Composition for treating pulmonary fibrosis comprising thiazole derivative compound

Abstract

The present invention relates to a medical use of a novel thiazole derivative compound and, more specifically, provides a pharmaceutical composition and a health functional food composition for treating or preventing pulmonary fibrosis, the compositions comprising, as an active ingredient, a compound selected from among a novel thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof, and a stereoisomer thereof. The compositions have excellent TGF-β1 inhibitory activity and anti-fibrotic activity, and thus alleviate the problems of existing pulmonary fibrosis treatments performed by inhibiting immunity or inflammation, and can more effectively treat, alleviate, or prevent pulmonary fibrosis.

Description

Composition for treating pulmonary fibrosis comprising a thiazole derivative compound

[0001] The present invention relates to the medical use of a novel thiazole derivative compound, and more particularly, to a composition for treating or preventing pulmonary fibrosis comprising a thiazole derivative compound.

[0002] Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease of unknown etiology characterized by fibrosis of the lung interstitium. It is a fatal disease that progresses and ultimately leads to death. IPF carries a poor prognosis, with a median survival of only 3-4 years after diagnosis in patients without antifibrotic drug treatment. As the disease progresses, lung function declines, leading to dyspnea, decreased physical abilities, and a diminished quality of life. Patients with IPF can experience acute exacerbations, characterized by bilateral pulmonary infiltrates and decreased oxygen saturation. These exacerbations carry a high mortality rate, and most patients die from respiratory failure caused by acute exacerbations. While the cause is still unknown, it is believed to be triggered by intentional or unintentional exposure to environmental pollutants such as smoking and fine dust.

[0003] Currently, steroids (glucocorticoids), immunosuppressive agents, and cytokine agents (anti-viral cytokines) are representative treatments for pulmonary fibrosis. However, all of the above treatment modalities do not affect the alleviation of disease progression or patient survival rate. In addition, according to the 2011 ATS / ERS guidelines for idiopathic pulmonary fibrosis, the combination therapy of steroids and the immunosuppressant azathioprine showed disappointing results, increasing the mortality rate. In other words, existing treatments that show immune or inflammation suppression efficacy have limitations, so there is an urgent need to develop drugs that not only suppress inflammation but also directly inhibit the fibrotic process for idiopathic pulmonary fibrosis.

[0004] An object of the present invention is to provide a medical use of a compound selected from a novel thiazole derivative compound, a pharmaceutically acceptable salt thereof, a solvate thereof or a stereoisomer thereof.

[0005] In order to achieve the above purpose, the present invention provides a pharmaceutical composition for treating or preventing pulmonary fibrosis, comprising as an active ingredient 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:

[0006] [Chemical Formula 1]

[0007]

[0008] In the above chemical formula 1, A 1 is O or S, and A 2 is CH or N,

[0009] R 1 and R 2 may be the same or different, (C1-C4)alkyl, (C1-C4)alkylene, (C1-C4)alkoxy, trifluoromethyl (CF3), halo, NR 11R 12 , unsubstituted or substituted (C3-C8)cycloalkyl, unsubstituted or substituted (C5-C10)aryl and unsubstituted or substituted heteroaryl having 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 may be 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 of 5 to 10 atoms is substituted by (C1-C5)alkyl,

[0010] n is one of 0 to 3,

[0011] Ar is an unsubstituted or substituted (C5-C10)aryl or an unsubstituted or substituted 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, wherein the substituted (C5-C10)aryl or substituted 5 to 10-membered heteroaryl is R 3 is replaced,

[0012] The above R 3 is -R 3-1 or -(C1-C5)alkyl-R 3-1 And,

[0013] The above 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 , , , , , and One of them,

[0014] The above R 31-1 , R 31-2 , R 32 , R 33 , R 34 , R 35-1 and R 35-2 may be the same or different, and are hydrogen, hydroxy, trifluoromethyl, (C1-C5)alkyl, (C3-C8)cycloalkyl, -SO2-(C1-C3)alkyl, -(C1-C3)alkyl-R 301 and And,

[0015] The above R 301 Silver (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, (C3-C8)cycloalkyl, and One of them,

[0016] The above R 3001 is hydrogen or (C1-C5)alkyl,

[0017] The above R 302 is a halogen,

[0018] The above R 303 and R 304 may be the same or different, and are hydrogen or (C1-C3)alkyl,

[0019] The above R 36 and R 37 may be the same or different, or And,

[0020] The above R 305 is hydrogen or (C1-C5)alkyl,

[0021] The above R 306 is any one of hydrogen, amino, (C1-C4)alkylamino and di[(C1-C4)alkyl]amino,

[0022] The above R 38 and R 39may be the same or different, and are any one of hydrogen, (C1-C3)alkyl, and -(C1-C3)alkyl-(C1-C3)alkoxy.

[0023] In addition, the present invention provides a health functional food composition for improving or preventing pulmonary fibrosis, comprising as an active ingredient a compound selected from the thiazole derivative compound represented by the above chemical formula 1, a food-wise acceptable salt thereof, a solvate thereof, or a stereoisomer thereof.

[0024] The pharmaceutical composition comprising the novel thiazole derivative compound according to the present invention has excellent TGF-β1 inhibitory activity and antifibrotic activity, and thus can improve the limitations of conventional treatment of pulmonary fibrosis through immune or inflammation suppression.

[0025] By using the pharmaceutical composition and health functional food composition according to the present invention, diseases related to pulmonary fibrosis, which has been recognized as an incurable disease, can be treated, improved or prevented more effectively.

[0026] Figure 1 shows the in vitro anti-fibrotic activity of various compounds.

[0027] Figure 2 shows an analysis of changes in protein expression in human fibroblasts.

[0028] Figure 3 shows an analysis of changes in collagen expression in human fibroblasts.

[0029] Figure 4 is an administration protocol in a bleomycin (BLM)-induced pulmonary fibrosis mouse model according to an experimental example of the present invention.

[0030] Figure 5 shows changes in mouse body weight and lung weight according to treatment with compound A-192 or A-250.

[0031] Figure 6 shows the analysis of protein expression levels in lung tissue following treatment with compound A-192 or A-250 in an in vivo mouse model.

[0032] Figure 7 shows the analysis of cytokines in lung lavage fluid and lung tissue following treatment with compound A-192 or A-250 in an in vivo mouse model.

[0033] Figure 8 shows the H&E staining results according to treatment with compound A-192 or A-250 in an in vivo mouse model.

[0034] Figure 9 shows the results of Masson Trichrome staining following treatment with compound A-192 or A-250 in an in vivo mouse model.

[0035] Figure 10 is an administration protocol in mice with bleomycin-induced idiopathic pulmonary fibrosis according to another experimental example of the present invention.

[0036] Figure 11 is about the analysis of fibrosis markers according to compound A-250 treatment in an in vivo mouse model.

[0037] Figure 12 shows the results of analysis of inflammatory cells in alveolar lavage fluid following treatment with compound A-250 in an in vivo mouse model.

[0038] Figure 13 shows the results of cytokine analysis in lung tissue following treatment with compound A-250 in an in vivo mouse model.

[0039] Figure 14 shows the results of cytokine analysis in alveolar lavage fluid following treatment with compound A-250 in an in vivo mouse model.

[0040] Figure 15 shows the Ashcroft score and H&E staining results according to compound A-250 treatment in an in vivo mouse model.

[0041] Figure 16 shows the fibrosis score and Masson Trichrome staining results according to compound A-250 treatment in an in vivo mouse model.

[0042] Figure 17 is an administration protocol in mice with bleomycin-induced idiopathic pulmonary fibrosis according to another experimental example of the present invention.

[0043] Figure 18 shows the change in mouse body weight due to A-250 inhalation in an in vivo mouse model.

[0044] Figure 19 shows the changes in collagen content and pSMAD / SMAD in mouse lung tissue due to A-250 inhalation in an in vivo mouse model.

[0045] Hereinafter, the present invention will be described in more detail.

[0046]

[0047] The present inventors have synthesized a novel thiazole derivative compound, and have confirmed that the compound has TGF-β inhibitory activity and has antifibrotic activity through in vitro experiments on lung fibroblasts and in vivo experiments on a mouse model of pulmonary fibrosis, thereby completing the present invention.

[0048]

[0049] The present invention provides a pharmaceutical composition for treating or preventing pulmonary fibrosis, comprising as an active ingredient 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:

[0050] [Chemical Formula 1]

[0051]

[0052] 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 may be the same or different, (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 having 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 may be the same or different, and are any one of hydrogen, (C1-C5)alkyl and (C3-C8)cycloalkyl, wherein 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 at least one heteroatom 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 is -R 3-1 or -(C1-C5)alkyl-R 3-1 and the above 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 , , , , and One of the above R 31-1 , R 31-2 , R 32 , R 33 , R 34 , R 35-1 and R35-2 may be 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 and the above R 301 Silver (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, (C3-C8)cycloalkyl, and One of the above R 3001 is hydrogen or (C1-C5)alkyl, and the above R 302 is a halogen, and the above R 303 and R 304 may be the same or different, and are hydrogen or (C1-C3)alkyl, and the above R 36 and R 37 may be the same or different, or and the above R 305 is hydrogen or (C1-C5)alkyl, and R 306 is any one of hydrogen, amino, (C1-C4)alkylamino and di[(C1-C4)alkyl]amino, and R 38 and R 39 may be the same or different, and may be any one of hydrogen, (C1-C3)alkyl, and -(C1-C3)alkyl-(C1-C3)alkoxy.

[0053] Preferably, R in the above chemical formula 1 1 Silver (C1-C3)alkyl, (C1-C3)alkylene, methoxy, trifluoromethyl (CF3), bromine (Br), (C3-C6)cycloalkyl and NR 11 R 12 One of the above R 11 and R 12 may be the same or different, and are any one of hydrogen, (C1-C3)alkyl and cyclopropyl, and R 2 Is or naphthyl, and the above A 3 is CH or N, and the above R21 is hydrogen or methyl, n is one of 0 to 2, and Ar is , and One of the above R 3 is -R 3-1 or -(C1-C3)alkyl-R 3-1 and the above 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 , , , , and One of the above R 31-1 , R 31-2 , R 32 , R 33 , R 34 , R 35-1 and R 35-2 may be the same or different, and are hydrogen, hydroxy, trifluoromethyl, (C1-C3)alkyl, (C3-C6)cycloalkyl, -SO2CH3, -(C1-C3)alkyl-R 301 and and the above R 301 Silver methylamino, dimethylamino, cyclopropyl, and One of the above R 3001 is hydrogen or (C1-C3)alkyl, and R 302 is fluorine, and the above R 303 and R 304 may be the same or different, and are hydrogen or methyl, and the R 36 and R 37 may be the same or different, or and the above R 305 is (C1-C3)alkyl, and the above R 306 is any one of hydrogen, amino and methylamino, and R 38 and R 39 may be the same or different, and may be any one of hydrogen, (C1-C3)alkyl, and -(C1-C3)alkyl-methoxy.

[0054] More preferably, R in the above chemical formula 1 1 Silver methyl, ethyl, isopropyl, methoxy, ethylene, trifluoromethyl (CF3), bromine (Br), cyclopropyl, cyclopentyl, cyclohexyl and NR 11 R 12 One of the above R 11 and R 12 may be the same or different, and are any one of hydrogen, methyl and cyclopropyl, and R 2 Is , and is one of, n is one of 0 to 2, and Ar is , and One of the above R 3 is -R 3-1 or -(C1-C3)alkyl-R 3-1 and the above R 3-1 Silver 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-C2)alkyl-R 37 , , , , and One of the above R31-1 and R 31-2 may be the same or different, and are hydrogen, methyl, isopropyl, hydroxy, -SO2CH3, -(C1-C2)alkyl-R 301 and and the above R 301 Silver dimethylamino, cyclopropyl, and One of the above R 3001 is one of methyl, ethyl and isopropyl, and R 302 is fluorine, and the above R 303 and R 304 is methyl, and the above R 32 is one of hydrogen, methyl and -(C1-C2)alkyl-dimethylamino, and R 33 is one of methyl, ethyl, cyclopropyl and trifluoromethyl, and R 34 is one of hydroxy, methyl, ethyl, cyclopropyl and trifluoromethyl, and R 35-1 and R 35-2 may be the same or different, and is one of hydrogen, methyl and cyclopropyl, and R 36 silver or and the above R 305 is methyl, and the above R 306 is amino or methylamino, and the R 37 silver or and the above R 38 is methyl or -CH2CH2OCH3, and the R 39 can be hydrogen or methyl.

[0055] Specifically, the compound represented by the above chemical formula 1 may be any one selected from the following group of compounds:

[0056] (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-dimethylbenzenesulfonamide; (14)N-(3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide;(15) 5-((2-((3-(Methylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (16) N-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopropanesulfonamide; (17) 4-Phenyl-5-((2-((3-((trifluoromethyl)sulfonyl)phenyl)amino)pyridin-4-yl)oxy)thiazol-2-amine; (18) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid; (19) 5-((2-((3-((Methylsulfonyl)methyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (20) 3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-cyclopropylbenzenesulfonamide;(21) 5-((2-((3-Fluorobenzyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (22) 2-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide; (23) 3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; (24) 5-((2-((2-methoxypyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (25) 5-((2-(Benzylamino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (26) 4-Phenyl-5-((2-((pyridin-4-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine; (27) 5-((2-((2-Chloropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine;(28) 4-Phenyl-5-((2-((pyridin-3-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine; (29) (3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide; (30) 5-((2-((2-Fluoropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (31) 5-((2-((6-Methoxypyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (32) 5-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (33) 6-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; (34) 5-((2-((3-(Ethylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine;(35) 5-((2-((6-Chloropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (36) N-(3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide; (37) 5-((2-((1-Methyl-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (38) 5-((2-((1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (39) 4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (40) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (41) 2-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol;(42) 2-(4-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (43) 2-(5-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (44) 2-(3-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; (45) 3-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)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)phenyl)propan-2-ol; (51) 3-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (52) 3-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (53) 4-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide;(54) 2-(4-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (55) 2-(5-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (56) 4-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (57) 3-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (58) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (59) 2-(4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol;(60) 3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (61) 2-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; (62) 5-((2-((1-(Methylsulfonyl)-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (63) 4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (64) 4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (65) 2-(5-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (66) 2-Methyl-2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoic acid;(67)N,N-Dimethyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (68) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid; (69)N-Methyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (70) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(3-(methylsulfonyl)phenyl)pyridin-2-amine; (71)N-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide; (72) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((trifluoromethyl)sulfonyl)phenyl)pyridin-2-amine;(73)N-Methyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (74)N,N-Dimethyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (75)N-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopropanesulfonamide; (76)N-Cyclopropyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (77)N-(3-(Ethylsulfonyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (78) (3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide;(79) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((methylsulfonyl)methyl)phenyl)pyridin-2-amine; (80) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-ylmethyl)pyridin-2-amine; (81) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-ylmethyl)pyridin-2-amine; (82) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-yl)pyridin-2-amine; (83)N-(6-Fluoropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (84)N-(6-Chloropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (85)N-(6-Methoxypyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine;(86) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-yl)pyridin-2-amine; (87) N-(2-Fluoropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (88)N-(2-Methoxypyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (89)N-(2-Chloropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (90) 6-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (91) 5-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; (92) 5-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide;(93) 2-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide; (94) N-Benzyl-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (95) N-(4-Fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (96)N-(3-Fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (97) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(1-(methylsulfonyl)-1H-pyrazol-4-yl)pyridin-2-amine; (98)N-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (99)N-(1-Methyl-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine;(100) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(1H-pyrazol-4-yl)pyridin-2-amine; (101) 6-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; (102) 4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; (103) N-(4-methoxyphenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (104) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(piperazin-1-yl)phenyl)pyridin-2-amine; (105) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(2-(piperidin-1-yl)ethoxy)phenyl)pyridin-2-amine; (106)N-(3-Methoxy-4-(4-methylpiperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine;(107) 1,1,1-Trifluoro-N-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide; (108) N-(4-(4-(2-methoxyethyl)piperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (109) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (110) 4-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (111) 2-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)acetonitrile; (112)N-(3-((1H-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)phenyl)propan-2-ol; (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)phenyl)-1,1,1-trifluoromethanesulfonamide;(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)pyridin-3-yl)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-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (148)N-Methyl-4-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (149) 6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid;(150)N-Methyl-6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (151) 3-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (152) 4-((4-((4-Phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (153) 2-(3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; (154) 3-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (155) 3-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide;(156) 4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (157) 4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (158) 2-(4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (159) 2-(5-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (160) 6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; (161) 6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide;(162) Methyl 6-((4-((2-(Dimethylamino)-4-phenyl thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate; (163) 6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (164) 4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; (165) 6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; (166) 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; (167) 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid;(168) 4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (169) 6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid; (170) Methyl 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate; (171) 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (172) 3-((4-((2-Bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (173) 6-((4-((2-Cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (174) 6-((4-((2-Cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid;(175) 4-((4-((2-Cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (176) 6-((4-((2-Cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; (177) 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (178) 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; (179) 4-((4-((2-Cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (180) 6-((4-((2-Cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; (181) 3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide;(182) 2-(3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; (183) 3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; (183) 3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (184) 4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (185) 4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (186) 2-(4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (187) 2-(5-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (188)N-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)ethanesulfonamide;(189) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; (190) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (191) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate; (192) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; (193) 6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; (194) 3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (195) 4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid;(196) 6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-isopropylnicotinamide; (197) (6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(4-methylpiperazin-1-yl)methanone; (198) (3-Aminopyrrolidin-1-yl)(6-(4-(2-ethyl-4-phenylthiazol-5-yloxy)pyridin-2-ylamino)pyridin-3-yl)methanone; (199) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(pyrrolidin-1-yl)ethyl)nicotinamide; (200) (6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(3-(methylamino)pyrrolidin-1-yl)methanone((6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(3-(methylamino)pyrrolidin-1-yl)methanone);(201) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-methylpiperazin-1-yl)ethyl)nicotinamide; (202) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-isopropylpiperazin-1-yl)ethyl)nicotinamide; (203) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-ethylpiperazin-1-yl)ethyl)nicotinamide; (204) 5-(3-aminopyrrolidin-1-yl)-N-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)pyridin-2-amine; (205)N; 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-isopropylpiperazin-1-yl)ethyl)benzene-1,4-diamine(N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-isopropylpiperazin-1-yl)ethyl)benzene-1,4-diamine); (206)N 1-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-methylpiperazin-1-yl)ethyl)benzene-1,4-diamine(N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-methylpiperazin-1-yl)ethyl)benzene-1,4-diamine); (207)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-ethylpropylpiperazin-1-yl)ethyl)benzene-1,4-diamine(N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-ethylpiperazin-1-yl)ethyl)benzene-1,4-diamine); (208)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(pyrrolidin-1-yl)ethyl)benzene-1,4-diamine(N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(pyrrolidin-1-yl)ethyl)benzene-1,4-diamine); (209)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-methylpiperazin-1-yl)ethyl)pyridine-2,5-diamine(N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-methylpiperazin-1-yl)ethyl)pyridine-2,5-diamine); (210)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5-(2-(pyrrolidin-1-yl)ethyl)pyridine-2,5-diamine(N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(pyrrolidin-1-yl)ethyl)pyridine-2,5-diamine); (211)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-ethylpiperazin-1-yl)ethyl)pyridine-2,5-diamine(N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-ethylpiperazin-1-yl)ethyl)pyridine-2,5-diamine); (212)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-isopropylpiperazin-1-yl)ethyl)pyridine-2,5-diamine(N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5-(2-(4-isopropylpiperazin-1-yl)ethyl)pyridine-2,5-diamine); (213)N-(5-(1H-pyrazol-4-yl)pyridin-2-yl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine(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-((4-((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)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)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)nicotinamido)-5-fluorobenzoate;(274) 3-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (275) 6-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (276) 2-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide; (277) 3-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (278) 6-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide;(279) 6-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide; (280) 2-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylisonicotinamide; (281) 3-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; (282) 6-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; (283) 3-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide;(284) 6-((4-((2-(Dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (285) 6-((4-((2-(Dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; (286) 6-((4-((2-(Dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; (287) 3-((4-((2-Isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (288) 6-((4-((2-Isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide;(289) 3-((4-((4-(6-Methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (290) 6-((4-((2-Isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (291) 3-((4-((4-(6-Methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (292) 3-((4-((2-(methylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (293) 6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; (294) 6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide;(295) 4-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (296) 3-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (297) 3-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; (298) 3-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (299) 6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; (300) 3-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (301) 6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid;(302) 6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide; (303) 3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (304) 2-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)acetonitrile; (305)N-(3-((1H-tetrazol-5-yl)methyl)phenyl)-4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-amine; (306) 3-(3-((4-((2-Methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)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(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)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-trifluorosulfonamide;and (312) 4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)-N-(5-(3-(methylamino)pyrrolidin-1-yl)pyridin-2-yl)pyridin-2-amine.;

[0057] Preferably, the compound is (58) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide, (136) 4-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid, (192) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid, (195) 4-((4-((2-ethyl-4-phenylthiazol-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 or (275) 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide, but is not limited thereto.

[0058]

[0059] The above compound can be used in the form of a pharmaceutically or food-wise acceptable salt within the range having the same efficacy.

[0060] As used herein, “pharmaceutically or food-wise acceptable” means a salt that is non-toxic to cells or humans exposed to the composition and has a safety and efficacy profile suitable for administration to humans.

[0061] The above salt may be used in the form of either a basic salt or an acid salt that is pharmaceutically or food-wise acceptable. The basic salt may be used in the form of either an organic basic salt or an inorganic basic salt, and may be selected from the group consisting of sodium salt, potassium salt, calcium salt, lithium salt, magnesium salt, cesium salt, aminium salt, ammonium salt, triethylaminium salt, and pyridinium salt.

[0062] Acid salts are useful as acid addition salts formed by free acids. Inorganic acids and organic acids can be used as free acids, and inorganic acids include hydrochloric acid, hydrobromic acid, sulfuric acid, sulfurous acid, phosphoric acid, diphosphoric acid, nitric acid, etc., and organic acids include citric acid, acetic acid, maleic acid, malic acid, fumaric acid, gluconic acid, methanesulfonic acid, benzenesulfonic acid, camphorsulfonic acid, oxalic acid, malonic acid, glutaric acid, acetic acid, glycolic acid, succinic acid, tartaric acid, 4-toluenesulfonic acid, galacturonic acid, embonic acid, glutamic acid, citric acid, aspartic acid, stearic acid, etc., but are not limited thereto, and all salts formed using various inorganic acids and organic acids commonly used in the art can be included.

[0063] In addition, the compound may include not only the above salts, but also all salts, hydrates, solvates, derivatives, etc. that can be prepared by conventional methods. Addition salts can be prepared by conventional methods, and can be prepared by dissolving in a water-miscible organic solvent such as acetone, methanol, ethanol, or acetonitrile, adding an excess amount of organic base, or adding an aqueous base solution of an inorganic base, and then precipitating or crystallizing. Alternatively, the addition salt can be obtained by evaporating the solvent or excess base from the mixture and then drying, or by suction filtration of the precipitated salt.

