

[0795] 1H-NMR (400 MHz, DMSO-d6):δ 9.05 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.83 (2H, d, J = 7.6 Hz), 7.61 (1H, d, J = 8.0 Hz), 7.49 (1H, s), 7.41 (2H, t, J = 7.6 Hz), 7.31 (1H, t, J = 7.2 Hz), 7.15 (1H, t, J = 7.6 Hz), 6.97 (1H, d, J = 8.0 Hz), 6.59 (1H, dd, J = 2.0 Hz,5.8 Hz), 6.43 (1H, d, J = 2.4 Hz), 4.91 (1H, s), 3.32-3.25 (1H, m), 1.39-1.38 (12H, m). MS calculated: 445.58; MS found: 446.2 (M+H+).

[0796] (220) A-220: 3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0797] 1H-NMR (400 MHz, DMSO-d6):δ 9.23 (1H, s), 8.13 (1H, d, J = 6.0 Hz), 7.96 (1H, s), 7.84-7.80 (4H, m), 7.42 (2H, t, J = 7.2 Hz), 7.35 (1H, t, J =8.0 Hz), 7.29 (3H, t, J = 8.0 Hz), 6.64 (1H, dd, J = 2.4 Hz,5.6 Hz), 6.44 (1H, d, J = 2.0 Hz), 3.30-3.25 (1H, m), 1.39 (6H, d, J = 6.8 Hz). MS calculated: 430.52; MS detected: 431.2 (M+H+)

[0798] (221) A-221: 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0799] 1H-NMR (400 MHz, DMSO-d6):δ 9.50 (1H, s), 8.17 (1H, d, J = 6.0 Hz), 7.81 (2H, d, J = 8.0 Hz), 7.75 (2H, d, J = 8.4 Hz), 7.65 (2H, d, J = 9.2 Hz), 7.40 (2H, t, J = 7.6 Hz), 7.30 (1H, t, J = 7.2 Hz), 7.11 (2H, s), 6.71 (1H, dd, J = 2.0 Hz,5.8 Hz), 6.47 (1H, d, J = 4.0 Hz), 3.29-3.25 (1H, m), 1.37 (6H, d, J = 7.2 Hz). MS calculated: 466.58; MS found: 467.2 (M+H+)

[0800] (222) A-222: 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0801] 1H-NMR (400 MHz, DMSO-d6):δ 9.39 (1H, s), 8.18 (1H, d, J = 6.0 Hz), 7.83 (2H, d, J = 7.2 Hz), 7.76 (3H, d, J = 9.2 Hz), 7.67 (2H, d, J = 9.2 Hz), 7.42 (2H, t, J = 7.2 Hz), 7.32 (1H, t, J = 7.6 Hz), 7.11 (1H, s), 6.70 (1H, dd, J = 2.4 Hz,6.0 Hz), 6.48 (1H, d, J = 2.0 Hz), 3.32-3.26 (1H, m), 1.39 (6H, d, J = 7.2 Hz). MS calculated: 430.52; MS found: 431.2 (M+H+)

[0802] (223) A-223: 2-(4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0803] 1H-NMR (400 MHz, DMSO-d6):δ 9.55 (1H, s), 8.21 (2H, t, J =5.6 Hz), 7.83 (2H, d, J = 7.2 Hz), 7.68-7.65 (2H, m), 7.42 (2H, t, J = 7.2 Hz), 7.32 (1H, t, J = 7.2 Hz), 6.75 (1H, dd, J = 6.0 Hz), 6.54 (1H, d, J = 2.4 Hz), 5.09 (1H, s), 3.32-3.28 (1H, m), 1.39 (12H, d, J = 9.2 Hz). MS calculated: 446.56; MS detected: 447.2 (M+H+)

[0804] (224) A-224: 2-(5-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

[0805] 1H-NMR (400 MHz, DMSO-d6):δ 9.19 (1H, s), 8.56 (1H, d, J = 2.4 Hz), 8.09 (1H, d, J = 6.0 Hz), 8.04 (1H, dd, J = 2.4 Hz,9.0 Hz), 7.81 (2H, d, J = 6.8 Hz), 7.48 (1H, d, J = 8.8 Hz), 7.40 (2H, t, J = 8.0 Hz), 7.30 (1H, t, J = 7.2 Hz), 6.64 (1H, dd, J = 2.4 Hz,5.6 Hz), 6.39 (1H, d, J = 2.4 Hz), 5.04 (1H, s), 3.29-3.27 (1H, m), 1.37 (12H, d, J = 6.8 Hz). MS calculated: 446.56; MS found: 447.3 (M+H+).

[0806] (225) A-225: 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0807] 1H-NMR (400 MHz, DMSO-d6):δ 9.87 (1H, s), 8.19 (1H, d, J = 6.0 Hz), 8.02 (1H, s), 7.93 (1H, d, J = 8.4 Hz), 7.83-7.78 (3H, m), 7.47 (1H, d, J = 6.8 Hz), 7.41 (2H, t, J = 7.6 Hz), 7.31-7.28 (2H, m), 6.74 (1H, d, J = 3.6 Hz), 3.25-3.23 (1H, m), 2.76 (3H, d, J = 4.4 Hz), 1.35 (6H, d, J = 6.8 Hz). MS calculated: 445.54 Detected: 446.2 (M+H+)

[0808] (226) A-226: 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0809] 1H-NMR (400 MHz, DMSO-d6):δ 9.87 (1H, s), 8.19 (1H, d, J = 6.0 Hz), 7.96 (1H, d, J = 8.4 Hz), 7.83-7.79 (3H, m), 7.59 (1H, s), 7.50-7.44 (2H, m), 7.40 (2H, t, J = 7.6 Hz), 7.30-7.24 (2H, m), 6.72 (1H, dd, J = 5.6, 2.4 Hz), 3.27-3.26 (1H, m), 1.37 (6H, d, J = 6.4 Hz). MS Calculated: 431.51 Detected: 432.2 (M+H+)

[0810] (227) A-227: 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0811] 1H-NMR (400 MHz, DMSO-d6):δ 10.14 (1H, s), 8.64 (1H, s), 8.20 (1H, d, J = 4.2 Hz), 8.06 (1H, d, J = 8.4 Hz), 7.88 (1H, s), 7.82 (2H, d, J = 6.8 Hz), 7.69 (1H, d, J = 8.8 Hz), 7.61 (1H, s), 7.41 (2H, t, J = 7.2 Hz), 7.30 (2H, t, J = 7.6 Hz), 6.72 (1H, d, J = 4.2 Hz), 3.28-3.26 (1H, m), 1.38 (6H, d, J = 6.8 Hz). MS calculated: 431.51 Found: 432.2 (M+H+)

[0812] (228) A-228: 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0813] 1H-NMR (400 MHz, DMSO-d6):δ 10.12 (1H, s), 8.59 (1H, s), 8.34 (1H, brs), 8.20 (1H, d, J = 6.4 Hz), 8.01 (1H, m), 7.82 (2H, d, J = 8.0 Hz), 7.70 (1H, d, J = 9.2 Hz), 7.60 (1H, s), 7.39-7.37 (2H, m), 7.30 (1H, d, J = 7.2 Hz), 6.72-6.70 (1H, m), 2.75 (3H, d, J = 4.4 Hz), 1.38 (6H, d, J = 7.2 Hz). MS calculated: 445.54; MS detected: 446.2 (M+H+)

[0814] (229) A-229: 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0815] 1H-NMR (400 MHz, DMSO-d6):δ 9.35 (1H, s), 8.17 (2H, t, J = 4.2 Hz), 7.82 (2H, d, J = 7.6 Hz), 7.22 (4H, q, J = 8.8 Hz), 7.81 (2H, t, J = 7.2 Hz), 7.31 (1H, t, J = 8.0 Hz), 6.68 (1H, dd, J = 5.6, 2.4 Hz), 6.46 (1H, d, J = 2.0 Hz), 3.27-3.25 (1H, m), 2.73 (3H, d, J = 4.4 Hz), 1.38 (6H, d, J = 7.2 Hz).MS Calculated: 444.16 Found: 445.2 (M+H+)

[0816] (230) A-230: 3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0817] 1H-NMR (400 MHz, DMSO-d6): δ12.85 (1H, s), 9.31 (1H, s), 8.22 (1H, s), 8.15 (1H, d, J = 6.0 Hz), 7.88-7.83 (3H, m), 7.46-7.40 (2H, m), 7.36-7.30 (3H, m), 6.66 (1H, dd, J = 2.0 Hz,5.8 Hz), 6.44 (1H, d, J = 2.0 Hz), 3.32-3.25 (1H, m), 1.39 (6H, d, J = 7.2 Hz). MS calculated: 431.51; MS detection: 432.2 (M+H+)

[0818] (231) A-231: 4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0819] 1H-NMR (400 MHz, DMSO-d6):δ 12.43 (1H, s), 9.52 (1H, s), 8.20 (1H, d, J = 6.0 Hz), 7.84-7.81 (4H, m), 7.73 (2H, d, J = 8.4 Hz), 7.42 (2H, t, J = 7.2 Hz), 7.34-7.30 (1H, m), 6.73 (1H, dd, J = 2.0 Hz,5.6 Hz), 6.51 (1H, d, J = 2.0 Hz), 3.32-3.26 (1H, m), 1.39 (6H, d, J = 7.2 Hz). MS calculated: 431.51; MS detected: 432.2 (M+H+)

[0820] (232) A-232: 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0821] 1H-NMR (400 MHz, DMSO-d6): δ12.79 (1H, brs), 10.29 (1H, s), 8.65 (1H, s), 8.21 (1H, d, J = 6.0 Hz), 8.08 (1H, d, J = 8.8 Hz), 7.81 (2H, d, J = 7.2 Hz), 7.71 (1H, d, J = 8.8 Hz), 7.66 (1H, s), 7.40 (2H, t, J = 7.6 Hz), 7.30 (1H, t, J = 7.6 Hz), 6.76 (1H, d, J = 6.0 Hz), 3.26-3.25 (1H, m), 1.38 (6H, d, J = 7.2 Hz). MS calculated: 432.49 Found: 433.2 (M+H+)

[0822] (233) A-233: 3-((4-((2-(methylamino)-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0823] 1H-NMR (400 MHz, DMSO-d6): δ 9.43 (1H, s), 8.30 (1H, s), 8.18 (1H, s), 8.14 (1H, d, J = 5.6 Hz), 7.91-7.83 (4H, m), 7.80 (1H, d, J = 8.0 Hz), 7.74 (1H, d, J = 5.2 Hz), 7.49-7.47 (2H, m), 7.39 (1H, t, J = 7.6 Hz), 7.30 (1H, d, J = 6.4 Hz), 7.26 (2H, s), 6.75 (1H, dd, J = 2.4 Hz,5.6 Hz), 6.57 (1H, d, J = 2.0 Hz), 2.94 (3H, d, J = 4.4 Hz). MS calculated: 503.6; MS detected: 504.2 (M+H+)

[0824] (234) A-234: 3-((4-((2-amino-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0825] 1H-NMR (400 MHz, DMSO-d6): δ 9.47 (1H, s), 8.26 (1H, s), 8.17-8.13 (2H, m), 7.85-7.79 (4H, m), 7.49-7.47 (2H, m), 7.42 (1H, t, J = 8.0 Hz), 7.38-7.24 (4H, m), 6.75 (1H, dd, J = 2.0 Hz, 5.8 Hz), 6.58 (1H, s). *Two protons from NH2 were not observed. MS calculated: 489.57; MS found: 490.1 (M+H+).

[0826] (235) A-235: 3-((4-((2-(dimethylamino)-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0827] 1H-NMR (400 MHz, DMSO-d6):δ 9.43 (1H, s), 8.33 (1H, s), 8.18 (1H, s), 8.15 (1H, d, J = 6.0 Hz), 7.93-7.84 (4H, m), 7.78 (1H, d, J = 8.0 Hz), 7.50-7.48 (2H, m), 7.39 (1H, t, J = 8.0 Hz), 7.31-7.27 (3H, m), 6.75 (1H, dd, J = 2.4 Hz,6.0 Hz) 6.56 (1H, d, J = 2.0 Hz), 3.12 (6H, s). MS calculated: 517.62; MS detected: 518.2 (M+H+)

[0828] (236) A-236: 3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide

[0829] 1H-NMR (400 MHz, MeOD-d4): δ 7.98-7.97 (2H, m), 7.61 (1H, d, J = 7.6 Hz), 7.54 (1H, d, J = 8.0 Hz), 7.49-7.42 (3H, m), 7.37-7.30 (3H, m), 7.22-7.18 (1H, m), 7.13 (1H, d, J = 8.0 Hz), 6.83 (1H, d, J = 8.0 Hz), 5.77 (1H, s). *Two protons from NH2 were not observed. MS calculated: 440.50; MS found: 441.1 (M+H+).

[0830] (237) A-237: 3-((6-((2-methyl-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide

[0831] 1H-NMR (400 MHz, DMSO-d6):δ 9.75 (1H, s), 8.26 (1H, s), 7.83 (1H, s), 7.59-7.57 (1H, m), 7.57-7.48 (4H, m), 7.47-7.32 (5H, m), 5.67 (1H, s), 2.72 (3H, s). MS calculated: 439.51; MS detected: 440.1 (M+H+)

[0832] (238) A-238: 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzenesulfonamide

[0833] 1H-NMR (400 MHz, DMSO-d6): δ 10.0 (1H, s), 8.47 (1H, d, J = 6.0 Hz), 8.11 (1H, s), 7.82 (3H, d, J = 8.4 Hz), 7.39 (4H, t, J = 7.4 Hz), 7.29 (3H, s), 6.75 (1H, d, J = 4.8 Hz), 2.67 (3H, s). MS calculated: 439.51; MS detected: 440.1 (M+H+)

[0834] (239) A-239: 3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide

[0835] 1H-NMR (400 MHz, DMSO-d6): δ 10.1 (1H, s), 8.43 (1H, d, J = 5.2 Hz), 8.09 (1H, s), 7.97 (1H, s), 7.68 (1H, d, J = 8.0 Hz), 7.38 (1H, d, J = 4.8 Hz), 7.33 (2H, d, J = 7.2 Hz), 7.25-7.20 (1H, m), 6.99 (2H, s), 6.65 (1H, d, J = 5.2 Hz), 6.55 (1H, s). * Three protons from NH and NH2 were not observed. MS calculated: 440.50; MS found: 441.1 (M+H+).

[0836] (240) A-240: 3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide

[0837] 1H-NMR (400 MHz, DMSO-d6):δ 10.06 (1H, s), 8.48 (1H, d, J = 5.6 Hz), 8.08 (1H, brs), 7.83 (3H, d, J = 8.0 Hz), 7.42-7.35 (4H, m), 7.31-7.28 (3H, m), 6.75 (1H, d, J = 5.6 Hz), 3.00 (2H, q, J = 7.3 Hz), 1.33 (3H, t, J = 7.6 Hz). MS calculated: 453.09; MS detected: 454.1 (M+H+)

[0838] (241) A-241: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)picolinamide

[0839] 1H-NMR (400 MHz, DMSO-d6):δ 9.95 (1H, s), 8.54 (1H, d, J = 6.0 Hz), 8.02 (1H, d, J = 8.4 Hz), 7.83-7.77 (4H, m), 7.65 (1H, s), 7.58 (1H, d, J = 7.2 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.31-7.29 (1H, m), 6.86 (1H, d, J = 5.6 Hz), 3.01 (2H, q, J = 7.6 Hz), 1.34 (3H, t, J = 7.8 Hz). MS calculated: 418.12; MS detected: 419.2 (M+H+)

[0840] (242) A-242: 2-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)isonicotinamide

[0841] 1H-NMR (400 MHz, DMSO-d6):δ 10.23 (1H, s), 8.53 (1H, d, J = 5.6 Hz), 8.36 (1H, d, J = 5.2 Hz), 8.31 (1H, s), 8.08 (1H, s), 7.85 (2H, d, J = 7.2 Hz), 7.65 (1H, s), 7.41 (2H, t, J = 7.6 Hz), 7.35-7.30 (2H, m), 6.81 (1H, d, J = 5.2 Hz), 2.96 (2H, q, J = 7.6 Hz), 1.30 (3H, t, J = 7.6 Hz). MS calculated: 418.12; MS Detected: 419.2 (M+H+)

[0842] (243) A-243: 3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzamide

[0843] 1H-NMR (400 MHz, DMSO-d6):δ 9.86 (1H, s), 8.45 (1H, d, J = 5.6 Hz), 7.99 (1H, s), 7.83 (3H, d, J = 7.6 Hz), 7.71 (1H, d, J = 9.6 Hz), 7.42-7.38 (3H, m), 7.29-7.22 (3H, m), 6.70 (1H, d, J = 5.6 Hz), 2.98 (2H, q, J = 7.5 Hz), 1.32 (3H, t, J = 7.4 Hz). MS calculated: 417.13; MS detected: 418.2 (M+H+)

[0844] (244) A-244: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)nicotinic acid

[0845] 1H-NMR (400 MHz, DMSO-d6):δ 10.9 (1H, brs), 8.77 (1H, s), 8.58 (1H, d, J = 6.0 Hz), 8.09 (1H, d, J = 8.8 Hz), 7.90 (1H, d, J = 8.8 Hz), 7.82 (2H, d, J = 7.2 Hz), 7.39 (3H, t, J = 7.6 Hz), 7.30-7.27 (1H, m), 6.94 (1H, d, J = 5.6 Hz), 3.01 (2H, q, J = 7.5 Hz), 1.34 (3H, t, J = 7.4 Hz). MS calculated: 419.11; MS detected: 420.1 (M+H+)

[0846] (245) A-245: 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)nicotinamide

[0847] 1H-NMR (400 MHz, DMSO-d6):δ 10.44 (1H, s), 8.73 (1H, s), 8.54 (1H, d, J = 5.6 Hz), 8.02-8.01 (2H, m), 7.90-7.87 (1H, m), 7.83 (2H, d, MS calculated: 418.12; MS detection: 419.2 (M+H+)

[0848] (246) A-246: 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzoic acid

[0849] 1H-NMR (400 MHz, DMSO-d6):δ 12.57 (1H, s), 10.16 (1H, s), 8.50 (1H, d, J = 5.2 Hz), 7.81 (2H, d, J = 7.6 Hz), 7.75 (2H, d, J = 8.8 Hz), 7.64 (2H, d, J = 8.0 Hz), 7.39 (2H, t, J = 7.4 Hz), 7.30-7.27 (1H, m), 6.79 (1H, d, J = 5.6 Hz), 3.01 (2H, q, J = 7.3 Hz), 1.35 (3H, t, J = 7.4 Hz). MS Calculated: 418.11; MS Detected: 419.2 (M+H+)

[0850] (247) A-247: 3-((4-((2-amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0851] 1H-NMR (400 MHz, DMSO-d6): δ 9.35 (1H, s), 8.22 (1H, s), 8.09 (1H, d, J = 5.6 Hz), 7.80 (1H, d, J = 8.4 Hz), 7.65 (1H, t, J = 7.6 Hz), 7.54 (1H, d, J = 8.0 Hz), 7.39 (1H, t, J = 7.8 Hz), 7.30 (1H, d, J = 7.6 Hz), 7.27 (2H, s), 7.16 (2H, s), 7.03 (1H, d, J = 7.6 Hz), 6.60 (1H, dd, J = 5.6, 2.4 Hz), 6.47 (1H, d, J = 2.0 Hz), 2.20 (3H, s). MS calculated: 454.53; MS detected: 455.1 (M+H+)

[0852] (248) A-248: 4-((4-((2-amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0853] 1H-NMR (400 MHz, DMSO-d6): δ 9.50 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 7.81 (2H, d, J = 9.2 Hz), 7.72 (3H, d, J = 8.8 Hz), 7.59 (1H, d, J = 7.6 Hz), 7.31 (2H, s), 7.13 (1H, d, J = 7.2 Hz), 6.68 (1H, d, J = 6.4 Hz), 6.55 (1H, d, J = 2.0 Hz), 2.28 (3H, s). *The two protons from OH and TFA were not observed. MS calculated: 419.46; MS found: 420.1 (M+H+)

[0854] (249) A-249: 3-((4-((2-amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0855] 1H-NMR (400 MHz, DMSO-d6): δ 9.38 (1H, s), 8.21 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.85 (1H, d, J = 8.4 Hz), 7.76 (1H, t, J = 7.6 Hz), 7.59 (1H, d, J = 8.4 Hz), 7.48 (1H, d, J = 6.8 Hz), 7.36 (1H, t, J = 8.0 Hz), 7.34 (2H, s), 7.14 (1H, d, J = 7.6 Hz), 6.65 (1H, d, J = 3.2 Hz), 6.50 (1H, d, J = 2.0 Hz), 2.30 (3H, s). * Two protons from OH and TFA were not observed. MS calculated: 419.46; MS found: 420.1 (M+H+)

