WO2025063820A1 - Composition for treating pulmonary fibrosis comprising thiazole derivative compound - Google Patents

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

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

Idiopathic pulmonary fibrosis (IPF) is a chronic disease of unknown etiology characterized by pulmonary interstitial fibrosis, which progresses continuously and ultimately leads to death. Idiopathic pulmonary fibrosis has a poor prognosis, with a median survival of only 3-4 years after diagnosis for patients who do not receive antifibrotic drug treatment. As the disease progresses, pulmonary function declines, dyspnea and physical abilities deteriorate, and the quality of life also deteriorates. Patients with idiopathic pulmonary fibrosis can experience acute exacerbations characterized by bilateral pulmonary infiltrates and decreased oxygen saturation at any time, in which case the mortality rate is high, and most patients with idiopathic pulmonary fibrosis die from respiratory failure caused by acute exacerbations. The cause is still unknown, but it is thought to be caused by intentional or unintentional exposure to environmental pollutants such as smoking and fine dust.

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

The 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.

In order to achieve the above object, 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:

[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 and are one of (C1-C4)alkyl, (C1-C4)alkylene, (C1-C4)alkoxy, trifluoromethyl (CF ₃ ), halo, NR ¹¹ R ¹² , unsubstituted or substituted (C3-C8)cycloalkyl, unsubstituted or substituted (C5-C10)aryl and unsubstituted or substituted heteroaryl of 5 to 10 members containing one or more heteroatoms selected from the group consisting of N, O and S, wherein said 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 wherein said substituted (C3-C8)cycloalkyl, substituted (C5-C10)aryl or substituted heteroaryl of 5 to 10 members is (C1-C5)alkyl substituted,

n is one of 0 to 3,

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

The above R ³ is -R ^3-1 or -(C1-C5)alkyl-R ^3-1 ,

,

,

,

, 및

중 어느 하나이고,The above R ^3-1 is hydrogen, halogen, hydroxy, cyano, (C1-C5)alkyl, (C1-C5)alkoxy, -CONR ^31-1 R ^31-2 , -COOR ³² , -NHSO ₂ R ³³ , -SO ₂ R ³⁴ , -SO ₂ NR ^35-1 R ^35-2 , -COR ³⁶ , -NH-(C1-C3)alkyl-R ³⁷ ,

,

,

,

, and

One of them,

이고,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, -SO ₂ -(C1-C3)alkyl, -(C1-C3)alkyl-R ³⁰¹ and

And,

및

중 어느 하나이고,The above R ³⁰¹ is (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,

또는

이고,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.

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

A pharmaceutical composition comprising a 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.

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.

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

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

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

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

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

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

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.

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

Figure 9 shows the results of Masson's Trichrome staining according to treatment with compound A-192 or A-250 in an in vivo mouse model.

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

Figure 11 shows the analysis of fibrosis markers following compound A-250 treatment in an in vivo mouse model.

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.

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

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

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

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

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

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

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.

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

The present inventors have synthesized a novel thiazole derivative compound, and have confirmed that the compound has TGF-β inhibitory activity and 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.

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:

[Chemical Formula 1]

,

,

,

및

중 어느 하나이고, 상기 R^31-1, R^31-2, R³², R³³, R³⁴, R^35-1 및 R^35-2은 각각 같거나 다를 수 있으며, 수소, 하이드록시, 트리플루오로메틸, (C1-C5)알킬, (C3-C8)사이클로알킬, -SO₂-(C1-C3)알킬, -(C1-C3)알킬-R³⁰¹ 및

이고, 상기 R³⁰¹은 (C1-C4)알킬아미노, 디[(C1-C4)알킬]아미노, (C3-C8)사이클로알킬,

및

중 어느 하나이고, 상기 R³⁰⁰¹은 수소 또는 (C1-C5)알킬이고, 상기 R³⁰²는 할로겐이고, 상기 R³⁰³ 및 R³⁰⁴는 각각 같거나 다를 수 있으며, 수소 또는 (C1-C3)알킬이고, 상기 R³⁶ 및 R³⁷은 각각 같거나 다를 수 있으며,