[0064]

[0065] The composition can reduce the expression level of one or more fibrotic factors selected from the group consisting of Collagen I, a-SMA, N-cadherin, vimentin, and pSMAD2 / 3, the expression of which increases when pulmonary fibrosis is induced, and can suppress one or more inflammatory cytokines selected from the group consisting of TNF-α, IL-1b, IL-6, and TGF-β1.

[0066] In addition, the composition reduces collagen accumulation in lung tissue and inhibits the infiltration and increase of inflammatory cells, and thus can be used to treat or prevent pulmonary fibrosis.

[0067]

[0068] In the present invention, the pulmonary fibrosis is interstitial pulmonary fibrosis selected from the group consisting of chronic fibrosing interstitial lung disease, interstitial lung disease associated with rheumatoid arthritis, interstitial lung disease associated with connective tissue disease, drug-induced interstitial lung disease, post-infectious interstitial lung disease, post-inflammatory interstitial lung disease, and interstitial lung disease associated with systemic sclerosis; It may be selected from the group consisting of idiopathic pulmonary fibrosis (IPF), familial PF, pulmonary fibrosis associated with asthma, fibrosis associated with chronic obstructive pulmonary disease, inflammatory pulmonary fibrosis, cryptogenic fibrosing alveolitis, pulmonary disease associated with complex connective tissue disease, pulmonary disease associated with systemic lupus erythematosus, pulmonary disease associated with dermatomyositis / polymyositis, pulmonary disease associated with Sjogren's disease, pulmonary disease associated with ankylosing spondylitis, diffuse vasculitic lung disease, pulmonary disease associated with hemosiderosis, radiation fibrosis, obliterative bronchiolitis, chronic eosinophilic pneumonia, lymphocytic infiltrative lung disease, silica-induced fibrosis, asbestos-induced fibrosis, and chemotherapy-induced pulmonary fibrosis.

[0069] Preferably, the pulmonary fibrosis may be pulmonary fibrosis caused by or associated with a lung disease selected from the group consisting of interstitial lung disease such as idiopathic pulmonary fibrosis (PFILD), systemic sclerosis-associated interstitial lung disease (SSC-ILD), familial pulmonary fibrosis, interstitial lung disease associated with rheumatoid arthritis, interstitial lung disease associated with connective tissue disease, drug-induced interstitial lung disease, post-infectious interstitial lung disease, and inflammatory interstitial lung disease, but is not limited thereto.

[0070]

[0071] As used herein, “pharmaceutical composition” means a composition administered for a specific purpose, and for the purposes of the present invention, means administered to prevent or treat pulmonary fibrosis or at least one symptom thereof.

[0072] The pharmaceutical composition according to the present invention can be prepared according to a conventional method in the pharmaceutical field. The pharmaceutical composition can be combined with an appropriate pharmaceutically acceptable carrier depending on the formulation, and, if necessary, can be prepared by further including an excipient, diluent, dispersant, emulsifier, buffer, stabilizer, binder, disintegrant, solvent, etc. The appropriate carrier, etc., can be selected differently depending on the dosage form and formulation as long as it does not inhibit the activity and properties of the compound according to the present invention or a pharmaceutically acceptable salt thereof, solvate thereof, or stereoisomer thereof.

[0073] The pharmaceutical composition according to the present invention can be applied in any dosage form, and more specifically, it can be formulated and used as a parenteral dosage form, such as an oral dosage form, an aerosol dosage form, an external preparation, a suppository, and a sterile injection solution, according to a conventional method.

[0074] Among the oral dosage forms, the solid dosage form may be in the form of tablets, pills, powders, granules, capsules, etc., and may be prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose, lactose, sorbitol, mannitol, cellulose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be included. In addition, in the case of a capsule dosage form, in addition to the above-mentioned substances, a liquid carrier such as fatty oil may be further included.

[0075] Among the above oral dosage forms, liquid dosage forms include suspensions, solutions, emulsions, syrups, etc., and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included.

[0076] The above parenteral formulations may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases may include witepsol, macrogol, Tween 61, cacao butter, laurin, glycerogelatin, and the like. Without limitation, any suitable formulation known in the art may be used.

[0077]

[0078] In the pharmaceutical composition according to the present invention, the pharmaceutical composition can be administered in a pharmaceutically effective amount.

[0079] As used herein, “pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment and not causing adverse effects.

[0080] The effective dosage level of the pharmaceutical composition may vary depending on the intended use, the patient's age, sex, weight, and health condition, the type and severity of the disease, the activity and sensitivity of the drug, the method of administration, the time of administration, the route of administration, and the excretion rate, the duration of treatment, the drugs used in combination or concurrently, and other factors well known in the medical field. For example, although not fixed, it may generally be administered once or several times daily at a dosage of 0.001 to 1000 mg / kg, preferably 0.01 to 100 mg / kg. The above dosage does not limit the scope of the present invention in any way.

[0081]

[0082] The pharmaceutical composition according to the present invention can be administered to any animal capable of developing pulmonary fibrosis, and the animal can include, for example, humans and primates, as well as livestock such as cows, pigs, horses, and dogs.

[0083] The pharmaceutical composition according to the present invention can be administered via an appropriate route of administration depending on the formulation form, and can be administered via various routes, either oral or parenteral, as long as it can reach the target tissue. The method of administration is not particularly limited, and can be administered by conventional methods such as oral, rectal, intravenous, intramuscular, or skin application, respiratory inhalation, intrauterine epidural, or intracerebroventricular injection.

[0084] Preferably, the pharmaceutical composition may be prepared in an aerosol formulation and administered using an aerosol device, a nebulizer device, a dry powder inhaler (DPI), or a metered dose inhaler (MDI).

[0085] The pharmaceutical composition according to the present invention can be used alone for the prevention or treatment of pulmonary fibrosis, or can be used in combination with surgery or other drug treatments.

[0086]

[0087] In addition, the present invention provides a health functional food composition for improving or preventing pulmonary fibrosis, comprising as an active ingredient a compound selected from a thiazole derivative compound represented by the following chemical formula 1, a food-acceptable salt thereof, a solvate thereof, or a stereoisomer thereof:

[0088] [Chemical Formula 1]

[0089]

[0090] 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 may be the same or different, (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 having 5 to 10 atoms containing one or more heteroatoms selected from the group consisting of N, O and S, wherein R 11 and R 12may be the same or different, and are any one of hydrogen, (C1-C5)alkyl and (C3-C8)cycloalkyl, wherein 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 at least one heteroatom 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 is -R 3-1 or -(C1-C5)alkyl-R 3-1 and the above 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 , , , , and One of the above R 31-1 , R 31-2 , R 32 , R 33 , R 34 , R 35-1 and R 35-2 may be the same or different, and are hydrogen, hydroxy, trifluoromethyl, (C1-C5)alkyl, (C3-C8)cycloalkyl, -SO2-(C1-C3)alkyl, -(C1-C3)alkyl-R 301 and and the above R 301Silver (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, (C3-C8)cycloalkyl, and One of the above R 3001 is hydrogen or (C1-C5)alkyl, and the above R 302 is a halogen, and the above R 303 and R 304 may be the same or different, and are hydrogen or (C1-C3)alkyl, and the above R 36 and R 37 may be the same or different, or and the above R 305 is hydrogen or (C1-C5)alkyl, and R 306 is any one of hydrogen, amino, (C1-C4)alkylamino and di[(C1-C4)alkyl]amino, and R 38 and R 39 may be the same or different, and may be any one of hydrogen, (C1-C3)alkyl, and -(C1-C3)alkyl-(C1-C3)alkoxy.

[0091] The corresponding features can be replaced by those described above.

[0092]

[0093] In this specification, "health functional food" includes food manufactured and processed using raw materials or ingredients with functionality useful to the human body according to Act No. 6727 on Health Functional Foods, and means a food with high medical and healthcare effects processed to efficiently exhibit bioregulatory functions such as prevention of pulmonary fibrosis, biodefense, immunity, and recovery for the purpose of the present invention in addition to nutritional supply.

[0094]

[0095] In the health functional food composition according to the present invention, the health functional food may be manufactured in the form of powder, granules, tablets, capsules, syrup, or beverage, etc., for the purpose of preventing or improving pulmonary fibrosis. There is no limitation on the form that the health functional food may take, and it may be formulated in the same manner as the pharmaceutical composition and used as a functional food or added to various foods.

[0096] In the health functional food composition according to the present invention, the health functional food may include all foods in the conventional sense. For example, the health functional food may include beverages and various drinks, fruits and processed foods thereof (canned fruits, jams, etc.), fish, meats and processed foods thereof (ham, bacon, etc.), breads and noodles, cookies and snacks, dairy products (butter, cheese, etc.), etc., and may include all functional foods in the conventional sense. In addition, foods used as animal feed may also be included.

[0097]

[0098] The health functional food composition according to the present invention can be manufactured by further including food additives (food additives) that are commonly used in the art and are food-relatedly acceptable and other appropriate auxiliary ingredients. Unless otherwise specified, the suitability as a food additive can be determined by the specifications and standards for the relevant item in accordance with the general provisions and general test methods of the Food Additives Codex approved by the Ministry of Food and Drug Safety. Items listed in the above 'Food Additives Codex' include, for example, chemical synthetics such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; natural additives such as persimmon pigment, licorice extract, crystalline cellulose, sucrose pigment, and guar gum; and mixed preparations such as sodium L-glutamate preparations, alkaline agents for noodles, preservative preparations, and tar color preparations.

[0099] The above other auxiliary ingredients may additionally contain, for example, flavoring agents, natural carbohydrates, sweeteners, vitamins, electrolytes, coloring agents, pectic acid, alginic acid, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonating agents, etc. In particular, as the natural carbohydrates, monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol, and erythritol can be used, and as the sweetener, natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame can be used.

[0100]

[0101] The effective dosage of the compound contained in the health functional food according to the present invention can be appropriately adjusted depending on the purpose of use, such as prevention or improvement of pulmonary fibrosis.

[0102] The above health functional food composition has the advantage of not having side effects that may occur with long-term use of general medicines as it is made from food, and is highly portable, so it can be taken as a supplement for preventing or improving pulmonary fibrosis.

[0103] Hereinafter, to aid understanding of the present invention, examples will be given in detail. However, the following examples are intended only to illustrate the scope of the present invention and are not intended to limit its scope. These examples are provided to more fully explain the present invention to those of average skill in the art.

[0104]

[0105] [NMR and MS data of the compound]

[0106] (1)3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-1)

[0107] 1 H-NMR (400 MHz, MeOD-d4): δ8.20-8.21 (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, 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 NH2were not observed. MS Calcd.: 439.51; MS Found: 440.1 (M+H + ).

[0108] (2)3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-2)

[0109] 1H-NMR (400 MHz, DMSO-d6): δ9.26 (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 Calcd.: 403.46; MS Found: 404.1 (M+H + ).

[0110] (3) Methyl 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate (Methyl 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate; hereinafter referred to as A-3)

[0111] 1 H-NMR (400 MHz, MeOD-d4): δ8.16 (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 NH2were not observed. MS Calcd.: 418.47; MS Found: 419.1 (M+H + ).

[0112] (4)4-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (4-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-4)

[0113] 1 H-NMR (400 MHz, DMSO-d6): δ9.53 (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 Hz), 7.25-7.19 (1H, m), 7.16 (2H, s), 7.11 (2H, s), 6.70 (1H, dd,J= 5.8, 2.2 Hz), 6.56 (1H, d,J= 2.4 Hz). MS Calcd.: 439.51; MS Found: 440.1 (M+H + ).

[0114] (5)4-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (4-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-5)

[0115] 1 H-NMR (400 MHz, DMSO-d6): δ9.41 (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 Hz), 7.17 (2H, s), 7.10 (1H, s), 6.68 (1H, dd,J= 2.4 Hz, 5.6 Hz), 6.55 (1H, d,J= 2.0 Hz). MS Calcd.: 403.46; MS Found: 404.1 (M+H + ).

[0116] (6)4-Phenyl-5-((2-(pyridin-3-ylamino)pyridin-4-yl)oxy)thiazol-2-amine (4-Phenyl-5-((2-(pyridin-3-ylamino)pyridin-4-yl)oxy)thiazol-2-amine; hereinafter referred to as A-6)

[0117] 1H-NMR (400 MHz, DMSO-d6): δ9.30 (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 Calcd.: 361.42 Found: 362.1 (M+H + ).

[0118] (7)5-((2-((6-Fluoropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (5-((2-((6-Fluoropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; hereinafter referred to as A-7)

[0119] 1 H-NMR (400 MHz, DMSO-d6): δ9.37 (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 Calcd.: 379.41 Found: 380.1 (M+H + ).

[0120] (8)4-Phenyl-5-((2-(pyridin-4-ylamino)pyridin-4-yl)oxy)thiazol-2-amine (4-Phenyl-5-((2-(pyridin-4-ylamino)pyridin-4-yl)oxy)thiazol-2-amine; hereinafter referred to as A-8)

[0121] 1 H-NMR (400 MHz, DMSO-d6): δ9.57 (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 Calcd.: 361.42 Found: 362.1 (M+H + ).

[0122] (9)6-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (6-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-9)

[0123] 1 H-NMR (400 MHz, DMSO-d6): δ10.1 (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 Calcd.: 404.45 Found: 405.1 (M+H + ).

[0124] (10)3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylbenzamide (3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylbenzamide; hereinafter referred to as A-10)

[0125] 1 H-NMR (400 MHz, MeOH-D4): δ8.04 (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). * one proton from NH was not observed. MS Calcd.: 431.51 Found: 432.2 (M+H + ).

[0126] (11)5-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (5-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; hereinafter referred to as A-11)

[0127] 1H-NMR (400 MHz, DMSO-d6): δ9.66 (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 Calcd.: 404.45 Found: 405.1 (M+H + ).

[0128] (12)3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzenesulfonamide (3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzenesulfonamide; hereinafter referred to as A-12)

[0129] 1 H-NMR (400 MHz, DMSO-d6): δ9.48 (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 Calcd.: 453.54 Found: 454.1 (M+H + ).

[0130] (13)3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylbenzenesulfonamide (3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylbenzenesulfonamide; hereinafter referred to as A-13)

[0131] 1 H-NMR (400 MHz, DMSO-d6): δ9.52 (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 Calcd.: 467.56 Found: 468.1 (M+H + ).

[0132] (14)N-(3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide (N-(3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide; hereinafter referred to as A-14)

[0133] 1H-NMR (400 MHz, DMSO-d6): δ9.63 (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 Calcd.: 453.54 Found: 454.1 (M+H + ).

[0134] (15)5-((2-((3-(methylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (5-((2-((3-(Methylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; hereinafter referred to as A-15)

[0135] 1 H-NMR (400 MHz, DMSO-d6): δ9.55 (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 Calcd.: 438.52 Found: 439.1 (M+H + ).

[0136] (16)N-(3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopropanesulfonamide (N-(3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopropanesulfonamide; hereinafter referred to as A-16)

[0137] 1 H-NMR (400 MHz, DMSO-d6): δ9.60 (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 Calcd.: 479.57 Found: 480.1 (M+H + ).

[0138] (17)4-Phenyl-5-((2-((3-((trifluoromethyl)sulfonyl)phenyl)amino)pyridin-4-yl)oxy)thiazol-2-amine (4-Phenyl-5-((2-((3-((trifluoromethyl)sulfonyl)phenyl)amino)pyridin-4-yl)oxy)thiazol-2-amine; hereinafter referred to as A-17)

[0139] 1H-NMR (400 MHz, DMSO-d6): δ9.79 (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 Calcd.: 492.49 Found: 493.0 (M+H + ).

[0140] (18)3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid (3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid; hereinafter referred to as A-18)

[0141] 1 H-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 no observed. MS Calcd.: 440.50 Found: 441.1 (M+H + ).

[0142] (19)5-((2-((3-((methylsulfonyl)methyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (5-((2-((3-((Methylsulfonyl)methyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; hereinafter referred to as A-19)

[0143] 1 H-NMR (400 MHz, DMSO-d6): δ9.21 (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 Calcd.: 452.5 Found: 453.1 (M+H + ).

[0144] (20)3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-cyclopropylbenzenesulfonamide (3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-cyclopropylbenzenesulfonamide; hereinafter referred to as A-20)

[0145] 1 H-NMR (400 MHz, DMSO-d6): δ9.48 (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 Calcd.: 479.11 Found: 480.1 (M+H + ).

[0146] (21)5-((2-((3-Fluorobenzyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (5-((2-((3-Fluorobenzyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; hereinafter referred to as A-21)

[0147] 1 H-NMR (400 MHz, DMSO-d6): δ7.84 (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 NH2were not observed. MS Calcd.:392.45 Found: 393.1 (M+H + ).

[0148] (22)2-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide (2-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide; hereinafter referred to as A-22)

[0149] 1H-NMR (400 MHz, DMSO-d6): δ9.92 (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= 7.2Hz), 7.60 (1H, s), 7.55 (1H, s), 7.33 (2H, t,J= 7.6Hz), 7.22 (2H, t,J= 8.0 Hz), 7.12 (2H, s), 6.69 (1H, dd,J= 8.4, 2.4 Hz). MS Calcd.: 404.45 Found: 405.1 (M+H + ).

[0150] (23)3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide (3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; hereinafter referred to as A-23)

[0151] 1 H-NMR (400 MHz, DMSO-d6): δ9.25 (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 Calcd.: 417.48; MS Found: 418.1 (M+H + ).

[0152] (24)5-((2-((2-methoxypyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (5-((2-((2-Methoxypyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; hereinafter referred to as A-24)

[0153] 1 H-NMR (400 MHz, DMSO-d6): δ9.53 (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 Calcd.: 391.45; MS Found: 392.1 (M+H + ).

[0154] (25)5-((2-(Benzylamino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (5-((2-(Benzylamino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; hereinafter referred to as A-25)

[0155] 1 H-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 Calcd.: 374.46 Found: 375.1 (M+H + ).

[0156] (26)4-Phenyl-5-((2-((pyridin-4-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine (4-Phenyl-5-((2-((pyridin-4-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine; hereinafter referred to as A-26)

[0157] 1 H-NMR (400 MHz, DMSO-d6): δ8.43 (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 Calcd.: 375.45 Found: 376.1 (M+H + ).

[0158] (27)5-((2-((2-chloropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (5-((2-((2-Chloropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; hereinafter referred to as A-27)

[0159] 1H-NMR (400 MHz, MeOH-d4): δ8.20 (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 NH2 were not observed. MS Calcd.: 395.87; MS Found: 396.1 (M+H + ).

[0160] (28)4-Phenyl-5-((2-((pyridin-3-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine (4-Phenyl-5-((2-((pyridin-3-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine; hereinafter referred to as A-28)

[0161] 1 H-NMR (400 MHz, MeOH-d4): δ8.46 (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). * Three protons from NH and NH2were not observed. MS Calcd.: 375.45; MS Found: 376.1 (M+H + ).

[0162] (29)(3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide ((3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide; hereinafter referred to as A-29)

[0163] 1 H-NMR (400 MHz, DMSO-d6): δ9.21 (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 Calcd.: 453.54 Found: 454.1 (M+H + ).

[0164] (30)5-((2-((2-Fluoropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (5-((2-((2-Fluoropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; hereinafter referred to as A-30)

[0165] 1 H-NMR (400 MHz, DMSO-d6): δ9.91 (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 Calcd.: 379.41 Found: 380.1 (M+H+ ).

[0166] (31)5-((2-((6-Methoxypyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (5-((2-((6-Methoxypyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; hereinafter referred to as A-31)

[0167] 1 H-NMR (400 MHz, DMSO-d6): δ9.01 (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 Calcd.: 391.45 Found: 392.1 (M+H + ).

[0168] (32)5-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (5-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-32)

[0169] 1H-NMR (400 MHz, DMSO-d6): δ9.46 (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 Calcd.: 404.45 Found: 405.1 (M+H + ).

[0170] (33)6-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (6-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; hereinafter referred to as A-33)

[0171] 1 H-NMR (400 MHz, DMSO-d6): δ9.89 (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= 7.6 Hz), 7.52-7.45 (3H, m), 7.33-7.27 (3H, m), 7.22 (1H, t,J= 7.6 Hz), 7.12 (2H, s), 6.72 (1H, dd,J= 4.2, 2.4 Hz). MS Calcd.: 404.45 Found: 405.1 (M+H + ).

[0172] (34)5-((2-((3-(ethylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (5-((2-((3-(Ethylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; hereinafter referred to as A-34)

[0173] 1 H-NMR (400 MHz, DMSO-d6): δ9.55 (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 Calcd.: 425.55 Found: 453.1 (M+H + ).

[0174] (35)5-((2-((6-Chloropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (5-((2-((6-Chloropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; hereinafter referred to as A-35)

[0175] 1 H-NMR (400 MHz, DMSO-d6): δ9.46 (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 Calcd.: 395.87 Found: 396.0 (M+H + ).

[0176] (36)N-(3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide (N-(3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide; hereinafter referred to as A-36)

[0177] 1 H-NMR (400 MHz, DMSO-d6): δ9.35 (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 Calcd.: 507.51; MS Found: 508.1 (M+H+).

[0178] (37)5-((2-((1-Methyl-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (5-((2-((1-Methyl-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; hereinafter referred to as A-37)

[0179] 1H-NMR (400 MHz, DMSO-d6): δ8.85 (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 Calcd.: 364.42 Found: 365.1 (M+H + ).

[0180] (38)5-((2-((1H-Pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (5-((2-((1H-Pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; hereinafter referred to as A-38)

[0181] 1 H-NMR (400 MHz, DMSO-d6): δ12.4 (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 Calcd.: 350.40; MS Found: 351.1 (M+H + ).

[0182] (39)4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-39)

[0183] 1H-NMR (400 MHz, DMSO-d6): δ12.4 (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 Calcd.: 404.44; MS Found: 405.1 (M+H + ).

[0184] (40)3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-40)

[0185] 1 H-NMR (400 MHz, MeOD-d4): δ9.14 (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 Calcd.: 404.44; MS Found: 405.1 (M+H + ).

[0186] (41)2-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (2-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; hereinafter referred to as A-41)

[0187] 1 H-NMR (400 MHz, CDCl3): δ8.08 (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). * A protons from OH was not observed. MS Calcd.: 418.51; MS Found: 419.2(M+H + ).

[0188] (42)2-(4-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (2-(4-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; hereinafter referred to as A-42)

[0189] 1 H-NMR (400 MHz, DMSO-d6): δ9.59 (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 Calcd.: 419.50; MS Found: 420.2(M+H + ).

[0190] (43)2-(5-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (2-(5-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; hereinafter referred to as A-43)

[0191] 1 H-NMR (400 MHz, DMSO-d6): δ9.21 (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 Calcd.: 419.50; MS Found: 420.2(M+H + ).

[0192] (44)2-(3-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (2-(3-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; hereinafter referred to as A-44)

[0193] 1H-NMR (400 MHz, DMSO-d6): δ9.06 (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 Calcd.: 458.58; MS Found: 459.2 (M+H + ).