[0856] (250) A-250: 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0857] 1H-NMR (400 MHz, DMSO-d6): δ 9.33 (1H, s), 8.18 (1H, s), 8.09 (1H, d, J = 6.0 Hz), 7.77 (1H, d, J = 8.0 Hz), 7.71-7.69 (2H, m), 7.39 (1H, t, J = 8.0 Hz), 7.28 (1H, d, J = 7.6 Hz), 7.27 (2H, s), 7.09 (1H, d, J = 6.8 Hz), 6.60 (1H, dd, J = 5.6, 4.0 Hz), 6.36 (1H, d, J = 2.0 Hz), 3.04 (2H, q, J = 8.0 Hz), 2.20 (3H, s), 1.36 (3H, t, J = 7.2 Hz). MS Calculated: 467.56 Found: 468.1 (M+H+)

[0858] (251) A-251: 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0859] 1H-NMR (400 MHz, DMSO-d6): δ 10.0 (1H, s), 8.63 (1H, d, J = 2.4 Hz), 8.13 (1H, d, J = 6.0 Hz), 8.05 (1H, dd, J = 9.0, 2.2 Hz), 7.87 (1H, s), 7.72-7.66 (3H, m), 7.51 (1H, d, J = 2.4 Hz), 7.26 (1H, s), 7.07 (1H, d, J = 6.4 Hz), 6.61 (1H, dd, J = 6.0, 2.4 Hz), 3.02 (2H, q, J = 7.5 Hz), 2.19 (3H, s), 1.35 (3H, t, J = 7.4 Hz). MS calculated: 432.50; MS detected: 433.2 (M+H+)

[0860] (252) A-252: 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0861] 1H-NMR (400 MHz, DMSO-d6): δ 12.5 (1H, s), 8.84 (1H, d, J = 2.4 Hz), 8.39 (1H, d, J = 7.6 Hz), 8.30 (1H, dd, J = 8.6, 2.2 Hz), 7.89-7.78 (2H, m), 7.32 (1H, d, J = 8.4 Hz), 7.18-7.15 (3H, m), 3.05 (2H, q, J = 7.6 Hz), 2.19 (3H, s), 1.36 (3H, t, J = 7.6 Hz). * Protons from OH not observed. MS calculated: 433.48; MS found: 434.2 (M+H+)

[0862] (253) A-253: 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0863] 1H-NMR (400 MHz, DMSO-d6): δ 10.0 (1H, s), 8.59 (1H, s), 8.32 (1H, s), 8.13 (1H, d, J = 5.2 Hz), 8.02 (1H, d, J = 9.6 Hz), 7.70-7.65 (3H, m), 7.48 (1H, s), 7.07 (1H, d, J = 7.2 Hz), 6.63 (1H, s), 3.02 (2H, q, J = 7.6 Hz), 2.75 (3H, d, J = 4.4 Hz), 2.19 (3H, s), 1.35 (3H, t, J = 7.6 Hz). MS calculated: 446.52; MS detected: 447.2 (M+H+)

[0864] (254) A-254: 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0865] 1H-NMR (400 MHz, DMSO-d6): δ 9.97 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.86 (1H, d, J = 8.0 Hz), 7.78 (1H, t, J = 7.8 Hz), 7.71-7.65 (3H, m), 7.50 (1H, d, J = 6.8 Hz), 7.06 (1H, d, J = 5.6 Hz), 6.56 (1H, dd, J = 5.6, 2.4 Hz), 3.01 (2H, q, J = 7.6 Hz), 2.19 (3H, s), 1.34 (3H, t, J = 7.6 Hz). * Protons from OH not observed. MS calculated: 433.48; MS found: 434.1 (M+H+)

[0866] (255) A-255: 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0867] 1H-NMR (400 MHz, DMSO-d6): δ 9.77 (1H, s), 8.13 (1H, d, J = 6.0 Hz), 7.93 (1H, d, J = 8.4 Hz), 7.80 (1H, t, J = 7.6 Hz), 7.70-7.57 (2H, m), 7.60 (1H, s), 7.47 (1H, d, J = 7.2 Hz), 7.38 (1H, s), 7.15 (1H, d, J = 2.4 Hz), 7.07 (1H, d, J = 7.2 Hz), 6.64 (1H, d, J = 5.6 Hz), 3.02 (2H, q, J = 7.6 Hz), 2.18 (3H, s), 1.35 (3H, t, J = 7.6 Hz). MS Calculated: 432.50 Found: 433.2 (M+H+)

[0868] (256) A-256: 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0869] 1H-NMR (400 MHz, DMSO-d6):δ 9.75 (1H, s), 8.13 (1H, d, J = 5.6 Hz), 8.00 (1H, s), 7.94 (1H, d, J = 6.8 Hz), 7.79 (1H, t, J = 8.0 Hz), 7.70-7.67 (2H, m), 7.45 (1H, d, J = 7.2 Hz), 7.12 (1H, s), 7.08 (1H, d, J = 8.8 Hz), 6.66 (1H, s), 3.00 (2H, q, J = 7.5 Hz), 2.78 (3H, d, J = 5.2 Hz), 2.19 (3H, s), 1.33 (3H, t, J = 7.4 Hz). 446.52; MS detection: 447.2 (M+H+)

[0870] (257) A-257: 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0871] 1H-NMR (400 MHz, DMSO-d6): δ 9.18 (1H, s), 8.21 (1H, s), 8.08 (1H, d, J = 6.0 Hz), 7.83 (1H, d, J = 8.0 Hz), 7.72-7.68 (2H, m), 7.41 (1H, d, J = 7.2 Hz), 7.30 (1H, t, J = 7.8 Hz), 7.08 (1H, d, J = 7.6 Hz), 6.56 (1H, d, J = 6.0 Hz), 6.34 (1H, d, J = 1.6 Hz), 3.01 (2H, q, J = 7.6 Hz), 2.22 (3H, s), 1.34 (3H, t, J = 7.4 Hz). * No protons from OH observed. MS calculated: 432.49; MS found: 433.2 (M+H+)

[0872] (258) A-258: 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0873] 1H-NMR (400 MHz, DMSO-d6): δ 9.10 (1H, s), 8.07 (1H, d, J = 5.6 Hz), 7.99 (1H, s), 7.80-7.78 (2H, m), 7.70-7.69 (2H, m), 7.32 (1H, d, J = 8.4 Hz), 7.26-7.23 (2H, m), 7.09 (1H, dd, J = 6.0, 2.4 Hz), 6.55 (1H, dd, J = 5.6, 3.2 Hz), 6.35 (1H, d, J = 2.0 Hz), 3.03 (2H, q, J = 8.0 Hz), 2.22 (3H, s), 1.36 (3H, t, J = 7.2 Hz). MS calculated: 431.52 found: 432.2 (M+H+)

[0874] (259) A-259: 3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0875] 1H-NMR (400 MHz, DMSO-d6): δ 9.12 (1H, s), 8.27 (1H, d, J = 4.4 Hz), 8.07 (1H, d, J = 5.6 Hz), 7.97 (1H, s), 7.77 (1H, s), 7.70-7.69 (2H, m), 7.26 (2H, d, J = 5.6 Hz), 7.08 (1H, dd, J = 8.8. 2.4 Hz), 6.55 (1H, dd, J = 5.2, 3.2 Hz), 6.35 (1H, d, J = 2.4 Hz), 3.03 (2H, q, J = 7.6 Hz), 2.73 (3H, d, J = 4.4 Hz), 2.22 (3H, s), 1.36 (3H, t, J = 7.2 Hz). MS Calculated: 445.16 Found: 446.2 (M+H+)

[0876] (260) A-260: 5-(4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0877] 1H-NMR (400 MHz, DMSO-d6): δ 9.42 (1H, s), 8.84 (1H, d, J = 2.8 Hz), 8.73 (1H, s), 8.54 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 7.72-7.67 (2H, m), 7.09 (1H, d, J = 6.8 Hz), 6.64 (1H, dd, J = 6.0, 1.8 Hz), 6.37 (1H, d, J = 1.6 Hz), 3.09 (2H, q, J = 7.7 Hz), 2.20 (3H, s), 1.35 (3H, t, J = 7.6 Hz). * No proton from OH observed. MS calculated: 433.48; MS found: 434.2 (M+H+)

[0878] (261) A-261: 5-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0879] 1H-NMR (400 MHz, DMSO-d6): δ 9.32 (1H, s), 8.79 (1H, d, J = 2.4 Hz), 8.53 (1H, s), 8.49 (1H, s), 8.12 (1H, d, J = 4.2 Hz), 8.03 (1H, s), 7.73-7.67 (2H, m), 7.48 (1H, s), 7.09 (1H, d, J = 8.0 Hz), 6.63 (1H, dd, J = 6.0, 3.6 Hz), 6.63 (1H, dd, J = 6.0, 4.6 Hz), 6.37 (1H, d, J = 2.0 Hz), 3.04 (2H, q, J = 7.6 Hz), 2.30 (3H, s), 1.36 (3H, t, J = 7.2 Hz). MS Calculated: 432.50 Found: 433.2 (M+H+)

[0880] (262) A-262: 5-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0881] 1H-NMR (400 MHz, DMSO-d6):δ 9.34 (1H, s), 8.79 (1H, d, J = 2.8 Hz), 8.52-8.49 (2H, m), 8.44 (1H, s), 8.12 (1H, d, J = 5.6 Hz), 7.65-7.58 (2H, m), 7.09 (1H, d, J = 7.2 Hz), 6.63 (1H, dd, J = 5.6, 1.8 Hz), 6.37 (1H, d, J = 1.6 Hz), 3.02 (2H, q, J = 7.5 Hz), 2.76 (3H, d, J = 4.4 Hz), 2.21 (3H, s), 1.35 (3H, t, J = 7.4 Hz). MS calculated: 446.52; MS detected: 447.2 (M+H+)

[0882] (263) A-263: 4-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0883] 1H-NMR (400 MHz, DMSO-d6): δ 10.2 (1H, s), 8.29-8.25 (3H, m), 7.93 (1H, s), 7.75-7.68 (2H, m), 7.08 (1H, d, J = 7.2 Hz), 6.81 (1H, d, J = 5.2 Hz), 6.523 (1H, s), 3.02 (2H, q, J = 7.5 Hz), 2.16 (3H, s), 1.35 (3H, t, J = 7.4 Hz). * No protons from OH observed. MS calculated: 433.48; MS found: 434.2 (M+H+).

[0884] (264) A-264: 4-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0885] 1H-NMR (400 MHz, DMSO-d6):δ 9.69 (1H, s), 8.29 (1H, d, J = 5.6 Hz), 8.22-8.19 (2H, m), 7.97 (1H, s), 7.80 (1H, d, J = 4.0 Hz), 7.74-7.67 (2H, m), 7.51 (1H, s), 7.07 (1H, d, J = 7.2 Hz), 6.71 (1H, d, J = 4.0 Hz), 6.44 (1H, s), 3.01 (2H, q, J = 7.6 Hz), 2.18 (3H, s), 1.34 (3H, t, J = 7.4 Hz). MS calculated: 432.50; MS detected: 433.2 (M+H+)

[0886] (265) A-265: 4-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0887] 1H-NMR (400 MHz, DMSO-d6): δ 9.72 (1H, s), 8.64 (1H, s), 8.30 (1H, d, J = 5.6 Hz), 8.20 (1H, d, J = 5.6 Hz), 8.16 (1H, s), 7.86 (1H, d, J = 4.0 Hz), 7.74-7.68 (2H, m), 7.08 (1H, d, J = 7.2 Hz), 6.71 (1H, d, J = 5.6 Hz), 6.45 (1H, d, J = 1.2 Hz), 3.02 (2H, q, J = 7.5 Hz), 2.77 (3H, d, J = 4.8 Hz), 2.18 (3H, s), 1.35 (3H, t, J = 7.6 Hz). MS calculated: 446.52; MS found: 447.2 (M+H+)

[0888] (266) A-266: 2-(4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinic acid

[0889] 1H-NMR (400 MHz, DMSO-d6): δ 8.35 (1H, d, J = 5.6 Hz), 8.25 (1H, d, J = 6.4 Hz), 7.78 (1H, d, J = 7.6 Hz), 7.71-7.66 (2H, m), 7.53 (1H, d, J = 5.6 Hz), 7.09 (1H, d, J = 8.0 Hz), 6.97-6.93 (2H, m), 3.07 (2H, q, J = 7.5 Hz), 2.29 (3H, s), 1.44 (3H, t, J = 7.4 Hz). *Two protons from NH and OH were not observed. MS calculated: 433.48; MS found: 434.2 (M+H+)

[0890] (267) A-267: 2-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide

[0891] 1H-NMR (400 MHz, DMSO-d6): δ 9.82 (1H, s), 8.21 (1H, d, J = 5.2 Hz), 8.11 (1H, d, J = 5.6 Hz), 8.05-8.02 (2H, m), 7.69-7.67 (2H, m), 7.58 (1H, s), 7.49 (1H, s), 7.17 (1H, d, J = 4.0 Hz), 7.07 (1H, d, J = 6.8 Hz), 6.57 (1H, d, J = 4.4 Hz), 3.04 (2H, q, J = 7.6 Hz), 2.19 (3H, s), 1.36 (3H, t, J = 7.6 Hz). MS calculated: 432.50; found: 433.2 (M+H+)

[0892] (268) A-268: 2-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylisonicotinamide

[0893] 1H-NMR (400 MHz, DMSO-d6):δ 8.23 ​​(1H, d, J = 5.2 Hz), 8.09 (1H, d, J = 6.0 Hz), 7.86 (1H, s), 7.67-7.66 (2H, m), 7.44 (1H, s), 7.14 (1H, d, J = 5.6 Hz), 7.10 (1H, t, J = 4.0 Hz), 6.63 (1H, dd, J = 6.0, 2.0 Hz), 3.07 (2H, q, J = 7.8 Hz), 2.91 (3H, s), 2.38 (3H, s), 1.44 (3H, t, J = 7.6 Hz). * The two protons from NH were not observed. MS calculated: 446.52; MS found: 447.2 (M+H+).

[0894] (269) A-269: N-(2-(dimethylamino)ethyl)-6-(4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0895] 1H-NMR (400 MHz, DMSO-d6): δ 10.2 (1H, s), 9.25 (1H, s), 8.63 (1H, s), 8.58-8.57 (1H, m), 8.14 (1H, d, J = 6.0 Hz), 8.04 (1H, d, J = 11.2 Hz), 7.78 (1H, d, J = 8.4 Hz), 7.74-7.67 (1H, m), 7.58 (1H, s), 7.14 (1H, d, J = 17.6 Hz), 6.63 (1H, d, J = 3.2 Hz), 3.61-3.51 (2H, m), 3.26-3.19 (2H, m), 3.02 (2H, q, J = 7.6 Hz), 2.82 (6H, s), 2.19 (3H, s), 1.35 (3H, t, J = 7.4 Hz). MS calculated: 503.62; MS found: 504.3 (M+H+)

[0896] (270) A-270: N-(cyclopropylmethyl)-6-(4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0897] 1H-NMR (400 MHz, DMSO-d6): δ 10.2 (1H, s), 8.68 (1H, d, J = 2.0 Hz), 8.15 (1H, d, J = 5.2 Hz), 8.09 (1H, d, J = 9.6 Hz), 7.77 (1H, d, J = 8.8 Hz), 7.73-7.66 (2H, m), 7.54 (1H, s), 7.06 (1H, d, J = 6.8 Hz), 6.66 (1H, d, J = 6.0 Hz), 4.07 (2H, d, J = 7.2 Hz), 3.01 (2H, q, J = 7.5 Hz), 1.33 (3H, t, J = 7.6 Hz), 0.77-0.89 (1H, m), 0.56-0.52 (2H, m), 0.35-0.31 (2H, m). MS calculated: 487.57; MS detected: 488.2 (M+H+)

[0898] (271) A-271: 2-(Dimethylamino)ethyl 6-(4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate

[0899] 1H-NMR (400 MHz, DMSO-d6):δ 8.78 (1H, d, J = 2.0 Hz), 8.16 (1H, dd, J = 8.4, 2.4 Hz), 8.12 (1H, d, J = 6.0 Hz), 7.69-7.64 (2H, m), 7.59 (1H, d, J = 2.0 Hz), 7.56 (1H, d, J = 8.8 Hz), 7.10 (1H, dd, J = 8.4, 2.0 Hz), 6.67 (1H, dd, J = 5.8. 1.8 Hz), 4.44 (2H, t, J = 5.6 Hz), 3.07 (2H, q, J = 7.6 Hz), 2.81 (2H, t, J = 5.6 Hz), 2.39 (6H, s), 2.37 (3H, s), 1.44 (3H, t, J = 7.6 Hz). *No proton from NH was observed. MS calculated: 504.60; MS found: 505.3 (M+H+).

[0900] (272) A-272: N-(3-(4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide

[0901] 1H-NMR (400 MHz, DMSO-d6): δ 9.63 (1H, s), 9.06 (1H, s), 8.04 (1H, d, J = 6.0 Hz), 7.70-7.69 (2H, m), 7.43 (2H, s), 7.14-7.09 (2H, m), 6.68 (1H, d, J = 6.8 Hz), 6.54 (1H, d, J = 3.6 Hz), 6.33 (1H, s), 3.03 (2H, q, J = 8.0 Hz), 2.89 (3H, s), 2.30 (3H, s), 1.35 (3H, t, J = 7.2 Hz). MS calculated: 481.59; detected: 482.2 (M+H+)

[0902] (273) A-273: 2-(Dimethylamino)ethyl 3-(6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide)-5-fluorobenzoate

[0903] 1H-NMR (400 MHz, DMSO-d6): δ 8.76 (1H, s), 8.17-8.13 (3H, m), 7.95 (1H, d, J = 10.4 Hz), 7.70-7.62 (2H, m), 7.61 (2H, d, J = 8.4 Hz), 7.54 (1H, d, J = 8.8 Hz), 7.11 (1H, d, J = 6.0 Hz), 6.67 (1H, d, J = 4.0 Hz), 4.49 (2H, t, J = 5.4 Hz), 3.08 (2H, q, J = 7.6 Hz), 2.70-2.60 (2H, m), 2.42 (3H, s), 2.37 (6H, d, J = 8.4 Hz), 1.45 (3H, t, J = 7.4 Hz). *Two protons from NH were not observed. MS calculated: 641.72; MS found: 642.3 (M+H+).

[0904] (274) A-274: 3-(4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0905] 1H-NMR (400 MHz, DMSO-d6):δ 9.12 (1H, s), 8.06 (1H, d, J = 6.0 Hz), 8.00 (1H, s), 7.83-7.78 (2H, m), 7.71-7.66 (2H, m), 7.32 (1H, d, J = 8.0 Hz), 7.27-7.23 (2H, m), 7.07 (1 H, dd, J = 6.4, 2.0 Hz), 6.85 (1H, dd, J = 5.6, 2.0 Hz), 6.34 (1H, d, J = 2.0 Hz), 2.45-2.40 (1 H, m), 2.21 (3 H, s), 1.66-1.13 (2H, m), 1.07-1.03 (2H, m). MS calculated: 443.53; MS found: 444.28 (M+H+)

[0906] (275) A-275: 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0907] 1H-NMR (400 MHz, DMSO-d6): δ 10.01 (1H, s), 8.64 (1H, d, J = 1.6 Hz), 8.12 (1H, d, J = 5.6 Hz), 8.05 (1H, dd, J = 9.2,2.4 Hz), 7.88 (1H, s), 7.75 (1H, d, J = 9.2 Hz), 7.68-7.67 (2H, m), 7.46 (1H, d, J = 1.6 Hz), 7.28 (1H, s), 7.05 (1H, t, J = 4.0 Hz), 6.61 (1H, dd, J = 5.6, 2.4 Hz), 2.44-2.40 (1H, m), 2.17 (3H, s), 1.17-1.13 (2H, m), 1.07-1.04 (2H, m). MS calculated: 444.51; MS found: 445.27 (M+H+)

[0908] (276) A-276: 2-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide

[0909] 1H-NMR (400 MHz, DMSO-d6): δ 9.81 (s, 1H), 8.21 (d, J = 4.8 Hz, 1H), 8.10 (d, J = 6.0 Hz, 1H), 8.05 (s, 1H), 7.44 (d, J = 2.4 Hz, 1H), 7.18 (d, J = 5.2 Hz, 1H), 7.06 (t, J = 4.4 Hz, 1H), 6.57 (dd, J = 6.0, 2.4 Hz, 1H), 2.44-2.30 (m, 2H), 2.18 (s,3H), 1.21-1.12 (m, 2H), 1.09-1.03 (m, 2H). MS calculated: 444.51; MS detected: 445.27 (M+H+)

[0910] (277) A-277: 3-(4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0911] 1H-NMR (400 MHz, DMSO-d6):δ 9.33 (1H, s), 8.19 (1H, s), 8.09 (1H, d, J = 6.0 Hz), 7.76 (1H, d, J = 7.6 Hz), 7.70-7.68 (2H, m), 7.34 (1H, t, J = 8.0 Hz), 7.29-7.27 (3H, m), 7.09-7.07 (1H, m), 6.65 (1H, dd, J = 5.6, 2.4 Hz), 6.36 (1H, d, J = 2.0 Hz), 2.45-2.40 (1H, m), 2.20 (3H, s), 1.18-1.13 (2H, m), 1.08-1.04 (2H, m). MS calculated: 479.57; MS found: 480.29 (M+H+)