또는

이고, 상기 R³⁰⁵는 수소 또는 (C1-C5)알킬이고, 상기 R³⁰⁶은 수소, 아미노, (C1-C4)알킬아미노 및 디[(C1-C4)알킬]아미노 중 어느 하나이고, 상기 R³⁸ 및 R³⁹는 각각 같거나 다를 수 있으며, 수소, (C1-C3)알킬 및 -(C1-C3)알킬-(C1-C3)알콕시 중 어느 하나일 수 있다.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, and are one of (C1-C4)alkyl, (C1-C4)alkylene, (C1-C4)alkoxy, trifluoromethyl (CF ₃ ), 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 including 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 A 5 to 10-membered heteroaryl is a (C1-C5)alkyl substituted, 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 comprising at least one heteroatom selected from the group consisting of N, O and S, wherein the substituted (C5-C10)aryl or the substituted 5 to 10-membered heteroaryl is substituted at R ³ , wherein R ³ is -R ^3-1 or -(C1-C5)alkyl-R ^3-1 , wherein R ^3-1 is hydrogen, halogen, hydroxy, cyano, (C1-C5)alkyl, (C1-C5)alkoxy, -CONR ^31-1 R ^31-2 , -COOR ³² , -NHSO ₂ R ³³ , -SO ₂ R ³⁴ , -SO ₂ NR ^35-1 R ^35-2 , -COR ³⁶ , -NH-(C1-C3)alkyl-R ³⁷ ,

,

,

,

and

and wherein 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, -SO ₂ -(C1-C3)alkyl, -(C1-C3)alkyl-R ³⁰¹ and

and the above R ³⁰¹ is (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, (C3-C8)cycloalkyl,

and

wherein R ³⁰⁰¹ is hydrogen or (C1-C5)alkyl, R ³⁰² is halogen, R 303 and R ³⁰⁴ may be the same or different, and are hydrogen or (C1-C3)alkyl, ^and R ³⁶ and R ³⁷ may be the same or different,

or

, wherein R ³⁰⁵ is hydrogen or (C1-C5)alkyl, wherein R ³⁰⁶ is any one of hydrogen, amino, (C1-C4)alkylamino and di[(C1-C4)alkyl]amino, wherein 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.

또는 나프틸이고, 상기 A³는 CH 또는 N이고, 상기 R²¹은 수소 또는 메틸이고, n은 0 내지 2 중 하나이고, Ar은

,

및

중 어느 하나이고, 상기 R³는 -R^3-1 또는 -(C1-C3)알킬-R^3-1이고, 상기 R^3-1은 수소, 플루오린, 염소, 하이드록시, 시아노, (C1-C3)알킬, (C1-C3)알콕시, -CONR^31-1R^31-2, -COOR³², -NHSO₂R³³, -SO₂R³⁴, -SO₂NR^35-1R^35-2, -COR³⁶, -NH-(C1-C3)알킬-R³⁷,

,

,

,

및

중 어느 하나이고, 상기 R^31-1, R^31-2, R³², R³³, R³⁴, R^35-1 및 R^35-2은 각각 같거나 다를 수 있으며, 수소, 하이드록시, 트리플루오로메틸, (C1-C3)알킬, (C3-C6)사이클로알킬, -SO₂CH₃, -(C1-C3)알킬-R³⁰¹ 및

이고, 상기 R³⁰¹은 메틸아미노, 디메틸아미노, 사이클로프로필,

및

중 어느 하나이고, 상기 R³⁰⁰¹은 수소 또는 (C1-C3)알킬이고, 상기 R³⁰²는 플루오린이고, 상기 R³⁰³ 및 R³⁰⁴는 각각 같거나 다를 수 있으며, 수소 또는 메틸이고, 상기 R³⁶ 및 R³⁷은 각각 같거나 다를 수 있으며,

또는

이고, 상기 R³⁰⁵는 (C1-C3)알킬이고, 상기 R³⁰⁶은 수소, 아미노 및 메틸아미노 중 어느 하나이고, 상기 R³⁸ 및 R³⁹는 각각 같거나 다를 수 있으며, 수소, (C1-C3)알킬 및 -(C1-C3)알킬-메톡시 중 어느 하나일 수 있다.Preferably, in the chemical formula 1, R ¹ is any one of (C1-C3) alkyl, (C1-C3) alkylene, methoxy, trifluoromethyl (CF ₃ ), bromine (Br), (C3-C6) cycloalkyl and NR ¹¹ R ¹² , wherein 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, wherein A ³ is CH or N, wherein R ²¹ is hydrogen or methyl, n is one of 0 to 2, and Ar is

,

and

wherein R ³ is -R ^3-1 or -(C1-C3)alkyl-R ^3-1 , and R ^3-1 is hydrogen, fluorine, chlorine, hydroxy, cyano, (C1-C3)alkyl, (C1-C3)alkoxy, -CONR ^31-1 R ^31-2 , -COOR ³² , -NHSO ₂ R 33 ^, -SO 2 R ³⁴ , -SO ₂ NR ^{35-1 R 35-2 ,} -COR ₃₆ , -NH-(C1-C3)alkyl-R ³⁷ ,

,

,

,

and

and wherein 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, -SO ₂ CH ₃ , -(C1-C3)alkyl-R ³⁰¹ and

and the above R ³⁰¹ is methylamino, dimethylamino, cyclopropyl,

and

wherein R ³⁰⁰¹ is hydrogen or (C1-C3) alkyl, R ³⁰² is fluorine, R ³⁰³ and R ³⁰⁴ may be the same or different, and are hydrogen or methyl, and R ³⁶ and R ³⁷ may be the same or different,

or

, wherein R ³⁰⁵ is (C1-C3)alkyl, 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.