[0194] (45)3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-45)

[0195] 1H-NMR (400 MHz, CDCl3): δ9.14 (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 Calcd.: 479.57; MS Found: 480.1 (M+H + ).

[0196] (46)3-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (3-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-46)

[0197] 1 H-NMR (400 MHz, DMSO-d6): δ9.24 (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 Calcd.: 443.52; MS Found: 444.2 (M+H + ).

[0198] (47)4-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (4-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-47)

[0199] 1 H-NMR (400 MHz, DMSO-d6): δ9.40 (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 Calcd.: 443.52; MS Found: 444.2 (M+H + ).

[0200] (48)3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (3-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-48)

[0201] 1H-NMR (400 MHz, DMSO-d6): δ9.33 (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 Calcd.: 444.51; MS Found: 445.1 (M+H + ).

[0202] (49)4-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (4-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-49)

[0203] 1 H-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). * Four protons from NH2and OH were not observed. MS Calcd.: 444.51; MS Found: 445.2 (M+H+ ).

[0204] (50)2-(3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (2-(3-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; hereinafter referred to as A-50)

[0205] 1 H-NMR (400 MHz, CDCl3): δ8.08 (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 OH and NH peaks were not observed. MS Calcd.: 432.54; MS Found: 433.2 (M+H + ).

[0206] (51)3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-51)

[0207] 1H-NMR (400 MHz, DMSO-d6): δ9.45 (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). * A proton form NH was not observed. MS Calcd.: 453.54; MS Found: 454.1 (M+H + ).

[0208] (52)3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (3-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-52)

[0209] 1 H-NMR (400 MHz, DMSO-d6): δ9.24 (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 Calcd.: 417.48; MS Found: 418.2 (M+H + ).

[0210] (53)4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (4-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-53)

[0211] 1 H-NMR (400 MHz, DMSO-d6): δ9.53 (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 Calcd.: 453.54; MS Found: 454.1 (M+H + ).

[0212] (54)2-(4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (2-(4-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; hereinafter referred to as A-54)

[0213] 1H-NMR (400 MHz, DMSO-d6): δ9.53 (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 Calcd.: 433.53; MS Found: 434.2 (M+H + ).

[0214] (55)2-(5-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (2-(5-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; hereinafter referred to as A-55)

[0215] 1 H-NMR (400 MHz, DMSO-d6): δ9.19 (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 Calcd.: 433.53; MS Found: 434.1 (M+H + ).

[0216] (56)4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (4-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-56)

[0217] 1 H-NMR (400 MHz, DMSO-d6): δ12.43 (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 Calcd.: 418.47; MS Found: 419.1 (M+H + ).

[0218] (57)3-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (3-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-57)

[0219] 1H-NMR (400 MHz, DMSO-d6): δ9.32 (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). * A proton form OH was not observed. MS Calcd.: 418.47; MS Found: 419.1 (M+H + ).

[0220] (58)3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-58)

[0221] 1 H-NMR (400 MHz, DMSO-d6): δ9.45 (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 Calcd.: 438.52; MS Found: 439.1 (M+H + ).

[0222] (59)2-(4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (2-(4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; hereinafter referred to as A-59)

[0223] 1 H-NMR (400 MHz, CDCl3): δ8.29 (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). * A proton from OH was not observed. MS Calcd.: 418.51; MS Found: 419.2 (M+H + ).

[0224] (60)3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-60)

[0225] 1H-NMR (400 MHz, DMSO-d6): δ9.23 (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 Calcd.: 402.47; MS Found: 403.1 (M+H + ).

[0226] (61)2-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (2-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; hereinafter referred to as A-61)

[0227] 1 H-NMR (400 MHz, DMSO-d6): δ9.05 (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 Calcd.: 418.2; MS Found: 439.1 (M+H + ).

[0228] (62)5-((2-((1-(methylsulfonyl)-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine (5-((2-((1-(Methylsulfonyl)-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; hereinafter referred to as A-62)

[0229] 1 H-NMR (400 MHz, MeOH-d4): δ8.46(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 Calcd.: 428.49 Found: 429.1 (M+H + ).

[0230] (63)4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-63)

[0231] 1H-NMR (400 MHz, CDCl3): δ9.38 (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), 7.41 (2H, t,J= 7.2 Hz), 7.33-7.29 (1H, m), 7.11 (1H, s), 6.53 (1H, dd,J= 2.4 Hz, 6.0 Hz), 6.48 (1H, d,J= 2.4 Hz), 2.70 (3H, s). MS Calcd.: 402.47; MS Found: 403.1 (M+H + ).

[0232] (64)4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-64)

[0233] 1 H-NMR (400 MHz, DMSO-d6): δ9.52 (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 Calcd.: 438.52; MS Found: 439.1 (M+H + ).

[0234] (65)2-(5-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (2-(5-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; hereinafter referred to as A-65)

[0235] 1 H-NMR (400 MHz, DMSO-d6): δ9.21 (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 Calcd.: 418.51; MS Found: 419.2 (M+H + ).

[0236] (66)2-Methyl-2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoic acid (2-Methyl-2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoic acid; hereinafter referred to as A-66)

[0237] 1H-NMR (400 MHz, DMSO-d6): δ9.14 (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). * A proton from OH was not observed. MS Calcd.: 445.53; MS Found: 446.2 (M+H + ).

[0238] (67)N,N-Dimethyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (N,N-Dimethyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-67)

[0239] 1 H-NMR (400 MHz, DMSO-d6): δ9.22 (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 Calcd.: 430.52; MS Found: 431.1 (M+H + ).

[0240] (68)3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid (3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid; hereinafter referred to as A-68)

[0241] 1 H-NMR (400 MHz, DMSO-d6): δ9.15 (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). * A proton from OH was not observed. MS Calcd.: 439.51; MS Found: 440.1 (M+H + ).

[0242] (69)N-Methyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (N-Methyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-69)

[0243] 1H-NMR (400 MHz, DMSO-d6): δ9.24 (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,J= 7.8 Hz), 7.31-7.27 (3H, m), 6.63 (1H, dd,J= 5.6, 2.0 Hz), 6.43 (1H, d,J= 2.0 Hz), 2.73 (3H, d,J= 4.8 Hz), 2.68 (3H, m). MS Calcd.: 416.50; MS Found: 417.1 (M+H + ).

[0244] (70)4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(3-(methylsulfonyl)phenyl)pyridin-2-amine (4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(3-(methylsulfonyl)phenyl)pyridin-2-amine; hereinafter referred to as A-70)

[0245] 1 H-NMR (400 MHz, DMSO-d6): δ9.53 (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 Calcd.: 437.53; MS Found: 438.0 (M+H + ).

[0246] (71)N-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide (N-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide; hereinafter referred to as A-71)

[0247] 1 H-NMR (400 MHz, DMSO-d6): δ9.64 (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 Calcd.: 452.55; MS Found: 453.1 (M+H + ).

[0248] (72)4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((trifluoromethyl)sulfonyl)phenyl)pyridin-2-amine (4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((trifluoromethyl)sulfonyl)phenyl)pyridin-2-amine; hereinafter referred to as A-72)

[0249] 1H-NMR (400 MHz, DMSO-d6): δ9.97 (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 Calcd.: 491.51; MS Found: 492.0 (M+H + ).

[0250] (73)N-Methyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (N-Methyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-73)

[0251] 1 H-NMR (400 MHz, DMSO-d6): δ9.46 (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 Calcd.: 452.55; MS Found: 453.1 (M+H + ).

[0252] (74)N,N-Dimethyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (N,N-Dimethyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-74)

[0253] 1 H-NMR (400 MHz, DMSO-d6): δ9.50 (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 Calcd.: 466.58; MS Found: 467.1 (M+H + ).

[0254] (75)N-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopropanesulfonamide (N-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopropanesulfonamide; hereinafter referred to as A-75)

[0255] 1H-NMR (400 MHz, DMSO-d6): δ9.61 (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 Calcd.: 478.59; MS Found: 479.1 (M+H + ).

[0256] (76)N-Cyclopropyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (N-Cyclopropyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-76)

[0257] 1 H-NMR (400 MHz, DMSO-d6): δ9.47 (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). * A proton from NH was not observed. MS Calcd.: 478.59; MS Found: 479.1 (M+H + ).

[0258] (77)N-(3-(Ethylsulfonyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(3-(Ethylsulfonyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-77)

[0259] 1 H-NMR (400 MHz, DMSO-d6): δ9.60 (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 Calcd.: 438.52 Found: 439.1 (M+H + ).

[0260] (78)(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide ((3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide; hereinafter referred to as A-78)

[0261] 1H-NMR (400 MHz, DMSO-d6): δ9.16 (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 NH2were not observed. MS Calcd.: 452.55; MS Found: 453.1 (M+H + ).

[0262] (79)4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((methylsulfonyl)methyl)phenyl)pyridin-2-amine (4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((methylsulfonyl)methyl)phenyl)pyridin-2-amine; hereinafter referred to as A-79)

[0263] 1 H-NMR (400 MHz, DMSO-d6): δ9.19 (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 Calcd.: 451.56; MS Found: 452.1 (M+H + ).

[0264] (80)4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-ylmethyl)pyridin-2-amine (4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-ylmethyl)pyridin-2-amine; hereinafter referred to as A-80)

[0265] 1 H-NMR (400 MHz, DMSO-d6): δ8.43 (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 Calcd.: 374.46; MS Found: 375.1 (M+H + ).

[0266] (81)4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-ylmethyl)pyridin-2-amine (4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-ylmethyl)pyridin-2-amine; hereinafter referred to as A-81)

[0267] 1H-NMR (400 MHz, DMSO-d6): δ8.47 (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 Calcd.: 374.46; MS Found: 375.1 (M+H + ).

[0268] (82)4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-yl)pyridin-2-amine (4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-yl)pyridin-2-amine; hereinafter referred to as A-82)

[0269] 1 H-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 Calcd.: 360.43; MS Found: 361.1 (M+H + ).

[0270] (83)N-(6-Fluoropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(6-Fluoropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-83)

[0271] 1 H-NMR (400 MHz, DMSO-d6): δ9.33 (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 Calcd.: 378.42; MS Found: 379.1 (M+H + ).

[0272] (84)N-(6-Chloropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(6-Chloropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-84)

[0273] 1H-NMR (400 MHz, DMSO-d6): δ9.45 (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, d,J= 8.0 Hz), 7.41-7.34 (3H, m), 7.30 (1H, t,J= 7.6 Hz), 6.72 (1H, dd,J= 5.2, 2.4 Hz), 6.43 (1H, d,J= 2.0 Hz), 2.68 (3H, s). MS Calcd.: 394.88; MS Found: 395.1 (M+H + ).

[0274] (85)N-(6-Methoxypyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(6-Methoxypyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-85)

[0275] 1 H-NMR (400 MHz, DMSO-d6): δ9.00 (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 Calcd.: 390.46; MS Found: 391.1 (M+H + ).

[0276] (86)4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-yl)pyridin-2-amine (4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-yl)pyridin-2-amine; hereinafter referred to as A-86)

[0277] 1 H-NMR (400 MHz, DMSO-d6): δ9.56 (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, t,J= 7.6 Hz), 7.29 (1H, t,J= 7.4 Hz), 6.78 (1H, dd,J= 5.8, 2.6 Hz), 6.50 (1H, d,J= 2.0 Hz), 2.68 (3H, s). MS Calcd.: 360.43; MS Found: 361.1 (M+H + ).

[0278] (87)N-(2-Fluoropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(2-Fluoropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-87)

[0279] 1H-NMR (400 MHz, DMSO-d6): δ9.89 (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 Calcd.: 378.42; MS Found: 379.1 (M+H + ).

[0280] (88)N-(2-Methoxypyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(2-Methoxypyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-88)

[0281] 1 H-NMR (400 MHz, DMSO-d6): δ9.51 (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=7.6 Hz), 7.31-7.28 (2H, m), 6.97 (1H, d,J= 5.6 Hz), 6.76 (1H, d,J= 6.0 Hz), 6.48 (1H,d,J= 2.0 Hz), 3.76 (3H, s), 2.68 (3H, s). MS Calcd.: 390.46; MS Found: 391.1 (M+H + ).

[0282] (89)N-(2-Chloropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(2-Chloropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-89)

[0283] 1 H-NMR (400 MHz, DMSO-d6): δ9.83 (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= 7.6 Hz), 7.41-7.34 (3H, m), 7.30 (1H, t,J= 7.4 Hz), 6.84 (1H, dd,J= 5.8, 2.2 Hz), 6.51 (1H, d,J= 2.4 Hz), 2.69 (3H, s). MS Calcd.: 394.88; MS Found: 395.1 (M+H + ).

[0284] (90)6-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (6-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-90)

[0285] 1H-NMR (400 MHz, DMSO-d6): δ10.1 (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 Calcd.: 403.46; MS Found: 404.1 (M+H + ).

[0286] (91)5-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (5-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; hereinafter referred to as A-91)

[0287] 1 H-NMR (400 MHz, DMSO-d6): δ9.64 (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 Calcd.: 403.46; MS Found: 404.1 (M+H + ).

[0288] (92)5-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (5-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-92)

[0289] 1 H-NMR (400 MHz, DMSO-d6): δ9.56 (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 Calcd.: 403.46; MS Found: 404.1 (M+H + ).

[0290] (93)2-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide (2-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide; hereinafter referred to as A-93)

[0291] 1H-NMR (400 MHz, DMSO-d6): δ9.94 (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 Calcd.: 403.46; MS Found: 404.1 (M+H + ).

[0292] (94)N-Benzyl-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-Benzyl-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-94)

[0293] 1 H-NMR (400 MHz, DMSO-d6): δ7.89 (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 Calcd.: 373.47; MS Found: 374.1 (M+H + ).

[0294] (95)N-(4-Fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(4-Fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-95)

[0295] 1H-NMR (400 MHz, DMSO-d6): δ7.24 (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,J= 6.0 Hz), 7.08 (2H, d,J= 9.0 Hz), 6.33 (1H, dd,J= 5.6, 2.4 Hz), 6.11 (1H, d,J= 2.0 Hz), 4.37 (2H, d,J= 6.4 Hz), 2.65 (3H, s). MS Calcd.: 391.46; MS Found: 392.1 (M+H + ).

[0296] (96)N-(3-Fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(3-Fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-96)

[0297] 1 H-NMR (400 MHz, DMSO-d6): δ8.00 (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 Calcd.: 394.46; MS Found: 392.1 (M+H + ).

[0298] (97)4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(1-(methylsulfonyl)-1H-pyrazol-4-yl)pyridin-2-amine (4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(1-(methylsulfonyl)-1H-pyrazol-4-yl)pyridin-2-amine; hereinafter referred to as A-97)

[0299] 1 H-NMR (400 MHz, DMSO-d6): δ9.40 (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,J= 7.8 Hz), 7.29 (1H, t,J= 5.8 Hz), 6.62 (1H, dd,J= 7.6, 2.0 Hz), 6.33 (1H, d,J= 2.4 Hz), 3.41 (3H, s), 2.68 (3H, s). MS Calcd.: 427.50; MS Found: 428.1 (M+H + ).

[0300] (98)N-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-98)

[0301] 1 H-NMR (400 MHz, DMSO-d6): δ9.40 (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 Calcd.: 453.54; MS Found: 454.1 (M+H + ).

[0302] (99)N-(1-Methyl-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(1-Methyl-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-99)

[0303] 1 H-NMR (400 MHz, DMSO-d6): δ8.85 (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 Calcd.: 363.44; MS Found: 364.1 (M+H + ).

[0304] (100)4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(1H-pyrazol-4-yl)pyridin-2-amine (4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(1H-pyrazol-4-yl)pyridin-2-amine; hereinafter referred to as A-100)

[0305] 1 H-NMR (400 MHz, DMSO-d6): δ12.4 (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, t,J= 7.6 Hz), 7.29 (1H, t,J= 7.8 Hz), 6.45 (1H, dd,J= 5.8, 2.2 Hz), 6.22 (1H, d,J= 2.0 Hz), 2.66 (3H, s). MS Calcd.: 349.41; MS Found: 350.1 (M+H + ).

[0306] (101)6-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (6-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; hereinafter referred to as A-101)

[0307] 1 H-NMR (400 MHz, DMSO-d6): δ9.89 (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 Calcd.: 403.46; MS Found: 404.1 (M+H + ).

[0308] (102)4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; hereinafter referred to as A-102)

[0309] 1 H-NMR (400 MHz, DMSO-d6): δ9.79 (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 Calcd.: 403.46; MS Found: 404.1 (M+H + ).

[0310] (103)N-(4-methoxyphenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(4-Methoxyphenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-103)

[0311] 1 H-NMR (400 MHz, DMSO-d6): δ8.86 (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 Calcd.: 389.47; MS Found: 390.1 (M+H + ).

[0312] (104)4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(piperazin-1-yl)phenyl)pyridin-2-amine (4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(piperazin-1-yl)phenyl)pyridin-2-amine; hereinafter referred to as A-104)

[0313] 1H-NMR (400 MHz, DMSO-d6): δ8.80 (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). * A proton from NH was not observed. MS Calcd.: 443.56; MS Found: 444.2 (M+H + ).

[0314] (105)4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(2-(piperidin-1-yl)ethoxy)phenyl)pyridin-2-amine (4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(2-(piperidin-1-yl)ethoxy)phenyl)pyridin-2-amine; hereinafter referred to as A-105)

[0315] 1 H-NMR (400 MHz, DMSO-d6): δ8.86 (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 Calcd.: 486.63; MS Found: 487.2 (M+H + ).

[0316] (106)N-(3-Methoxy-4-(4-methylpiperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(3-Methoxy-4-(4-methylpiperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-106)

[0317] 1 H-NMR (400 MHz, DMSO-d6): δ8.90 (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 Calcd.: 487.62; MS Found: 488.2 (M+H + ).

[0318] (107)1,1,1-Trifluoro-N-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide (1,1,1-Trifluoro-N-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide; hereinafter referred to as A-107)

[0319] 1H-NMR (400 MHz, DMSO-d6): δ9.25 (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). * A proton from NH was not observed. MS Calcd.: 506.07; MS Found: 507.1 (M+H + ).

[0320] (108)N-(4-(4-(2-methoxyethyl)piperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(4-(4-(2-Methoxyethyl)piperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-108)

[0321] 1 H-NMR (400 MHz, DMSO-d6): δ8.79 (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 Calcd.: 501.64; MS Found: 502.2 (M+H + ).

[0322] (109)3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-109)

[0323] 1 H-NMR (400 MHz, DMSO-d6): δ12.8 (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, d,J= 7.2 Hz), 7.47-7.40 (3H, m), 7.37-7.30 (2H, m), 6.68 (1H, dd,J= 6.0, 2.0 Hz), 6.45 (1H, d,J= 2.0 Hz), 2.70 (3H, s). MS Calcd.: 403.45; MS Found: 404.1 (M+H + ).

[0324] (110)4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-110)

[0325] 1 H-NMR (400 MHz, DMSO-d6): δ9.50 (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). *A proton from OH was not observed. MS Calcd.: 403.65; MS Found: 404.1 (M+H + ).

[0326] (111)2-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)acetonitrile (2-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)acetonitrile; hereinafter referred to as A-111)

[0327] 1 H-NMR (400 MHz, CDCl3): δ8.11 (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).

[0328] (112)N-(3-((1H-tetrazol-5-yl)methyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(3-((1H-tetrazol-5-yl)methyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-112)

[0329] 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). * A proton from NH was not observed. MS Calcd.: 441.51 Found: 442.2 (M+H + ).

[0330] (113)3-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanenitrile (3-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanenitrile; hereinafter referred to as A-113)

[0331] 1 H-NMR (400 MHz, DMSO-d6): δ9.08 (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 Calcd.: 412.5 Found: 413.2 (M+H + ).

[0332] (114)N-(3-(2-(2H-tetrazol-5-yl)ethyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(3-(2-(2H-Tetrazol-5-yl)ethyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-114)

[0333] 1 H-NMR (400 MHz, DMSO-d6): δ9.03 (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). * A proton from NH was not observed. MS Calcd.: 455.53 Found: 456.2 (M+H + ).

[0334] (115)2-(3-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (2-(3-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; hereinafter referred to as A-115)

[0335] 1H-NMR (400 MHz, CDCl3):δ8.09 (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). * A proton from NH was not observed. MS Calcd.: 443.56 ; MS Found: 444.2 (M+H + ).

[0336] (116)3-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-116)

[0337] 1 H-NMR (400 MHz, CDCl3): δ8.12 (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 Calcd.: 464.56; MS Found: 465.1 (M+H + ).

[0338] (117)3-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (3-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-117)

[0339] 1 H-NMR (400 MHz, CDCl3): δ8.12 (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). * A proton from NH was not observed. MS Calcd.: 428.51 ; MS Found: 429.2 (M+H + ).

[0340] (118)4-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (4-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-118)

[0341] 1H-NMR (400 MHz, DMSO-d6): δ9.53 (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 Calcd.: 464.56; MS Found: 465.1 (M+H + ).

[0342] (119)4-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (4-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-119)

[0343] 1 H-NMR (400 MHz, DMSO-d6): δ9.39 (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 Calcd.: 428.51; MS Found: 429.2 (M+H + ).

[0344] (120)2-(4-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (2-(4-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; hereinafter referred to as A-120)

[0345] 1 H-NMR (400 MHz, DMSO-d6): δ9.52 (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 Calcd.: 444.55; MS Found: 445.2(M+H + ).

[0346] (121)2-(5-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (2-(5-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; hereinafter referred to as A-121)

[0347] 1H-NMR (400 MHz, DMSO-d6): δ9.19 (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 Calcd.: 444.55; MS Found: 445.2 (M+H + ).

[0348] (122)N-(3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)ethanesulfonamide (N-(3-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)ethanesulfonamide; hereinafter referred to as A-122)

[0349] 1H-NMR (400 MHz, DMSO-d6): δ9.67 (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, 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 Calcd.: 492.13; MS Found: 493.2 (M+H + ).

[0350] (123)N-(3-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide (N-(3-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide; hereinafter referred to as A-123)

[0351] 1H-NMR (400 MHz, DMSO-d6): δ11.7 (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 Calcd.: 532.09; MS Found: 533.1 (M+H + ).

[0352] (124)6-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (6-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; hereinafter referred to as A-124)

[0353] 1 H-NMR (400 MHz, DMSO-d6): δ9.86 (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 Calcd.: 429.49 Found: 430.1 (M+H + ).

[0354] (125)6-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide (6-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide; hereinafter referred to as A-125)

[0355] 1 H-NMR (400 MHz, DMSO-d6): δ9.85 (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 Calcd.: 443.52 Found: 444.2 (M+H + ).

[0356] (126)4-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide (4-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; hereinafter referred to as A-126)

[0357] 1H-NMR (400 MHz, DMSO-d6): δ9.34 (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 Calcd.: 442.53 Found: 443.2 (M+H + ).

[0358] (127)N-(6-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)methanesulfonamide (N-(6-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)methanesulfonamide; hereinafter referred to as A-127)

[0359] 1 H-NMR (400 MHz, DMSO-d6): δ9.79 (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 Calcd.: 479.57; MS Found: 480.2 (M+H + ).