[0912] (278) A-278: 6-(4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0913] 1H-NMR (400 MHz, DMSO-d6):δ 9.76 (1H, s), 8.12 (1H, d, J = 5.6 Hz), 7.79 (1H, t, J = 7.6 Hz), 7.68-7.65 (2H, m), 7.59 (1H, br s), 7.47 (1H, d, J = 7.2 Hz), 7.41 (1H, br s), 7.10 (1H, d, J = 2.4 Hz), 7.05 (1H, dd, J = 6.0, 2.4 Hz), 6.63 (1H, dd, J = 5.6, 2.4 Hz), 2.47-2.41 (1H, m), 2.17 (3H, s), 1.16-1.12 (2H, m), 1.10-1.05 (2H, m). MS calculated: 444.51; MS found: 445.32 (M+H+)

[0914] (279) A-279: 6-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0915] 1H-NMR (400 MHz, DMSO-d6):δ 9.75 (1H, s), 8.13 (1H, d, J = 5.2 Hz), 8.01-7.95 (2H, m), 7.79 (1H, t, J = 7.2 Hz), 7.68-7.65 (2H, m), 7.45 (1H, d, J = 7.6 Hz), 7.09 (1H, d, J = 4.4 Hz), 6.65 (1H, dd, J = 5.6, 2.4 Hz), 2.78 (3 H, d, J = 5.2 Hz), 2.44-2.38 (1H, m), 2.18 (3H, s), 1.66-1.12 (2H, m), 1.05-1.01 (2H, m). MS calculated: 458.54; MS found: 459.31 (M+H+)

[0916] (280) A-280: 2-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylisonicotinamide

[0917] 1H-NMR (400 MHz, DMSO-d6):δ 9.84 (1H, s), 8.56 (1H, d, J = 4.8 Hz), 8.22 (1H, d, J = 5.2 Hz), 8.11 (1H, d, J = 6.1 Hz), 8.04 (1H, s), 7.63 (2H, d, J = 4.8 Hz), 7.44 (1H, d, J = 2.4 Hz), 7.14 (1H, d, J = 1.6 Hz), 7.06 (1H, t, J = 4.4 Hz), 6.57 (1H, dd, J = 6.0, 2.4 Hz), 2.75 (3H, d, J = 4.2 Hz), 2.46-2.31 (1H, m), 2.07 (3H, s), 1.21-1.27 (2 H, m), 1.07-1.03 (2H, m). MS calculated: 458.54; MS found: 459.37 (M+H+)

[0918] (281) A-281: 3-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0919] 1H-NMR (400 MHz, DMSO-d6):δ 9.14 (1H, s), 8.30 (1H, d, J = 4.9 Hz), 8.06 (1H, d, J = 5.7 Hz), 7.98 (1H, s), 7.78 (1H, dd, J = 6.7, 3.0 Hz), 7.73-7.63 (2H, m), 7.25 (2H, d, J = 4.7 Hz), 7.07 (1H, dd, J = 5.6, 2.7 Hz), 6.55 (1H, dd, J = 5.6, 1.8 Hz), 6.33 (1H, d, J = 2.0 Hz), 2.73 (3H, d, J = 4.4 Hz), 2.42 (1H, dd, J = 9.1, 4.6 Hz), 2.21 (3 H, s), 1.19-1.11 (2H, m), 1.07-1.00 (2H, m). MS calculated: 457.55; MS detected: 458.24 (M+H+)

[0920] (282) A-282: 6-((4-((2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0921] 1H-NMR (400 MHz, DMSO-d6):δ 10.01 (1H, s), 8.59 (1H, d, J = 2.2 Hz), 8.35 (1H, d, J = 4.3 Hz), 8.12 (1H, d, J = 5.7 Hz), 8.01 (1H, dd, J = 9.1, 2.4 Hz), 7.76 (1H, d, J = 8.6 Hz), 7.68 (2H, dd, J = 6.3, 2.3 Hz), 7.44 (1H, d, J = 1.9 Hz), 7.09-7.02 (1H, m), 6.65-6.57 (1H, m), 2.74 (2H, d, J = 4.4 Hz), 2.41 (1H, dd, J = 13.2, 1.0 Hz), 2.17 (2H, s), 1.19-1.11 (2H, m), 1.06-1.03 (2H, m). MS calculated: 458.54; MS detected: 459.25 (M+H+)

[0922] (283) A-283: 3-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0923] 1H-NMR (400 MHz, DMSO-d6):δ 9.32 (1H, s), 8.22 (1H, s), 8.09 (1H, d, J = 5.6 Hz), 7.78 (1H, d, J = 8.4 Hz), 7.70-7.65 (2H, m), 7.39 (1H, t, J = 8.0 Hz), 7.30-7.26 (3H, m), 7.07-7.04 (1H, m), 6.61 (1H, dd, J = 2.0 Hz,5.8 Hz), 6.45 (1H, d, J = 2.0 Hz), 3.08 (6H, s), 2.08 (3H, s). MS calculated: 482.58; MS detected: 483.2 (M+H+)

[0924] (284) A-284: 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0925] 1H-NMR (400 MHz, DMSO-d6):δ 9.98 (1H, s), 8.64 (1H, d, J = 2.0 Hz), 8.11 (1H, d, J = 6.0 Hz), 8.05 (1H, dd, J = 8.8. 2.4 Hz), 7.87 (1H, s), 7.76 (1H, d, J = 8.8 Hz), 7.65 (2H, d, J = 4.4 Hz), 7.48 (1H, d, J = 2.0 Hz), 7.27 (1H, s), 7.01 (1H, t, J = 4.2 Hz), 6.61 (1H, dd, J = 6.0, 2.4 Hz), 3.07 (6H, s), 2.16 (3H, s). MS calculated: 447.51; MS found: 448.2 (M+H+)

[0926] (285) A-285: 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0927] 1H-NMR (400 MHz, DMSO-d6): δ 8.79 (1H, s), 8.31 (1H, d, J = 6.8 Hz), 8.24 (1H, d, J = 8.8 Hz), 7.72 (2H, s), 7.33 (1H, s), 7.14-7.03 (3H, m), 3.09 (6H, s), 2.16 (3H, s). *Two protons from NH and OH were not observed. MS calculated: 448.50; MS found: 449.2 (M+H+).

[0928] (286) A-286: 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide

[0929] 1H-NMR (400 MHz, DMSO-d6):δ 9.96 (1H, s), 8.60 (1H, s), 8.32 (1H, d, J = 4.0 Hz), 8.11 (1H, d, J = 5.6 Hz), 8.01 (1H, dd, J = 9.2,2.4 2.2 Hz), 3.07 (6H, s), 2.75 (3H, d, J = 4.0 Hz), 2.16 (3H, s). MS calculated: 461.54; MS found: 462.2 (M+H+)

[0930] (287) A-287: 3-(4-((2-isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0931] 1H-NMR (400 MHz, DMSO-d6):δ 9.33 (1H, s), 8.18 (1H, s), 8.09 (1H, d, J = 6.0 Hz), 7.78-7.68 (3H, m), 7.38 (1H, t, J = 7.8 Hz), 7.28 (1H, d, J = 7.8 Hz), 7.26 (2H, s), 7.08 (1H, d, J = 6.0 Hz), 6.59 (1H, dd, J = 5.6, 2.4 Hz), 6.36 (1H, d, J = 2.4 Hz), 3.31-3.27 (1H, m), 2.21 (3H, s), 1.38 (6H, d, J = 7.2 Hz). MS calculated: 481.59 Found: 482.2 (M+H+)

[0932] (288) A-288: 6-((4-((2-isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0933] 1H-NMR (400 MHz, DMSO-d6):δ 10.01 (1H, s), 8.62 (1H, s), 8.13(1H, d, J = 6.4 Hz), 8.05 (1H, d, J = 9.2 Hz), 7.86 (1H, s), 7.71-7.68 (3H, m), 7.50 (1H, s), 7.25 (1H, s), 7.07 (1H, d, J = 6.4 Hz), 6.62 (1H, d, J = 6.4 Hz), 3.32-3.25 (1H, m), 2.06 (3H, s), 1.39 (6H, d, J = 7.2 Hz). MS Calculated: 446.52 Detected: 447.2 (M+H+)

[0934] (289) A-289: 3-(4-((4-(6-methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0935] 1H-NMR (400 MHz, DMSO-d6):δ 9.34 (1H, s), 8.17 (1H, s), 8.13 (1H, d, J = 6.0 Hz), 7.79-7.76 (3H, m), 7.39 (1H, t, J = 8.0 Hz), 7.30 (1H, d, J = 9.2 Hz), 7.27 (2H, s), 7.19 (1H, dd, J = 6.4, 2.8 Hz), 6.69 (1H, dd, J = 6.0, 2.4 Hz), 6.41 (1H, d, J = 2.0 Hz), 2.25 (3H, s). MS Calculated: 507.51 Found: 508.1 (M+H+)

[0936] (290) A-290: 6-(4-((2-isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0937] 1H NMR (400 MHz, CDCl3): δ 8.63 (s, 1H), 8.17 (d, J = 5.8 Hz, 1H), 8.05 (d, J = 8.6 Hz, 1H), 7.82 (d, J = 8.4 Hz, 2H), 7.62 (t, J = 7.7 Hz, MS Calculated: 472.45 Detected: 473.27 (M+H+)

[0938] (291) A-291: 3-((4-((6-methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0939] 1H-NMR (400 MHz, DMSO-d6):δ 9.14 (s, 1H), 8.10 (d, J = 6.0 Hz, 1H), 7.99 (br s, 1H), 7.83 (br s, 1H), 7.80-7.74 (m, 3H), 7.33 (d, J = 7.2 Hz, 1H), 7.28-7.24 (m, 2H), 7.19 (dd, J = 6.4, 2.0 Hz, 1H), 6.64 (dd, J = 6.0, 2.0 Hz, 1H), 6.39 (d, J = 2.0 Hz, 1H), 2.26 (s,3H). MS Calculated: 471.46 Found: 472.28 (M+H+)

[0940] (292) A-292: 3-(4-((2-(methylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0941] 1H-NMR (400 MHz, DMSO-d6):δ 9.33 (1H, s), 8.22 (1H, s), 8.09 (1H, d, J = 5.6 Hz), 7.79 (1H, d, J = 8.0 Hz), 7.69-7.67 (2H, m), 7.65-7.62 (1H, m), 7.39 (1H, t, J = 8.0 Hz), 7.30 (1H, d, J = 6.0 Hz), 7.27 (2H, s), 7.04 (1H, d, J = 7.2 Hz), 6.61 (1H, dd, J = 5.6, 2.4 Hz), 6.46 (1H, d, J = 2.4 Hz), 2.89 (3H, d, J = 4.8 Hz), 2.20 (3H, s). MS calculated: 468.55 found: 469.2 (M+H+)

[0942] (293) A-293: 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid

[0943] 1H-NMR (400 MHz, DMSO-d6): δ 10.4 (1H, brs), 8.68 (1H, s), 8.25 (1H, d, J = 5.2 Hz), 8.10 (1H, d, J = 9.2 Hz), 7.71 (1H, d, J = 8.8 Hz), 7.63-7.61 (3H, m), 7.38 (2H, t, J = 7.6 Hz), 7.26 (1H, t, J = 7.6 Hz), 6.80 (1H, d, J = 5.6 Hz), 2.17-2.13 (1H, m), 1.08-0.99 (4H, m). * Protons from NH were not observed. MS calculated: 414.41; MS found: 415.2 (M+H+)

[0944] (294) A-294: 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide

[0945] 1H-NMR (400 MHz, DMSO-d6): δ 10.2 (1H, s), 8.66 (1H, s), 8.23 ​​(1H, d, J = 5.6 Hz), 8.08 (1H, d, J = 8.4 Hz), 7.92 (1H, s), 7.70 (1H, d, J = 8.8 Hz), 7.63-7.58 (3H, m), 7.38 (2H, t, J = 7.4 Hz), 7.31 (1H, s), 7.26 (1H, t, J = 7.6 Hz), 6.74 (1H, d, J = 6.0 Hz), 2.19-2.10 (1H, m), 1.10-1.00 (4H, m). MS Calculated: 446.52; MS Found: 414.2 (M+H+)

[0946] (295) A-295: 4-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid

[0947] 1H-NMR (400 MHz, DMSO-d6): δ 9.54 (1H, s), 8.21 (1H, d, J = 6.0 Hz), 7.81 (2H, d, J = 8.4 Hz), 7.72 (2H, d, J = 8.4 Hz), 7.61 (2H, d, J = 7.6 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.25 (1H, t, J = 7.2 Hz), 6.73 (1H, d, J = 6.0 Hz), 6.46 (1H, s), 2.18-2.11 (1H, m), 1.08-1.01 (4H, m). * Protons from OH were not observed. MS calculated: 413.43; MS found: 414.2 (M+H+)

[0948] (296) A-296: 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0949] 1H-NMR (400 MHz, DMSO-d6):δ 9.28 (s, 1H), 8.17 (d, J = 5.8 Hz, 1H), 8.02 (s, 1H), 788-7.83 (m, 2H), 7.64 (d, J = 7.4 Hz, 2H), 7.44-7.37 (m, 3H), 7.32-7.28 (m, 3H), 6.66 (d, J = 5.8. 2.0 Hz, 1H), 6.41 (d, J = 2.0 Hz, 1H), 2.19-2.15 (m, 1H), 1.10-1.03 (m, 4H). (M+H+)MS calculated: 412.45; MS detected: 413.30 (M+H+)

[0950] (297) A-297: 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide

[0951] 1H-NMR (400 MHz, DMSO-d6):δ 9.28 (s, 1H), 8.32 (d, J = 5.5 Hz, 1H), 8.15 (d, J = 5.8 Hz, 1H), 7.97 (s, 1H), 7.86-7.76 (m, 1H), 7.61 (d, J = 7.4 Hz, 2H), 7.39 (t, J = 7.5 Hz, 2H), 7.28 (d, J = 10.6 Hz,3H), 6.64 (dd, J = 5.8. 2.2 Hz, 1H), 6.38 (d, J = 2.3 Hz, 1H), 2.73 (d, J = 4.4 Hz, 3H), 2.14 (s, 1H), 1.11-0.96 (m, 4H). MS calculated: 426.48; MS found: 427.29 (M+H+)

[0952] (298) A-298: 3-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0953] 1H-NMR (400 MHz, DMSO-d6):δ 9.47 (s, 1H), 8.21-8.13 (m, 2H), 7.80 (d, J = 7.5 Hz, 1H), 7.62 (d, J = 8.0 Hz, 2H), 7.43-7.37 (m, 3H), 7.32-7.30 (m, 4H), 6.69 (d, J = 4.4 Hz, 1H), 6.40 (s, 1H), 2.17-2.11 (m, 1H), 1.13-0.95 (m, 4H). MS calculated: 448.50; MS detected: 449.23 (M+H+)

[0954] (299) A-299: 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide

[0955] 1H-NMR (400 MHz, DMSO-d6): δ 10.19 (s, 1H), 8.66 (d, J = 2.1 Hz, 1H), 8.23 ​​(d, J = 5.7 Hz, 1H), 8.07 (dd, J = 8.8. 2.3 Hz, 1H), 7.91 (s, 1H), 7.70 (d, J = 8.8 Hz, 1H), 7.62 (d, J = 7.6 Hz, 2H), 7.58 (d, J = 2.2 Hz, 1H), 7.39 (t, J = 7.7 Hz, 2H), 7.32 (s, 1H), 7.27 (t, J = 7.3 Hz, 1H), 6.75 (dd, J = 5.8. 2.4 Hz, 1H), 2.20-2.09 (m, 1H), 1.13-0.97 (m, 4H). MS calcd: 413.15; MS found: 414.31 (M+H+)

[0956] (300) A-300 : 3-((4-((2-シクロプロピル-4-フェニルオキサゾール-5-イル)オキシ)ピリジン-2-イル)アミノ)benzoic acid

[0957] 1H-NMR (400 MHz, DMSO-d6): δ 12.85 (s, 1H), 9.34 (s, 1H), 8.22 (s, 1H), 8.18 (d, J = 5.7 Hz, 1H), 7.87 (d, J = 8.9 Hz, 1H), 7.62 (d, J = 7.7 Hz, 2H), 7.45 (d, J = 7.9 Hz, 1H), 7.40 (t, J = 7.6 Hz, 2H), 7.34 (t, J = 7.9 Hz, 1H), 7.27 (t, J = 7.3 Hz, 1H), 6.67 (d, J = 5.5 Hz, 1H), 6.38 (s, 1H), 2.15 (d, J = 4.9 Hz, 1H), 1.12-0.97 (m, 4H). MS calcd: 413.14; MS found: 414.25 (M+H+)

[0958] (301) A-301: 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid

[0959] 1H-NMR (400 MHz, DMSO-d6):δ 13.05 (br s, 1H), 10.99 (br s, 1H), 8.73 (d, J = 2.1 Hz, 1H), 8.32 (d, J = 6.1 Hz, 1H), 8.18 (dd, J = 8.7, 2.0 Hz, 1H), 7.67 - 7.56 (m, 3H), 7.40 (dd, J = 15.6, 8.1 Hz,3H), 7.28 (t, J = 7.4 Hz, 1H), 6.95 (d, J = 4.5 Hz, 1H), 2.16 (m, 1H), 1.14 - 0.99 (m, 4H). MS calculated: 414.42; MS detected: 415.26 (M+H+)

[0960] (302) A-302: 6-((4-((2-cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide

[0961] 1H-NMR (400 MHz, DMSO-d6):δ 11.04 (s, 1H), 8.70 (s, 1H), 8.55 (d, J = 4.9 Hz, 1H), 8.34 (d, J = 6.4 Hz, 1H), 8.20 (d, J = 8.7 Hz, 1H), 7.63 (d, J = 7.8 Hz, 2H), 7.53-7.35 (m, 3H), 7.29 (t, J = 7.4 Hz, 1H), 7.20 (s, 1H), 7.03 (s, 1H), 2.77 (d, J = 4.4 Hz,3H), 2.20-2.13 (m, 1H), 1.13-0.99 (m, 4H). MS Calculated: 427.46; MS found: 428.24 (M+H+)

[0962] (303) A-303: 3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide

[0963] 1H-NMR (400 MHz, DMSO-d6):δ 9.47 (1H, s), 8.18 (1H, s), 8.09 (1H, d, J = 6.0 Hz), 7.76 (1H, d, J = 8.0 Hz), 7.70-7.67 (2H, m), 7.37 (1H, t, J = 8.0 Hz), 7.29-7.27 (3H, m), 7.09-7.05 (1H, m), 6.59 (1H, dd, J = 7.6, 2.0 Hz), 6.36 (1H, d, J = 2.0 Hz), 2.69 (3H, s), 2.21 (3H, s). MS Calculated: 453.54 Found: 454.1 (M+H+)

[0964] (304) A-304: 2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)acetonitrile

[0965] 1H-NMR (400 MHz, DMSO-d6):δ 9.10 (1H, s), 8.06 (1H, d, J = 6.0 Hz), 7.70-7.69 (2H, m), 7.61 (1H, s), 7.55 (1H, d, J = 8.4 Hz), 7.20 (1H, t, J = 7.8 Hz), 7.08 (1H, t, J = 4.6 Hz), 6.79 (1H, d, J = 8.0 Hz), 6.55 (1H, dd, J = 5.8. 2.2 Hz), 6.34 (1H, d, J = 2.4 Hz), 3.96 (2H, s), 2.68 (3H, s), 2.21 (3H, s). MS calculated: 413.49 Found: 414.2 (M+H+)

[0966] (305) A-305: N-(3-((1H-tetrazol-5-yl)methyl)phenyl)-4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-amine

[0967] 1H-NMR (400 MHz, DMSO-d6):δ 8.99 (1H, s), 8.03 (1H, d, J = 5.6 Hz), 7.69 (2H, d, J = 4.4 Hz), 7.55 (1H, d, J = 7.6 Hz), 7.37 (1H, s), 7.15 (1H, t, J = 7.8 Hz), 7.08 (1H, t, J = 4.4 Hz), 6.72 (1H, d, J = 7.6 Hz), 6.53 (1H, d, J = 5.6 Hz), 6.31 (1H, d, J = 2.0 Hz), 4.18 (2H, s), 2.68 (3H, s), 2.21 (3H, *No protons from NH were observed. MS calculated: 456.52; found: 457.2 (M+H+)

[0968] (306) A-306: 3-(4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanenitrile

[0969] 1H-NMR (400 MHz, DMSO-d6):δ 8.98 (1H, s), 8.05 (1H, d, J = 6.0 Hz), 7.69 (2H, d, J = 4.8 Hz), 7.49 (1H, d, J = 8.0 Hz), 7.41 (1H, s), 7.15 (1H, t, J = 8.0 Hz), 7.08 (1H, t, J = 4.4 Hz), 6.77 (1H, d, J = 6.8 Hz), 6.53 (1H, dd, J = 6.0, 2.0 Hz), 6.34 (1H, d, J = 2.4 Hz), 2.78-2.73 (4H, m), 2.68 (3H, s), 2.22 (3H, s). MS calculated: 427.52; found: 428.2 (M+H+)

[0970] (307) A-307: N-(3-(2-(2H-tetrazol-5-yl)ethyl)phenyl)-4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-amine

[0971] 1H-NMR (400 MHz, DMSO-d6): δ 8.92 (1H, s), 8.06 (1H, d, J = 5.6 Hz), 7.69 (2H, d, J = 4.0 Hz), 7.43-7.39 (2H, m), 7.20-7.06 (2H, m), 6.71 (1H, d, J = 7.6 Hz), 6.52 (1H, d, J = 6.4 Hz), 6.33 (1H, s), 2.92-2.88 (2H, m), 2.87-2.80 (2H, m), 2.65 (3H, s), 2.23 (3H, s). * Protons from NH were not observed. MS calculated: 470.55; Found: 471.2 (M+H+)

[0972] (308) A-308: Methyl 2-methyl-2-(3-(4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoate

[0973] 1H-NMR (400 MHz, CDCl3):δ 9.00 (1H, s), 8.06 (1H, d, J = 6.0 Hz), 7.12 (2H, d, J =4.4 Hz), 7.63 (1H, d, J = 8.0 Hz), 7.40 (1H, s), 7.17 (1H, t, J = 7.6 Hz), 7.10 (1H, t, J = 4.8 Hz), 6.80 (1H, d, J = 8.4 Hz), 6.55-6.54 (1H, m), 6.33 (1H, d, J =1.6 Hz), 3.58 (3H, s), 2.70 (3H, s), 2.24 (3H, s), 1.45 (6H, s). MS calculated: 474.57; MS found: 475.2 (M+H+)

[0974] (309) A-309: 2-methyl-2-(3-(4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoic acid

[0975] 1H-NMR (400 MHz, DMSO-d6): δ 8.06 (1H, d, J = 6.8 Hz), 7.80-7.78 (2H, m), 7.41 (1H, brs), 7.31-7.25 (2H, m), 7.19 (1H, d, J = 6.8 Hz), 7.04 (1H, brs), 6.73 (1H, brs), 6.45 (1H, s), 2.71 (3H, s), 2.28 (3H, s), 1.43 (6H, s). *Two protons from OH and NH were not observed. MS calculated: 460.55; MS found: 461.2 (M+H+).