,

및

중 하나이고, n은 0 내지 2 중 하나이고, Ar은

,

및

중 어느 하나이고, 상기 R³는 -R^3-1 또는 -(C1-C3)알킬-R^3-1이고, 상기 R^3-1은 수소, 플루오린, 염소, 하이드록시, 시아노, 메틸, 메톡시, -CONR^31-1R^31-2, -COOR³², -NHSO₂R³³, -SO₂R³⁴, -SO₂NR^35-1R^35-2, -COR³⁶, -NH-(C1-C2)알킬-R³⁷,

,

,

,

및

중 어느 하나이고, 상기 R^31-1 및 R^31-2은 각각 같거나 다를 수 있으며, 수소, 메틸, 이소프로필, 하이드록시, -SO₂CH₃, -(C1-C2)알킬-R³⁰¹ 및

이고, 상기 R³⁰¹은 디메틸아미노, 사이클로프로필,

및

중 어느 하나이고, 상기 R³⁰⁰¹은 메틸, 에틸 및 이소프로필 중 하나이고, 상기 R³⁰²는 플루오린이고, 상기 R³⁰³ 및 R³⁰⁴는 메틸이고, 상기 R³²는 수소, 메틸 및 -(C1-C2)알킬-디메틸아미노 중 하나이고, 상기 R³³은 메틸, 에틸, 사이클로프로필 및 트리플루오로메틸 중 하나이고, 상기 R³⁴는 하이드록시, 메틸, 에틸, 사이클로프로필 및 트리플루오로메틸 중 하나이고, 상기 R^35-1 및 R^35-2은 각각 같거나 다를 수 있으며, 수소, 메틸 및 사이클로프로필 중 하나이고, 상기 R³⁶은

또는

이고, 상기 R³⁰⁵는 메틸이고, 상기 R³⁰⁶은 아미노 또는 메틸아미노이고, 상기 R³⁷은

또는

이고, 상기 R³⁸은 메틸 또는 -CH₂CH₂OCH₃이고, 상기 R³⁹는 수소 또는 메틸일 수 있다.More preferably, in the chemical formula 1, R ¹ is any one of methyl, ethyl, isopropyl, methoxy, ethylene, trifluoromethyl (CF ₃ ), bromine (Br), cyclopropyl, cyclopentyl, cyclohexyl and NR ¹¹ R ¹² , wherein 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

wherein R ³ is -R ^3-1 or -(C1-C3)alkyl-R ^3-1 , and R ^3-1 is hydrogen, fluorine, chlorine, hydroxy, cyano, methyl, methoxy, -CONR ^31-1 R ^31-2 , -COOR ³² , -NHSO ₂ R 33, -SO ₂ R ³⁴ , -SO ² _NR ^35-1 R ^35-2 , -COR ³⁶ , -NH-(C1-C2)alkyl-R ³⁷ ,

,

,

,

and

wherein R ^31-1 and R ^31-2 may be the same or different, and are hydrogen, methyl, isopropyl, hydroxy, -SO ₂ CH ₃ , -(C1-C2)alkyl-R ³⁰¹ and

and the above R ³⁰¹ is dimethylamino, cyclopropyl,

and

wherein R ³⁰⁰¹ is one of methyl, ethyl and isopropyl, R ³⁰² is fluorine, R ³⁰³ and R ³⁰⁴ are methyl, R 32 is one of hydrogen, methyl and -(C1-C2)alkyl-dimethylamino, R ³³ is one of methyl, ethyl, cyclopropyl and trifluoromethyl, R ³⁴ is one of hydroxy, methyl, ethyl, cyclopropyl and trifluoromethyl, R ^{35-1 and R 35-2 may} be the same or different, and are one of hydrogen, methyl and cyclopropyl, and R ³⁶ is

or

, wherein R ³⁰⁵ is methyl, R ³⁰⁶ is amino or methylamino, and R ³⁷ is

or

, wherein R ³⁸ is methyl or -CH ₂ CH ₂ OCH ₃ , and R ³⁹ can be hydrogen or methyl.