[0360] (128)N-(4-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide (N-(4-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide; hereinafter referred to as A-128)

[0361] 1 H-NMR (400 MHz, DMSO-d6): δ9.33 (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 Calcd.: 478.59 Found: 479.2 (M+H + ).

[0362] (129)6-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (6-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-129)

[0363] 1H-NMR (400 MHz, DMSO-d6): δ10.09 (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 Calcd.: 429.49 Found: 430.2 (M+H + ).

[0364] (130) Methyl 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate (Methyl 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate; hereinafter referred to as A-130)

[0365] 1 H-NMR (400 MHz, DMSO-d6): δ10.32 (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 Calcd.: 444.13; MS Found: 445.1 (M+H + ).

[0366] (131) Methyl 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate (Methyl 6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate; hereinafter referred to as A-131)

[0367] 1 H-NMR (400 MHz, DMSO-d6): δ10.16 (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 Calcd.: 444.51 Found: 445.2 (M+H + ).

[0368] (132)6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; hereinafter referred to as A-132)

[0369] 1H-NMR (400 MHz, DMSO-d6): δ10.65 (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). * A proton from NH was not observed. MS Calcd.: 430.48; MS Found: 431.1 (M+H + ).

[0370] (133)6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; hereinafter referred to as A-133)

[0371] 1 H-NMR (400 MHz, DMSO-d6): δ10.08 (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, 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 Calcd.: 443.53; MS Found: 444.1 (M+H + ).

[0372] (134)6-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid (6-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid; hereinafter referred to as A-134)

[0373] 1 H-NMR (400 MHz, DMSO-d6): δ10.06 (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). * A proton from OH was not observed. MS Calcd.: 430.48 Found: 431.1 (M+H + ).

[0374] (135)3-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (3-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-135)

[0375] 1H-NMR (400 MHz, DMSO-d6): δ12.9 (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 Calcd.: 429.49; MS Found: 430.2 (M+H + ).

[0376] (136)4-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (4-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-136)

[0377] 1 H-NMR (400 MHz, DMSO-d6): δ9.52 (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 Calcd.: 429.49; MS Found: 430.2 (M+H + ).

[0378] (137)6-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid (6-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid; hereinafter referred to as A-137)

[0379] 1 H-NMR (400 MHz, DMSO-d6): δ9.40 (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 Calcd.: 454.53 Found: 455.1 (M+H + ).

[0380] (138)6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-hydroxynicotinamide (6-((4-((2-cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-hydroxynicotinamide; hereinafter referred to as A-138)

[0381] 1H-NMR (400 MHz, DMSO-d6): δ11.1 (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 Calcd.: 445.49; MS Found: 446.2 (M+H + ).

[0382] (139)4-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-hydroxybenzamide (4-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-hydroxybenzamide; hereinafter referred to as A-139)

[0383] 1 H-NMR (400 MHz, DMSO-d6): δ11.0 (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). * A proton from OH was not observed. MS Calcd.: 444.51; MS Found: 445.2 (M+H + ).

[0384] (140)6-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(methylsulfonyl)nicotinamide (6-((4-((2-Cyclopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(methylsulfonyl)nicotinamide; hereinafter referred to as A-140)

[0385] 1 H-NMR (400 MHz, DMSO-d6): δ9.97 (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 Calcd.: 507.58; MS Found: 508.1 (M+H + ).

[0386] (141)2-(3-((4-((2-Methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (2-(3-((4-((2-Methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; hereinafter referred to as A-141)

[0387] 1H-NMR (400 MHz, CDCl3): δ8.10 (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). * A proton from NH was not observed. MS Calcd.: 433.52 ; MS Found: 434.1 (M+H + ).

[0388] (142)3-((4-((2-Methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-Methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-142)

[0389] 1 H-NMR (400 MHz, CDCl3): δ8.16 (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 Calcd.: 454.52; MS Found: 455.1 (M+H + ).

[0390] (143)3-((4-((2-Methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (3-((4-((2-Methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-143)

[0391] 1 H-NMR (400 MHz, DMSO-d6): δ9.25 (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 Calcd.: 418.47; MS Found: 419.1 (M+H + ).

[0392] (144)3-((4-((2-Methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (3-((4-((2-Methoxy-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-144)

[0393] 1 H-NMR (400 MHz, DMSO-d6): δ12.8 (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, d,J= 7.6 Hz), 7.48 (1H, d,J= 7.2 Hz), 7.44-7.30 (4H, m), 6.71 (1H, d,J= 6.0 Hz), 6.53 (1H, s), 4.13 (3H, s). MS Calcd.: 419.45; MS Found: 420.1 (M+H + ).

[0394] (145)3-((4-((4-Phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((4-Phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-145)

[0395] 1 H-NMR (400 MHz, DMSO-d6): δ9.46 (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 Calcd.: 492.49; MS Found: 493.1 (M+H + ).

[0396] (146)6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-146)

[0397] 1H-NMR (400 MHz, DMSO-d6): δ10.15 (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). [M+H] + calcd for 457.43, found 458.15.(M+H + ).

[0398] (147)4-((4-((4-Phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (4-((4-((4-Phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-147)

[0399] 1 H-NMR (400 MHz, DMSO-d6): δ9.37 (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, 2H), 7.47 (t,J= 7.2 Hz, 1H), 7.10 (s, 1H), 6.78 (dd,J= 5.6, 2.4 Hz, 1H), 6.51 (d,J= 2.4 Hz, 1H). [M+H] + calcd for 456.44, found 457.22 (M+H + ).

[0400] (148)N-Methyl-4-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (N-Methyl-4-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-148)

[0401] 1 H-NMR (400 MHz, DMSO-d6): δ9.36 (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] + calcd for 470.47, found 471.22 (M+H + ).

[0402] (149)6-((4-((4-Phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (6-((4-((4-Phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; hereinafter referred to as A-149)

[0403] 1 H-NMR (400 MHz, DMSO-d6): δ11.50 (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] +calcd for 458.42, found 459.20

[0404] (150)N-Methyl-6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (N-Methyl-6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-150)

[0405] 1 H-NMR (400 MHz, DMSO-d6): δ10.15 (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 Calcd.: 471.46; Found: 472.21 (M+H + ).

[0406] (151)3-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (3-((4-((4-Phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-151)

[0407] 1H-NMR (400 MHz, DMSO-d6): δ9.34 (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). * A proton from OH was not observed. MS Calcd.: 457.43; Found: 458.1 (M+H + ).

[0408] (152)4-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (4-((4-((4-Phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-152)

[0409] 1 H-NMR (400 MHz, DMSO-d6): δ12.4 (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 Calcd.: 457.43; Found: 458.1 (M+H + ).

[0410] (153)2-(3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (2-(3-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; hereinafter referred to as A-153)

[0411] 1H-NMR (400 MHz, CDCl3): δ8.07 (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). * A proton form NH was not observed. MS Calcd.: 446.56; MS Found: 447.2 (M+H + ).

[0412] (154)3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-154)

[0413] 1 H-NMR (400 MHz, DMSO-d6): δ9.43 (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 Calcd.: 467.56; MS Found: 468.2 (M+H + ).

[0414] (155)3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (3-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-155)

[0415] 1 H-NMR (400 MHz, DMSO-d6): δ9.22 (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 Calcd.: 431.51; MS Found: 432.2 (M+H + ).

[0416] (156)4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-156)

[0417] 1 H-NMR (400 MHz, DMSO-d6): δ9.52 (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 Hz), 7.27 (1H, t,J= 7.2 Hz), 7.19 (2H, s), 6.73 (1H, dd,J= 2.0 Hz, 5.8 Hz), 6.56 (1H, d,J= 1.6 Hz), 3.08 (6H, s). MS Calcd.: 467.56; MS Found: 468.2 (M+H + ).

[0418] (157)4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-157)

[0419] 1 H-NMR (400 MHz, DMSO-d6): δ9.38 (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 Hz), 7.28-7.25 (1H, m), 7.11 (1H, m), 6.70 (1H, dd,J= 2.0 Hz, 5.8 Hz), 6.54-6.50 (2H, m), 3.08 (6H, s). MS Calcd.: 431.51; MS Found: 432.2 (M+H + ).

[0420] (158)2-(4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (2-(4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; hereinafter referred to as A-158)

[0421] 1H-NMR (400 MHz, DMSO-d6): δ9.51 (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 Calcd.: 447.55; MS Found: 448.2 (M+H + ).

[0422] (159)2-(5-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (2-(5-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; hereinafter referred to as A-159)

[0423] 1 H-NMR (400 MHz, DMSO-d6): δ9.18 (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 Calcd.: 447.55; MS Found: 448.2 (M+H + ).

[0424] (160)6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; hereinafter referred to as A-160)

[0425] 1 H-NMR (400 MHz, DMSO-d6): δ9.84 (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 Calcd.: 432.50; MS Found: 433.2 (M+H + ).

[0426] (161)6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide (6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide; hereinafter referred to as A-161)

[0427] 1 H-NMR (400 MHz, DMSO-d6): δ9.83 (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 Calcd.: 446.52; MS Found: 447.2 (M+H + ).

[0428] (162) Methyl 6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate (Methyl 6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate; hereinafter referred to as A-162)

[0429] 1 H-(400 MHz, DMSO-d6):δ10.1 (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 Hz), 7.34 (2H, t,J= 7.6 Hz), 7.24 (1H, t,J= 8.0 Hz), 6.68 (1H, dd,J= 5.8, 2.2 Hz), 3.80 (3H, s), 3.06 (6H, s). MS Calcd.: 447.51; MS Found: 448.2 (M+H + ).

[0430] (163)6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-163)

[0431] 1H-NMR (400 MHz, DMSO-d6): δ10.1 (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 Calcd.: 432.50; MS Found: 433.2 (M+H + ).

[0432] (164)4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide (4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; hereinafter referred to as A-164)

[0433] 1 H-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 Hz), 7.25 (1H, t,J= 7.6 Hz), 6.68 (1H, dd,J= 5.6, 2.4 Hz), 6.52 (1H, d,J= 2.0 Hz), 3.06 (6H, s), 2.73 (3H, d,J= 4.4 Hz). MS Calcd.: 445.54; MS Found: 446.2 (M+H + ).

[0434] (165)6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; hereinafter referred to as A-165)

[0435] 1 H-NMR (400 MHz, DMSO-d6): δ8.71 (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 Calcd.: 433.48; MS Found: 434.1 (M+H + ).

[0436] (166)6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; hereinafter referred to as A-166)

[0437] 1H-NMR (400 MHz, DMSO-d6): δ10.1 (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 Calcd.: 446.52; MS Found: 447.2 (M+H + ).

[0438] (167)3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-167)

[0439] 1 H-NMR (400 MHz, DMSO-d6): δ9.38 (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). * A proton from OH was not observed. MS Calcd.: 432.49; MS Found: 433.2 (M+H + ).

[0440] (168)4-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-168)

[0441] 1 H-NMR (400 MHz, DMSO-d6): δ9.49 (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). * A protons from NH was not observed. MS Calcd.: 432.49; MS Found: 433.2 (M+H + ).

[0442] (169)6-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid (6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid; hereinafter referred to as A-169)

[0443] 1H-NMR (400 MHz, DMSO-d6): δ10.1 (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). * A proton from OH was not observed. MS Calcd.: 433.48; MS Found: 434.1 (M+H + ).

[0444] (170) Methyl 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate (Methyl 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate; hereinafter referred to as A-170)

[0445] 1 H-NMR (400 MHz, DMSO-d6): δ9.38 (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 Calcd.: 482.35; MS Found: 484.0 (M+H + ).

[0446] (171)3-((4-((2-Bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (3-((4-((2-Bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-171)

[0447] 1H-NMR (400 MHz, CDCl3): δ9.85 (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). * A proton from OH was not observed. MS Calcd.: 468.32; MS Found: 469.0 (M+H + ).

[0448] (172)3-((4-((2-Bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (3-((4-((2-Bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-172)

[0449] 1 H-NMR (400 MHz, MeOD-d4): δ8.15 (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). * Three protons from NH and NH2were not observed. MS Calcd.:467.34; MS Found: 468.0 (M+H + ).

[0450] (173)6-((4-((2-Cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (6-((4-((2-Cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-173)

[0451] 1 H-NMR (400 MHz, DMSO-d6): δ10.1 (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 Calcd.: 457.55; MS Found: 458.2 (M+H + ).

[0452] (174)6-((4-((2-Cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (6-((4-((2-Cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; hereinafter referred to as A-174)

[0453] 1H-NMR (400 MHz, DMSO-d6): δ10.70 (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). * A proton from OH was not observed. MS Calcd.: 458.53 Found: 459.2 (M+H + ).

[0454] (175)4-((4-((2-Cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (4-((4-((2-Cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-175)

[0455] 1H-NMR (400 MHz, DMSO-d6): δ9.52 (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). * A proton from OH was not observed. MS Calcd.: 457.54 Found: 458.2 (M+H + ).

[0456] (176)6-((4-((2-Cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (6-((4-((2-Cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; hereinafter referred to as A-176)

[0457] 1H-NMR (400 MHz, DMSO-d6): δ10.12 (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= 8.0 Hz), 2.75 (3H, d,J= 4.8 Hz), 2.15-2.13 (2H, m), 1.84-1.76 (4H, m), 1.66 (2H, m). MS Calcd.: 471.17; MS Found: 472.2 (M+H + ).

[0458] (177)6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-177)

[0459] 1H-NMR (400 MHz, CDCl3): δ8.67 (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 NH2were not observed. MS Calcd.: 471.57; MS Found: 472.2 (M+H + ).

[0460] (178)6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; hereinafter referred to as A-178)

[0461] 1H-NMR (400 MHz, DMSO-d6): δ11.12 (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).* A proton from OH was not observed. MS Calcd.: 472.56 Found: 473.2 (M+H + ).

[0462] (179)4-((4-((2-Cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (4-((4-((2-Cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-179)

[0463] 1H-NMR (400 MHz, DMSO-d6): δ9.51 (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). * A proton from OH was not observed. MS Calcd.: 471.57 Found: 472.2 (M+H + ).

[0464] (180)6-((4-((2-Cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (6-((4-((2-Cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; hereinafter referred to as A-180)

[0465] 1H-NMR (400 MHz, DMSO-d6): δ10.13 (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= 4.4 Hz), 2.12-2.08 (2H, m), 1.80-1.77 (2H, m), 1.54-1.51 (1H, m), 1.54-1.51 (2H, m), 1.42-1.39 (2H, m), 1.27-1.20 (1H, m). MS Calcd.: 485.60; MS Found: 486.3 (M+H + ).

[0466] (181)3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-181)

[0467] 1 H-NMR (400 MHz, DMSO-d6): δ9.44 (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 Calcd.: 452.55; MS Found: 453.1 (M+H + ).

[0468] (182)2-(3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (2-(3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; hereinafter referred to as A-182)

[0469] 1 H-NMR (400 MHz, DMSO-d6): δ9.06 (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 Calcd.: 431.55; MS Found: 432.2 (M+H + ).

[0470] (183)3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-183)

[0471] 1H-NMR (400 MHz, DMSO-d6): δ9.24 (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 Found: 417.2 (M+H + ).

[0472] (184)4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-184)

[0473] 1 H-NMR (400 MHz, DMSO-d6): δ9.53 (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 Calcd.: 452.55; MS Found: 453.1 (M+H + ).

[0474] (185)4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-185)

[0475] 1 H-NMR (400 MHz, DMSO-d6): δ9.39 (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 Calcd.: 416.50; MS Found: 417.2 (M+H + ).

[0476] (186)2-(4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (2-(4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; hereinafter referred to as A-186)

[0477] 1H-NMR (400 MHz, DMSO-d6): δ9.55 (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 Calcd.: 432.54; MS Found: 433.2 (M+H + ).

[0478] (187)2-(5-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (2-(5-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; hereinafter referred to as A-187)

[0479] 1 H-NMR (400 MHz, DMSO-d6): δ9.21 (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 Calcd.: 432.54; MS Found: 433.2 (M+H +).

[0480] (188)N-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)ethanesulfonamide (N-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)ethanesulfonamide; hereinafter referred to as A-188)

[0481] 1 H-NMR (400 MHz, DMSO-d6): δ9.66 (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 Calcd.: 480.13; MS Found: 481.1 (M+H + ).

[0482] (189)4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide (4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; hereinafter referred to as A-189)

[0483] 1H-NMR (400 MHz, DMSO-d6): δ9.35 (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 Calcd.: 430.52 Found: 431.2 (M+H + ).

[0484] (190)6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-190)

[0485] 1 H-NMR (400 MHz, DMSO-d6): δ10.1 (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 Calcd.: 432.50 Found: 433.2 (M+H + ).

[0486] (191)6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate (6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate; hereinafter referred to as A-191)

[0487] 1 H-NMR (400 MHz, DMSO-d6): δ10.33 (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 Calcd.: 432.13; MS Found: 433.1 (M+H + ).

[0488] (192)6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; hereinafter referred to as A-192)

[0489] 1H-NMR (400 MHz, DMSO-d6): δ8.75 (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 Calcd.: 418.11; MS Found: 419.1 (M+H + ).

[0490] (193)6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; hereinafter referred to as A-193)

[0491] 1 H-NMR (400 MHz, DMSO-d6): δ10.11 (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 Calcd.: 431.14; MS Found: 432.1 (M+H + ).

[0492] (194)3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-194)

[0493] 1 H-NMR (400 MHz, DMSO-d6): δ9.36 (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). * A proton from OH was not observed. MS Calcd.: 417.48; MS Found: 418.2 (M+H + ).

[0494] (195)4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-195)

[0495] 1H-NMR (400 MHz, DMSO-d6): δ9.54 (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). * A proton form OH was not observed. MS Calcd.: 417.48; MS Found: 418.1 (M+H + ).

[0496] (196)6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-isopropylnicotinamide (6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-isopropylnicotinamide; hereinafter referred to as A-196)

[0497] 1 H-NMR (400 MHz, DMSO-d6): δ8.61 (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 Calcd.: 459.56; MS Found: 460.3 (M+H + ).

[0498] (197)(6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(4-methylpiperazin-1-yl)methanone ((6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(4-methylpiperazin-1-yl)methanone; hereinafter referred to as A-197)

[0499] 1 H-NMR (400 MHz, DMSO-d6): δ10.1 (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 Calcd.: 500.62; MS Found: 501.3 (M+H + ).

[0500] (198)(3-Aminopyrrolidin-1-yl)(6-(4-(2-ethyl-4-phenylthiazol-5-yloxy)pyridin-2-ylamino)pyridin-3-yl)methanone ((3-Aminopyrrolidin-1-yl)(6-(4-(2-ethyl-4-phenylthiazol-5-yloxy)pyridin-2-ylamino)pyridin-3-yl)methanone; hereinafter referred to as A-198)

[0501] 1H-NMR (400 MHz, DMSO-d6): δ10.1 (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 NH2were not observed. MS Calcd.:486.59; MS Found: 487.2 (M+H + ).

[0502] (199)6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(pyrrolidin-1-yl)ethyl)nicotinamide (6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(pyrrolidin-1-yl)ethyl)nicotinamide; hereinafter referred to as A-199)

[0503] 1H-NMR (400 MHz, MeOH-d4): δ8.64 (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 Calcd.: 514.64; MS Found: 515.3 (M+H + ).

[0504] (200)(6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(3-(methylamino)pyrrolidin-1-yl)methanone ((6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(3-(methylamino)pyrrolidin-1-yl)methanone; hereinafter referred to as A-200)

[0505] 1H-NMR (400 MHz, MeOH-d4): δ8.39 (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). * A proton from NH was not observed. MS Calcd.: 500.62; MS Found: 501.2 (M+H + ).

[0506] (201)6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-methylpiperazin-1-yl)ethyl)nicotinamide (6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-methylpiperazin-1-yl)ethyl)nicotinamide; hereinafter referred to as A-201)

[0507] 1H-NMR (400 MHz, DMSO-d6): δ10.1 (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 Calcd.: 543.68; MS Found: 544.3 (M+H + ).

[0508] (202)6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-isopropylpiperazin-1-yl)ethyl)nicotinamide (6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-isopropylpiperazin-1-yl)ethyl)nicotinamide; hereinafter referred to as A-202)

[0509] 1H-NMR (400 MHz, DMSO-d6): δ10.15 (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= 7.2 Hz), 2.54 (1H, t,J= 6.4 Hz), 2.48-2.38 (10H, m), 1.33 (3H, t,J= 7.4 Hz), 0.91 (6H, d,J= 6.0 Hz). MS Calcd.: 571.74; MS Found: 572.3 (M+H + ).

[0510] (203)6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-ethylpiperazin-1-yl)ethyl)nicotinamide (6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-ethylpiperazin-1-yl)ethyl)nicotinamide; hereinafter referred to as A-203)

[0511] 1H-NMR (400 MHz, DMSO-d6): δ10.16 (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), 3.34-3.31 (2H, m), 3.00 (2H, q,J= 7.6 Hz), 2.48-2.39 (6H, m), 2.28-2.23 (6H, m), 1.34 (3H, t,J= 7.6 Hz), 0.95 (3H, t,J= 7.4 Hz). MS Calcd.: 557.71; MS Found: 558.3 ​​(M+H + ).

[0512] (204)5-(3-aminopyrrolidin-1-yl)-N-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)pyridin-2-amine (5-(3-aminopyrrolidin-1-yl)-N-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)pyridin-2-amine; hereinafter referred to as A-204)

[0513] 1H-NMR (400 MHz, CDCl3): δ8.03 (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 NH2were not observed. MS Calcd.: 458.58; MS Found: 459.3 (M+H + ).

[0514] (205)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-isopropylpiperazin-1-yl)ethyl)benzene-1,4-diamine (N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-isopropylpiperazin-1-yl)ethyl)benzene-1,4-diamine; hereinafter referred to as A-205)

[0515] 1H-NMR (400 MHz, MeOH-d4): δ7.88 (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 Calcd.: 542.74; MS Found: 543.4 (M+H + ).

[0516] (206)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-methylpiperazin-1-yl)ethyl)benzene-1,4-diamine (N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-methylpiperazin-1-yl)ethyl)benzene-1,4-diamine; hereinafter referred to as A-206)

[0517] 1H-NMR (400 MHz, DMSO-d6): δ8.58 (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 Calcd.: 514.68; MS Found: 515.3 (M+H + ).

[0518] (207)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-ethylpropylpiperazin-1-yl)ethyl)benzene-1,4-diamine (N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-ethylpiperazin-1-yl)ethyl)benzene-1,4-diamine; hereinafter referred to as A-207)

[0519] 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 Calcd.: 528.71; MS Found: 529.3 (M+H + ).

[0520] (208)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(pyrrolidin-1-yl)ethyl)benzene-1,4-diamine (N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(pyrrolidin-1-yl)ethyl)benzene-1,4-diamine; hereinafter referred to as A-208)

[0521] 1H-NMR (400 MHz, DMSO-d6): δ8.58 (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 Hz), 2.56 (2H, t,J= 6.8 Hz), 2.44 (4H, s), 1.66 (4H, s), 1.31 (3H, t,J= 7.4 Hz). MS Calcd.: 485.64; MS Found: 486.3 (M+H + ).