[0976] (310) A-310: 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide

[0977] 1H-NMR (400 MHz, DMSO-d6): δ 9.39 (1H, s), 8.15 (1H, d, J = 5.6 Hz), 7.77-7.74 (4H, m), 7.69-7.67 (3H, m), 7.35 (2H, t, J = 7.6 Hz), 7.25 (1H, t, J = 7.2 Hz), 7.10 (1H, s), 6.69 (1H, dd, J = 2.0 Hz, 5.6 Hz), 6.55 (1H, d, J = 2.4 Hz), 2.89 (3H, d, J = 4.8 Hz). * Protons from NH were not observed. MS calculated: 417.48; MS found: 418.2 (M+H+)

[0978] (311) A-311: N-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide

[0979] 1H-NMR (400 MHz, DMSO-d6):δ 9.23 (1H, brs), 8.11 (1H, d, J = 5.6 Hz), 7.81 (2H, d, J = 7.2 Hz), 7.59 (1H, brs), 7.51 (1H, brs), 7.40 (2H, t, J = 7.6 Hz), 7.29-7.31 (1H, m), 7.19-7.21 (1H, m), 6.72 (1H, d, J = 9.2 Hz), 6.64 (1H, d, J = 3.2 Hz), 6.43 (1H, s), 3.00 (2H, t, J = 7.5 Hz), 1.33 (3H, t, J = 7.6 Hz). *No protons from NH were observed. MS calculated: 520.55; MS found: 521.1 (M+H+)

[0980] (312) A-312: 4-((2-ethyl-4-phenylthiazol-5-yl)oxy)-N-(5-(3-(methylamino)pyrrolidin-1-yl)pyridin-2-yl)pyridin-2-amine

[0981] 1H-NMR (400 MHz, CDCl3):δ 8.04 (1H, d, J = 5.2 Hz), 7.87 (2H, d, J = 8.4 Hz), 7.58 (1H, s), 7.35 (2H, t, J = 7.2 Hz), 7.26-7.20 (3H, m), 6.88 (1H, d, J = 10.4 Hz), 6.48 (1H, dd, J = 5.6 Hz), 3.46-3.41 (3H, m), 3.27-3.18 (2H, m), 3.01 (2H, q, J = 7.2 Hz), 2.52 (3H, s), 2.24-1.94 (2H, m), 1.42 (3H, t, J = 7.6 Hz). *Two protons from NH were not observed. MS calculated: 472.61; MS found: 473.3 (M+H+)

[0982] [Synthesis Example 2] Method for synthesizing novel thiazole derivatives

[0983] 1. Synthesis of Intermediates 1-6 and 1-6'

[0984] [ka]

[0985] (1) Preparation of 2-((2-chloropyridin-4-yl)oxy)-1-phenylethanone (1-3)

[0986] To a solution of 2-bromo-1-phenylethanone (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 potassium carbonate (8.00 g, 57.9 mmol) at room temperature. After stirring at room temperature for 4 hours, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 2:1) to give 1-3 (6.00 g, 63%) as a yellow solid.

[0987] 1H-NMR (400 MHz, CDCl3): δ8.21 (1H, d, J = 5.2 Hz) ,7.98 (2H, d, J = 7.2Hz) ,7.67 (1H, t, J = 7.6 Hz) ,7.54 (2H, t, J = 7.0 Hz) ,6.85 (1H, d, J = 2.4 Hz) ,6.79 (1H, dd, J = 6.0, 2.4 Hz) ,5.38 (2H, s).

[0988] (2) Preparation of 2-bromo-2-((2-chloropyridin-4-yl)oxy)-1-phenylethan-1-one (1-4)

[0989] To a solution of 1-3 (6.00 g, 24.2 mmol) in chloroform (242 mL) was slowly added aluminum chloride (1.29 g, 9.69 mmol) and bromine (1.87 mL, 36.3 mmol) at room temperature. The mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with saturated sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 4:1) to give 1-4 (5.74 g, 73%) as a yellow solid.

[0990] 1H-NMR (400 MHz, CDCl3):δ 8.38 (1H, t, J = 5.4 Hz), 8.16 (2H, t, J = 7.2 Hz), 7.68 (1H, t, J = 7.4 Hz), 7.55 (2H, t, J = 7.6 Hz), 7.21 (1H, dd, J = 14.8. 2.0 Hz), 7.13 (1H, dd, J = 5.4, 1.8 Hz), 7.08 (1H, s).

[0991] (3) Preparation of 5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazol-2-amine

[0992] A mixture of 1-4 (4.70 g, 14.4 mmol) and thiourea (2.19 g, 28.8 mmol) in ethanol (144 mL) was heated at 80 °C for 10 min. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on NH-silica (dichloromethane:methanol = 100:1) to give 1-5 (2.72 g, 62%) as a pale yellow solid.

[0993] 1H-NMR (400 MHz, DMSO-d6): δ7.55 (1H, d, J = 8.31 Hz), 7.65 (2H, d, J = 8.0 Hz), 7.33 (2H, t, J = 4.2 Hz), 7.26 (1H, d, J = 2.4 Hz), 7.24-7.21 (1H, m), 7.20 (2H, s), 7.16 (1H, dd, J = 5.8. 2.2 Hz).

[0994] (4) Preparation of tert-butyl (5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazol-2-yl)carbamate (1-6'), (1-6)

[0995] To a solution of 1-5 (2.72 g, 8.95 mmol) in tetrahydrofuran (90 mL) at room temperature, di-tert-butyl dicarbonate (5.86 g, 26.9 mmol), triethylamine (3.74 mL, 26.9 mmol), and 4-dimethylaminopyridine (438 mg, 3.58 mmol) were added. The mixture was stirred at room temperature for 18 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 7:1 to 4:1) to give 1-6 (1.50 g, 33% yield) and 1-6' (1.10 g, 30% yield) as pale yellow solids.

[0996] 1H-NMR (400 MHz, DMSO-d6):δ 8.34-8.31 (1H, m), 7.71-7.69 (2H, m), 7.40-7.38 (2H, m), 7.34-7.32 (1H, m), 7.32-7.25 (1H, m), 7.22-7.19 (1H, m), 1.51 (18H, s).

[0997] 2. Synthesis of A-1

[0998] [ka]

[0999] (1) Synthesis of tert-butyl (4-phenyl-5-((2-((3-sulfamoylphenyl)amino)pyridin-4-yl)oxy)thiazol-2-yl)carbamate (1-7)

[1000] To a solution of the mixture of compounds 1-6 & 1-6' (200 mg, 0.50 mmol) in N,N-dimethylformamide (5.0 mL) was added 3-aminobenzenesulfonamide (128 mg, 0.74 mmol) and potassium carbonate (205 mg, 1.49 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon several times. After adding BrettPhos Pd G1 (chloro[2-dicyclohexylphosphino)-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl][2-(2-aminoethyl)phenyl]palladium(II)), methyl t-butyl ether adduct (185 mg, 0.20 mmol), the reaction mixture was heated at 100 °C for 4 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=3:2) to give 1-7 (140 mg, 52%) as a brown solid.

[1001] 1H-NMR (400 MHz, CDCl3): δ 9.80 (1H, brs), 8.14 (1H, d, J = 6.0 Hz), 7.76-7.72 (3H, m), 7.72-7.42 (1H, m), 7.34-7.21 (5H, m), 6.63 (1H, dd, J = 2.0 Hz, 6.0 Hz), 6.51 (1H, d, J = 2.0 Hz), 5.18 (2H, brs), 1.47 (9H, s). * Protonated NH was not observed.

[1002] (2) Preparation of A-1

[1003] To a solution of 1-7 (140 mg, 0.26 mmol) in dichloromethane (3 mL) was added trifluoroacetic acid (0.2 mL, 2.60 mmol) and stirred at room temperature for 18 hours. The reaction mixture was quenched with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 3:2 to 1:1) to give A-1 (52 mg, 45%) as a white solid.

[1004] The following A-2 to A-38 were synthesized using the procedure described in the synthesis of A-1.

[1005] 3. Synthesis of A-39

[1006] [ka]

[1007] (1) Preparation of 4-((4-((2-((tert-butoxycarbonyl)amino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (1-9)

[1008] To a solution of 1-(270 mg, 0.51 mmol) in tetrahydrofuran (5.0 mL) and water (5.0 mL) was added lithium hydroxide (42.0 mg, 1.01 mmol) at room temperature. After stirring at 50 °C for 4 days, the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was acidified with 2N hydrochloric acid solution. The precipitated solid was collected by filtration to give 1-9 (185 mg, 72%) as a brown solid.

[1009] 1H-NMR (400 MHz, DMSO-d6): δ 11.8 (1H, s), 9.66 (1H, s), 8.18 (1H, d, J = 6.0 Hz), 7.83 (2H, d, J = 7.2 Hz), 7.76 (2H, d, J = 8.0 Hz), 7.72 (2H, d, J = 8.8 Hz), 7.40 (2H, t, J = 7.0 Hz), 7.32-7.28 (1H, m), 6.79 (1H, dd, J = 6.0, 2.0 Hz), 6.59 (1H, d, J = 2.4 Hz), 1.50 (9H, s). * Protons from NH were not observed.

[1010] (2) Preparation of A-39

[1011] To a solution of 1-9 (270 mg, 0.51 mmol) in dichloromethane (3.7 mL) was added trifluoroacetic acid (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 quenched with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was triturated with dichloromethane. The precipitated solid was collected by filtration to give A-39 (37.4 mg, 25%) as a beige solid.

[1012] The following A-40 was synthesized using the procedure described in the synthesis of A-39.

[1013] 4. Synthesis of A-41

[1014] [ka]

[1015] (1) Synthesis of 2-bromo-5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazole (1-10)

[1016] 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 mixture was stirred at 0 °C for 30 min. The reaction mixture was quenched with aqueous ammonia and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 3:1) to give 1-10 (358 mg, 64%) as a yellow solid.

[1017] (2) Preparation of N-(5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazol-2-yl)-1,1-diphenylmethamine (1-11)

[1018] To a solution of 1-10 (100 mg, 0.27 mmol) in dioxane (2.7 mL), diphenylmethanamine (0.07 mL, 0.41 mmol), Xantphos (16.0 mg, 0.03 mmol), and cesium carbonate (266 mg, 0.82 mmol) were added at room temperature. The mixture was purged, degassed, and refilled with argon in several portions. After adding Pd2(dba)3 (tris(dibenzylideneacetone)dipalladium(0)) (16.0 mg, 0.03 mmol), the reaction mixture was heated at 100 °C for 18 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=5:1) to give N-(5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazol-2-yl)-1,1-diphenylmethanamine (1-11) (62.0 mg, 49%) as a yellow solid.

[1019] 1H-NMR (400 MHz, DMSO-d6):δ 8.33 (1H, d, J = 6.0 Hz), 7.79 (2H, d, J = 7.6 Hz), 7.75-7.70 (4H, m), 7.67-7.63 (4H, m), 7.42-7.38 (4H, m), 7.33-7.30 (1H, m), 7.16 (1H, d, J = 2.4 Hz), 7.07 (1H, dd, J = 6.0, 2.4 Hz).

[1020] (3) Preparation of 2-(3-((4-((2-((diphenylmethylene)amino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (1-12)

[1021] To a solution of 1-11 (62.0 mg, 0.13 mmol) in N,N-dimethylformamide (2.7 mL) was added 2-(3-aminophenyl)propan-2-ol (30.0 mg, 0.20 mmol) and potassium carbonate (55.0 mg, 0.40 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (24.0 mg, 0.03 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo, and the residue was purified by column chromatography on silica (hexane:ethyl acetate=1:1) to give 1-12 (15.4 mg, 20%) as a yellow solid.

[1022] 1H-NMR (400 MHz, DMSO-d6):δ 9.04 (1H, s), 8.06 (1H, d, J = 6.0 Hz), 7.79-7.74 (4H, m), 7.64-7.59 (1H, m), 7.59-7.55 (6H, m), 7.53 (1H, s), 7.53-7.42 (4H, m), 7.33-7.29 (1H, m), 7.16 (1H, t, J = 7.8 Hz), 6.98 (1H, d, J = 8.4 Hz), 6.45 (1H, dd, J = 6.2, 2.2 Hz), 6.37 (1H, d, J = 2.0 Hz), 4.93 (1H, s), 1.38 (6H, s).

[1023] (4) Preparation of A-41

[1024] To a solution of 1-12 (15.0 mg, 0.03 mmol) in methanol (0.50 mL) was added hydroxylamine hydrochloride (3.58 mg, 0.05 mmol) at room temperature. After stirring at room temperature for 3 h, the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on NH-silica (dichloromethane:methanol = 100:1 to 50:1) to give A-41 (2.20 mg, 20%) as a white solid.

[1025] The following A-42 and A-43 were synthesized using the procedure described for the synthesis of A-41.

[1026] 5. Synthesis of A-44

[1027] [ka]

[1028] (1) Synthesis of 5-((2-chloropyridin-4-yl)oxy)-N-cyclopropyl-4-phenylthiazol-2-amine (2-1)

[1029] A mixture of 2-bromo-2-((2-chloropyridin-4-yl)oxy)-1-phenylethan-1-one (200 mg, 0.61 mmol) and 1-cyclopropylthiourea (142 mg, 1.23 mmol) in ethanol was heated at 80 °C for 10 min. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 2:1) to give 2-1 (74.0 mg, 35%) as a yellow solid.

[1030] 1H-NMR (400 MHz, DMSO-d6):δ 8.34 (1H, d, J = 5.2 Hz), 8.24 (1H, d, J = 1.6 Hz), 7.69 (2H, d, J = 7.6 Hz), 7.36 (2H, t, J = 7.6 Hz), 7.31 (1H, d, J = 2.0 Hz), 7.27 (1H, d, J = 7.6 Hz), 7.20 (1H, dd, J = 5.8, 2.2 Hz), 2.60-2.54 (1H, m), 0.76-0.71 (2H, m), 0.59-0.57 (2H, m).

[1031] (2) Preparation of A-44

[1032] To a solution of 2-1 (70.0 mg, 0.20 mmol) in N,N-dimethylformamide (4.1 mL) was added 2-(3-aminophenyl)propan-2-ol (46.0 mg, 0.31 mmol) and potassium carbonate (84.0 mg, 0.61 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (37.0 mg, 0.04 mmol), the reaction mixture was heated at 100 °C for 2 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by NH-silica column chromatography to give A-44 (19.6 mg, 21%) as a dentin solid.

[1033] The following A-45 to A-47 were synthesized by the procedure described in the synthesis of A-44.

[1034] 6. Synthesis of A-48

[1035] [ka]

[1036] (1) Preparation of methyl 3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate (2-2)

[1037] To a solution of 2-1 (200 mg, 0.58 mmol) in N,N-dimethylformamide (12 mL) was added methyl 3-aminobenzoate (132 mg, 0.87 mmol) and potassium carbonate (241 mg, 1.75 mmol) at room temperature. The mixture was degassed by purging and backfilled with argon in several portions. After the addition of BrettPhos Pd G1 (chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (207 mg, 0.23 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 4:1) to give 2-2 (103 mg, 39%) as a yellow solid.

[1038] 1H-NMR (400 MHz, CDCl3):δ 8.12 (1H, d, J = 5.6 Hz), 7.94 (1H, t, J = 1.8 Hz), 7.75 (2H, d, J = 8.0 Hz), 7.69 (1H, d, J = 7.2 Hz), 7.55 (1H, dd, J = 8.0, 2.0 Hz), 7.37-7.32 (3H, m), 7.26-7.24 (1H, m), 6.71 (1H, s), 6.59 (1H, dd, J = 5.6, 2.0 Hz), 6.52 (1H, d, J = 2.4 Hz), 3.90 (3H, s), 2.62-2.57 (1H, m), 0.79-0.77 (2H, m), 0.72-0.68 (2H, m). * No protons from NH were observed.

[1039] (2) Preparation of A-48

[1040] To a solution of 2-2 (60.0 mg, 0.13 mmol) in tetrahydrofuran (2.0 mL) and water (0.65 mL) was added lithium hydroxide (55.0 mg, 1.31 mmol) at room temperature. After stirring at room temperature for 18 hours, the reaction mixture was concentrated under reduced pressure. The residue was acidified with 2N hydrochloric acid solution. The precipitated solid was collected by filtration to give A-48 (1.0 mg, 1.7%) as a denatured solid.

[1041] Using the procedure described in the synthesis of A-48, the following A-49 was synthesized.

[1042] 7. Synthesis of A-50

[1043] [ka]

[1044] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-N-methyl-4-phenylthiazol-2-amine (3-1)

[1045] A mixture of (300 mg, 0.92 mmol) and (120 mg, 1.38 mmol) in ethanol (10 mL) was stirred at 80 °C for 10 min. After cooling at room temperature, the solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate and washed with water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 4:1) to give 3-1 (58.0 mg, 20%) as a yellow oil.

[1046] 1H-NMR (400 MHz, CDCl3): δ 8.24 (1H, d, J = 5.6 Hz), 7.74-7.71 (2H, m), 7.33-7.29 (2H, m), 7.26-7.24 (1H, m), 7.04 (1H, d, J = 2.4 Hz), 6.96 (1H, dd, J = 5.9 Hz, 2.0 Hz), 2.97 (3H, d, J = 4.8 Hz). * Protonated NH was not observed.

[1047] (2) Preparation of A-50

[1048] To a solution of 3-1 (57.0 mg, 0.18 mmol) in N,N-dimethylformamide (2.0 mL) was added 2-(3-aminophenyl)propan-2-ol (41.0 mg, 0.27 mmol) and potassium carbonate (74.0 mg, 0.54 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon several times. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (30.0 mg, 0.04 mmol), the reaction mixture was heated at 100 °C for 18 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica (hexane:ethyl acetate=1:1) to give A-50 (3.4 mg, 4%) as a dendritic solid.

[1049] The following A-51 to A-55 were synthesized using the procedure described for the synthesis of A-50.

[1050] 8. Synthesis of A-56 and A-56 Salt

[1051] [ka]

[1052] (1) Preparation of methyl 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate (3-2)

[1053] To a solution (20.0 mL) of N,N-dimethylformamide (800 mg, 2.52 mmol), methyl 4-aminobenzoate (570 mg, 3.78 mmol) and potassium carbonate (1.04 g, 7.55 mmol) were added at room temperature. The mixture was degassed by purging and backfilling with argon several times. After the addition of BrettPhos Pd G1 (chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (580 mg, 0.63 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on MPLC (hexane:ethyl acetate = 7:3) to give 3-2 (630 mg, 58%) as a brown oil.

[1054] 1H-NMR (400 MHz, CDCl3): δ 8.15 (1H, d, J = 5.6 Hz), 7.96-7.93 (2H, m), 7.79-7.77 (2H, m), 7.38-7.32 (2H, m), 7.28-7.22 (2H, m), 6.94 (1H, s), 6.64 (1H, dd, J = 2.0 Hz, 5.6 Hz), 6.58 (1H, d, J = 2.4 Hz), 3.88 (3H, s), 2.99 (3H, d, J = 6.4 Hz). *Two protons from the two NHs were not observed.

[1055] (2) Preparation of A-56

[1056] To a mixture of 3-2 (630 mg, 1.46 mmol) in tetrahydrofuran / water (v / v = 1 / 1, 30.0 mL) was added lithium hydroxide (1.22 g, 29.1 mmol) and stirred at room temperature up to 50 °C for 5 days. After cooling at room temperature, the reaction mixture was neutralized with aqueous 1N ammonium hydroxide solution and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 2:3) and triturated with dichloromethane to give A-56 (180 mg, 30%) as a denatured solid.