Specifically, the compound represented by the chemical formula 1 may be 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)benzoate; (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-1 H -pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine; (38) 5-((2-((1 H -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)phenyl)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)-1 H -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)-1 H -pyrazol-4- yl )pyridin-2 - amine; (98) N -(1-(Cyclopropylsulfonyl)-1 H -pyrazol-4-yl)-4-((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin - 2-amine; (99) N - (1-Methyl-1 H -pyrazol-4-yl) -4 -((2-methyl-4 - phenylthiazol-5-yl)oxy)pyridin-2-amine; (100) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)- N -(1 H -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-((1 H -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-(2 H -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-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)benzamide; (184) 4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzenesulfonamide; (185) 4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzamide; (186) 2-(4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (187) 2-(5-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol; (188) N -(3-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)phenyl)ethanesulfonamide; (189) 4 -((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)- N -methylbenzamide ; (190) 6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinamide; (191) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinate; (192) 6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)nicotinic acid; (193) 6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)- N -methylnicotinamide ; (194) 3-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (195) 4-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)benzoic acid; (196) 6-((4-((2-Ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino) -N -isopropylnicotinamide; (197) (6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy ) pyridin-2-yl)amino)pyridin-3-yl)(4-methylpiperazin-1-yl)methanone; (198) (3-Aminopyrrolidin-1-yl)(6-(4-(2-ethyl-4-phenylthiazol-5-yloxy)pyridin-2-ylamino)pyridin-3-yl)methanone; (199) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)- N - ( 2-(pyrrolidin-1-yl)ethyl)nicotinamide; (200) (6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)pyridin-3-yl)(3-(methylamino)pyrrolidin-1-yl)methanone); (201) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)- N -(2-( 4 -methylpiperazin-1-yl)ethyl)nicotinamide; (202) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)- N -(2-( 4 -isopropylpiperazin-1-yl)ethyl)nicotinamide; (203) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)- N -(2-(4-ethylpiperazin-1-yl)ethyl)nicotinamide; ( 204) 5-(3-aminopyrrolidin-1-yl)- N -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)pyridin-2 - amine; (205) N ¹ -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)- N ⁴ -(2-(4 - isopropylpiperazin-1- yl )ethyl)benzene-1,4- ^{diamine ;} (206) N ¹ -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)- N ^{4 -} ( ^2- (4 - methylpiperazin-1- yl )ethyl)benzene-1,4-diamine (207) N ¹ -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)- N ⁴ -( ^2- (4 - ^{ethylpropylpiperazin} -1- yl )ethyl)benzene-1,4-diamine (208) N ¹ -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)- N ⁴ -(2-(pyrrolidin ^- 1-yl ) ethyl)benzene- ^1,4 - diamine (209) N ² -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)- N ^{5 -} ( ^2- (4 - methylpiperazin-1- yl )ethyl)pyridine-2,5-diamine (210) N ² -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2- yl )- N ⁵ -(2-(pyrrolidin ^- 1-yl)ethyl)pyridine- ^2,5 - diamine (211) N ² -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)- N ⁵ -( ^2- (4 - ethylpiperazin-1-yl)ethyl)pyridine-2,5 - ^diamine (212) N ² -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)- N ^{5 -} (2-(4 - isopropylpiperazin-1- yl )ethyl)pyridine ^- 2,5-diamine (213) N -(5-(1H-pyrazol-4-yl)pyridin-2-yl)-4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (214 ) N -(4-(3-aminopyrrolidin-1-yl)phenyl) -4 -((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (215) 4-((2-ethyl-4-phenylthiazol-5-yl)oxy)- N -(4-(3-(methylamino)pyrrolidin-1-yl) phenyl )pyridin-2-amine; (216) 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-((1 H -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-(2 H -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.

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.

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

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.

The above salt can be used in the form of either a basic salt or an acid salt acceptable from a pharmaceutical or food perspective. The basic salt can be used in the form of either an organic basic salt or an inorganic basic salt, and can be selected from the group consisting of a sodium salt, a potassium salt, a calcium salt, a lithium salt, a magnesium salt, a cesium salt, an aluminum salt, an ammonium salt, a triethylaminium salt, and a pyridinium salt.

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.

In addition, the compound may include not only the salts mentioned above, but also all salts, hydrates, solvates, derivatives, etc. that can be prepared by a conventional method. The addition salt may be prepared by a conventional method, and may 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 may be obtained by evaporating the solvent or the excess amount of base from the mixture and then drying, or the precipitated salt may be prepared by suction filtration.