[0522] (209)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-methylpiperazin-1-yl)ethyl)pyridine-2,5-diamine (N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-methylpiperazin-1-yl)ethyl)pyridine-2,5-diamine; hereinafter referred to as A-209)

[0523] 1H-NMR (400 MHz, DMSO-d6): δ9.30 (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 Calcd.: 516.3; MS Found: 515.25 (M+H + ).

[0524] (210)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(pyrrolidin-1-yl)ethyl)pyridine-2,5-diamine (N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(pyrrolidin-1-yl)ethyl)pyridine-2,5-diamine; hereinafter referred to as A-210)

[0525] 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, 2.6 Hz), 6.50 (1H, dd,J= 5.6, 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,J= 6.6 Hz), 2.44-2.48 (4H, m), 1.60-1.70 (4H, m), 1.33 (3H, t,J= 7.4 Hz). MS Calcd.: 487.3; MS Found: 486.2 (M+H + ).

[0526] (211)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-ethylpiperazin-1-yl)ethyl)pyridine-2,5-diamine (N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-ethylpiperazin-1-yl)ethyl)pyridine-2,5-diamine; hereinafter referred to as A-211)

[0527] 1H-NMR (400 MHz, DMSO-d6): δ9.29 (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= 7.3 Hz), 1.33 (3H, t,J= 7.4 Hz), 0.95 (3H, t,J= 7.2 Hz). MS Calcd.: 529.2; MS Found: 530.3 (M+H + ).

[0528] (212)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-isopropylpiperazin-1-yl)ethyl)pyridine-2,5-diamine (N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-isopropylpiperazin-1-yl)ethyl)pyridine-2,5-diamine; hereinafter referred to as A-212)

[0529] 1H-NMR (400 MHz, DMSO-d6): δ9.29 (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 Calcd.: 543.7; MS Found: 544.3 (M+H + ).

[0530] (213)N-(5-(1H-pyrazol-4-yl)pyridin-2-yl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(5-(1H-pyrazol-4-yl)pyridin-2-yl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-213)

[0531] 1 H-NMR (400 MHz, DMSO-d6): δ12.9 (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 Calcd.: 440.52; MS Found: 441.2 (M+H + ).

[0532] (214)N-(4-(3-aminopyrrolidin-1-yl)phenyl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine (N-(4-(3-aminopyrrolidin-1-yl)phenyl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-214)

[0533] 1 H-NMR (400 MHz, CDCl3): δ7.96 (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 NH2were not observed. MS Calcd.: 457.19; MS Found: 458.3 (M+H + ).

[0534] (215)4-((2-ethyl-4-phenylthiazol-5-yl)oxy)-N-(4-(3-(methylamino)pyrrolidin-1-yl)phenyl)pyridin-2-amine (4-((2-ethyl-4-phenylthiazol-5-yl)oxy)-N-(4-(3-(methylamino)pyrrolidin-1-yl)phenyl)pyridin-2-amine; hereinafter referred to as A-215)

[0535] 1H-NMR (400 MHz, DMSO-d6): δ8.73 (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 Calcd.: 471.62; MS Found: 472.3 (M+H + ).

[0536] (216) Methyl 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate (Methyl 6-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate; hereinafter referred to as A-216)

[0537] 1 H-NMR (400 MHz, DMSO-d6): δ10.15 (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 Calcd.: 446.52 Found: 447.2 (M+H + ).

[0538] (217)6-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid (6-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid; hereinafter referred to as A-217)

[0539] 1 H-NMR (400 MHz, DMSO-d6): δ10.31 (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) * A proton from OH was not observed. MS Calcd.: 432.49 Found: 433.2 (M+H + ).

[0540] (218)3-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-218)

[0541] 1 H-NMR (400 MHz, DMSO-d6): δ9.44 (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, dd,J= 2.4 Hz, 5.8 Hz), 6.46 (1H, d,J= 2.4 Hz), 3.29-3.26 (1H, m), 1.39 (6H, d,J= 7.2 Hz). MS Calcd.: 466.58; MS Found: 467.1 (M+H + ).

[0542] (219)2-(3-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (2-(3-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; hereinafter referred to as A-219)

[0543] 1 H-NMR (400 MHz, DMSO-d6): δ9.05 (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 Calcd.: 445.58; MS Found: 446.2 (M+H + ).

[0544] (220)3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (3-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-220)

[0545] 1H-NMR (400 MHz, DMSO-d6): δ9.23 (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 Calcd.: 430.52; MS Found: 431.2 (M+H + ).

[0546] (221)4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (4-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-221)

[0547] 1 H-NMR (400 MHz, DMSO-d6): δ9.50 (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 Calcd.: 466.58; MS Found: 467.2 (M+H + ).

[0548] (222)4-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (4-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-222)

[0549] 1 H-NMR (400 MHz, DMSO-d6): δ9.39 (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 Calcd.: 430.52; MS Found: 431.2 (M+H + ).

[0550] (223)2-(4-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (2-(4-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; hereinafter referred to as A-223)

[0551] 1H-NMR (400 MHz, DMSO-d6): δ9.55 (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 Calcd.: 446.56; MS Found: 447.2 (M+H + ).

[0552] (224)2-(5-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol (2-(5-((4-((2-isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; hereinafter referred to as A-224)

[0553] 1 H-NMR (400 MHz, DMSO-d6): δ9.19 (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 Calcd.: 446.56; MS Found: 447.3 (M+H + ).

[0554] (225)6-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide (6-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide; hereinafter referred to as A-225)

[0555] 1 H-NMR (400 MHz, DMSO-d6): δ9.87 (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 Calcd.: 445.54 Found: 446.2 (M+H + ).

[0556] (226)6-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (6-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; hereinafter referred to as A-226)

[0557] 1H-NMR (400 MHz, DMSO-d6): δ9.87 (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 Calcd.: 431.51 Found: 432.2 (M+H + ).

[0558] (227)6-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (6-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-227)

[0559] 1 H-NMR (400 MHz, DMSO-d6): δ10.14 (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 Calcd.: 431.51 Found: 432.2 (M+H + ).

[0560] (228)6-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (6-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; hereinafter referred to as A-228)

[0561] 1 H-NMR (400 MHz, DMSO-d6): δ10.12 (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 Calcd.: 445.54; MS Found: 446.2 (M+H + ).

[0562] (229)4-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide (4-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; hereinafter referred to as A-229)

[0563] 1H-NMR (400 MHz, DMSO-d6): δ9.35 (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 Calcd.: 444.16 Found: 445.2 (M+H + ).

[0564] (230)3-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (3-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-230)

[0565] 1 H-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 Calcd.: 431.51; MS Found: 432.2 (M+H + ).

[0566] (231)4-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (4-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-231)

[0567] 1 H-NMR (400 MHz, DMSO-d6): δ12.43 (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 Calcd.: 431.51; MS Found: 432.2 (M+H + ).

[0568] (232)6-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (6-((4-((2-Isopropyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; hereinafter referred to as A-232)

[0569] 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 Calcd.: 432.49 Found: 433.2 (M+H + ).

[0570] (233)3-((4-((2-(methylamino)-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-(methylamino)-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-233)

[0571] 1 H-NMR (400 MHz, DMSO-d6): δ9.43 (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 Calcd.: 503.6; MS Found: 504.2 (M+H + ).

[0572] (234)3-((4-((2-amino-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-amino-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-234)

[0573] 1 H-NMR (400 MHz, DMSO-d6): δ9.47 (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 proton form NH2were not observed. MS Calcd.: 489.57; MS Found: 490.1 (M+H + ).

[0574] (235)3-((4-((2-(dimethylamino)-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-(dimethylamino)-4-(naphthalen-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-235)

[0575] 1H-NMR (400 MHz, DMSO-d6): δ9.43 (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 Calcd.: 517.62; MS Found: 518.2 (M+H + ).

[0576] (236)3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide (3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide; hereinafter referred to as A-236)

[0577] 1 H-NMR (400 MHz, MeOD-d4): δ7.98-7.97 (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 NH2were not observed. MS Calcd.: 440.50; MS Found: 441.1 (M+H + ).

[0578] (237)3-((6-((2-methyl-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide (3-((6-((2-methyl-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide; hereinafter referred to as A-237)

[0579] 1 H-NMR (400 MHz, DMSO-d6): δ9.75 (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 Calcd.: 439.51; MS Found: 440.1 (M+H + ).

[0580] (238)3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide (3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-238)

[0581] 1 H-NMR (400 MHz, DMSO-d6): δ10.0 (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 Calcd.: 439.51; MS Found: 440.1 (M+H + ).

[0582] (239)3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide (3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide; hereinafter referred to as A-239)

[0583] 1 H-NMR (400 MHz, DMSO-d6): δ10.1 (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 NH2were not observed. MS Calcd.: 440.50; MS Found: 441.1 (M+H + ).

[0584] (240)3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide (3-((6-((2-amino-4-phenylthiazol-5-yl)oxy)pyrimidin-4-yl)amino)benzenesulfonamide; hereinafter referred to as A-240)

[0585] 1 H-NMR (400 MHz, DMSO-d6): δ10.06 (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 Calcd.: 453.09; MS Found: 454.1 (M+H+ ).

[0586] (241)6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)picolinamide (6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)picolinamide; hereinafter referred to as A-241)

[0587] 1 H-NMR (400 MHz, DMSO-d6): δ9.95 (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 Calcd.: 418.12; MS Found: 419.2 (M+H + ).

[0588] (242)2-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)isonicotinamide (2-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)isonicotinamide; hereinafter referred to as A-242)

[0589] 1H-NMR (400 MHz, DMSO-d6): δ10.23 (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 Calcd.: 418.12; MS Found: 419.2 (M+H + ).

[0590] (243)3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzamide (3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzamide; hereinafter referred to as A-243)

[0591] 1 H-NMR (400 MHz, DMSO-d6): δ9.86 (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 Calcd.: 417.13; MS Found: 418.2 (M+H + ).

[0592] (244)6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)nicotinic acid (6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)nicotinic acid; hereinafter referred to as A-244)

[0593] 1 H-NMR (400 MHz, DMSO-d6): δ10.9 (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 Calcd.: 419.11; MS Found: 420.1 (M+H + ).

[0594] (245)6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)nicotinamide (6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)nicotinamide; hereinafter referred to as A-245)

[0595] 1 H-NMR (400 MHz, DMSO-d6): δ10.44 (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,J= 7.6 Hz), 7.41-7.37 (3H, m), 7.31-7.27 (1H, m), 6.86 (1H, d,J= 6.0 Hz), 3.02 (2H, q,J= 7.6 Hz), 1.34 (3H, t,J= 7.6 Hz). MS Calcd.: 418.12; MS Found: 419.2 (M+H + ).

[0596] (246)4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzoic acid (4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyrimidin-2-yl)amino)benzoic acid; hereinafter referred to as A-246)

[0597] 1 H-NMR (400 MHz, DMSO-d6): δ12.57 (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 Calcd.: 418.11; MS Found: 419.2 (M+H + ).

[0598] (247)3-((4-((2-Amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-Amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-247)

[0599] 1H-NMR (400 MHz, DMSO-d6): δ9.35 (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 Calcd.: 454.53; MS Found: 455.1 (M+H + ).

[0600] (248)4-((4-((2-Amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (4-((4-((2-Amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-248)

[0601] 1 H-NMR (400 MHz, DMSO-d6): δ9.50 (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). * Two protons from OH and TFA were not observed. MS Calcd.: 419.46; MS Found: 420.1(M+H + ).

[0602] (249)3-((4-((2-Amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (3-((4-((2-Amino-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-249)

[0603] 1 H-NMR (400 MHz, DMSO-d6): δ9.38 (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 Calcd.: 419.46; MS Found: 420.1 (M+H + ).

[0604] (250)3-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-250)

[0605] 1H-NMR (400 MHz, DMSO-d6): δ9.33 (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 Calcd.: 467.56 Found: 468.1 (M+H + ).

[0606] (251)6-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (6-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-251)

[0607] 1 H-NMR (400 MHz, DMSO-d6): δ10.0 (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 Calcd.: 432.50; MS Found: 433.2 (M+H + ).

[0608] (252)6-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (6-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; hereinafter referred to as A-252)

[0609] 1 H-NMR (400 MHz, DMSO-d6): δ12.5 (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). * A proton from OH was not observed. MS Calcd.: 433.48; MS Found: 434.2 (M+H + ).

[0610] (253)6-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (6-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; hereinafter referred to as A-253)

[0611] 1H-NMR (400 MHz, DMSO-d6): δ10.0 (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 Calcd.: 446.52; MS Found: 447.2 (M+H + ).

[0612] (254)6-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid (6-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid; hereinafter referred to as A-254)

[0613] 1 H-NMR (400 MHz, DMSO-d6): δ9.97 (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). * A proton from OH was not observed. MS Calcd.: 433.48; MS Found: 434.1 (M+H + ).

[0614] (255)6-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (6-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; hereinafter referred to as A-255)

[0615] 1 H-NMR (400 MHz, DMSO-d6): δ9.77 (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 Calcd.: 432.50 Found: 433.2 (M+H + ).

[0616] (256)6-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide (6-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide; hereinafter referred to as A-256)

[0617] 1H-NMR (400 MHz, DMSO-d6): δ9.75 (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 Found: 447.2 (M+H + ).

[0618] (257)3-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (3-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-257)

[0619] 1 H-NMR (400 MHz, DMSO-d6): δ9.18 (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). * A proton from OH was not observed. MS Calcd.: 432.49; MS Found: 433.2 (M+H + ).

[0620] (258)3-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (3-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-258)

[0621] 1 H-NMR (400 MHz, DMSO-d6): δ9.10 (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 Calcd.: 431.52 Found: 432.2 (M+H + ).

[0622] (259)3-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide (3-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; hereinafter referred to as A-259)

[0623] 1H-NMR (400 MHz, DMSO-d6): δ9.12 (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 Calcd.: 445.16 Found: 446.2 (M+H + ).

[0624] (260)5-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (5-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; hereinafter referred to as A-260)

[0625] 1 H-NMR (400 MHz, DMSO-d6): δ9.42 (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). * A proton from OH was not observed. MS Calcd.: 433.48; MS Found: 434.2 (M+H + ).

[0626] (261)5-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (5-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-261)

[0627] 1 H-NMR (400 MHz, DMSO-d6): δ9.32 (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 Calcd.: 432.50 Found: 433.2 (M+H + ).

[0628] (262)5-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (5-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; hereinafter referred to as A-262)

[0629] 1H-NMR (400 MHz, DMSO-d6): δ9.34 (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 Calcd.: 446.52; MS Found: 447.2 (M+H + ).

[0630] (263)4-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid (4-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid; hereinafter referred to as A-263)

[0631] 1 H-NMR (400 MHz, DMSO-d6): δ10.2 (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). * A proton from OH was not observed. MS Calcd.: 433.48; MS Found: 434.2 (M+H + ).

[0632] (264)4-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (4-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; hereinafter referred to as A-264)

[0633] 1 H-NMR (400 MHz, DMSO-d6): δ9.69 (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 Calcd.: 432.50; MS Found: 433.2 (M+H + ).

[0634] (265)4-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide (4-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide; hereinafter referred to as A-265)

[0635] 1H-NMR (400 MHz, DMSO-d6): δ9.72 (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 Calcd.: 446.52; MS Found: 447.2 (M+H + ).

[0636] (266)2-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinic acid (2-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinic acid; hereinafter referred to as A-266)

[0637] 1 H-NMR (400 MHz, DMSO-d6): δ8.35 (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 Calcd.: 433.48; MS Found: 434.2 (M+H + ).

[0638] (267)2-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide (2-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide; hereinafter referred to as A-267)

[0639] 1 H-NMR (400 MHz, DMSO-d6): δ9.82 (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 Calcd.: 432.50; Found: 433.2 (M+H + ).

[0640] (268)2-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylisonicotinamide (2-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylisonicotinamide; hereinafter referred to as A-268)

[0641] 1H-NMR (400 MHz, DMSO-d6): δ8.23 (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). * Two protons from NH were not observed. MS Calcd.: 446.52; MS Found: 447.2 (M+H + ).

[0642] (269)N-(2-(dimethylamino)ethyl)-6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (N-(2-(Dimethylamino)ethyl)-6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino) nicotinamide; hereinafter referred to as A-269)

[0643] 1H-NMR (400 MHz, DMSO-d6): δ10.2 (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 Calcd.: 503.62; MS Found: 504.3 (M+H + ).

[0644] (270)N-(Cyclopropylmethyl)-6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (N-(Cyclopropylmethyl)-6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-270)

[0645] 1H-NMR (400 MHz, DMSO-d6): δ10.2 (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 Calcd.: 487.57; MS Found: 488.2 (M+H + ).

[0646] (271)2-(Dimethylamino)ethyl 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate (2-(Dimethylamino)ethyl 6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate; hereinafter referred to as A-271)

[0647] 1H-NMR (400 MHz, DMSO-d6): δ8.78 (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). * A proton from NH was not observed. MS Calcd.: 504.60; MS Found: 505.3 (M+H + ).

[0648] (272)N-(3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide (N-(3-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide; hereinafter referred to as A-272)

[0649] 1H-NMR (400 MHz, DMSO-d6): δ9.63 (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 Calcd.: 481.59; Found: 482.2 (M+H + ).

[0650] (273)2-(Dimethylamino)ethyl 3-(6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamido)-5-fluorobenzoate (2-(Dimethylamino)ethyl 3-(6-((4-((2-ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamido)-5-fluorobenzoate; hereinafter referred to as A-273)

[0651] 1H-NMR (400 MHz, DMSO-d6): δ8.76 (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 Calcd.: 641.72; MS Found: 642.3 (M+H + ).

[0652] (274)3-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (3-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-274)

[0653] 1H-NMR (400 MHz, DMSO-d6): δ9.12 (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 (2 H, m), 1.07-1.03 (2 H, m). MS Calcd.: 443.53; MS Found: 444.28 (M+H + ).

[0654] (275)6-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (6-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-275)

[0655] 1 H-NMR (400 MHz, DMSO-d6): δ10.01 (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 Calcd.: 444.51; MS Found: 445.27 (M+H + ).

[0656] (276)2-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide (2-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide; hereinafter referred to as A-276)

[0657] 1 H-NMR (400 MHz, DMSO-d6): δ9.81 (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 Calcd.: 444.51; MS Found: 445.27 (M+H + ).

[0658] (277)3-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-277)

[0659] 1H-NMR (400 MHz, DMSO-d6): δ9.33 (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 Calcd.: 479.57; MS Found: 480.29 (M+H + ).

[0660] (278)6-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (6-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; hereinafter referred to as A-278)

[0661] 1 H-NMR (400 MHz, DMSO-d6): δ9.76 (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 Calcd.: 444.51; MS Found: 445.32 (M+H + ).

[0662] (279)6-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide (6-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide; hereinafter referred to as A-279)

[0663] 1 H-NMR (400 MHz, DMSO-d6): δ9.75 (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 Calcd.: 458.54; MS Found: 459.31 (M+H + ).

[0664] (280)2-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylisonicotinamide (2-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylisonicotinamide; hereinafter referred to as A-280)

[0665] 1H-NMR (400 MHz, DMSO-d6): δ9.84 (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 (2H, m), 1.07-1.03 (2H, m). MS Calcd.: 458.54; MS Found: 459.37 (M+H + ).

[0666] (281)3-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide (3-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; hereinafter referred to as A-281)

[0667] 1H-NMR (400 MHz, DMSO-d6): δ9.14 (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 (1 H, 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 Calcd.: 457.55; MS Found: 458.24 (M+H + ).

[0668] (282)6-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (6-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; hereinafter referred to as A-282)

[0669] 1H-NMR (400 MHz, DMSO-d6): δ10.01 (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 Calcd.: 458.54; MS Found: 459.25 (M+H + ).

[0670] (283)3-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-283)

[0671] 1 H-NMR (400 MHz, DMSO-d6): δ9.32 (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 Calcd.: 482.58; MS Found: 483.2 (M+H + ).

[0672] (284)6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (6-((4-((2-(Dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-284)

[0673] 1 H-NMR (400 MHz, DMSO-d6): δ9.98 (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 Calcd.: 447.51; MS Found: 448.2 (M+H + ).

[0674] (285)6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (6-((4-((2-(Dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; hereinafter referred to as A-285)

[0675] 1H-NMR (400 MHz, DMSO-d6): δ8.79 (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 Calcd.: 448.50; MS Found: 449.2 (M+H + ).

[0676] (286)6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide (6-((4-((2-(Dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; hereinafter referred to as A-286)

[0677] 1 H-NMR (400 MHz, DMSO-d6): δ9.96 (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 Hz), 7.78 (1H, d,J= 8.8 Hz), 7.65 (2H, d,J= 4.8 Hz), 7.46 (1H, d,J= 1.6 Hz), 7.01 (1H, t,J= 4.6 Hz), 6.61 (1H, dd,J= 5.8, 2.2 Hz), 3.07 (6H, s), 2.75 (3H, d, J = 4.0 Hz), 2.16 (3H, s). MS Calcd.: 461.54; MS Found: 462.2 (M+H + ).

[0678] (287)3-((4-((2-Isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-Isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-287)

[0679] 1 H-NMR (400 MHz, DMSO-d6): δ9.33 (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 Calcd.: 481.59 Found: 482.2 (M+H + ).

[0680] (288)6-((4-((2-Isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (6-((4-((2-Isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-288)

[0681] 1H-NMR (400 MHz, DMSO-d6): δ10.01 (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 Calcd.: 446.52 Found: 447.2 (M+H + ).

[0682] (289)3-((4-((4-(6-Methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((4-(6-Methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-289)

[0683] 1 H-NMR (400 MHz, DMSO-d6): δ9.34 (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 Calcd.: 507.51 Found: 508.1 (M+H + ).

[0684] (290)6-((4-((2-Isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (6-((4-((2-Isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-290)

[0685] 1 H NMR (400 MHz, CDCl3): δ8.63 (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, 1H), 7.54 (s, 1H), 7.46 (d,J= 8.8 Hz, 1H), 7.04 (d,J= 7.7 Hz, 1H), 6.62 (d,J= 5.8 Hz, 1H). MS Calcd.: 472.45 Found: 473.27 (M+H + ).

[0686] (291)3-((4-((4-(6-Methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (3-((4-((4-(6-Methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-291)

[0687] 1H-NMR (400 MHz, DMSO-d6): δ9.14 (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 Calcd.: 471.46 Found: 472.28 (M+H + ).

[0688] (292)3-((4-((2-(methylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-(Methylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-292)

[0689] 1 H-NMR (400 MHz, DMSO-d6): δ9.33 (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 Calcd.: 468.55 Found: 469.2 (M+H + ).

[0690] (293)6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid (6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; hereinafter referred to as A-293)

[0691] 1 H-NMR (400 MHz, DMSO-d6): δ10.4 (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). * A proton from NH was not observed. MS Calcd.: 414.41; MS Found: 415.2 (M+H + ).