[1057] (3) A-56 Salt Preparation

[1058] To a solution of A-56 (30.0 mg, 0.07 mmol) in methanol (1.5 mL) was added benzophenone (2 M in methanol, 0.08 mL, 0.15 mmol). The reaction mixture was stirred at room temperature for 2 hours, and the solvent was removed under reduced pressure. The precipitated solid was filtered and washed with diethyl ether to give A-56 salt (17.0 mg, 52%) as a yellow solid.

[1059] 1H-NMR (400 MHz, DMSO-d6): δ 9.70 (1H, s), 8.16 (1H, d, J = 6.4 Hz), 7.83 (2H, d, J = 8.8 Hz), 7.75-7.70 (5H, m), 7.36 (2H, t, J = 7.6 Hz), 7.26 (1H, t, J = 7.6 Hz), 6.76 (1H, dd, J = 2.4 Hz, 6.2 Hz), 6.62 (1H, d, J = 2.4 Hz), 2.83 (3H, s). *No proton from NH was observed. MS calculated: 418.47; MS found: 419.1 (M+H+).

[1060] The following A-57 was synthesized using the procedure described for the synthesis of A-56.

[1061] 9. Synthesis of A-58

[1062] [ka]

[1063] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-methyl-4-phenylthiazole (4-1)

[1064] To a solution of 1-10 (1.50 g, 4.08 mmol) in dioxane (37 mL) and water (3.7 mL), methylboronic acid (733 mg, 12.2 mmol), Sphos (2-dicyclohexylphosphino-2',6'-dimethoxybiphenyldicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine) (837 mg, 2.04 mmol), and potassium carbonate (1.69 mg, 12.2 mmol) were added at room temperature. The mixture was degassed by purging and refilled with argon in several portions. After adding palladium(II) acetate (229 mg, 1.02 mmol), the reaction mixture was heated at 100 °C for 18 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=10:1 to 7:1) to give 4-1 (403 mg, 33%) as a yellow solid.

[1065] 1H-NMR (400 MHz, DMSO-d6):δ 8.35 (1H, d, J = 5.6 Hz), 7.79 (2H, d, J = 8.0 Hz), 7.41 (2H, t, J = 7.8 Hz), 7.35 (1H, d, J = 2.0 Hz), 7.32 (1H, t, J = 7.6 Hz), 7.21 (1H, dd, J = 5.4, 2.2 Hz), 2.69 (3H, s).

[1066] (2) Preparation of A-58

[1067] To a solution of 4-1 (18.0 mg, 0.06 mmol) in N,N-dimethylformamide (1.2 mL) was added 3-aminobenzenesulfonamide (15.0 mg, 0.09 mmol) and potassium carbonate (25.0 mg, 0.18 mmol) at room temperature. The mixture was degassed by purging and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate) (10.8 mg, 0.01 mmol), the reaction mixture was heated at 100 °C for 4 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by NH-silica column chromatography (hexane:ethyl acetate=1:1) to give A-58 (6.6 mg, 25%) as a dentin solid.

[1068] The following A-59 to A-108 were synthesized by following the procedure of step 2 from the synthesis of A-58.

[1069] 10. Synthesis of A-109

[1070] [ka]

[1071] (1) Preparation of methyl 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate (4-2)

[1072] To a solution of 4-1 (50.0 mg, 0.17 mmol) in N,N-dimethylformamide (3.3 mL) were added methyl 3-aminobenzoate (37.0 mg, 0.25 mmol) and potassium carbonate (68.0 mg, 0.50 mmol) at room temperature. The mixture was degassed by purging and refilled with argon in several portions. After the addition of BrettPhos Pd G1 (chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (44.0 mg, 0.05 mmol), the reaction mixture was heated at 100 °C for 4 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 3:1) to give 4-2 (61.0 mg, 88%) as a yellow oil.

[1073] 1H-NMR (400 MHz, DMSO-d6):δ 9.37 (1H, s), 8.26 (1H, s), 8.16 (1H, d, J = 6.0 Hz), 7.92 (1H, d, J = 8.0 Hz), 7.83 (2H, d, J = 7.6 Hz), 7.48-7.30 (5H, m), 6.69 (1H, d, J = 4.4 Hz), 6.45 (1H, d, J = 1.6 Hz), 3.84 (3H, s), 2.71 (3H, s).

[1074] (2) Preparation of A-109

[1075] To a solution of 4-2 (61.0 mg, 0.15 mmol) in tetrahydrofuran / water (v / v = 1 / 1, 3 mL) was added lithium hydroxide (61.0 mg, 1.46 mmol) at room temperature. After stirring at room temperature for 18 h, the reaction mixture was concentrated under reduced pressure. The residue was acidified with 2 N aqueous HCl solution. The precipitated solid was collected by filtration to give A-109 (21 mg, 36%) as a denatured solid.

[1076] Using the procedure described for the synthesis of A-109, the following A-110 was synthesized.

[1077] 11. Synthesis of A-111 and A-112

[1078] [ka]

[1079] (1) Preparation of A-111

[1080] To a solution of 4-1 (300 mg, 0.99 mmol) in N,N-dimethylformamide (9.9 mL), 2-(3-aminophenyl)acetonitrile (196 mg, 1.49 mmol) and potassium carbonate (411 mg, 2.97 mmol) were added at room temperature. The mixture was purged and backfilled with argon several times. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (269 mg, 0.30 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=1:4) to give A-111 (343 mg, 87%) as a pale yellow solid.

[1081] (2) Preparation of A-112

[1082] To a solution of A-111 (150 mg, 0.376 mmol) in dioxane (4.7 mL) was added dibutyltin oxide (187 mg, 0.75 mmol) and trimethylsilyl azide (0.25 mL, 1.88 mmol) at room temperature. 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 ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica column chromatography to give A-112 (23.5 mg, 14%) as a dendritic solid.

[1083] The following A-113 was synthesized using the same procedure as for the synthesis of A-111.

[1084] The following A-114 was synthesized using the same procedure as for the synthesis of A-112.

[1085] 12. Synthesis of A-115

[1086] [ka]

[1087] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-cyclopropyl-4-phenylthiazole (5-1)

[1088] To a solution of 1-10 (358 mg, 0.97 mmol) in dioxane (7.3 mL) and water (2.4 mL) was added cyclopropylboronic acid (335 mg, 3.90 mmol) and potassium carbonate (404 mg, 2.92 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon in several portions, followed by the addition of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (143 mg, 0.20 mmol) at room temperature. The reaction mixture was heated at 90 °C for 18 h. After cooling to room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 1:1) to give 5-1 (92.0 mg, 29%) as a white solid.

[1089] 1H-NMR (400 MHz, DMSO-d6): δ 8.32 (1H, dd, J = 6.0 Hz), 7.73 (2H, d, J = 7.2 Hz), 7.39-7.33 (3H, m), 7.31-7.27 (1H, m), 7.17 (1H, dd, J = 5.8, 2.2 Hz), 2.42-2.37 (1H, m), 1.15-1.11 (2H, m), 1.09-1.03 (2H, m).

[1090] (2) Preparation of A-115

[1091] To a solution of 5-1 (20 mg, 0.06 mmol) in N,N-dimethylformamide (1.2 mL) was added 2-(3-aminophenyl)propan-2-ol (14.0 mg, 0.09 mmol) and potassium carbonate (25.0 mg, 0.18 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (11.0 mg, 0.01 mmol), the reaction mixture was heated at 100 °C for 2 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=2:1) ​​to give A-115 (10.7 mg, 40%) as a yellow solid.

[1092] The following A-116 to A-122 were synthesized using the procedure described in the synthesis of A-106.

[1093] 13.Synthesis of A-132 and A-133

[1094] [ka]

[1095] (1) Preparation of A-132

[1096] To a solution of A-130 (50.0 mg, 0.11 mmol) in tetrahydrofuran (0.94 mL) and water (0.19 mL) was added lithium hydroxide (27.0 mg, 1.12 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 4 hours. After cooling to 0 °C, the reaction mixture was acidified with aqueous 1 N HCl and concentrated under reduced pressure to give A-132 (40.0 mg, 83%) as a white solid, which was used in the next step without further purification.

[1097] (2) Preparation of A-133

[1098] A mixture of A-132 (40.0 mg, 0.09 mmol), HATU (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate) (53.0 mg, 0.14 mmol), N,N-diisopropylethylamine (0.049 mL, 0.28 mmol), and methanamine (2.0 M in tetrahydrofuran, 0.07 mL, 0.14 mmol) in N,N-dimethylformamide (0.93 mL) was stirred at room temperature for 2 hours. The reaction mixture was dissolved in ethyl acetate and washed with water and brine. The separated organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica column chromatography (dichloromethane:methanol = 10:1) to give A-133 (35.0 mg, 85%) as a white solid.

[1099] The following A-134 to A-136 were synthesized by following the procedure of step 1 from the synthesis of A-134.

[1100] 14. Synthesis of A-138

[1101] [ka]

[1102] To a solution of A-130 (50.0 mg, 0.11 mmol) in tetrahydrofuran (1.0 mL) and methanol (1.0 mL) was added sodium hydroxide (22.0 mg, 0.56 mmol) and aqueous HCl. Hydroxylamine (50% wt, 0.17 mL, 0.11 mmol) was added at room temperature. The mixture was heated at 50°C for 2 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was acidified with 2 N aqueous HCl. The precipitated solid was collected by filtration to give A-138 (8.9 mg, 18%) as a white solid.

[1103] The following A-139 was synthesized using the procedure described for the synthesis of A-138.

[1104] 15.Synthesis of A-140

[1105] [ka]

[1106] To a solution of A-132 (35.0 mg, 0.08 mmol) in N,N-dimethylformamide (1.6 mL) was added methanesulfonamide (2) (9.28 mg, 0.10 mmol), 4-dimethylaminopyridine (10.9 mg, 0.09 mmol), 2-chloro-1-methylpyridinium iodide (31.0 mg, 0.12 mmol), and triethylamine (34.0 μL, 0.24 mmol) at room temperature. The mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was triturated with dichloromethane and hexane, and the resulting solid was collected by filtration and dried under reduced pressure to give A-140 (11.0 mg, 27%) as a pale red solid.

[1107] 16. Synthesis of A-141

[1108] [ka]

[1109] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-methoxy-4-phenylthiazole (6-1)

[1110] To a solution of (60.0 mg, 0.16 mmol) in methanol (1.6 mL) was added sodium methoxide (25 wt% in methanol, 0.65 mmol) at room temperature. After stirring for 4 hours, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=3:1) to give 5-((2-chloropyridin-4-yl)oxy)-2-methoxy-4-phenylthiazole (6-1) (13.0 mg, 25%) as a yellow solid.

[1111] MS calculated: 318.78; MS found: 319.02 (M+H+)

[1112] (2) Preparation of A-141

[1113] To a solution of 6-1 (13 mg, 0.0410 mmol) in N,N-dimethylformamide (1.0 mL) was added 2-(3-aminophenyl)propan-2-ol (9.3 mg, 0.0610 mmol) and potassium carbonate (17.0 mg, 0.122 mmol) at room temperature. The mixture was degassed by purging and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (7.4 mg, 8.16 μmol), the reaction mixture was heated at 100 °C for 2 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=3:1) to give A-141 (1.1 mg, 6%) as a yellow solid.

[1114] A-142 to A-144 were synthesized by following the procedure of step 2 from the synthesis of A-141.

[1115] 17. Synthesis of A-145

[1116] [ka]

[1117] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-4-phenyl-2-(trifluoromethyl)thiazole (7-1) To a solution of 1-10 (200 mg, 0.54 mmol) in N,N-dimethylformamide (11 mL) was added methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (0.35 mL, 2.72 mmol), copper iodide (518 mg, 2.72 mmol), and triphenylarsine (67.0 mg, 0.22 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon in several portions. After adding Pd2(dba)3 (tris(dibenzylideneacetone)dipalladium(0)) (25.0 mg, 0.03 mmol), the reaction mixture was heated at 100 °C for 1 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=20:1) to give 7-1 (95.0 mg, 49%) as a yellow solid.

[1118] (2) Preparation of A-145

[1119] To a solution of 7-1 (100 mg, 0.28 mmol) in N,N-dimethylformamide (2.8 mL) was added 3-aminobenzenesulfonamide (72.0 mg, 0.14 mmol) and potassium carbonate (116 mg, 0.84 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (47.0 mg, 0.06 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=1:1) to give A-145 (10.0 mg, 7%) as a white solid.

[1120] The following A-146 to A-148 were synthesized using the procedure in step 2 from the synthesis of A-145.

[1121] 18. Synthesis of A-149 and A-150

[1122] [ka]

[1123] (1) Preparation of methyl 6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate (7-2)

[1124] To a solution of 7-1 (184.3 mg, 0.52 mmol) in N,N-dimethylformamide (2.0 mL) was added methyl 6-aminonicotinate (86.0 mg, 0.57 mmol) and potassium carbonate (214.0 mg, 1.55 mmol) at room temperature. The mixture was degassed by purging and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate) (187.0 mg, 0.21 mmol), the reaction mixture was heated at 100 °C for 14 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (127.6 mg, 52%) to give 7-2 as a crude yellow solid.

[1125] MS Calcd: 472.44, MS Detected 473.14 (M+H+)

[1126] (2) Preparation of A-149

[1127] To a solution of 7-2 (127.6 mg, 0.27 mmol) in tetrahydrofuran (2.0 mL) and water (2.0 mL) was added lithium hydroxide (34.0 mg, 0.81 mmol) at room temperature. The mixture was heated at 50 °C for 12 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was acidified with 1 N aqueous hydrochloric acid solution. The precipitated solid was collected by filtration to give A-149 (66.6 mg, 54%) as a white solid.

[1128] (3) Preparation of A-150

[1129] To a solution of A-149 (30.0 mg, 0.07 mmol) in N,N-dimethylformamide (4.0 mL) was added HATU (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate) (37.3 mg, 0.11 mmol), N,N-diisopropylethylamine (0.02 mL, 0.11 mmol), and 2 M methylamine in tetrahydrofuran solution (0.05 mL, 0.11 mmol) at room temperature. The mixture was stirred at room temperature for 17 hours. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (dichloromethane:methanol = 10:1) to give A-149 (3.1 mg, 10%) as a white solid.

[1130] The following A-151 and A-152 were synthesized using the procedure described for the synthesis of A-149.

[1131] 19. Synthesis of A-153

[1132] [ka]

[1133] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-N,N-dimethyl-4-phenylthiazol-2-amine (8-1)

[1134] To a solution of compound 1-10 (100 mg, 0.27 mmol) in N,N-dimethylformamide (5.5 mL), dimethylamine (2 M in tetrahydrofuran, 0.20 ml, 0.41 mmol) was added and stirred at 80 °C for 18 h. The reaction mixture was washed with water and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate:=3:2) to give 8-1 (32 mg, 36%) as a yellow oil.

[1135] 1H-NMR (400 MHz, CDCl3): δ 8.23 ​​(1H, d, J = 6.0 Hz), 7.81-7.78 (2H, m), 7.40-7.32 (3H, m), 7.03 (1H, m), 7.00-6.99 (1H, m), 3.12 (6H, s).

[1136] (2) Preparation of A-153

[1137] To a solution of compound 8-1 (30.0 mg, 0.09 mmol) in N,N-dimethylformamide (1.0 mL) was added 2-(3-aminophenyl)propan-2-ol (21.0 mg, 0.14 mmol) and potassium carbonate (37.0 mg, 0.27 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon several times. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (15.0 mg, 0.02 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=1:1) to give A-153 (1.3 mg, 3%) as a white solid.

[1138] The following A-154 to A-164 were synthesized using the procedure described in the synthesis of A-154.

[1139] 20. Synthesis of A-165 and A-166

[1140] [ka]

[1141] (1) Preparation of A-165

[1142] To a solution of 8-2 (100 mg, 0.22 mmol) in tetrahydrofuran (2.2 mL) and water (2.2 mL) was added lithium hydroxide (94.0 mg, 2.24 mmol) at room temperature. The mixture was heated at 50 °C for 18 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was acidified with 2 N hydrochloric acid solution. The precipitated solid was collected by filtration to give A-165 (19.5 mg, 20%) as a yellow solid.

[1143] (2) Preparation of A-166

[1144] To a solution of A-165 (60.0 mg, 0.14 mmol) in N,N-dimethylformamide (1.4 mL) was added HATU (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate) (79.0 mg, 0.21 mmol), MeNH (2 M in tetrahydrofuran, 10.4 μL, 0.201 mmol), and N,N-diisopropylethylamine (73.0 μL, 0.42 mmol) at room temperature. The mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was triturated with dichloromethane, and the resulting solid was filtered to give A-166 (26.0 mg, 42%) as a beige solid.

[1145] The following A-167 to A-169 were synthesized using the procedure described in the synthesis of A-165.

[1146] 21. Synthesis of A-170 and A-171

[1147] [ka]

[1148] (1) Preparation of A-170

[1149] To a solution of A-3 (104 mg, 0.25 mmol) in acetonitrile (2.5 mL) was added copper(II) bromide (56.0 mg, 0.25 mmol) and tert-butyl nitrite (38.0 mg, 0.37 mmol) at 0 °C. The mixture was stirred at 0 °C for 30 min. The reaction mixture was quenched with aqueous ammonia and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 3:1) to give A-170 (47.8 mg, 40%) as a pale yellow solid.

[1150] (2) Preparation of A-171

[1151] To a solution of A-170 (7.50 mg, 0.02 mmol) in tetrahydrofuran (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 under reduced pressure. The residue was acidified with 2N hydrochloric acid solution. The precipitated solid was collected by filtration to give A-171 (1.50 mg, 21%) as a white solid.

[1152] 22. Synthesis of A-172

[1153] [ka]

[1154] To a solution of 1-13 (15.0 mg, 0.03 mmol) in water (0.24 mL) and ethanol (1.4 mL), sodium hydroxide (1.34 mg, 0.03 mmol), dimethyl sulfoxide (3.55 μL, 0.05 mmol), and hydrogen peroxide (30 wt%, 3.92 μL, 0.05 mmol) were added at room temperature. After stirring at room temperature for 30 minutes, the reaction mixture was quenched with aqueous ammonia and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on NH-silica (dichloromethane:ethyl acetate = 1:1) to give A-172 (11.0 mg, 71%) as a yellow solid.

[1155] 23. Synthesis of A-173

[1156] [ka]

[1157] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-(cyclopent-1-en-1-yl)-4-phenylthiazole (9-1)

[1158] To a solution of (300 mg, 0.82 mmol) in dioxane (6.1 mL) and water (2.0 mL), cyclopentenylboronic acid (100 mg, 0.90 mmol) and potassium carbonate (189 mg, 1.37 mmol) were added at room temperature. The mixture was degassed by purging and refilled with argon in several portions. After adding palladium(II) chloride (119 mg, 0.16 mmol), the reaction mixture was heated at 90 °C for 18 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 10:1) to give 9-1 (125 mg, 42%) as a brown oil.

[1159] 1H-NMR (400 MHz, DMSO-d6):δ 8.33 (1H, d, J = 5.6 Hz), 7.79 (2H, d, J = 7.2 Hz), 7.42-7.39 (3H, m), 7.32 (1H, t, J = 7.4 Hz), 7.22 (1H, dd, J = 6.0, 2.4 Hz), 6.67 (1H, s), 2.78 (2H, t, J = 6.4 Hz), 2.54-2.51 (2H, m), 1.99 (2H, quint, J = 7.6 Hz)

[1160] (2) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-cyclopentyl-4-phenylthiazole (9-2)

[1161] To a solution of 9-1 (125 mg, 0.35 mmol) in methanol (3.5 mL) was added platinum(IV) oxide (96.0 mg, 0.42 mmol). The mixture was stirred at room temperature under a H atmosphere (balloon) for 2 hours. The reaction mixture was filtered through a Celite pad. The filtrate was concentrated under reduced pressure to give 9-2 (113 mg, 90%) as a yellow oil, which was used in the next step without further purification.

[1162] 1H-NMR (400 MHz, DMSO-d6): δ8.33 (1H, d, J = 5.6 Hz) ,7.77 (2H, d, J = 7.2 Hz) ,7.41-7.28 (4H, m),7.17 (1H, dd, J = 6.0, 2.4 Hz) ,3.43 (1H, quint, J = 8.2 Hz) ,2.16-2.08 (2H, m), 1.85-1.73 (4H, m), 1.67-1.65 (2H, m).

[1163] (3) Preparation of A-173

[1164] To a solution of 9-2 (113 mg, 0.32 mmol) in N,N-dimethylformamide (6.3 mL) was added 6-aminonicotinamide (48.0 mg, 0.35 mmol) and potassium carbonate (131 mg, 0.95 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (86.0 mg, 95.0 μmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica column chromatography (39.0 mg, 27%) to give A-173 as a white solid.

[1165] The following A-174 to A-176 were synthesized using the procedure described for the synthesis of A-173.

[1166] 24. Synthesis of A-177

[1167] [ka]

[1168] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-(cyclohex-1-en-1-yl)-4-phenylthiazole

[1169] A solution of 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), potassium carbonate (1.12 g, 8.16 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (398 mg, 0.54 mmol) was flushed with argon, and the mixture was stirred at 90 °C for 18 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (ethyl acetate:hexane = 1:10) to give 10-1 (728 mg, 72%) as a yellow solid.

[1170] 1H-NMR (400 MHz, CDCl3):δ 8.27 (1H, d, J = 6.0 Hz), 7.85 (2H, d, J = 7.2 Hz), 7.37 (2H, t, J = 6.8 Hz), 7.30 (1H, d, J = 7.2 Hz), 7.02 (1H, d, J = 2.4 Hz), 6.95 (1H, dd, J = 6.0, 2.4 Hz), 6.63 (1H, s), 2.58 (2H, m), 2.27-2.26 (2H, m), 1.81-1.78 (2H, m), 1.73-1.69 (2H, m).

[1171] (2) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-cyclohexyl-4-phenylthiazole (10-2)

[1172] To a mixture of 10-1 (710 mg, 1.92 mmol) in methanol (19 mL) was added platinum(IV) oxide (524 mg, 2.3 mmol) and stirred at room temperature for 1 h under an atmosphere of H2 delivered from a latex balloon. The mixture was filtered through a pad of Celite and washed with methanol. The filtrate was concentrated in vacuo to give 10-2 (210 mg, 30%) as a white solid.

[1173] 1H-NMR (400 MHz, CDCl3):δ 8.27 (1H, d, J = 6.0 Hz), 7.82 (2H, 7.2 Hz), 7.37 (2H, t, J = 6.8 Hz), 7.27 (1H, d, J = 8.8 Hz), 7.00 (1H, d, J = 2.0 Hz), 6.93 (1H, dd, J = 6.0, 2.4 Hz), 2.96 (1H, m), 2.21-2.18 (2H, m), 2.09 (1H, s), 1.89-1.86 (2H, m), 1.77-1.74 (1H, m), 1.48-1.45 (2H, m), 0.82-0.80 (2H, m).

[1174] (3) Preparation of A-177

[1175] To a solution of 10-2 (50.0 mg, 0.13 mmol) in N,N-dimethylformamide (1.3 mL) were added 6-aminonicotinamide (22 mg, 0.16 mmol) and potassium carbonate (55 mg, 0.4 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon in several portions. After BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate methanesulfonate) (36.0 mg, 0.04 mmol) was added, the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was washed with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (dichloromethane:methanol=9:1) to give A-177 (1.8 mg, 2%) as a pink solid.

[1176] The following A-178 to A-180 were synthesized using the procedure described in the synthesis of A-177.

[1177] 25. Synthesis of A-181

[1178] [ka]

[1179] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-4-phenyl-2-vinylthiazole

[1180] To a solution of 1-10 (900 mg, 2.45 mmol) in 1,4-dioxane (22 mL) and water (2.2 mL) was added 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (754 mg, 4.90 mmol) and sodium carbonate (778 mg, 7.34 mmol) at room temperature. The mixture was degassed by purging and refilled with argon in several portions. After adding [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (269 mg, 0.37 mmol), the reaction mixture was heated at 100 °C for 18 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica (hexane:ethyl acetate=10:1) to give 11-1 (443 mg, 58%) as a yellow solid.

[1181] 1H-NMR (400 MHz, DMSO-d6):δ 8.37 (1H, d, J = 5.6 Hz), 7.81 (2H, d, J = 7.6 Hz), 7.45-7.41 (3H, m), 7.37-7.33 (1H, m), 7.27 (1H, dd, J = 5.4, ​​1.8 Hz), 6.96 (1H, dd, J = 17.6, 11.2 Hz), 6.11 (1H, d, J = 17.2 Hz), 5.70 (1H, d, J = 10.8 Hz).

[1182] (2) Method for producing 5-((2-chloropyridin-4-yl)oxy)-2-ethyl-4-phenylthiazole (11-2)

[1183] A mixture of 11-1 (443 mg, 1.41 mmol) and palladium on carbon (10 wt%, 150 mg, 0.14 mmol) in methanol (14 mL) was stirred at room temperature under a H atmosphere (balloon) for 1 h. After filtration through a Celite pad, the filtrate was concentrated in vacuo to give 11-2 (333 mg, 75%) as a yellow oil, which was used without further purification.

[1184] 1H-NMR (400 MHz, DMSO-d6):δ 8.33 (1H, d, J = 5.6 Hz), 7.77 (2H, d, J = 8.0 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.33-7.38 (2H, m), 7.18 (1H, dd, J = 5.6, 1.6 Hz), 2.99 (2H, q, J = 7.7 Hz), 1.32 (3H, t, J = 7.6 Hz).

[1185] (3) Preparation of A-181

[1186] To a solution of 11-2 (30.0 mg, 0.0950 mmol) in N,N-dimethylformamide (1.9 mL) was added 3-aminobenzenesulfonamide (24.0 mg, 0.14 mmol) and potassium carbonate (39.0 mg, 0.284 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (17.0 mg, 0.02 mmol), the reaction mixture was heated at 100 °C for 4 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica column chromatography (hexane:ethyl acetate=1:1) to give A-181 (21 mg, 49%) as a white solid.

[1187] The following A-182 to A-190 were synthesized using the procedure described in the synthesis of A-181.

[1188] 26. Synthesis of A-193 from A-191

[1189] [ka]

[1190] (1) Preparation of A-191

[1191] Methyl 6-aminonicotinate (96.0 mg, 0.63 mmol) and potassium carbonate (87.0 mg, 0.63 mmol) in 6.31 mL of N,N-dimethylformamide, 11-2 (200 mg, 0.63 mmol), and potassium carbonate (87.0 mg, 0.63 mmol) were degassed by purging and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (572 mg, 0.63 mmol), the reaction mixture was stirred at 100 °C for 4 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The separated organic layer was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give methyl 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate (A-191) (120 mg, 44%) as a yellow solid.

[1192] (2) Preparation of A-192

[1193] To a solution of A-191 (70.0 mg, 0.16 mmol) in tetrahydrofuran (1.29 mL) and water (0.32 mL) was added lithium hydroxide (39.0 mg, 1.62 mmol) at 0 °C. The reaction mixture was stirred at 50 °C for 24 h. After cooling to 0 °C, the reaction mixture was acidified with aqueous toluene and concentrated under reduced pressure to give A-192 (90.0 mg, quantitative) as a white solid, which was used in the next step without further purification.

[1194] (3) Preparation of A-193

[1195] A mixture of A-192 (50.0 mg, 0.12 mmol), HATU (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate) (68.0 mg, 0.18 mmol), N,N-diisopropylethylamine (0.06 mL, 0.36 mmol), and methanamine (0.09 mL, 0.18 mmol) in N,N-dimethylformamide (1.19 mL) was stirred at room temperature for 2 h. The reaction mixture was dissolved in ethyl acetate and washed with water and brine. The separated organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (dichloromethane:methanol = 10:1) to give A-193 (43.0 mg, 83%) as a white solid.

[1196] The following A-194 and A-195 were synthesized using the procedure described in the synthesis of A-192.

[1197] The following A-196 to A-215 were synthesized using the procedures described for the synthesis of A-191 or A-193.

[1198] 27. Synthesis of A-216 and A-217

[1199] [ka]

[1200] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-4-phenyl-2-(prop-1-en-2-yl)thiazole (12-1)

[1201] A solution of 1-10 (40.0 mg, 0.11 mmol) was added to potassium isopropenyltrifluoroborate (24.0 mg, 0.16 mmol), sodium carbonate (81.0 mg, 0.76 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (8.9 mg, 0.01 mmol) and flushed with argon. The mixture was stirred at 60 °C for 8 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (ethyl acetate:hexane = 1:4) to give 1-10 (24.0 mg, 67%) as a yellow oil.

[1202] 1H-NMR (400 MHz, CDCl3):δ 8.26 (1H, d, J = 6.0 Hz), 7.88-7.85 (2H, m), 7.39-7.35 (2H, m), 7.39-7.25 (1H, m), 7.02 (1H, d, J = 2.0 Hz), 6.95-6.93 (1H, m), 5.77 (1H, s), 5.37 (1H, d, J = 1.2 Hz), 2.26 (3H, s).

[1203] (2) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-isopropyl-4-phenylthiazole (12-2)

[1204] A mixture of 12-1 (300 mg, 0.91 mmol) in dichloromethane (10 mL) was added to 10% palladium on carbon (97.0 mg, 0.09 mmol) and stirred at room temperature for 30 min under an atmosphere of H2 delivered from a latex balloon. The mixture was filtered through a pad of Celite and washed with dichloromethane. The filtrate was concentrated in vacuo to give 12-2 (170 mg, 56%) as a colorless oil.

[1205] 1H-NMR (400 MHz, CDCl3):δ 8.26 (1H, d, J = 8.8 Hz), 7.83 (2H, d, J = 8.4 Hz), 7.35 (2H, t, J = 6.0 Hz), 7.27 (1H, t, J = 4.8 Hz), 7.00 (1H, d, J = 2.4 Hz), 6.92 (1H, dd, J = 2.4 Hz,6.0 Hz), 3.31-3.24 (1H, m), 1.42 (6H, 5.2 Hz).

[1206] (3) Preparation of A-216

[1207] To a solution of 12-2 (80.0 mg, 0.24 mmol) in N,N-dimethylformamide (2.4 mL) was added methyl 6-aminopicolinate (55.0 mg, 0.36 mmol) and potassium carbonate (100 mg, 0.72 mmol) at room temperature. The mixture was degassed by purging and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (65.0 mg, 0.07 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was washed with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=3:1) to give A-216 (41.0 mg, 38%) as a yellow solid.

[1208] (4) Preparation of A-217

[1209] To a solution of A-217 (41.0 mg, 0.09 mmol) in tetrahydrofuran (0.9 mL) and water (0.9 mL) was added lithium hydroxide (38.0 mg, 0.91 mmol) at 0 °C, and the reaction mixture was stirred at 50 °C for 18 h. After cooling to 0 °C, the reaction mixture was acidified with aqueous 1 N HCl solution and concentrated under reduced pressure to give A-217 (24.0 mg, 60%) as a yellow solid.

[1210] The following A-218 to A-229 were synthesized using the procedure described for the synthesis of A-216.

[1211] The following A-230 to A-232 were synthesized using the procedure described for the synthesis of A-217.

[1212] 28. Synthesis of A-233

[1213] [ka]

[1214] (1) Preparation of 2-((2-chloropyridin-4-yl)oxy)-1-(naphthalen-2-yl)ethan-1-one (13-2)

[1215] A mixture of 13-1 (1.50 g, 11.58 mmol), 2-bromo-1-(naphthalen-2-yl)ethane (3.46 g, 13.89 mmol), and potassium carbonate (2.40 g, 17.37 mmol) in acetone (20 mL) was stirred at room temperature for 18 hours. The reaction mixture was washed with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to give 13-2 (2.77 g, 80% yield) as a yellow foam, which was used in the next step without further purification.

[1216] 1H-NMR (400 MHz, CDCl3): δ 8.49 (1H, s), 8.21 (1H, d, J = 5.6 Hz), 8.01-7.86 (4H, m), 7.67-7.58 (2H, m), 6.88 (1H, d, J = 2.4 Hz), 6.82 (1H, dd, J = 2.4 Hz, 5.6 Hz), 5.49 (2H, s).

[1217] (2) Preparation of 2-bromo-2-((2-chloropyridin-4-yl)oxy)-1-(naphthalen-2-yl)ethan-1-one (13-3)

[1218] To a solution of 13-2 (230 mg, 0.77 mmol) in chloroform (8.0 mL) was added bromine (0.06 mL, 1.16 mmol) and aluminum chloride (21.0 mg, 0.15 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was washed with saturated aqueous sodium bicarbonate solution at 0 °C and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to give 13-3 (300 mg, quantitative) as a yellow foam, which was used in the next step without further purification.

[1219] 1H-NMR (400 MHz, CDCl3):δ 8.73 (1H, s), 8.40 (1H, d, J = 5.6 Hz), 8.14 (1H, d, J = 8.8 Hz), 8.03 -7.90 (3H, m), 7.69-7.59 (2H, m), 7.27 (1H, s), 7.16 (1H, s).

[1220] (3) Preparation of 5-((2-chloropyridin-4-yl)oxy)-N-methyl-4-(naphthalen-2-yl)thiazol-2-amine (13-4)

[1221] A mixture of 13-3 (480 mg, 1.27 mmol) and methylthiourea (115 mg, 1.27 mmol) in ethanol (13.0 mL) was stirred at 75 °C for 20 min. After cooling to room temperature, the solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate and washed with water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on NH-silica (dichloromethane) to give 13-3 (160 mg, 34%) as a yellow solid.

[1222] 1H-NMR (400 MHz, CDCl3):δ 8.25 (2H, d, J = 5.2 Hz), 7.85-7.76 (4H, m), 7.47-7.43 (2H, m), 7.08 (1H, d, J = 2.0 Hz), 7.00 (1H, dd, J = 2.4 Hz, 5.6 Hz), 5.59-5.57 (1H, m), 3.00 (3H, d, J = 4.8 Hz).

[1223] (4) Preparation of A-233

[1224] To a solution of 13-4 (80.0 mg, 0.22 mmol) in N,N-dimethylformamide (5.0 mL) was added potassium carbonate (90.0 mg, 0.65 mmol) and 3-aminobenzenesulfonamide (56.0 mg, 0.33 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon several times. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (39.0 mg, 0.04 mmol), the reaction mixture was heated at 100 °C for 5 h. After cooling at room temperature, the reaction mixture was washed with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on NH-silica (dichloromethane:methanol=98:2) to give A-233 (8.2 mg, 7%) as a beige solid.

[1225] 29. Synthesis of A-234

[1226] [ka]

[1227] (1) Preparation of 5-(2-chloropyridin-4-yloxy)-4-(naphthalen-2-yl)thiazol-2-amine

[1228] A mixture of 13-2 (300 mg, 0.80 mmol) and thiourea (61.0 mg, 0.80 mmol) in 7.9 mL of ethanol was heated at 70 °C for 20 min. After cooling to room temperature, the solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate and washed with water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on NH-silica (120 mg, 42%) to give 13-5 as a yellow solid.

[1229] 1H-NMR (400 MHz, CDCl3):δ 8.49 (1H, S), 8.21 (1H, d, J = 5.6 Hz), 7.90-8.02 (4H, m), 7.59-7.68 (2H, m), 6.89 (1H, d, J = 2.4 Hz), 6.82 (1H, dd, J = 2.4 Hz,5.6 Hz), 5.50 (2H, s).

[1230] (2) Preparation of di-tert-butyl 5-(2-chloropyridin-4-yloxy)-4-(naphthalen-2-yl)thiazol-2-ylcarbamate (13-6)

[1231] A mixture of 13-5 (300 mg, 0.85 mmol), di-tert-butyl dicarbonate (2.34 mL, 1.02 mmol), triethylamine (0.14 mL, 1.02 mmol), and 4-dimethylaminopyridine (10.4 mg, 0.08 mmol) in dichloromethane (30 mL) was stirred at room temperature for 18 hours. The reaction mixture was quenched with water and extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by medium-pressure liquid chromatography (330 mg, 70%) to give 13-6 as a yellow foam.

[1232] 1H-NMR (400 MHz, CDCl3):δ 8.29 (1H, s), 8.26 (1H, d, J = 5.6 Hz), 7.89 (1H, dd, J = 1.6 Hz,8.4 Hz), 7.80-7.75 (3H, m), 7.45 (2H, dd, J = 2.8 Hz,6.2 Hz), 7.06 (1H, d, J = 2.0 Hz), 7.06-6.99 (1H, m), 1.60 (18H, s).

[1233] (3) Preparation of tert-butyl 4-(naphthalen-2-yl)-5-(2-(3-sulfamoylphenylamino)pyridin-4-yloxy)thiazol-2-ylcarbamate

[1234] To a solution of 13-6 (200 mg, 0.36 mmol) in N,N-dimethylformamide (8 mL) was added potassium carbonate (150 mg, 1.08 mmol) and 3-aminobenzenesulfonamide (93.0 mg, 0.54 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon several times. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (65.0 mg, 0.07 mmol), the reaction mixture was heated at 100 °C for 18 h. After cooling at room temperature, the reaction mixture was washed with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=4:1) to give the title compound (120 mg, 56%) as a dark brown solid.

[1235] MS calculated: 689.8; MS found: 690.12 (M+H+)

[1236] (4) Preparation of A-234

[1237] To a solution of 13-7 (120 mg, 0.20 mmol) in dichloromethane (5.0 mL) was added trifluoroacetic acid (0.18 mL, 2.03 mmol) and stirred at room temperature for 18 h. The reaction mixture was neutralized with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on NH-silica (dichloromethane:methanol=95:5) to give A-234 (10.0 mg, 10%) as a beige solid.

[1238] 30.Synthesis of A-235

[1239] [ka]

[1240] (1) Preparation of 2-bromo-5-(2-chloropyridin-4-yloxy)-4-(naphthalen-2-yl)thiazole (13-8)

[1241] 13-5 (9.49 g, 26.8 mmol) was dissolved in acetonitrile (90 ml) at 0 °C, followed by the addition of copper(II) bromide (5.40 ml, 40.2 mmol) and isopentyl nitrite. The reaction mixture was stirred at 0 °C for 90 min. The reaction mixture was quenched with NH4OH and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 1:4) to give 13-8 (5.40 g, 48%) as a brown solid.

[1242] 1H-NMR (400 MHz, CDCl3):δ 8.33 (1H, s), 8.29 (1H, dd, J = 6.0 Hz), 7.88-7.78 (4H, m), 7.50-7.45 (2H, m), 7.06 (1H, d, J = 2.5 Hz), 6.98-6.96 (1H, m).

[1243] (2) Preparation of 5-(2-chloropyridin-4-yloxy)-N,N-dimethyl-4-(naphthalen-2-yl)thiazol-2-amine (13-9)

[1244] A mixture of N,N-dimethylformamide (100 mg, 0.24 mmol) with dimethylamine (2 M in tetrahydrofuran, 0.18 ml, 0.36 mmol) was stirred at room temperature up to 50 °C for 2 days. After cooling at room temperature, it was washed with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 3:2) to give 13-9 (23.0 mg, 25%) as a yellow oil.

[1245] 1H-NMR (400 MHz, CDCl3):δ 8.30 (1H, s), 8.25 (1H, d, J = 6.0 Hz), 7.90 (1H, dd, J = 1.6 Hz,8.6 Hz), 7.82-7.71 (3H, m), 7.46-7.41 (2H, m), 7.08 (1H, d, J = 2.0 Hz), 7.00 (1H, dd, J = 2.4 Hz,6.0 Hz), 3.16 (6H, s).

[1246] (3) Preparation of A-235

[1247] To a solution of 13-9 (23.0 mg, 0.06 mmol) in N,N-dimethylformamide (2 mL) was added potassium carbonate (33.0 mg, 0.24 mmol) and 3-aminobenzenesulfonamide (16.0 mg, 0.09 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon several times. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (11.0 mg, 0.01 mmol), the reaction mixture was heated at 100 °C for 18 h. After cooling at room temperature, the reaction mixture was washed with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=1:1) to give A-235 (5.8 mg, 18%) as a pale yellow solid.

[1248] 31. Synthesis of A-236

[1249] [ka]

[1250] (1) Preparation of 2-(6-chloropyrimidin-4-yloxy)-1-phenylethanone (14-1)

[1251] To a solution of 1-1 (5.03 g, 25.3 mmol) in acetone (46 mL), 6-chloropyrimidin-4-ol (3.00 g, 23.0 mmol) and potassium carbonate (4.76 g, 34.5 mmol) were added at room temperature. After stirring at room temperature for 4 hours, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 1:2) to give 14-1 (5.55 g, 97%) as a white solid.

[1252] 1H-NMR (400 MHz, CDCl3): δ 8.01 (2H, d, J = 8.0 Hz), 7.96 (1H, s), 7.68 (1H, t, J = 7.4 Hz), 7.54 (2H, t, J = 7.8 Hz), 6.59 (1H, s), 5.36 (2H, s).

[1253] (2) Preparation of 2-bromo-2-(6-chloropyrimidin-4-yloxy)-1-phenylethanone (14-2)

[1254] To a solution of 14-1 (5.55 g, 22.3 mmol) in chloroform (74 mL) was slowly added aluminum chloride (1.19 g, 8.93 mmol) and bromine (1.73 mL, 33.5 mmol) at room temperature. The mixture was stirred at room temperature for 18 hours. The reaction mixture was quenched with saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 5:1) to give 14-2 (4.71 g, 64%) as a white solid.

[1255] 1H-NMR (400 MHz, CDCl3): δ 8.53 (1H, s), 8.14 (1H, s), 8.08 (2H, d, J = 8.08 Hz), 7.70 (1H, t, J = 7.8 Hz), 7.56 (2H, t, J = 7.6 Hz), 6.53 (1H, s).