[0692] (294)6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide (6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; hereinafter referred to as A-294)

[0693] 1H-NMR (400 MHz, DMSO-d6): δ10.2 (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 Calcd.: 446.52; MS Found: 414.2 (M+H + ).

[0694] (295)4-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (4-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-295)

[0695] 1 H-NMR (400 MHz, DMSO-d6): δ9.54 (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). * A proton from OH was not observed. MS Calcd.: 413.43; MS Found: 414.2 (M+H + ).

[0696] (296)3-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (3-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-296)

[0697] 1 H-NMR (400 MHz, DMSO-d6): δ9.28 (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 Calcd.: 412.45; MS Found: 413.30 (M+H + ).

[0698] (297)3-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide (3-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; hereinafter referred to as A-297)

[0699] 1H-NMR (400 MHz, DMSO-d6): δ9.28 (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 Calcd.: 426.48; MS Found: 427.29 (M+H + ).

[0700] (298)3-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-298)

[0701] 1 H-NMR (400 MHz, DMSO-d6): δ9.47 (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 Calcd.: 448.50; MS Found: 449.23 (M+H + ).

[0702] (299)6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide (6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; hereinafter referred to as A-299)

[0703] 1 H-NMR (400 MHz, DMSO-d6): δ10.19 (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 + ).

[0704] (300)3-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (3-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as A-300)

[0705] 1H-NMR (400 MHz, DMSO-d6): δ12.85 (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 + ).

[0706] (301)6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid (6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid; hereinafter referred to as A-301)

[0707] 1 H-NMR (400 MHz, DMSO-d6): δ13.05 (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 Calcd.: 414.42; MS Found: 415.26 (M+H + ).

[0708] (302)6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide (6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide; hereinafter referred to as A-302)

[0709] 1 H-NMR (400 MHz, DMSO-d6): δ11.04 (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 Calcd.: 427.46; MS Found: 428.24 (M+H + ).

[0710] (303)3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide (3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; hereinafter referred to as A-303)

[0711] 1H-NMR (400 MHz, DMSO-d6): δ9.47 (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 Calcd.: 453.54 Found: 454.1 (M+H + ).

[0712] (304)2-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)acetonitrile (2-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)acetonitrile; hereinafter referred to as A-304)

[0713] 1 H-NMR (400 MHz, DMSO-d6): δ9.10 (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 Calcd.: 413.49 Found: 414.2 (M+H + ).

[0714] (305)N-(3-((1H-tetrazol-5-yl)methyl)phenyl)-4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-amine (N-(3-((1H-tetrazol-5-yl)methyl)phenyl)-4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-305)

[0715] 1 H-NMR (400 MHz, DMSO-d6): δ8.99 (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, s). * A proton from NH was not observed. MS Calcd.: 456.52; Found: 457.2 (M+H + ).

[0716] (306)3-(3-((4-((2-Methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanenitrile (3-(3-((4-((2-Methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanenitrile; hereinafter referred to as A-306)

[0717] 1H-NMR (400 MHz, DMSO-d6): δ8.98 (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 Calcd.: 427.52; Found: 428.2 (M+H + ).

[0718] (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 (N-(3-(2-(2H-tetrazol-5-yl)ethyl)phenyl)-4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-amine; hereinafter referred to as A-307)

[0719] 1 H-NMR (400 MHz, DMSO-d6): δ8.92 (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). * A proton from NH was not observed. MS Calcd.: 470.55; Found: 471.2 (M+H + ).

[0720] (308) Methyl 2-methyl-2-(3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoate (Methyl 2-methyl-2-(3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoate; hereinafter referred to as A-308)

[0721] 1 H-NMR (400 MHz, CDCl3): δ9.00 (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 Calcd.: 474.57; MS Found: 475.2 (M+H + ).

[0722] (309)2-Methyl-2-(3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoic acid (2-Methyl-2-(3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoic acid; hereinafter referred to as A-309)

[0723] 1H-NMR (400 MHz, DMSO-d6): δ8.06 (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, NH were not observed. MS Calcd.: 460.55; MS Found: 461.2 (M+H + ).

[0724] (310)4-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide (4-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; hereinafter referred to as A-310)

[0725] 1 H-NMR (400 MHz, DMSO-d6): δ9.39 (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). * A proton from NH was not observed. MS Calcd.: 417.48; MS Found: 418.2 (M+H + ).

[0726] (311)N-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluorosulfonamide (N-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide; hereinafter referred to as A-311)

[0727] 1 H-NMR (400 MHz, DMSO-d6): δ9.23 (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). * A proton from NH was not observed. MS Calcd.: 520.55; MS Found: 521.1 (M+H + ).

[0728] (312)4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)-N-(5-(3-(methylamino)pyrrolidin-1-yl)pyridin-2-yl)pyridin-2-amine (4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)-N-(5-(3-(methylamino)pyrrolidin-1-yl)pyridin-2-yl)pyridin-2-amine; hereinafter referred to as A-312)

[0729] 1H-NMR (400 MHz, CDCl3): δ8.04 (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 Calcd.: 472.61; MS Found: 473.3 (M+H + ).

[0730]

[0731] [Example] Synthesis of a novel thiazole derivative compound

[0732] 1. Preparation of intermediates 1-6 & 1-6'

[0733]

[0734] (1) Preparation of 2-((2-chloropyridin-4-yl)oxy)-1-phenylethanone (2-((2-chloropyridin-4-yl)oxy)-1-phenylethanone; hereinafter referred to as compound 1-3)

[0735] 2-Bromo-1-phenylethanone (hereinafter referred to as compound 1-1) (9.22 g, 46.3 mmol) was dissolved in acetone (129 mL), to which 2-chloropyridin-4-ol (hereinafter referred to as compound 1-2) (5.00 g, 38.6 mmol) and K2CO3 (8.00 g, 57.9 mmol) were added at room temperature. After stirring at room temperature for 4 h, the reaction mixture was poured into water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 2:1) to give compound 1-3 (6.00 g, 63%) as a yellow solid.

[0736] 1 H-NMR (400 MHz, CDCl3): δ8.21 (1H, d,J= 5.2 Hz), 7.98 (2H, d,J= 7.2 Hz), 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).

[0737] (2) Preparation of 2-bromo-2-((2-chloropyridin-4-yl)oxy)-1-phenylethan-1-one (2-bromo-2-((2-chloropyridin-4-yl)oxy)-1-phenylethan-1-one; hereinafter referred to as compound 1-4)

[0738] Compound 1-3 (6.00 g, 24.2 mmol) was dissolved in CHCl3 (242 mL) and slowly added AlCl3 (1.29 g, 9.69 mmol) and Br2 (1.87 mL, 36.3 mmol) at room temperature. The mixture was stirred at room temperature for 2 h and then extracted with NaHCO3 and EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 4:1) to give compound 1-4 (5.74 g, 73%) as a yellow solid.

[0739] 1 H-NMR (400 MHz, CDCl3): δ8.38 (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).

[0740] (3) Preparation of 5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazol-2-amine (5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazol-2-amine; hereinafter referred to as compound 1-5)

[0741] A mixture of compounds 1-4 (4.70 g, 14.4 mmol) and thiourea (2.19 g, 28.8 mmol) was dissolved in EtOH (144 mL) and heated at 80°C for 10 min. After cooling to room temperature, the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography on NH-SiO2 (DCM:MeOH = 100:1) to give compound 1-5 (2.72 g, 62%) as a pale yellow solid.

[0742] 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).

[0743] (4) Preparation of tert-butyl (5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazol-2-yl)carbamate (hereinafter referred to as compound 1-6) and tert-butyl (5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazol-2-ylcarbamate (hereinafter referred to as compound 1-6')

[0744] Compound 1-5 (2.72 g, 8.95 mmol) was dissolved in THF (90 mL) and Boc2O (5.86 g, 26.9 mmol), TEA (3.74 mL, 26.9 mmol), and DMAP (438 mg, 3.58 mmol) were added at room temperature. The mixture was stirred at room temperature for 18 h. The reaction mixture was poured into water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 7:1 to 4:1) to give compound 1-6 (1.50 g, 33%) and compound 1-6' (1.10 g, 30%) as pale yellow solids.

[0745] 1H-NMR (400 MHz, DMSO-d6): δ8.34-8.31 (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).

[0746]

[0747] 2. A-1 synthesis

[0748]

[0749] (1) Preparation of tert-butyl (4-phenyl-5-((2-((3-sulfamoylphenyl)amino)pyridin-4-yl)oxy)thiazol-2-yl)carbamate (tert-Butyl (4-phenyl-5-((2-((3-sulfamoylphenyl)amino)pyridin-4-yl)oxy)thiazol-2-yl)carbamate; hereinafter referred to as compound 1-7)

[0750] To a solution of compounds 1-6 and 1-6' (200 mg, 0.50 mmol) in DMF (5.0 mL) was added 3-aminobenzenesulfonamide (128 mg, 0.74 mmol) and K2CO3 (205 mg, 1.49 mmol) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After the addition of BrettPhos Pd G1, 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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 3:2) to obtain compound 1-7 (140 mg, 52%) as a brown solid.

[0751] 1H-NMR (400 MHz, CDCl3): δ9.80 (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). * A proton form NH was not observed.

[0752] (2) Manufacturing of A-1

[0753] TFA (0.2 mL, 2.60 mmol) was added to DCM (dichloromethane; 3 mL) containing compound 1-7, and the mixture was stirred at room temperature for 18 h. The reaction mixture was extracted with saturated aqueous NaHCO3 solution and EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 3:2 to 1:1) to give A-1 (52 mg, 45%) as a white solid.

[0754] A-2 to A-38 were synthesized using the procedure described in the synthesis of A-1 above.

[0755]

[0756] 3. A-39 composite

[0757]

[0758] (1) Preparation of 4-((4-((2-((tert-butoxycarbonyl)amino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid (4-((4-((2-((tert-Butoxycarbonyl)amino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; hereinafter referred to as compound 1-9)

[0759] 4-(4-(2-(tert-butoxycarbonylamino)-4-phenylthiazol-5-yloxy) pyridin-2-ylamino)benzoate (4-(4-(2-(tert-butoxycarbonylamino)-4-phenylthiazol-5-yloxy) pyridin-2-ylamino)benzoate; hereinafter referred to as compound 1-8) was dissolved in a mixture of THF (5.0 mL) and water (5.0 mL) containing LIOH. . H2O (42.0 mg, 1.01 mmol) was added at room temperature. After stirring at 50°C for 4 days, the reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was acidified with 2 N aq. hydrochloric acid solution. The precipitated solid was collected by filtration to give compound 1-9 (185 mg, 72%) as a brown solid.

[0760] 1 H-NMR (400 MHz, DMSO-d6): δ11.8 (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). * A proton from NH was not observed.

[0761] (2) A-39 Preparation

[0762] TFA (0.57 mL, 7.33 mmol) was added to DCM (3.7 mL) containing compound 1-9 dissolved at 0°C. After stirring at 40°C for 3 h, the reaction mixture was cooled to room temperature, quenched with sodium bicarbonate, and extracted with EtOAc. The residue was triturated with DCM. The precipitated solid was collected by filtration to give A-39 (37.4 mg, 25%) as a beige solid.

[0763] A-40 was synthesized using the procedure described above for A-39.

[0764]

[0765] 4. A-41 synthesis

[0766]

[0767] (1) Preparation of 2-bromo-5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazole (2-bromo-5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazole; hereinafter referred to as compound 1-10)

[0768] To a solution of compound 1-5 (460 mg, 1.51 mmol) at 0°C were added copper(II) bromide (338 mg, 1.51 mmol) and tert-butyl nitrite (0.27 mL, 2.27 mmol). The mixture was stirred at 0°C for 30 min. The reaction mixture was quenched with aqueous ammonia and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 3:1) to give compound 1-10 (358 mg, 64%) as a yellow solid.

[0769] (2) Preparation of N-(5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazol-2-yl)-1,1-diphenylmethanimine (N-(5-((2-chloropyridin-4-yl)oxy)-4-phenylthiazol-2-yl)-1,1-diphenylmethanimine; hereinafter referred to as compound 1-11)

[0770] Diphenylmethanimine (0.07 mL, 0.41 mmol), Xantphos (16.0 mg, 0.03 mmol), and Cs2CO3 (266 mg, 0.82 mmol) were added to a solution of compound 1-10 in dioxane (2.7 mL) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After Pd2(dba)3 (16.0 mg, 0.03 mmol) was added, 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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 5:1) to obtain compound 1-11 (62.0 mg, 49%) as a yellow solid.

[0771] 1 H-NMR (400 MHz, DMSO-d6): δ8.33 (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).

[0772] (3) Preparation of 2-(3-((4-((2-((diphenylmethylene)amino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol (2-(3-((4-((2-((Diphenylmethylene)amino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; hereinafter referred to as compound 1-12)

[0773] 2-(3-aminophenyl)propan-2-ol (30.0 mg, 0.20 mmol) and K2CO3 (55.0 mg, 0.40 mmol) were added to DMF (2.7 mL) containing compound 1-11 dissolved at room temperature. The mixture was degassed by purging and backfilled with argon several times. After adding BrettPhos Pd G3 (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 1:1) to give compound 1-12 (15.4 mg, 20%) as a yellow solid.

[0774] 1 H-NMR (400 MHz, DMSO-d6): δ9.04 (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).

[0775] (4) Manufacturing of A-41

[0776] Compound 1-12 (15.0 mg, 0.03 mmol) dissolved in methanol solution at room temperature with NH2OH .HCl (3.58 mg, 0.05 mmol) was added. After stirring at room temperature for 3 h, the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography on NH-SiO2 (DCM:MeOH = 100:1 to 50:1) to give A-41 (2.20 mg, 20%) as a white solid.

[0777] A-42 and A-43 were synthesized using the above A-41 synthesis procedure.

[0778]

[0779] 5. A-44 synthesis

[0780]

[0781] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-N-cyclopropyl-4-phenylthiazol-2-amine (5-((2-chloropyridin-4-yl)oxy)-N-cyclopropyl-4-phenylthiazol-2-amine; hereinafter referred to as compound 2-1)

[0782] A solution of compound 1-4 and 1-cyclopropylthiourea (142 mg, 1.23 mmol) in ethanol (6.1 mL) was heated at 80°C for 10 min. After cooling to room temperature, the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 2:1) to give compound 2-1 (74.0 mg, 35%) as a yellow solid.

[0783] 1H-NMR (400 MHz, DMSO-d6): δ8.34 (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).

[0784] (2) Manufacturing of A-44

[0785] To a solution of compound 2-1 (70.0 mg, 0.20 mmol) in DMF (4.1 mL) at room temperature were added 2-(3-aminophenyl)propan-2-ol (46.0 mg, 0.31 mmol) and K2CO3 (84.0 mg, 0.61 mmol). The mixture was degassed by purging and backfilled with argon several times. After the addition of BrettPhos Pd G3 (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography in NH-SiO2 (only DCM) to give A-44 (19.6 mg, 21%) as an ivory solid.

[0786] A-45 to A-47 were synthesized using the above A-44 synthesis procedure.

[0787]

[0788] 6. A-48 synthesis

[0789]

[0790] (1) Preparation of methyl 3-((4-((2-(cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate (methyl 3-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate; hereinafter referred to as compound 2-2)

[0791] To a solution of compound 2-1 (200 mg, 0.58 mmol) in DMF (12 mL) at room temperature were added 3-aminobenzoate (132 mg, 0.87 mmol) and K2CO3 (241 mg, 1.75 mmol). The mixture was degassed by purging and backfilled with argon several times. After adding BrettPhos Pd G1 (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 4:1) to give methyl compound 2-2 (103 mg, 39%) as a yellow solid.

[0792] 1H-NMR (400 MHz, CDCl3): δ8.12 (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). * A proton from NH was not observed.

[0793] (2) Manufacturing of A-48

[0794] Compound 2-2 (60.0 mg, 0.13 mmol) was dissolved in a mixed solution of THF (2.0 mL) and water (0.65 mL) at room temperature. LiOH . H2O (55.0 mg, 1.31 mmol) was added. After stirring at room temperature for 18 h, the reaction mixture was concentrated in vacuo. The residue was acidified with 2 N aq. HCl solution. The precipitated solid was collected by filtration to give A-48 (1.0 mg, 1.7%) as an ivory-colored solid.

[0795] A-49 was synthesized using the above A-48 synthesis procedure.

[0796]

[0797] 7. A-50 synthesis

[0798]

[0799] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-N-methyl-4-phenylthiazol-2-amine (5-((2-chloropyridin-4-yl)oxy)-N-methyl-4-phenylthiazol-2-amine; hereinafter referred to as compound 3-1)

[0800] Compound 1-4 (300 mg, 0.92 mmol) and 1-methylthiourea (120 mg, 1.38 mmol) were dissolved in ethanol (10 mL) and stirred at 80°C for 10 min. After cooling to room temperature, the solvent was removed in vacuo. The residue was dissolved in EtOAc and washed with water. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 4:1) to give compound 3-1 (58.0 mg, 20%) as a yellow oil.

[0801] 1 H-NMR (400 MHz, CDCl3): δ8.24 (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). * A proton form NH was not observed.

[0802] (2) Manufacturing of A-50

[0803] To a solution of compound 3-1 (57.0 mg, 0.18 mmol) in DMF (2.0 mL) at room temperature were added 2-(3-aminophenyl)propan-2-ol (41.0 mg, 0.27 mmol) and K2CO3 (74.0 mg, 0.54 mmol). The mixture was degassed by purging and backfilled with argon several times. After the addition of BrettPhos Pd G3 (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 1:1) to give A-50 (3.4 mg, 4%) as an ivory solid.

[0804] A-51 to A-55 were synthesized using the above A-50 synthesis procedure.

[0805]

[0806] 8. Synthesis of A-56 and A-56 hydrochloride (hereinafter referred to as A-56_salt)

[0807]

[0808] (1) Preparation of methyl 4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate (4-((4-((2-(methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate; hereinafter referred to as compound 3-2)

[0809] Methyl 4-aminobenzoate (570 mg, 3.78 mmol) and K2CO3 (1.04 g, 7.55 mmol) were added to DMF (20.0 mL) containing compound 3-1 (800 mg, 2.52 mmol) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After adding BrettPhos Pd G1 (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on MPLC (hexane:EtOAc = 7:3) to give methyl compound 3-2 (630 mg, 58%) as a brown oil.

[0810] 1 H-NMR (400 MHz, CDCl3):δ8.15 (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 two NH were not observed.

[0811] (2) Manufacturing of A-56

[0812] Compound 3-2 (630 mg, 1.46 mmol) was dissolved in a THF / H2O (v / v= 1 / 1, 30.0 mL) solution at room temperature. LiOH .H2O (1.22 g, 29.1 mmol) was added and stirred at 50°C for 5 days. After cooling to room temperature, the reaction mixture was poured into 1N aq. HCl solution and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 2:3) and triturated with DCM to give A-56 (180 mg, 30%) as an ivory solid.

[0813] (3) Manufacturing of A-56_salt

[0814] To a solution of A-56 (30.0 mg, 0.07 mmol) in methanol (1.5 mL) was added HCl (2 M in MeOH, 0.08 mL, 0.15 mmol). The reaction mixture was stirred at room temperature for 2 h, and the solvent was removed in vacuo. The precipitated solid was filtered and washed with EtO2 to obtain A-56_Salt (17.0 mg, 52%) as a yellow solid.

[0815] 1 H-NMR (400 MHz, DMSO-d6): δ9.70 (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). * A proton from NH was not observed. MS Calcd.: 418.47; MS Found: 419.1 (M+H + ).

[0816] A-57 was synthesized using the above A-56 synthesis procedure.

[0817]

[0818] 9. A-58 Synthesis

[0819]

[0820] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-methyl-4-phenylthiazole (5-((2-chloropyridin-4-yl)oxy)-2-methyl-4-phenylthiazole; hereinafter referred to as compound 4-1)

[0821] Compound 1-10 (1.50 g, 4.08 mmol) was dissolved in a mixture of dioxane (37 mL) and water (3.7 mL) at room temperature, and methylboronic acid (733 mg, 12.2 mmol), Sphos (837 mg, 2.04 mmol), and K2CO3 (1.69 mg, 12.2 mmol) were added. After adding Pd(OAc)2 (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 10:1 to 7:1) to give compound 4-1 (403 mg, 33%) as a yellow solid.

[0822] 1 H-NMR (400 MHz, DMSO-d6): δ8.35 (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).

[0823] (2) Manufacturing of A-58

[0824] To a solution of compound 4-1 (18.0 mg, 0.06 mmol) in DMF (1.2 mL) at room temperature were added 3-aminobenzenesulfonamide (15.0 mg, 0.09 mmol) and K2CO3 (25.0 mg, 0.18 mmol). The mixture was degassed by purging and backfilled with argon several times. After the addition of BrettPhos Pd G3 (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO2 (hexane:EtOAc = 1:1) to give A-58 (6.6 mg, 25%) as an ivory solid.

[0825] A-59 to A-108 were synthesized using the above A-58 synthesis procedure.

[0826]

[0827] 10. A-109 Synthesis

[0828]

[0829] (1) Preparation of methyl 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate (methyl 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate; hereinafter referred to as compound 4-2)

[0830] Compound 4-1 (50.0 mg, 0.17 mmol) was dissolved in DMF (3.3 mL) at room temperature, and methyl 3-aminobenzoate (37.0 mg, 0.25 mmol) and K2CO3 (68.0 mg, 0.50 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After the addition of BrettPhos Pd G1 (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 3:1) to give methyl compound 4-2 (61.0 mg, 88%) as a yellow oil.

[0831] 1 H-NMR (400 MHz, DMSO-d6): δ9.37 (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).

[0832] (2) Manufacturing of A-109

[0833] Compound 4-2 (61.0 mg, 0.15 mmol) was dissolved in a THF / water (v / v= 1 / 1, 3 mL) solution at room temperature with LiOH . H2O (61.0 mg, 1.46 mmol) was added. After stirring at room temperature for 18 h, the reaction mixture was concentrated in vacuo. The residue was acidified with 2 N aq. hydrochloric acid solution. The precipitated solid was collected by filtration to give A-109 (21 mg, 36%) as an ivory-colored solid.

[0834] A-110 was synthesized using the above A-109 synthesis procedure.

[0835]

[0836] 11. Synthesis of A-111 and A-112

[0837]

[0838] (1) Manufacturing of A-111

[0839] Compound 4-1 (300 mg, 0.99 mmol) was dissolved in DMF (9.9 mL) at room temperature, and 2-(3-aminophenyl)acetonitrile (196 mg, 1.49 mmol) and K2CO3 (411 mg, 2.97 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After the addition of Brettphos Pd G3 (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 1:4) to obtain A-111 (343 mg, 87%) as a pale yellow solid.

[0840] (2) Manufacturing of A-112

[0841] A-111 (150 mg, 0.376 mmol) was dissolved in dioxane (4.7 mL) at room temperature, to which were added Bu2SnO (187 mg, 0.75 mmol) and Me3SiN3 (0.25 mL, 1.88 mmol). The mixture was heated at 120°C for 4 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (only EtOAc) to give A-112 (23.5 mg, 14%) as an ivory solid.