[1256] (3) Preparation of 5-(6-chloropyrimidin-4-yloxy)-4-phenylthiazol-2-amine (14-3)

[1257] A mixture of 14-2 (4.70 g, 14.4 mmol) and thiourea (1.20 g, 15.8 mmol) in acetonitrile (48 mL) was heated at 80 °C for 30 min. After cooling to room temperature, the reaction mixture was quenched with saturated sodium hydroxide and extracted with sodium bicarbonate solution and ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to give 14-3 (4.03 g, 92%) as a yellow solid, which was used in the next step without further purification.

[1258] 1H-NMR (400 MHz, DMSO-d6): δ 8.44 (1H, d, J = 14.4 Hz), 8.06 (1H, d, J = 8.0 Hz), 7.60 (1H, t, J = 7.6 Hz), 7.43 (1H, s), 7.34-7.30 (3H, m). The two protons from NH2 were not observed.

[1259] (4) Synthesis of tert-butoxycarbonyl (5-((6-chloropyrimidin-4-yl)oxy)-4-phenylthiazol-2-yl)carbamate (14-4)

[1260] To a solution of 14-3 (1.00 g, 3.28 mmol) in tetrahydrofuran (33 mL) was added di-tert-butyl dicarbonate (2.15 g, 9.84 mmol), triethylamine (1.37 mL, 9.84 mmol), and 4-dimethylaminopyridine (80.0 mg, 0.67 mmol) at room temperature. The mixture was stirred at room temperature for 18 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 5:1 to 3:1) to give compound 14-4 (1.14 g, 69%) as a yellow solid.

[1261] 1H-NMR (400 MHz, CDCl3): δ 7.84 (1H, s), 7.44-7.41 (2H, m), 7.36-7.32 (3H, m), 6.67 (1H, s), 1.58 (18H, s).

[1262] (5) Preparation of tert-butyl 4-phenyl-5-(6-(3-sulfamoylphenylamino)pyrimidin-4-yl)-thizol-2-ylcarbamate (14-5)

[1263] To a solution of 14-4 (300 mg, 0.60 mmol) in N,N-dimethylformamide (6.0 mL) was added 3-aminobenzenesulfonamide (113 mg, 0.65 mmol) and potassium carbonate (246 mg, 1.78 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (162 mg, 0.18 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=1:3) to give 14-5 (106 mg, 28%) as a yellow solid.

[1264] 1H-NMR (400 MHz, DMSO-d6): δ 9.78 (1H, s), 8.30 (1H, s), 7.84 (1H, s), 7.59-7.57 (1H, m), 7.51-7.49 (2H, m), 7.36-7.33 (3H, m), 7.15 (2H, s), 6.98 (1H, s), 6.90 (1H, d, J = 7.6 Hz), 6.68 (1H, d, J = 6.8 Hz), 1.53 (9H, s).

[1265] *No protons from NH were observed.

[1266] (6) Preparation of A-236

[1267] To a solution of 14-5 (106 mg, 0.17 mmol) in dichloromethane (1.7 mL) was added trifluoroacetic acid (0.13 mL, 1.65 mmol) at 0 °C. The mixture was stirred at room temperature for 18 h. The reaction mixture was quenched with saturated sulfuric acid and extracted with sodium bicarbonate solution and ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on NH-silica (dichloromethane:methanol = 20:1) to give A-236 (7.6 mg, 10%) as a pale yellow solid.

[1268] 32. Synthesis of A-237

[1269] [ka]

[1270] (1) Preparation of 2-bromo-5-(6-chloropyrimidin-4-yloxy)-4-phenylthiazole (14-6)

[1271] To a solution of 14-3 (400 mg, 1.31 mmol) in acetonitrile (6.6 mL) was added copper(II) bromide (293 mg, 1.31 mmol) and isopentyl nitrite (0.26 mL, 1.97 mmol) at 0 °C. After stirring at room temperature for 1 h, the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 5:1) to give 14-6 (284 mg, 59%) as a pale yellow solid.

[1272] 1H-NMR (400 MHz, CDCl3): δ 7.81 (1H, s), 7.45-7.40 (5H, m), 6.69 (1H, s).

[1273] (2) Preparation of 5-(6-chloropyrimidin-4-yloxy)-2-methyl-4-phenylthiazole (14-7)

[1274] To a solution of 14-6 (284 mg, 0.77 mmol) in tetrahydrofuran (7.7 mL) was added MeZnCl (2 M in tetrahydrofuran, 0.96 ml, 1.93 mmol) and copper iodide (103 mg, 0.54 mmol) at room temperature. The mixture was degassed by purging and refilled with argon in several portions. After adding [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (113 mg, 0.15 mmol), the reaction mixture was refluxed for 1 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=1:1) to give 14-7 (111 mg, 47%) as a yellow solid.

[1275] 1H-NMR (400 MHz, CDCl3): δ 7.82 (1H, s), 7.45-7.43 (2H, m), 7.41-7.37 (3H, m), 6.67 (1H, s), 2.79 (3H, s).

[1276] (3) Preparation of A-237

[1277] To a solution of 14-7 (111 mg, 0.37 mmol) in N,N-dimethylformamide (3.7 mL) was added 3-aminobenzenesulfonamide (69.0 mg, 0.40 mmol) and potassium carbonate (152 mg, 1.10 mmol) at room temperature. The mixture was degassed by purging and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (99.0 mg, 0.11 mmol), the reaction mixture was heated at 80 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=1:3) to give A-237 (38 mg, 24%) as a yellow solid.

[1278] 33.Synthesis of A-238

[1279] [ka]

[1280] (1) Preparation of 2-(2-chloropyrimidin-4-yloxy)-1-phenylethanone (15-1)

[1281] To a solution of 1-1 (1.68 g, 8.43 mmol) in acetone (15 mL), 2-chloropyrimidin-4-ol (1.00 g, 7.66 mmol) and potassium carbonate (1.59 g, 11.5 mmol) were added at room temperature. After stirring at room temperature for 4 hours, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 1:2) to give 2-(2-chloropyrimidin-4-yloxy)-1-phenylethanone (15-1) (1.69 g, 89%) as a white solid.

[1282] 1H-NMR(400MHz, CDCl3): δ 8.37(1H, d, J = 5.2Hz), 7.97(2H, d, J = 8.0Hz), 7.65(1H, t, J = 7.2Hz), 7.53(2H, t, J = 7.8Hz), 6.89(1H, d, J = 5.6Hz), 5.71(2H, s).

[1283] (2) Preparation of 2-bromo-2-(2-chloropyrimidin-4-yloxy)-1-phenylethanone (15-2)

[1284] To a solution of 15-1 (1.69 g, 6.80 mmol) in chloroform (23 mL) was slowly added aluminum chloride (362 mg, 2.72 mmol) and bromine (0.525 mL, 10.2 mmol) at 0 °C. The mixture was stirred at room temperature for 18 h. The reaction mixture was quenched with saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 3:1) to give the title compound (1.55 g, 70% yield) as a white solid.

[1285] 1H-NMR(400MHz, CDCl3): δ 8.50(1H, d, J = 5.6Hz), 8.11(2H, d, J = 7.6Hz), 8.06(1H, s), 7.66(1H, t, J = 7.4Hz), 7.54(2H, t, J = 7.8Hz), 6.99(1H, d, J = 5.6Hz).

[1286] (3) Preparation of 5-(2-chloropyrimidin-4-yloxy)-4-phenylthiazol-2-amine (15-3)

[1287] A mixture of 15-2 (1.55 g, 4.73 mmol) and thiourea (396 mg, 5.21 mmol) in acetonitrile (16 mL) was heated at 80 °C for 30 min. After cooling to room temperature, the reaction mixture was quenched with saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to give 15-3 (1.13 g, 78%) as a yellow solid, which was used in the next step without further purification.

[1288] 1H-NMR (400 MHz, DMSO-d6):δ 8.67 (1H, d, J = 5.6 Hz), 7.67 (2H, d, J = 8.0 Hz), 7.37 (2H, d, J = 6.0 Hz), 7.32 (2H, d, J = 7.6 Hz), 7.12 (2H, s).

[1289] (4) Preparation of 2-bromo-5-(2-chloropyrimidin-4-yloxy)-4-phenylthiazole

[1290] To a solution of 15-3 (400 mg, 1.31 mmol) in acetonitrile (6.6 mL) were added copper(II) bromide (293 mg, 1.31 mmol) and isopentyl nitrite (0.26 mL, 1.97 mmol) at 0 °C, and the mixture was stirred at 0 °C for 1 h. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 3:1) to give 15-4 (159 mg, 33%) as a yellow solid.

[1291] 1H-NMR (400 MHz, DMSO-d6):δ 8.76 (1H, d, J = 6.0 Hz), 7.86 (2H, d, J = 7.2 Hz), 7.56 (1H, d, J = 6.0 Hz), 7.46 (2H, t, J = 7.4 Hz), 7.38 (1H, t, J = 7.4 Hz).

[1292] (5) Preparation of 5-(2-chloropyrimidin-4-yloxy)-2-methyl-4-phenylthiazole (15-5)

[1293] To a solution of 15-4 (159 mg, 0.43 mmol) in tetrahydrofuran (4.3 mL) at room temperature, methylzinc chloride (2 M in tetrahydrofuran, 0.54 mL, 1.08 mmol) and copper iodide (63.0 mg, 0.30 mmol) were added. The mixture was purged, degassed, and refilled with argon in several portions. After adding [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (63.0 mg, 0.09 mmol), the reaction mixture was refluxed for 1 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 3:1) to give 15-5 (57.0 mg, 44%) as a yellow solid.

[1294] 1H-NMR (400 MHz, DMSO-d6): δ 8.72 (1H, d, J = 5.2 Hz), 7.81 (2H, d, J = 7.2 Hz), 7.47 (1H, d, J = 5.6 Hz), 7.41 (2H, t, J = 7.6 Hz), 7.31 (1H, t, J = 7.4 Hz), 2.67 (3H, s).

[1295] (6) Preparation of A-238

[1296] 15-5 (57.0 mg, 0.19 mmol) was dissolved in N,N-dimethylformamide (1.9 mL), followed by the addition of 3-aminobenzenesulfonamide (36.0 mg, 0.21 mmol) and potassium carbonate (78.0 mg, 0.56 mmol) at room temperature. The mixture was degassed by purging and refilled with argon in several portions. After the addition of BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (51.0 mg, 0.06 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on NH-silica (dichloromethane:methanol=20:1) to give A-238 (8.8 mg, 11%) as a white solid.

[1297] 34. Synthesis of A-239

[1298] [ka]

[1299] (1) Preparation of tert-butyl (tert-butoxycarbonyl) (5- ( (2-chloropyrimidin-4-yl) oxy) -4-phenylthiazol-2-yl) carbamate (15-6)

[1300] To a solution of 15-3 (700 mg, 3.28 mmol) in tetrahydrofuran (23 mL) was added di-tert-butyl dicarbonate (1.50 g, 6.89 mmol), triethylamine (0.96 mL, 6.89 mmol), and 4-dimethylaminopyridine (56.0 mg, 0.46 mmol) at room temperature. The mixture was stirred at room temperature for 18 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 5:1 to 3:1) to give compound 15-6 (339 mg, 29%) as a yellow solid.

[1301] Compound 15-6: MS calculated: 504.99; MS found: 504.78 (M+H+)

[1302] (2) Preparation of tert-butyl 4-phenyl-5-(2-(3-sulfamoylphenylamino)pyrimidin-4-yloxy)-thizol-2-ylcarbamate (15-7)

[1303] To a solution of 15-6 (339 mg, 0.67 mmol) in N,N-dimethylformamide (6.0 mL), 3-aminobenzenesulfonamide (127 mg, 0.74 mmol) and potassium carbonate (278 mg, 2.01 mmol) were added at room temperature. The mixture was purged, degassed, and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (183 mg, 0.20 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate=1:1) to give (144 mg, 40%) as a beige solid.

[1304] 1H-NMR (400 MHz, DMSO-d6): δ11.6 (1H, s),10.0 (1H, s),8.45 (1H, d, J = 6.0 Hz) ,8.08 (1H, s),7.91 (1H, d, J = 6.8 Hz) ,7.74 (2H, d, J = 7.06 Hz) ,7.41-7.32 (4H, m),7.31-7.25 (3H, m),6.72 (1H, d, J = 5.2 Hz) ,1.48 (9H, s).

[1305] (3) Preparation of A-239

[1306] To a solution of 15-7 (144 mg, 0.27 mmol) in dichloromethane (2.7 mL) was added trifluoroacetic acid (0.31 mL, 4.00 mmol) at 0 °C. The mixture was stirred at room temperature for 18 h. The reaction mixture was quenched with saturated sodium bicarbonate solution and extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on NH-silica (dichloromethane:methanol = 10:1) to give A-239 (5.0 mg, 4%) as a white solid.

[1307] 35. Synthesis of A-240

[1308] [ka]

[1309] (1) Preparation of 5-(2-chloropyrimidin-4-yloxy)-4-phenyl-2-vinylthiazole (15-8)

[1310] To a solution of 15-4 (170 mg, 0.46 mmol) in dioxane (2.1 mL) and water (0.21 mL), 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (107 mg, 0.69 mmol) and sodium carbonate (147 mg, 1.38 mmol) were added at room temperature. The mixture was purged and backfilled with argon in several portions. After the addition of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (67.5 mg, 0.09 mmol), the reaction mixture was heated at 80 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica (hexane:ethyl acetate=9:1) to give 15-8 (59.0 mg, 41%) as an ivory oil.

[1311] 1H-NMR (400 MHz, CDCl3):δ 8.53 (1H, d, J = 6.0 Hz), 7.87 (2H, d, J = 7.6 Hz), 7.44-7.40 (2H, m), 7.35-7.33 (1H, m), 7.01 (1H, d, J = 5.6 Hz), 6.92-6.85 (1H, m), 6.07-6.02 (1H, m), 5.61-5.58 (1H, m).

[1312] (2) Preparation of 5-(2-chloropyrimidin-4-yloxy)-2-ethyl-4-phenylthiazol (15-9)

[1313] A mixture of 15-8 (59.0 mg, 0.19 mmol) and palladium on carbon (5 wt%, 9.94 mg, 0.09 mmol) in methanol (3.7 mL) was stirred at room temperature under a H atmosphere (balloon) for 3 h. After filtration through a Celite pad, 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.

[1314] 1H-NMR (400 MHz, CDCl3):δ 8.51 (1H, d, J = 5.2 Hz), 7.85 (1H, d, J = 7.2 Hz), 7.42-7.38 (2H, m), 7.33-7.29 (1H, m), 6.97 (1H, d, J = 5.2 Hz), 3.04 (2H, q, J = 7.6 Hz), 1.44 (3H, t, J = 7.4 Hz).

[1315] (3) Preparation of A-240

[1316] To a solution of 15-9 (51.0 mg, 0.16 mmol) in N,N-dimethylformamide (2.0 mL) was added 3-aminobenzenesulfonamide (33.2 mg, 0.19 mmol) and potassium carbonate (66.5 mg, 0.48 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (43.6 mg, 0.05 mmol), the reaction mixture was heated at 100 °C for 4 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by NH-silica column chromatography (8.5 mg, 12%) to give A-240 as a dentin solid.

[1317] The following A-241 to A-246 were synthesized using the procedure described for the synthesis of A-240.

[1318] 36. Preparation of Intermediate tert-Butyl (5-((2-chloropyridin-4-yl)oxy)-4-(6-methylpyridin-2-yl)thiazol-2-yl)carbamate (16-6)

[1319] [ka]

[1320] (1) Preparation of 2-bromo-1-(6-methylpyridin-2-yl)ethanone (16-2)

[1321] To a solution of 1-(6-methylpyridin-2-yl)ethanone (16-1) (10.0 g, 74.0 mmol) in dichloromethane (148 mL) was added hydrogen bromide (33% in acetic acid) (24.35 mL, 148 mmol) and bromine (4.58 mL, 89.0 mmol) at 0 °C. The mixture was stirred at room temperature for 3 h. The reaction mixture was neutralized with saturated sodium chloride. Sodium bicarbonate (aqueous) was added at 0 °C and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to give a yellow oil (15.52 g, 98% yield), which was used in the next step without further purification.

[1322] 1H-NMR (400 MHz, DMSO-d6): δ 7.90 (1H, t, J = 7.6 Hz), 7.81 (1H, d, J = 7.6 Hz), 7.55 (1H, d, J = 7.6 Hz), 4.99 (2H, s), 2.55 (3H, s).

[1323] (2) Preparation of 4-(6-methylpyridin-2-yl)thiazol-2-amine (16-3)

[1324] 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 neutralized with saturated fatty acid. Sodium bicarbonate (aqueous) was added at 0 °C and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to give 16-3 (12.3 g, 89%) as a yellow solid, which was used in the next step without further purification.

[1325] 1H-NMR (400 MHz, DMSO-d6):δ 7.66 (1H, t, J = 7.8 Hz), 7.59 (1H, d, J = 7.6 Hz), 7.16 (1H, s), 7.09 (1H, d, J = 7.2 Hz), 7.05 (2H, s), 2.45 (3H, s).

[1326] (3) Preparation of tert-butoxycarbonyl) (4-(6-methylpyridin-2-yl)thiazol-2-yl)carbamate (16-4)

[1327] To a solution of 16-3 (12.3 g, 64.3 mmol) in tetrahydrofuran (19 mL) was added di-tert-butyl dicarbonate (42.1 g, 193 mmol), 4-dimethylaminopyridine (2.35 g, 19.29 mmol), and triethylamine (26.7 mL, 193 mmol) at room temperature. The mixture was stirred at room temperature for 18 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 5:1) to give 16-4 (15.78 g, 62%) as a pale yellow solid.

[1328] 1H-NMR (400 MHz, DMSO-d6):δ 7.90 (1H, s,J = 7.6 Hz), 7.78 (1H, d, J = 8.0 Hz), 7.62 (1H, t, J = 8.0 Hz), 7.06 (1H, d, J = 7.6 Hz), 2.57 (3H, s), 1.53 (18H, s).

[1329] (4) Preparation of tert-butyl (5-bromo-4-(6-methylpyridin-2-yl)thiazol-2-yl) (tert-butoxycarbonyl)carbamate (16-5)

[1330] To a solution of 16-4 (15.7 g, 40.1 mmol) in N,N-dimethylformamide (201 mL) was slowly added N-bromosuccinimide (7.85 g, 44.1 mmol) at 0 °C, and the mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with saturated chlorine and extracted with sodium bicarbonate (aqueous) and ethyl acetate. The organic layer was washed several times with brine, then dried over sodium sulfate, filtered, and concentrated under reduced pressure to give 16-5 (16.3 g, 86%) as a brown oil, which was used in the next step without further purification.

[1331] 1H-NMR (400 MHz, DMSO-d6): δ 7.77 (1H, t, J = 7.6 Hz), 7.61 (1H, d, J = 8.0 Hz), 7.24 (1H, d, J = 7.2 Hz), 2.51 (3H, s), 1.51 (18H, s).

[1332] (5) Preparation of tert-butyl 5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)thiazol-2-ylcarbamate (16-6)

[1333] A mixture of 16-5 (15.5 g, 33.0 mmol), 2-chloropyridin-4-ol (4.70 g, 36.2 mmol), and potassium carbonate (9.11 g, 65.9 mmol) in N,N-dimethylformamide (165 mL) was stirred at 100 °C for 150 min, and the reaction was monitored hourly by LC-MS to confirm the consumption of compound 5. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed several times with brine, then dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on NH-silica (hexane:ethyl acetate=2:1) ​​to give 16-6 (6.4 g, 37%) as a yellow solid.

[1334] 1H-NMR (400 MHz, DMSO-d6): δ8.24 (1H, d, J = 5.6 Hz) ,7.68 (1H, t, J = 7.6 Hz) ,7.60 (1H, d, J = 7.2 Hz), 7.16 (1H, s), 7.08-7.04 (2H, m),2.09 (3H, s), 1.47 (9H, s). * No protons from NH were observed.

[1335] 37.Synthesis of A-247

[1336] [ka]

[1337] (1) Preparation of tert-butyl 4-(6-methylpyridin-2-yl)-5-(2-(3-sulfamoylphenylamino)pyridin-4-yloxy)thiazol-2-ylcarbamate (16-7)

[1338] To a solution of 16-6 (150 mg, 0.36 mmol) in N,N-dimethylformamide (7.2 mL) was added 3-aminobenzenesulfonamide (92.0 mg, 0.54 mmol) and cesium carbonate (350 mg, 1.07 mmol) at room temperature. The mixture was degassed by purging and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (97.0 mg, 0.11 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on NH-silica (ethyl acetate to ethyl acetate only:methanol=50:1) to give 16-7 (44.0 mg, 22%) as a yellow solid.

[1339] 1H-NMR (400 MHz, DMSO-d6): δ9.31 (1H, s), 8.20 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.80 (1H, d, J = 8.4 Hz), 7.70 (1H, t, J = 7.8 Hz),7.60 2.2 Hz) ,6.43 (1H, d, J = 2.0 Hz), 2.25 (3H, s), 1.50 (9H, s).* No proton from NH was observed.

[1340] (2) Preparation of A-247

[1341] Trifluoroacetic acid (0.122 mL, 1.59 mmol) was added to a solution (1.6 mL) of dichloromethane (44.0 mg, 0.08 mmol) at 0 °C. After stirring at room temperature for 1 h, the reaction mixture was quenched with saturated sulfuric acid. The mixture was extracted with sodium bicarbonate and 5% methanol in dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on NH-silica (ethyl acetate and ethyl acetate only:methanol = 10:1) to give A-247 (7.0 mg, 19%) as a pale orange solid.