[0842] A-113 was synthesized using the above A-111 synthesis procedure.

[0843] A-114 was synthesized using the above A-112 synthesis procedure.

[0844]

[0845] 12. A-115 Synthesis

[0846]

[0847] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-cyclopropyl-4-phenylthiazole (5-((2-chloropyridin-4-yl)oxy)-2-cyclopropyl-4-phenylthiazole; hereinafter referred to as compound 5-1)

[0848] To a solution of compound 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 K2CO3 (404 mg, 2.92 mmol) at room temperature. The mixture was degassed and backfilled with argon several times, and then PdCl2(dppf) (143 mg, 0.20 mmol) was added 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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 1:1) to give compound 5-1 (92.0 mg, 29%) as a white solid.

[0849] 1 H-NMR (400 MHz, DMSO-d6): δ8.32 (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).

[0850] (2) Manufacturing of A-115

[0851] Compound 5-1 (20 mg, 0.06 mmol) was dissolved in DMF (1.2 mL) at room temperature, and 2-(3-aminophenyl)propan-2-ol (14.0 mg, 0.09 mmol) and K2CO3 (25.0 mg, 0.18 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After the addition of BrettPhos Pd G3 (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 2:1) to give A-115 (10.7 mg, 40%) as a yellow solid.

[0852] A-116 to A-131 were synthesized using the above A-115 synthesis procedure.

[0853]

[0854] 13. Synthesis of A-132 and A-133

[0855]

[0856] (1) Manufacturing of A-132

[0857] LiOH·H2O (27.0 mg, 1.12 mmol) was added to a mixture of THF (0.94 mL) and water (0.19 mL) containing A-130 (50.0 mg, 0.11 mmol) at 0°C. The reaction mixture was stirred at room temperature for 4 h. After cooling to 0°C, the reaction mixture was added 1 N aq. HCl and concentrated in vacuo to give A-132 (40.0 mg, 83%) as a white solid. This was used in the next step without further purification.

[0858] (2) Manufacturing of A-133

[0859] A solution of A-132 (40.0 mg, 0.09 mmol), HATU (53.0 mg, 0.14 mmol), DIPEA (0.049 mL, 0.28 mmol), and methanamine (2.0 M in THF, 0.07 mL, 0.14 mmol) in DMF (0.93 mL) was stirred at room temperature for 2 h. The reaction mixture was dissolved in EtOAc and washed with water and brine. The separated organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (DCM:MeOH = 10:1) to give A-133 (35.0 mg, 85%) as a white solid.

[0860] A-134 to A-136 were synthesized using the above A-132 synthesis procedure.

[0861]

[0862] 14. A-138 Synthesis

[0863]

[0864] To a mixture of THF (1.0 mL) and MeOH (1.0 mL) containing A-130 (50.0 mg, 0.11 mmol) was added NaOH (22.0 mg, 0.56 mmol) and aq. NH2OH (50 wt%, 0.17 mL, 0.11 mmol) at room temperature. The mixture was heated at 50°C for 2 h. After cooling to room temperature, the reaction mixture was concentrated in vacuo. The residue was acidified with 2 N aq. HCl solution at 0°C. The precipitated solid was collected by filtration to give A-138 (8.9 mg, 18%) as a white solid.

[0865] A-139 was synthesized using the above A-138 synthesis procedure.

[0866]

[0867] 15. A-140 composite

[0868]

[0869] A-132 (35.0 mg, 0.08 mmol) was dissolved in DMF (1.6 mL) and methanesulfonamide (9.28 mg, 0.10 mmol), DMAP (10.9 mg, 0.09 mmol), 2-chloro-1-methylpyridinium iodide (31.0 mg, 0.12 mmol), and TEA (34.0 μL, 0.24 mmol) were added. The mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was triturated with DCM and hexane, and the resulting solid was collected by filtration and dried in vacuo to give A-140 (11.0 mg, 27%) as a pale red solid.

[0870]

[0871] 16. A-141 Synthesis

[0872]

[0873] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-methoxy-4-phenylthiazole (5-((2-chloropyridin-4-yl)oxy)-2-methoxy-4-phenylthiazole; hereinafter referred to as compound 6-1)

[0874] To a solution of compound 1-10 (60.0 mg, 0.16 mmol) in MeOH (1.6 mL) at room temperature was added sodium methoxide (25 wt% in MeOH, 0.15 mL, 0.65 mmol). After stirring for 4 h, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtAOc = 3:1) to give compound 6-1 (13.0 mg, 25%) as a yellow solid.

[0875] MS calculated: 318.78; MS observed: 319.02 (M+H+).

[0876] (2) Manufacturing of A-141

[0877] Compound 6-1 (13 mg, 0.0410 mmol) was dissolved in DMF (1.0 mL) at room temperature, and 2-(3-aminophenyl)propan-2-ol (9.3 mg, 0.0610 mmol) and K2CO3 (17.0 mg, 0.122 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After the addition of Brettphos Pd G3 (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 3:1) to give A-141 (1.1 mg, 6%) as a yellow solid.

[0878] A-142 to A-144 were synthesized using the above A-141 synthesis procedure.

[0879]

[0880] 17. A-145 Synthesis

[0881]

[0882] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-4-phenyl-2-(trifluoromethyl)thiazole (5-((2-chloropyridin-4-yl)oxy)-4-phenyl-2-(trifluoromethyl)thiazole; hereinafter referred to as compound 7-1)

[0883] Compound 1-10 (200 mg, 0.54 mmol) was dissolved in DMF (11 mL) at room temperature, and methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (0.35 mL, 2.72 mmol), CuI (518 mg, 2.72 mmol), and AsPh3 (67.0 mg, 0.22 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After Pd2(dba)3 (25.0 mg, 0.03 mmol) was added, 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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 20:1) to obtain compound 7-1 (95.0 mg, 49%) as a yellow solid.

[0884] (2) Manufacturing of A-145

[0885] To a solution of compound 7-1 (100 mg, 0.28 mmol) in DMF (2.8 mL) at room temperature were added 3-aminobenzenesulfonamide (72.0 mg, 0.14 mmol) and K2CO3 (116 mg, 0.84 mmol). The mixture was degassed by purging and backfilled with argon several times. After the addition of BrettPhos Pd G3 (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 1:1) to give A-145 (10.0 mg, 7%) as a white solid.

[0886] A-146 to A-148 were synthesized using the above A-145 synthesis procedure.

[0887]

[0888] 18. A-149 and A-150 composite

[0889]

[0890] (1) Preparation of methyl 6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate (methyl 6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate; hereinafter referred to as compound 7-2)

[0891] Methyl 6-aminonicotinate (86.0 mg, 0.57 mmol) and K2CO3 (214.0 mg, 1.55 mmol) were added to DMF (2.0 mL) containing compound 7-1 (184.3 mg, 0.52 mmol) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After adding BrettPhos Pd G3 (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 1:1) to obtain compound 7-2 (127.6 mg, 52%) as a yellow crude solid.

[0892] [M+H] + calcd for 472.44, found 473.14 (M+H + ).

[0893] (2) Manufacturing of A-149

[0894] LiOH·H2O (34.0 mg, 0.81 mmol) was added to a mixture of THF (2.0 mL) and water (2.0 mL) containing compound 7-2 (127.6 mg, 0.27 mmol) at room temperature. The mixture was heated at 50°C for 12 h. After cooling to room temperature, the reaction mixture was concentrated in vacuo. The residue was acidified with 1 N aq. hydrochloric acid solution. The precipitated solid was collected by filtration to give A-149 (66.6 mg, 54%) as a white solid.

[0895] (3) Manufacturing of A-150

[0896] A-149 (30.0 mg, 0.07 mmol) was dissolved in DMF (4.0 mL) at room temperature, and HATU (37.3 mg, 0.11 mmol), DIPEA (0.02 mL, 0.11 mmol), and 2 M methylamine (0.05 mL, 0.11 mmol) dissolved in THF were added. The mixture was stirred at room temperature for 17 h. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (DCM:MeOH = 10:1) to give A-150 (3.1 mg, 10%) as a white solid.

[0897] A-151 and A-152 were synthesized using the above A-149 synthesis procedure.

[0898]

[0899] 19. A-153 Synthesis

[0900]

[0901] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-N,N-dimethyl-4-phenylthiazol-2-amine (5-((2-chloropyridin-4-yl)oxy)-N,N-dimethyl-4-phenylthiazol-2-amine; hereinafter referred to as compound 8-1)

[0902] Dimethyl amine (2 M in THF, 0.20 mL, 0.41 mmol) was added to DMF (5.50 mL) containing compound 1-10 (100 mg, 0.27 mmol), and the mixture was stirred at 80°C for 18 h. The reaction mixture was washed with water and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc: = 3:2) to give compound 8-1 (32 mg, 36%) as a yellow oil.

[0903] 1 H-NMR (400 MHz, CDCl3): δ8.23 (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).

[0904] (2) Manufacturing of A-153

[0905] Compound 8-1 (30.0 mg, 0.09 mmol) was dissolved in DMF (1.0 mL) at room temperature, and 2-(3-aminophenyl)propan-2-ol (21.0 mg, 0.14 mmol) and K2CO3 (37.0 mg, 0.27 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After the addition of BrettPhos Pd G3 (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 1:1) to give A-153 (1.3 mg, 3%) as a white solid.

[0906] A-154 to A-164 were synthesized using the above A-153 synthesis procedure.

[0907]

[0908] 20. A-165 and A-166 synthesis

[0909]

[0910] (1) Manufacturing of A-165

[0911] LiOH·H2O (94.0 mg, 2.24 mmol) was added to a mixture of THF (2.2 mL) and water (2.2 mL) containing compound 8-2 (100 mg, 0.22 mmol) at room temperature. The mixture was heated at 50°C for 18 h. After cooling to room temperature, the reaction mixture was concentrated in vacuo. The residue was acidified with 2 N aq. hydrochloric acid solution. The precipitated solid was collected by filtration to give A-165 (19.5 mg, 20%) as a yellow solid.

[0912] (2) Manufacturing of A-166

[0913] A-165 (60.0 mg, 0.14 mmol) was dissolved in DMF (1.4 mL) at room temperature, and HATU (79.0 mg, 0.21 mmol), MeNH2 (2 M in THF, 10.4 μL, 0.201 mmol), and DIPEA (73.0 μL, 0.42 mmol) were added. The mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was triturated with DCM, and the resulting solid was filtered to give A-166 (26.0 mg, 42%) as a beige solid.

[0914] A-167 to A-169 were synthesized using the above A-165 synthesis procedure.

[0915]

[0916] 21. A-170 and A-171 composite

[0917]

[0918] (1) Manufacturing of A-170

[0919] A-3 (104 mg, 0.25 mmol) was dissolved in acetonitrile (ACN; 2.5 mL) at 0°C, to which copper (Ⅱ) bromide (56.0 mg, 0.25 mmol) and tert-butyl nitrite (38.0 mg, 0.37 mmol) were added. The mixture was stirred at 0°C for 30 min. The reaction mixture was quenched with aqueous ammonia and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 3:1) to give methyl A-170 (47.8 mg, 40%) as a pale yellow solid.

[0920] (2) Manufacturing of A-171

[0921] To a solution of methyl 3-(4-(2-bromo-4-phenylthiazol-5-yloxy)pyridin-2-ylamino)benzoate (7.50 mg, 0.02 mmol) in THF (0.23 mL) and water (0.08 mL) at room temperature was added lithium hydroxide hydrate (6.52 mg, 0.16 mmol). After stirring at room temperature for 18 h, the reaction mixture was concentrated in vacuo. The residue was acidified with 2 N aq. hydrochloric acid. The precipitated solid was collected by filtration to give A-171 (1.50 mg, 21%) as a white solid.

[0922]

[0923] 22. A-172 Synthesis

[0924]

[0925] Compound 1-13 (15.0 mg, 0.03 mol) was dissolved in a mixture of water (0.24 mL) and EtOH (1.4 mL) at room temperature, followed by the addition of NaOH (1.34 mg, 0.03 mmol), DMSO (3.55 μL, 0.05 mmol), and hydrogen peroxide (30 wt%, 3.92 μL, 0.05 mmol). After stirring at room temperature for 30 min, the reaction mixture was quenched with aqueous ammonia and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO2 (DCM:EtOAc = 1:1) to give A-172 (11.0 mg, 71%) as a yellow solid.

[0926]

[0927] 23. A-173 Synthesis

[0928]

[0929] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-(cyclopent-1-en-1-yl)-4-phenylthiazole (5-((2-chloropyridin-4-yl)oxy)-2-(cyclopent-1-en-1-yl)-4-phenylthiazole; hereinafter referred to as compound 9-1)

[0930] To a solution of compound 1-10 (300 mg, 0.82 mmol) in dioxane (6.1 mL) and water (2.0 mL) were added cyclopentenylboronic acid (100 mg, 0.90 mmol) and K2CO3 (189 mg, 1.37 mmol). The mixture was degassed by purging and backfilled with argon several times. After adding PdCl2(dppf) (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 10:1) to give compound 9-1 (125 mg, 42%) as a brown oil.

[0931] 1 H-NMR (400 MHz, DMSO-d6): δ8.33 (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)

[0932] (2) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-cyclopentyl-4-phenylthiazole (5-((2-chloropyridin-4-yl)oxy)-2-cyclopentyl-4-phenylthiazole; hereinafter referred to as compound 9-2)

[0933] Compound 9-1 (125 mg, 0.35 mmol) was dissolved in MeOH (3.5 mL) and PtO2 (96.0 mg, 0.42 mmol) was added. The mixture was stirred at room temperature for 2 h under a H2 atmosphere. The reaction mixture was filtered through a pad of Celite. The filtrate was concentrated in vacuo to give compound 9-2 (113 mg, 90%) as a yellow oil. The mixture was carried to the next step without further purification.

[0934] 1 H-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).

[0935] (3) Manufacturing of A-173

[0936] Compound 9-2 (113 mg, 0.32 mmol) was dissolved in DMF (dimethylformamide; 6.3 mL) and 6-aminonicotinamide (48.0 mg, 0.35 mmol) and K2CO3 (131 mg, 0.95 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After adding Brettphos Pd G3 (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (only EtOAc) to give A-173 (39.0 mg, 27%) as a white solid.

[0937] A-174 to A-176 were synthesized using the above A-173 synthesis procedure.

[0938]

[0939] 24. A-177 Synthesis

[0940]

[0941] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-(cyclohex-1-en-1-yl)-4-phenylthiazole (5-((2-chloropyridin-4-yl)oxy)-2-(cyclohex-1-en-1-yl)-4-phenylthiazole; hereinafter referred to as compound 10-1)

[0942] A solution of compound 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), K2CO3 (1.12 g, 8.16 mmol), and PdCl2(dppf) (398 mg, 0.54 mmol) was flushed with argon and stirred at 90 °C for 18 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (EtOAc:hexane = 1:10) to obtain compound 10-1 (728 mg, 72%) as a yellow solid.

[0943] 1H-NMR (400 MHz, CDCl3): δ8.27 (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).

[0944] (2) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-cyclohexyl-4-phenylthiazole (5-((2-chloropyridin-4-yl)oxy)-2-cyclohexyl-4-phenylthiazole; hereinafter referred to as compound 10-2)

[0945] Compound 10-1 (710 mg, 1.92 mmol) was mixed with PtO2 (524 mg, 2.3 mmol) in MeOH (19 mL), and the mixture was left to stand at room temperature for 1 h under a H2 atmosphere. The mixture was filtered through a pad of Celite and washed with MeOH. The filtrate was concentrated in vacuo to give compound 10-2 (210 mg, 30%) as a white solid.

[0946] 1 H-NMR (400 MHz, CDCl3): δ8.27 (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).

[0947] (3) Manufacturing of A-177

[0948] Compound 10-2 (50.0 mg, 0.13 mmol) was dissolved in DMF (1.3 mL) at room temperature, and 6-aminonicotinamide (22 mg, 0.16 mmol) and K2CO3 (55 mg, 0.4 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After adding BrettPhos Pd G3 (36.0 mg, 0.04 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was washed with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (DCM:MeOH = 9:1) to give A-177 (1.8 mg, 2%) as a pink solid.

[0949] A-178 to A-180 were synthesized using the above A-177 synthesis procedure.

[0950]

[0951] 25. A-181 Synthesis

[0952]

[0953] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-4-phenyl-2-vinylthiazole (5-((2-chloropyridin-4-yl)oxy)-4-phenyl-2-vinylthiazole; hereinafter referred to as compound 11-1)

[0954] To a solution of compound 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 Na2CO3 (778 mg, 7.34 mmol) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After adding PdCl2(dppf) (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 10:1) to give compound 11-1 (443 mg, 58%) as a yellow solid.

[0955] 1 H-NMR (400 MHz, DMSO-d6): δ8.37 (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).

[0956] (2) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-ethyl-4-phenylthiazole (5-((2-chloropyridin-4-yl)oxy)-2-ethyl-4-phenylthiazole; hereinafter referred to as compound 11-2)

[0957] A mixture of compound 11-1 (443 mg, 1.41 mmol) and Pd / C (10 wt%, 150 mg, 0.14 mmol) was dissolved in MeOH (14 mL) and stirred at room temperature for 1 h under a H2 atmosphere. After filtration through a pad of Celite, the filtrate was concentrated in vacuo to give compound 11-2 (333 mg, 75%) as a yellow oil. This was used in the next synthesis without further purification.

[0958] 1 H-NMR (400 MHz, DMSO-d6): δ8.33 (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).

[0959] (3) Manufacturing of A-181

[0960] Compound 11-2 (30.0 mg, 0.0950 mmol) was dissolved in DMF (1.9 mL) at room temperature, and 3-aminobenzenesulfonamide (24.0 mg, 0.14 mmol) and K2CO3 (39.0 mg, 0.284 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After adding Brettphos Pd G3 (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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 1:1) to give A-181 (21 mg, 49%) as a white solid.

[0961] A-182 to A-190 were synthesized using the above A-181 synthesis procedure.

[0962]

[0963] 26. Synthesis of A-191 to A-193

[0964]

[0965] (1) Manufacturing of A-191

[0966] Compound 11-2 (200 mg, 0.63 mmol), methyl 6-aminonicotinate (96.0 mg, 0.63 mmol), and K2CO3 (87.0 mg, 0.63 mmol) were dissolved in DMF (6.31 mL), which was purged to degas and backfilled with argon several times. After adding BrettPhos Pd G3 (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 EtOAc. The separated organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 1:1) to give A-191 (120 mg, 44%) as a yellow solid.

[0967] (2) Manufacturing of A-192

[0968] To a solution of methyl 6-(4-(2-ethyl-4-phenylthiazol-5-yloxy)pyridin-2-ylamino)nicotinate (70.0 mg, 0.16 mmol) dissolved in THF (1.29 mL) and water (0.32 mL) at 0°C was added LiOH·H2O (39.0 mg, 1.62 mmol). The mixture was stirred at 50°C for 24 h. After cooling to 0°C, the reaction mixture was acidified with 1 N aq. hydrochloric acid and concentrated in vacuo to give A-192 (90.0 mg) as a white solid, which was used in the next step without further purification.

[0969] (3) Manufacturing of A-193

[0970] A mixture of A-193 (50.0 mg, 0.12 mmol), HATU (68.0 mg, 0.18 mmol), DIPEA (0.06 mL, 0.36 mmol), and methanamine (0.09 mL, 0.18 mmol) in DMF (1.19 mL) was stirred at room temperature for 2 h. The reaction mixture was dissolved in EtOAc and washed with water and brine. The separated organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (DCM:MeOH = 10:1) to give A-193 (43.0 mg, 83%) as a white solid.

[0971] A-194 and A-195 were synthesized using the above A-192 synthesis procedure.

[0972] A-196 to A-215 were synthesized using the above A-191 or A-193 synthetic procedure.

[0973]

[0974] 27. Synthesis of A-216 and A-217

[0975]

[0976] (1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-4-phenyl-2-(prop-1-en-2-yl)thiazole (5-((2-chloropyridin-4-yl)oxy)-4-phenyl-2-(prop-1-en-2-yl)thiazole; hereinafter referred to as compound 12-1)

[0977] A mixture of compound 1-10 (40.0 mg, 0.11 mmol), potassium isopropenyltrifluoroborat (24.0 mg, 0.16 mmol), Na2CO3 (81.0 mg, 0.76 mmol), and PdCl2(dppf) (8.9 mg, 0.01 mmol) was flushed with argon, and 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 EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (EtOAc:hexane = 1:4) to give compound 12-1 (24.0 mg, 67%) as a yellow oil.

[0978] 1 H-NMR (400 MHz, CDCl3): δ8.26 (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).

[0979] (2) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-isopropyl-4-phenylthiazole (5-((2-chloropyridin-4-yl)oxy)-2-isopropyl-4-phenylthiazole; hereinafter referred to as compound 12-2)

[0980] Compound 12-1 (300 mg, 0.91 mmol) was dissolved in DCM (10 mL) and 10% Pd / C (97.0 mg, 0.09 mmol) was added, and the mixture was left to stand at room temperature for 30 min under a H2 atmosphere. The mixture was filtered through a pad of Celite and washed with DCM (dichloromethane). The filtrate was concentrated in vacuo to give compound 12-2 (170 mg, 56%) as a colorless oil.

[0981] 1 H-NMR (400 MHz, CDCl3): δ8.26 (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).

[0982] (3) Manufacturing of A-216

[0983] Methyl 6-aminopicolinate (55.0 mg, 0.36 mmol) and K2CO3 (100 mg, 0.72 mmol) were added to DMF (2.4 mL) containing compound 12-2 (80.0 mg, 0.24 mmol) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After adding Brettphos Pd G3 (65.0 mg, 0.07 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was washed with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 3:1) to give methyl A-216 (41.0 mg, 38%) as a yellow solid.

[0984] (4) Manufacturing of A-217

[0985] LiOH·H2O (38.0 mg, 0.91 mmol) was added to a mixture of THF (0.9 mL) and water (0.9 mL) containing A-216 (41.0 mg, 0.09 mmol) at 0°C. The reaction mixture was stirred at 50°C for 18 h. After cooling to 0°C, the reaction mixture was acidified with 1 N aq. hydrochloric acid solution and concentrated in vacuo to obtain A-217 (24.0 mg, 60%) as a yellow solid.

[0986] A-218 to A-229 were synthesized using the above A-216 synthesis procedure.

[0987] A-230 to A-232 were synthesized using the above A-217 synthesis procedure.

[0988]

[0989] 28. A-233 Synthesis

[0990]

[0991] (1) Preparation of 2-((2-chloropyridin-4-yl)oxy)-1-(naphthalen-2-yl)ethan-1-one (2-((2-chloropyridin-4-yl)oxy)-1-(naphthalen-2-yl)ethan-1-one; hereinafter referred to as compound 13-2)

[0992] Compound 13-1 (1.50 g, 11.58 mmol), 2-bromo-1-(naphthalene-2-yl)ethanone (3.46 g, 13.89 mmol), and K2CO3 (2.40 g, 17.37 mmol) were dissolved in acetone (20 mL) and stirred at room temperature for 18 h. The reaction mixture was washed with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to give compound 13-2 (2.77 g, 80%) as a yellow foam.

[0993] 1H-NMR (400 MHz, CDCl3): δ8.49 (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).

[0994] (2) Preparation of 2-bromo-2-((2-chloropyridin-4-yl)oxy)-1-(naphthalen-2-yl)ethan-1-one (2-bromo-2-((2-chloropyridin-4-yl)oxy)-1-(naphthalen-2-yl)ethan-1-one; hereinafter referred to as compound 13-3)

[0995] Compound 13-2 (230 mg, 0.77 mmol) was dissolved in CHCl3 (8.0 mL) at 0°C, to which Br2 (0.06 mL, 1.16 mmol) and AlCl3 (21.0 mg, 0.15 mol) were added. The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was washed with saturated aq. NaHCO3 solution at 0°C and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to give compound 13-3 (300 mg) as a yellow foam.

[0996] 1 H-NMR (400 MHz, CDCl3): δ8.73 (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).

[0997] (3) Preparation of 5-((2-chloropyridin-4-yl)oxy)-N-methyl-4-(naphthalen-2-yl)thiazol-2-amine (5-((2-chloropyridin-4-yl)oxy)-N-methyl-4-(naphthalen-2-yl)thiazol-2-amine; hereinafter referred to as compound 13-4)

[0998] A mixture of compound 13-3 (480 mg, 1.27 mmol) and 1-methylthiourea (115 mg, 1.27 mmol) dissolved in EtOH (13.0 mL) was stirred at 75°C for 20 min. After cooling to room temperature, the solvent was removed in vacuo. The residue was dissolved in EtOAc and washed with water. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO2 (DCM) to give compound 13-4 (160 mg, 34%) as a yellow solid.

[0999] 1 H-NMR (400 MHz, CDCl3): δ8.25 (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).

[1000] (4) Manufacturing of A-233

[1001] Compound 13-4 (80.0 mg, 0.22 mmol) was dissolved in DMF (5.0 mL) at room temperature, and K2CO3 (90.0 mg, 0.65 mmol) and 3-aminobenzenesulfonamide (56.0 mg, 0.33 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After the addition of BrettPhos Pd G3 (39.0 mg, 0.04 mmol), the reaction mixture was heated at 100 °C for 5 h. After cooling to room temperature, the reaction mixture was washed with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO2 (DCM:MeOH = 98:2) to give A-233 (8.2 mg, 7%) as a beige solid.

[1002]

[1003] 29. A-234 Synthesis

[1004]

[1005] (1) Preparation of 5-(2-chloropyridin-4-yloxy)-4-(naphthalen-2-yl)thiazol-2-amine (5-(2-chloropyridin-4-yloxy)-4-(naphthalen-2-yl)thiazol-2-amine; hereinafter referred to as compound 13-5)

[1006] A mixture of compound 13-2 and thiourea (61.0 mg, 0.80 mmol) dissolved in EtOH (7.9 mL) was heated at 70°C for 20 min. After cooling to room temperature, the solvent was removed in vacuo. The residue was dissolved in EtOAc and washed with water. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO2 (only DCM) to give compound 13-5 (120 mg, 42%) as a yellow solid.

[1007] 1 H-NMR (400 MHz, CDCl3): δ8.49 (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).

[1008] (2) Preparation of di-tert-butyl 5-(2-chloropyridin-4-yloxy)-4-(naphthalen-2-yl)thiazol-2-ylcarbamate (hereinafter referred to as compound 13-6)

[1009] A mixture of compound 13-5 (300 mg, 0.85 mmol), Boc2O (2.34 mL, 1.02 mmol), TEA (0.14 mL, 1.02 mmol), and DMAP (10.4 mg, 0.08 mmol) in DCM (30 mL) was stirred at room temperature for 18 h. The reaction mixture was quenched with water and extracted with DCM. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by MPLC (hexane / EtOAc) to give compound 13-6 (330 mg, 70%) as a yellow foam.

[1010] 1 H-NMR (400 MHz, CDCl3): δ8.29 (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).

[1011] (3) Preparation of tert-butyl 4-(naphthalene-2-yl)-5-(2-(3-sulfamoylphenylamino)pyridin-4-yloxy)thiazol-2-ylcarbamate (hereinafter referred to as compound 13-7)

[1012] Compound 13-6 (200 mg, 0.36 mmol) was dissolved in DMF (8 mL) at room temperature, and K2CO3 (150 mg, 1.08 mmol) and 3-aminobenzenesulfonamide (93.0 mg, 0.54 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After adding BrettPhos Pd G3 (65.0 mg, 0.07 mmol), the reaction mixture was heated at 100 °C for 18 h. After cooling to room temperature, the reaction mixture was washed with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (hexane:EtOAc = 4:1) to give compound 13-7 (120 mg, 56%) as a dark brown solid.

[1013] MS Calcd.: 689.8; MS Found: 690.12 (M+H + ).

[1014] (4) Manufacturing of A-234

[1015] Compound 13-7 (120 mg, 0.20 mmol) was dissolved in DCM (5.0 mL) and TFA (0.18 mL, 2.03 mmol) was added, and the mixture was stirred at room temperature for 18 h. The reaction mixtu...

Claims

1. A pharmaceutical composition for treating or preventing pulmonary fibrosis, comprising as an active ingredient 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: [Chemical Formula 1] In the above chemical formula 1, A 1 is O or S, A 2 is CH or N, R 1 and R 2 may be the same or different, (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 having 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 may be 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 of 5 to 10 atoms is substituted by (C1-C5)alkyl, n is one of 0 to 3, Ar is an unsubstituted or substituted (C5-C10)aryl or an unsubstituted or substituted 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, wherein the substituted (C5-C10)aryl or substituted 5 to 10-membered heteroaryl is R 3 is replaced, The above R 3 is -R 3-1 or -(C1-C5)alkyl-R 3-1 And, The above 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 , , , , and One of them, The above R 31-1 , R 31-2 , R 32 , R 33 , R 34 , R 35-1 and R 35-2 may be the same or different, and are hydrogen, hydroxy, trifluoromethyl, (C1-C5)alkyl, (C3-C8)cycloalkyl, -SO2-(C1-C3)alkyl, -(C1-C3)alkyl-R 301 and And, The above R 301 Silver (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, (C3-C8)cycloalkyl, and One of them, The above R 3001 is hydrogen or (C1-C5)alkyl, The above R 302 is a halogen, The above R 303 and R 304 may be the same or different, and are hydrogen or (C1-C3)alkyl, The above R 36 and R 37 may be the same or different, or And, The above R 305 is hydrogen or (C1-C5)alkyl, The above R 306 is any one of hydrogen, amino, (C1-C4)alkylamino and di[(C1-C4)alkyl]amino, The above R 38 and R 39 may be the same or different, and are any one of hydrogen, (C1-C3)alkyl, and -(C1-C3)alkyl-(C1-C3)alkoxy.

2. In claim 1, In the above chemical formula 1, R 1 Silver (C1-C3)alkyl, (C1-C3)alkylene, methoxy, trifluoromethyl (CF3), bromine (Br), (C3-C6)cycloalkyl and NR 11 R 12 One of the above R 11 and R 12 may be the same or different, and are any one of hydrogen, (C1-C3)alkyl and cyclopropyl, R 2 Is or naphthyl, and the above A 3 is CH or N, and the above R 21 is hydrogen or methyl, n is one of 0 to 2, Ar is , and One of them, The above R 3 is -R 3-1 or -(C1-C3)alkyl-R 3-1 And, The above 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 , , , , and One of them, The above R 31-1 , R 31-2 , R 32 , R 33 , R 34 , R 35-1 and R 35-2 may be the same or different, and are hydrogen, hydroxy, trifluoromethyl, (C1-C3)alkyl, (C3-C6)cycloalkyl, -SO2CH3, -(C1-C3)alkyl-R 301 and And, The above R 301 Silver methylamino, dimethylamino, cyclopropyl, and One of them, The above R 3001 is hydrogen or (C1-C3)alkyl, The above R 302 is fluorine, The above R 303 and R 304 may be the same or different, and are hydrogen or methyl, The above R 36 and R 37 may be the same or different, or And, The above R 305 is (C1-C3)alkyl, The above R 306 is any one of hydrogen, amino and methylamino, The above R 38 and R 39 A pharmaceutical composition, wherein each of which may be the same or different, is characterized by being any one of hydrogen, (C1-C3)alkyl and -(C1-C3)alkyl-methoxy.

3. In claim 1, In the above chemical formula 1, R 1 Silver methyl, ethyl, isopropyl, methoxy, ethylene, trifluoromethyl (CF3), bromine (Br), cyclopropyl, cyclopentyl, cyclohexyl and NR 11 R 12 One of the above R 11 and R 12 may be the same or different, and are any one of hydrogen, methyl and cyclopropyl, R 2 Is , and is one of them, n is one of 0 to 2, Ar is , and One of them, The above R 3 is -R 3-1 or -(C1-C3)alkyl-R 3-1 And, The above R 3-1 Silver 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-C2)alkyl-R 37 , , , , and One of them, The above R 31-1 and R 31-2 may be the same or different, and are hydrogen, methyl, isopropyl, hydroxy, -SO2CH3, -(C1-C2)alkyl-R 301 and And, The above R 301 Silver dimethylamino, cyclopropyl, and One of them, The above R 3001 is one of methyl, ethyl and isopropyl, The above R 302 is fluorine, The above R 303 and R 304 is methyl, The above R 32 is one of hydrogen, methyl and -(C1-C2)alkyl-dimethylamino, The above R 33 is one of methyl, ethyl, cyclopropyl and trifluoromethyl, The above R 34 is one of hydroxy, methyl, ethyl, cyclopropyl and trifluoromethyl, The above R 35-1 and R 35-2 may be the same or different, and are one of hydrogen, methyl and cyclopropyl, The above R 36 silver or And, The above R 305 is methyl, and the above R 306 is amino or methylamino, The above R 37 silver or And, The above R 38 is methyl or -CH2CH2OCH3, The above R 39 A pharmaceutical composition characterized in that it is hydrogen or methyl.

4. In claim 1, A pharmaceutical composition characterized in that the compound represented by the above chemical formula 1 is any one selected from the following group of compounds: (1) 3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (2) 3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (3) Methyl 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate; (4) 4-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (5) 4-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (6) 4-Phenyl-5-((2-(pyridin-3-ylamino)pyridin-4-yl)oxy)thiazol-2-amine; (7) 5-((2-((6-Fluoropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (8) 4-Phenyl-5-((2-(pyridin-4-ylamino)pyridin-4-yl)oxy)thiazol-2-amine; (9) 6-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (10) 3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylbenzamide; (11) 5-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; (12) 3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzenesulfonamide; (13) 3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N,N-dimethylbenzenesulfonamide; (14)N-(3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide; (15) 5-((2-((3-(Methylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (16)N-(3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopropanesulfonamide; (17) 4-Phenyl-5-((2-((3-((trifluoromethyl)sulfonyl)phenyl)amino)pyridin-4-yl)oxy)thiazol-2-amine; (18) 3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid; (19) 5-((2-((3-((methylsulfonyl)methyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (20) 3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-cyclopropylbenzenesulfonamide; (21) 5-((2-((3-Fluorobenzyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (22) 2-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide; (23) 3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; (24) 5-((2-((2-Methoxypyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (25) 5-((2-(Benzylamino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (26) 4-Phenyl-5-((2-((pyridin-4-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine; (27) 5-((2-((2-Chloropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (28) 4-Phenyl-5-((2-((pyridin-3-ylmethyl)amino)pyridin-4-yl)oxy)thiazol-2-amine; (29) (3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide); (30) 5-((2-((2-Fluoropyridin-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (31) 5-((2-((6-Methoxypyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (32) 5-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (33) 6-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; (34) 5-((2-((3-(Ethylsulfonyl)phenyl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (35) 5-((2-((6-Chloropyridin-3-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (36)N-(3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)-1,1,1-trifluoromethanesulfonamide; (37) 5-((2-((1-Methyl-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (38) 5-((2-((1H-Pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (39) 4-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (40) 3-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (41) 2-(3-((4-((2-amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; (42) 2-(4-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (43) 2-(5-((4-((2-Amino-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (44) 2-(3-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; (45) 3-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (46) 3-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (47) 4-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (48) 3-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (49) 4-((4-((2-(Cyclopropylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (50) 2-(3-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; (51) 3-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (52) 3-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (53) 4-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (54) 2-(4-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (55) 2-(5-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (56) 4-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (57) 3-((4-((2-(Methylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (58) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (59) 2-(4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (60) 3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (61) 2-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; (62) 5-((2-((1-(Methylsulfonyl)-1H-pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (63) 4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (64) 4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (65) 2-(5-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (66) 2-Methyl-2-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propanoic acid; (67)N,N-Dimethyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (68) 3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonic acid; (69)N-Methyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (70) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(3-(methylsulfonyl)phenyl)pyridin-2-amine; (71)N-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide; (72) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((trifluoromethyl)sulfonyl)phenyl)pyridin-2-amine; (73)N-Methyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (74)N,N-Dimethyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (75)N-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)cyclopropanesulfonamide; (76)N-Cyclopropyl-3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (77)N-(3-(Ethylsulfonyl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (78) (3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide); (79) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(3-((methylsulfonyl)methyl)phenyl)pyridin-2-amine; (80) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-ylmethyl)pyridin-2-amine; (81) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-ylmethyl)pyridin-2-amine; (82) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-3-yl)pyridin-2-amine; (83)N-(6-Fluoropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (84)N-(6-Chloropyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (85)N-(6-Methoxypyridin-3-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (86) 4-((2-methyl-4-phenylthiazol-5-yl)oxy)-N-(pyridin-4-yl)pyridin-2-amine; (87)N-(2-Fluoropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (88)N-(2-Methoxypyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (89)N-(2-Chloropyridin-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (90) 6-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (91) 5-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; (92) 5-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (93) 2-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide; (94)N-Benzyl-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (95)N-(4-Fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (96)N-(3-Fluorobenzyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (97) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(1-(methylsulfonyl)-1H-pyrazol-4-yl)pyridin-2-amine; (98)N-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (99)N-(1-Methyl-1H-pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (100) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(1H-pyrazol-4-yl)pyridin-2-amine; (101) 6-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; (102) 4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; (103)N-(4-Methoxyphenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (104) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(piperazin-1-yl)phenyl)pyridin-2-amine; (105) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)-N-(4-(2-(piperidin-1-yl)ethoxy)phenyl)pyridin-2-amine; (106)N-(3-Methoxy-4-(4-methylpiperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (107) 1,1,1-Trifluoro-N-(3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)methanesulfonamide; (108)N-(4-(4-(2-Methoxyethyl)piperazin-1-yl)phenyl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (109) 3-((4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (110) 4-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (111) 2-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)acetonitrile; (112)N-(3-((1H-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-((4-Phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (148)N-Methyl-4-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (149) 6-((4-((4-Phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; (150)N-Methyl-6-((4-((4-phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (151) 3-((4-((4-Phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (152) 4-((4-((4-Phenyl-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (153) 2-(3-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; (154) 3-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (155) 3-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (156) 4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (157) 4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (158) 2-(4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (159) 2-(5-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (160) 6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; (161) 6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide; (162) Methyl 6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinate; (163) 6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (164) 4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; (165) 6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; (166) 6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; (167) 3-((4-((2-(dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (168) 4-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (169) 6-((4-((2-(Dimethylamino)-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid; (170) Methyl 3-((4-((2-bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoate; (171) 3-((4-((2-Bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (172) 3-((4-((2-Bromo-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (173) 6-((4-((2-Cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (174) 6-((4-((2-Cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; (175) 4-((4-((2-Cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (176) 6-((4-((2-Cyclopentyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; (177) 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (178) 6-((4-((2-cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; (179) 4-((4-((2-Cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (180) 6-((4-((2-Cyclohexyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; (181) 3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (182) 2-(3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)propan-2-ol; (183) 3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (184) 4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (185) 4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (186) 2-(4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol); (187) 2-(5-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (188)N-(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)ethanesulfonamide; (189) 4-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; (190) 6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (191) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate; (192) 6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; (193) 6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; (194) 3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (195) 4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (196) 6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-isopropylnicotinamide; (197) (6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(4-methylpiperazin-1-yl)methanone); (198) (3-Aminopyrrolidin-1-yl)(6-(4-(2-ethyl-4-phenylthiazol-5-yloxy)pyridin-2-ylamino)pyridin-3-yl)methanone; (199) 6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(pyrrolidin-1-yl)ethyl)nicotinamide; (200) (6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(3-(methylamino)pyrrolidin-1-yl)methanone((6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(3-(methylamino)pyrrolidin-1-yl)methanone); (201) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-methylpiperazin-1-yl)ethyl)nicotinamide; (202) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-isopropylpiperazin-1-yl)ethyl)nicotinamide; (203) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)-N-(2-(4-ethylpiperazin-1-yl)ethyl)nicotinamide; (204) 5-(3-aminopyrrolidin-1-yl)-N-(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)pyridin-2-amine; (205)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-isopropylpiperazin-1-yl)ethyl)benzene-1,4-diamine(N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-isopropylpiperazin-1-yl)ethyl)benzene-1,4-diamine); (206)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-methylpiperazin-1-yl)ethyl)benzene-1,4-diamine(N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-methylpiperazin-1-yl)ethyl)benzene-1,4-diamine); (207)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-ethylpropylpiperazin-1-yl)ethyl)benzene-1,4-diamine(N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(4-ethylpiperazin-1-yl)ethyl)benzene-1,4-diamine); (208)N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(pyrrolidin-1-yl)ethyl)benzene-1,4-diamine(N 1 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 4 -(2-(pyrrolidin-1-yl)ethyl)benzene-1,4-diamine); (209)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-methylpiperazin-1-yl)ethyl)pyridine-2,5-diamine(N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-methylpiperazin-1-yl)ethyl)pyridine-2,5-diamine); (210)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(pyrrolidin-1-yl)ethyl)pyridine-2,5-diamine(N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(pyrrolidin-1-yl)ethyl)pyridine-2,5-diamine); (211)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-ethylpiperazin-1-yl)ethyl)pyridine-2,5-diamine(N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-ethylpiperazin-1-yl)ethyl)pyridine-2,5-diamine); (212)N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-isopropylpiperazin-1-yl)ethyl)pyridine-2,5-diamine(N 2 -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)-N 5 -(2-(4-isopropylpiperazin-1-yl)ethyl)pyridine-2,5-diamine); (213)N-(5-(1H-pyrazol-4-yl)pyridin-2-yl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (214)N-(4-(3-aminopyrrolidin-1-yl)phenyl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (215) 4-((2-ethyl-4-phenylthiazol-5-yl)oxy)-N-(4-(3-(methylamino)pyrrolidin-1-yl)phenyl)pyridin-2-amine; (216) 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-4-yl)amino)benzenesulfonamide; (239) 3-((4-((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)nicotinamido)-5-fluorobenzoate; (274) 3-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (275) 6-((4-((2-Ethyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (276) 2-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)isonicotinamide; (277) 3-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (278) 6-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; (279) 6-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide; (280) 2-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylisonicotinamide; (281) 3-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; (282) 6-((4-((2-Cyclopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; (283) 3-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (284) 6-((4-((2-(Dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (285) 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; (286) 6-((4-((2-(dimethylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylnicotinamide; (287) 3-((4-((2-Isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (288) 6-((4-((2-Isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (289) 3-((4-((4-(6-Methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (290) 6-((4-((2-Isopropyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (291) 3-((4-((4-(6-Methylpyridin-2-yl)-2-(trifluoromethyl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (292) 3-((4-((2-(Methylamino)-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (293) 6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; (294) 6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (295) 4-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (296) 3-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (297) 3-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylbenzamide; (298) 3-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (299) 6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)picolinamide; (300) 3-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (301) 6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)picolinic acid; (302) 6-((4-((2-Cyclopropyl-4-phenyloxazol-5-yl)oxy)pyridin-2-yl)amino)-N-methylpicolinamide; (303) 3-((4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (304) 2-(3-((4-((2-Methyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)acetonitrile; (305)N-(3-((1H-tetrazol-5-yl)methyl)phenyl)-4-((2-methyl-4-(6-methylpyridin-2-yl)thiazol-5-yl)oxy)pyridin-2-amine(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-(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(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-trifluorosulfonamide; and (312) 4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)-N-(5-(3-(methylamino)pyrrolidin-1-yl)pyridin-2-yl)pyridin-2-amine.

5. In claim 1, The above pulmonary fibrosis is, A pharmaceutical composition characterized in that the pulmonary fibrosis is caused by or associated with a lung disease selected from the group consisting of interstitial lung disease (PFILD) such as idiopathic pulmonary fibrosis (IPF), systemic sclerosis-associated interstitial lung disease (SSC-ILD), familial pulmonary fibrosis (familial PF), rheumatoid arthritis-associated interstitial lung disease, connective tissue disease-associated interstitial lung disease, drug-induced interstitial lung disease, post-infectious interstitial lung disease, and inflammatory interstitial lung disease.

6. In claim 1, The above composition, A pharmaceutical composition characterized in that it reduces the expression level of one or more fibrosis factors selected from the group consisting of collagen I, a-SMA, N-cadherin, vimentin, and pSMAD2 / 3, the expression of which increases when pulmonary fibrosis is induced.

7. A health functional food composition for improving or preventing pulmonary fibrosis, comprising as an active ingredient a compound selected from a thiazole derivative compound represented by the following chemical formula 1, a food-acceptable salt thereof, a solvate thereof, or a stereoisomer thereof: [Chemical Formula 1] In the above chemical formula 1, A 1 is O or S, A 2 is CH or N, R 1 and R 2 may be the same or different, (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 having 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 may be 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 of 5 to 10 atoms is substituted by (C1-C5)alkyl, n is one of 0 to 3, Ar is an unsubstituted or substituted (C5-C10)aryl or an unsubstituted or substituted 5 to 10-membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, wherein the substituted (C5-C10)aryl or substituted 5 to 10-membered heteroaryl is R 3 is replaced, The above R 3 is -R 3-1 or -(C1-C5)alkyl-R 3-1 And, The above 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 , , , , and One of them, The above R 31-1 , R 31-2 , R 32 , R 33 , R 34 , R 35-1 and R 35-2 may be the same or different, and are hydrogen, hydroxy, trifluoromethyl, (C1-C5)alkyl, (C3-C8)cycloalkyl, -SO2-(C1-C3)alkyl, -(C1-C3)alkyl-R 301 and And, The above R 301 Silver (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, (C3-C8)cycloalkyl, and One of them, The above R 3001 is hydrogen or (C1-C5)alkyl, The above R 302 is a halogen, The above R 303 and R 304 may be the same or different, and are hydrogen or (C1-C3)alkyl, The above R 36 and R 37 may be the same or different, or And, The above R 305 is hydrogen or (C1-C5)alkyl, The above R 306 is any one of hydrogen, amino, (C1-C4)alkylamino and di[(C1-C4)alkyl]amino, The above R 38 and R 39 may be the same or different, and are any one of hydrogen, (C1-C3)alkyl, and -(C1-C3)alkyl-(C1-C3)alkoxy.

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