[1342] The following A-248 and A-249 were synthesized using the procedure described in the synthesis of A-247.

[1343] 38.Synthesis of A-250

[1344] [ka]

[1345] (1) Preparation of 5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)thiazol-2-amine (16-8)

[1346] To a solution of 16-6 (6.4 g, 15.28 mmol) in dichloromethane (153 mL) was added trifluoroacetic acid (23.54 ml, 306 mmol) at 0 °C. After stirring at room temperature for 5 h, the reaction mixture was neutralized with saturated fatty acid. Sodium bicarbonate (aqueous) was added at 0 °C, and the mixture was extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to give 16-8 (4.3 g, 88%) as a red solid, which was used in the next step without further purification.

[1347] 1H-NMR (400 MHz, DMSO-d6): δ8.25 (1H, d, J = 5.6 Hz),7.64 (1H, d,, J = 6.8 Hz),7.54 (1H, d, J = 8.0 Hz), 7.22 (2H, s), 7.11 (1H, s),7.06 (1H, d, J = 6.0 Hz) ,7.01 (1H, d, J = 7.6 Hz), 2.05 (3H, s).

[1348] (2) Preparation of 2-bromo-5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)thiazole (16-9)

[1349] To a solution of copper(II) bromide (3.01 g, 13.49 mmol) and isofentyl nitrite (2.72 mL, 20.23 mmol) in acetonitrile (100 mL) was added 16-8 (4.3 g, 13.49 mmol) in acetonitrile (170 mL) at 0 °C. The reaction mixture was stirred at room temperature for 2 h, then quenched with NH4OH (100 mL) and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 5:1 to 3:1) to give 16-9 (1.57 g, 30% yield) as a yellow solid.

[1350] 1H-NMR (400 MHz, DMSO-d6):δ 8.28 (1H, d, J = 5.6 Hz), 7.75 -7.68 (2H, m), 7.30 (1H, d, J = 2.0 Hz), 7.16 (1H, dd, J = 5.6, 2.4 Hz), 7.12 (1H, d, J = 7.2 Hz), 2.08 (3H, s).

[1351] (3) Synthesis of 5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)-2-vinylthiazole (17-1)

[1352] To a solution of 16-9 (1.57 g, 4.10 mmol) in tetrahydrofuran (41 mL) was added tributyl(vinyl)stannane (1.91 mL, 6.56 mmol) at room temperature. The mixture was degassed with argon, and then bis(triphenylphosphine)palladium(II) dichloride (576 mg, 0.82 mmol) was added. The mixture was heated at 80 °C for 4 h. After cooling to room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 7:1 to 5:1) to give 17-1 (510 mg, 37%) as a yellow solid.

[1353] 1H-NMR (400 MHz, DMSO-d6):δ 8.27 (1H, d, J = 6.0 Hz), 7.78-7.70 (2H, m), 7.23 (1H, d, J = 2.0 Hz), 7.10 (2H, d, J = 6.4 Hz), 6.10 (1H, d, J = 17.6 Hz), 5.70 (1H, d, J = 10.8 Hz), 2.10 (3H, s).

[1354] (4) Preparation of 5-(2-chloropyridin-4-yloxy)-2-ethyl-4-(6-methylpyridin-2-yl)thiazole (17-2)

[1355] A mixture of 17-1 and platinum(IV) oxide (70.0 mg, 0.31 mmol) in methanol (18 mL) was stirred under a H atmosphere (balloon) at room temperature for 3 h. After filtration through a Celite pad, the filtrate was concentrated in vacuo. The residue was purified by column chromatography on silica (456 mg, 89%) to give 17-2 as a yellow solid.

[1356] 1H-NMR (400 MHz, DMSO-d6): δ 8.26 (1H, d, J = 6.0 Hz), 7.76-7.68 (2H, m), 7.16 (1H, d, J = 1.6 Hz), 7.08 (1H, d, J = 7.2 Hz), 7.05 (1H, dd, J = 6.0, 2.4 Hz), 3.01 (2H, q, J = 7.6 Hz), 2.09 (3H, s), 1.34 (3H, t, J = 7.8 Hz).

[1357] (5) Preparation of A-250

[1358] 17-2 (456 mg, 1.37 mmol) was dissolved in a solution of 13 in N,N-dimethylformamide, followed by the addition of 3-aminobenzenesulfonamide (355 mg, 2.06 mmol) and cesium carbonate at room temperature. The mixture was degassed by purging several times and refilled with argon. After the addition of BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (374 mg, 0.41 mmol), the reaction mixture was heated at 80 °C for 2 h. After cooling to room temperature, the reaction mixture was quenched with water, and EA was extracted. The organic layer was purified by column chromatography on NH-silica (hexane:EA=1:2 to 1:4) to give A-250 (151 mg, 23%) as a white solid.

[1359] The following A-251 to A-273 were synthesized using the same procedure as for the synthesis of A-250 in Step 5.

[1360] 39. Synthesis of A-274

[1361] [ka]

[1362] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazole (18-1)

[1363] To a solution of 16-9 (50 mg, 0.13 mmol) in dioxane (3 mL) was added cyclopropyltributylstannyl (86.5 mg, 0.26 mmol) and bis(triphenylphosphine)palladium(II) dichloride (18.3 mg, 0.03 mmol) at room temperature. The mixture was heated at 100 °C for 4 h. After cooling to room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 3:1) to give I (20.0 mg, 44.5%) as a yellow liquid.

[1364] MS calculated: 343.83; MS found: 344.26 (M+H+)

[1365] (2) Preparation of A-274

[1366] To a solution of 18-1 (20.0 mg, 0.06 mmol) in N,N-dimethylformamide (1.0 mL) was added 3-aminobenzamide (10.0 mg, 0.07 mmol) and potassium carbonate (24.1 mg, 0.18 mmol) at room temperature. The mixture was degassed by purging and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (21.0 mg, 0.02 mmol), the reaction mixture was heated at 100 °C for 2 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (dichloromethane:methanol = 10:1) to give A-274 (3.4 mg, 13.0%) as a dendritic solid.

[1367] The following A-275 to A-282 were synthesized using the procedure described for the synthesis of A-274.

[1368] 40. Synthesis of A-283

[1369] [ka]

[1370] (1) Preparation of 5-(2-chloropyridin-4-yloxy)-N,N-dimethyl-4-(6-methylpyridin-2-yl)thiazol-2-amine (19-1)

[1371] To a solution of 16-9 (290 mg, 0.76 mmol) in N,N-dimethylformamide (3.0 mL) was added dimethylamine (2.0 M in tetrahydrofuran, 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 ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to give 19-1 (100 mg, 38%) as a yellow oil, which was used in the next step without further purification.

[1372] 1H-NMR (400 MHz, CDCl3): δ 8.19 (1H, d, J = 5.6 Hz), 7.95 (1H, d, J = 6.0 Hz), 7.87 (1H, d, J = 7.6 Hz), 7.52 (1H, t, J = 8.0 Hz), 6.46 (1H, d, J = 2.4 Hz), 6.40-6.38 (1H, m), 3.11 (6H, s), 2.25 (3H, s).

[1373] (2) Preparation of A-283

[1374] To a solution of 19-1 (100 mg, 0.29 mmol) in N,N-dimethylformamide (3.0 mL) was added 3-aminobenzenesulfonamide (74.0 mg, 0.43 mmol) and potassium carbonate (120 mg, 0.87 mmol) at room temperature. The mixture was purged, degassed, and refilled with argon several times. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (52.0 mg, 0.06 mmol), the reaction mixture was heated at 100 °C for 2 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on NH-silica (dichloromethane:methanol=98:2) to give A-283 (55.4 mg, 40%) as a dentin solid.

[1375] The following A-284 to A-286 were synthesized using the procedure described for the synthesis of A-283.

[1376] 41. Synthesis of A-287

[1377] [ka]

[1378] (1) Preparation of 5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)-2-(prop-1-en-2-yl)thioazole (20-1)

[1379] To a solution of 16-9 (400 mg, 1.05 mmol) in tetrahydrofuran (5.2 mL) and water (5.2 mL), potassium isopropenyltrifluoroborate (232 mg, 1.57 mmol) and sodium carbonate (776 mg, 7.32 mmol) were added at room temperature. The mixture was degassed by purging and refilled with argon in several portions. After adding palladium(II) chloride (86.0 mg, 0.11 mmol), the reaction mixture was heated at 60 °C for 18 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 4:1) to give 16-9 (133 mg, 37%) as a yellow oil.

[1380] 1H-NMR (400 MHz, DMSO-d6):δ 8.27 (1H, d, J = 8.27 Hz), 7.80 (1H, d, J = 8.0 Hz), 7.73 (1H, t, J = 7.8 Hz), 7.22 (1H, s), 7.10 (2H, d, J = 7.6 Hz), 5.84 (1H, s), 5.50 (1H, s), 2.20 (3H, s), 2.09 (3H, s).

[1381] (2) Preparation of 5-(2-chloropyridin-4-yloxy)-2-isopropyl-4-(6-methylpyridin-2-yl)thiazole (20-2)

[1382] To a solution of 20-1 (173 mg, 0.503 mmol) in dichloromethane (2.5 mL) and methanol (2.5 mL) was added palladium on carbon (10 wt%, 54.0 mg, 0.05 mmol) at room temperature. The mixture was stirred under a hydrogen atmosphere at room temperature for 18 h. After filtration through a Celite pad, the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 3:1) to give 20-2 (60.0 mg, 35%) as a colorless oil.

[1383] 1H-NMR (400 MHz, CDCl3):δ 8.23 ​​(1H, d, J = 5.6 Hz), 7.76 (1H, d, J = 7.6 Hz), 7.58 (1H, t, J = 7.6 Hz), 6.98-6.96 (2H, m), 6.90 (1H, dd, J = 5.8. 2.2 Hz), 3.31 (1H, sep., J = 6.8 Hz), 2.28 (3H, s), 1.45 (6H, d, J = 6.4 Hz).

[1384] (3) Preparation of A-287

[1385] To a solution of 20-2 (60.0 mg, 0.17 mmol) in N,N-dimethylformamide (3.5 mL) was added 3-aminobenzenesulfonamide (45.0 mg, 0.26 mmol) and cesium carbonate (170 mg, 0.52 mmol) at room temperature. The mixture was degassed by purging and refilled with argon in several portions. After adding BrettPhos Pd G3 ([(2-dicyclohexylphosphino-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate) (47.0 mg, 0.05 mmol), the reaction mixture was heated at 80 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on NH-silica (hexane:ethyl acetate=1:2) to give A-287 (22.2 mg, 27%) as a white solid.

[1386] The procedure described for the synthesis of A-287 was used to synthesize the following A-288.

[1387] 42. Synthesis of A-289

[1388] [ka]

[1389] (1) Preparation of 5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)-2-(trifluoromethyl)thiazole (21-1)

[1390] To a solution of 16-9 (0.45 g, 1.18 mmol) in N,N-dimethylformamide (3 mL) was added copper iodide (403.1 mg, 2.12 mmol), hexamethylphosphoramide (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 ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (hexane:ethyl acetate = 5:1) to give 16-9 (50.0 mg, 11%) as a yellow liquid.

[1391] 1H-NMR (400 MHz, DMSO-d6):δ 8.32 (1H, d, J = 6.0 Hz), 7.80 (2H, s), 7.43 (1H, d, J = 28.8 Hz), 7.21 (2H, dd, J = 20.2, 3.0 Hz), 2.14 (3H, s)....

Claims

1. A compound selected from a thiazole derivative compound represented by the following chemical formula 1, a pharma- ceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof: 【Chemistry 1】 In the above Chemical Formula 1, A １ is O or S, A ２ is CH or N, R １ and R ２ are the same or different, and each represents a (C1-C4) alkyl, a (C1-C4) alkylene, a (C1-C4) alkoxy, a trifluoromethyl (CF ３ ), Haro, NR １１ R １２ , unsubstituted or substituted (C3-C8)cycloalkyl, unsubstituted or substituted (C5-C10)aryl, and unsubstituted or substituted heteroaryl of 5 to 10 atoms containing one or more heteroatoms selected from the group consisting of N, O, and S, １１ and R １２ are the same or different and are any one of hydrogen, (C1-C5) alkyl, and (C3-C8) cycloalkyl, and the substituted (C3-C8) cycloalkyl, substituted (C5-C10) aryl, or substituted 5-10 heteroaryl is substituted with (C1-C5) alkyl; n is one of 0 to 3, Ar is an unsubstituted or substituted (C5-C10)aryl or an unsubstituted or substituted heteroaryl of 5 to 10 atoms containing one or more heteroatoms selected from the group consisting of N, O, and S, and the substituted (C5-C10)aryl or substituted heteroaryl of 5 to 10 atoms is R ３ is replaced, The R ３ is -R ３－１ or -(C1-C5)alkyl-R ３－１ and The R ３－１ is hydrogen, halogen, hydroxy, 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 N.R. ３５－１ R ３５－２ , -COR ３６ , —NH—(C1-C3)alkyl-R ３７ , 【Chemistry 2】 Any one of the following: The 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 each represents hydrogen, hydroxy, trifluoromethyl, (C1-C5) alkyl, (C3-C8) cycloalkyl, -SO ２ -(C1-C3)alkyl, -(C1-C3)alkyl-R ３０１ and 【Chemistry 3】 and The R ３０１ is (C1-C4) alkylamino, di[(C1-C4) alkyl]amino, (C3-C8) cycloalkyl, 【Chemistry 4】 Any one of the following: The R ３００１ is hydrogen or (C1-C5) alkyl, The R ３０２ is a halogen, The R ３０３ and R ３０４ are the same or different and each is hydrogen or (C1-C3) alkyl; The R ３６ and R ３７ are the same or different, 【Chemistry 5】 and The R ３０５ is hydrogen or (C1-C5) alkyl, The R ３０６ is any one of hydrogen, amino, (C1-C4) alkylamino, and di[(C1-C4) alkyl]amino, The R ３８ and R ３９ are the same or different and each is one of hydrogen, (C1-C3) alkyl, and -(C1-C3) alkyl-(C1-C3) alkoxy.

2. In the above Chemical Formula 1, R １ is (C1-C3) alkyl, (C1-C3) alkylene, methoxy, trifluoromethyl (CF ３ ), bromine (Br), (C3-C6)cycloalkyl and NR １１ R １２ Any one of the above, １１ and R １２ are the same or different and each is any one of hydrogen, (C1-C3) alkyl, and cyclopropyl; R ２ teeth, 【Chemistry 6】 or naphthyl, ３ is CH or N, and said R ２１ is hydrogen or methyl, n is one of 0 to 2, Ar is 【Chemistry 7】 Any one of the above, ３ is -R ３－１ or -(C1-C3)alkyl-R ３－１ and R ３－１ is hydrogen, fluorine, chlorine, hydroxy, 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 N.R. ３５－１ R ３５－２ , -COR ３６ , -NH-(C1-C ３ ) alkyl-R ３７ , 【Chemistry 8】 Any one of the above, ３１－1, R ３１－２ , R ３２ , R ３３ , R ３４ , R ３５－１ and R ３５－２ are the same or different and each represents hydrogen, hydroxy, trifluoromethyl, (C1-C3) alkyl, (C3-C6) cycloalkyl, -SO ２ CH ３ , -(C1-C3)alkyl-R ３０１ and 【Chemistry 9】 and R ３０１ is methylamino, dimethylamino, cyclopropyl, 【Chemistry 10】 Any one of the above, ３００１ is hydrogen or (C1-C3) alkyl, and R ３０２ is fluorine, and the R ３０３ and R ３０４ are the same or different and each is hydrogen or methyl; ３６ and R ３７ are the same or different, 【Chemistry 11】 and R ３０５ is (C1-C3) alkyl, and said R ３０６ is any one of hydrogen, amino, and methylamino, and R ３８ and R ３９ The compound according to claim 1, characterized in that each of the thiazole derivative compounds, its pharma- ceutically acceptable salts, its solvates, or its stereoisomers is the same or different and is any one of hydrogen, (C1-C3) alkyl, and -(C1-C3) alkyl-methoxy.

3. In the above Chemical Formula 1, R １ is methyl, ethyl, isopropyl, methoxy, ethylene, trifluoromethyl (CF ３ ), bromine (Br), cyclopropyl, cyclopentyl, cyclohexyl and NR １１ R １２ Any one of the above, １１ and R １２ are the same or different and each is any one of hydrogen, methyl, and cyclopropyl; R ２ teeth, 【Chemistry 12】 It is one of n is one of 0 to 2, Ar is 【Chemistry 13】 Any one of the above, ３ is -R ３－１ or -(C1-C3)alkyl-R ３－１ and R ３－１ is hydrogen, fluorine, chlorine, hydroxy, cyano, methyl, methoxy, -CONR ３１－１ R ３１－２ , -COOR ３２ , -NHSO ２ R ３３ , -SO ２ R ３４ , -SO ２ N.R. ３５－１ R ３５－２ , -COR ３６ , -NH-(C1-C ３ ) alkyl-R ３７ , 【Chemistry 14】 Any one of the following: The R ３１－１ and R ３１－２ are the same or different and are hydrogen, methyl, isopropyl, hydroxy, -SO ２ CH ３ , -(C1-C2)alkyl-R ３０１ and 【Chemistry 15】 and R ３０１ is dimethylamino, cyclopropyl, 【Chemistry 16】 Any one of the above, ３００１ is one of methyl, ethyl, and isopropyl, and said R ３０２ is fluorine, and the R ３０３ and R ３０４ is methyl, The R ３２ is one of hydrogen, methyl, and -(C1-C2)alkyl-dimethylamino; The R ３３ is one of methyl, ethyl, cyclopropyl, and trifluoromethyl; The R ３４ is one of hydroxy, methyl, ethyl, cyclopropyl, and trifluoromethyl; The R ３５－１ and R ３５－２ are the same or different and each is one of hydrogen, methyl, and cyclopropyl; The R ３６ teeth, 【Chemistry 17】 and R ３０５ is methyl, and the R ３０６ is amino or methylamino, The R ３７ teeth, 【Chemistry 18】 and The R ３８ is methyl or -CH ２ CH ２ OCH ３ and The R ３９ The compound selected from the group consisting of thiazole derivative compounds, pharma- ceutically acceptable salts, solvates, and stereoisomers thereof according to claim 1, wherein R 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 following compound group: (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-((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-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)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-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)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)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-tetrazol-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)propanenitrile (114) N-(3-(2-(2H-tetrazol-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) Methyl 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-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-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-((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) 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid methyl ester (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-(((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) N1-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N4-(2-(4-isopropylpiperazin-1-yl)ethyl)benzene-1,4-diamine (206) N1-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N4-(2-(4-methylpiperazin-1-yl)ethyl)benzene-1,4-diamine (207) N1-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N4-(2-(4-methylpiperazin-1-yl)ethyl)benzene-1,4-diamine (208) N1-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N4-(2-(pyrrolidin-1-yl)ethyl)benzene-1,4-diamine (209) N2-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N5-(2-(4-methylpiperazin-1-yl)ethyl)pyridine-2,5-diamine (210) N2-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N5-(2-(pyrrolidin-1-yl)ethyl)pyridine-2,5-diamine (211) N2-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N5-(2-(4-ethylpiperazin-1-yl)ethyl)pyridine-2,5-diamine (212) N2-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N5-(2-(4-isopropylpiperazin-1-yl)ethyl)pyridine-2,5-diamine (213) N,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) Methyl 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate (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)nicotinate (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)nicotinamide)-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-((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-tetrazol-5-yl)methyl)phenyl)-4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-amine (306) 3-(4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanenitrile (307) N-(3-(2-(2H-tetrazol-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 disease, comprising a compound selected from the thiazole derivative compound according to claim 1, a pharma- ceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof as an active ingredient.

6. 6. The pharmaceutical composition for treating or preventing cancer diseases according to claim 5, characterized in that the cancer disease is selected from the group consisting of lung cancer, breast cancer, ovarian cancer, uterine cancer, pancreatic cancer, gastric cancer, liver cancer, colon cancer, skin cancer, head or neck cancer, brain cancer, laryngeal cancer, prostate cancer, bladder cancer, esophageal cancer, thyroid cancer, kidney cancer and rectal cancer.

7. The pharmaceutical composition for treating or preventing cancer according to claim 5, wherein the cancer is a TGFβ-related cancer.

8. The pharmaceutical composition for treating or preventing cancer diseases according to claim 5, wherein the pharmaceutical composition selectively inhibits TGFβR1.

9. A functional health food composition for improving or preventing cancer disease, comprising as an active ingredient a compound selected from the thiazole derivative compound according to claim 1, a pharma- ceutical acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

10. The health functional food composition according to claim 9, characterized in that the cancer disease is selected from the group consisting of lung cancer, breast cancer, ovarian cancer, uterine cancer, pancreatic cancer, stomach cancer, liver cancer, colon cancer, skin cancer, head or 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 TGFβ expression, comprising as an active ingredient a compound selected from the thiazole derivative compound according to claim 1, a pharma- ceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

12. The reagent composition according to claim 11, characterized in that the reagent composition selectively inhibits TGFβR1.

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