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.

In addition, the composition reduces collagen accumulation in lung tissue and inhibits the infiltration and increase of inflammatory cells, and thus can be utilized for the treatment or prevention of pulmonary fibrosis.

In the present invention, the pulmonary fibrosis is interstitial pulmonary fibrosis selected from the group consisting of chronic fibrosing interstitial lung disease, rheumatoid arthritis-related interstitial lung disease, connective tissue disease-related interstitial lung disease, drug-induced interstitial lung disease, post-infectious interstitial lung disease, post-inflammatory interstitial lung disease, and systemic sclerosis-related interstitial lung disease; The pulmonary fibrosis 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, complex connective tissue disease-associated pulmonary disease, systemic lupus erythematosus-associated pulmonary disease, dermatomyositis/polymyositis-associated pulmonary disease, Sjogren's disease-associated pulmonary disease, ankylosing spondylitis-associated pulmonary disease, diffuse vasculitic pulmonary disease, hemosiderosis-associated pulmonary disease, radiation fibrosis, obliterative bronchiolitis, chronic eosinophilic pneumonia, lymphocytic infiltrative lung disease, silica-induced fibrosis, asbestos-induced fibrosis, and chemotherapy-induced pulmonary fibrosis.

Preferably, the pulmonary fibrosis is 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, 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, but is not limited thereto.

As used herein, the term "pharmaceutical composition" means a composition administered for a specific purpose, and for the purposes of the present invention, it means administered to prevent or treat pulmonary fibrosis or at least one symptom thereof.

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 according to the formulation, and, if necessary, can be prepared by further including an excipient, a diluent, a dispersant, an emulsifier, a buffer, a stabilizer, a binder, a disintegrant, a solvent, etc. The appropriate carrier, etc., does not inhibit the activity and properties of the compound according to the present invention or a pharmaceutically acceptable salt thereof, a solvate thereof, or a stereoisomer thereof, and can be selected differently according to the dosage form and formulation.

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 of an oral dosage form, an aerosol dosage form, an external preparation, a suppository, and a sterile injection solution according to a conventional method.

Among the oral dosage forms, the solid dosage form is in the form of tablets, pills, powders, granules, capsules, etc., and can be prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, sorbitol, mannitol, cellulose, gelatin, etc., and in addition to simple excipients, lubricants such as magnesium stearate and talc can 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 can be further included.

Among the oral dosage forms mentioned above, 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.

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 butter, glycerogelatin, and the like. Without being limited thereto, any suitable formulation known in the art may be used.

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

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 without causing adverse effects.

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 of the drug, the sensitivity to the drug, the method of administration, the time of administration, the route of administration and the excretion rate, the duration of treatment, the drugs being combined or used simultaneously, and other factors well known in the medical field. For example, although not constant, it may generally be administered at 0.001 to 1000 mg/kg, preferably 0.01 to 100 mg/kg, once or several times a day. The above dosage does not limit the scope of the present invention in any way.

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.

The pharmaceutical composition according to the present invention can be administered by an appropriate route of administration according to the form of the preparation, and can be administered through 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, skin application, respiratory inhalation, intrauterine epidural or intracerebroventricular injection, for example.

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).

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.

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

[Chemical Formula 1]

,

,

,

및

중 어느 하나이고, 상기 R^31-1, R^31-2, R³², R³³, R³⁴, R^35-1 및 R^35-2은 각각 같거나 다를 수 있으며, 수소, 하이드록시, 트리플루오로메틸, (C1-C5)알킬, (C3-C8)사이클로알킬, -SO₂-(C1-C3)알킬, -(C1-C3)알킬-R³⁰¹ 및

이고, 상기 R³⁰¹은 (C1-C4)알킬아미노, 디[(C1-C4)알킬]아미노, (C3-C8)사이클로알킬,

및

중 어느 하나이고, 상기 R³⁰⁰¹은 수소 또는 (C1-C5)알킬이고, 상기 R³⁰²는 할로겐이고, 상기 R³⁰³ 및 R³⁰⁴는 각각 같거나 다를 수 있으며, 수소 또는 (C1-C3)알킬이고, 상기 R³⁶ 및 R³⁷은 각각 같거나 다를 수 있으며,

또는

이고, 상기 R³⁰⁵는 수소 또는 (C1-C5)알킬이고, 상기 R³⁰⁶은 수소, 아미노, (C1-C4)알킬아미노 및 디[(C1-C4)알킬]아미노 중 어느 하나이고, 상기 R³⁸ 및 R³⁹는 각각 같거나 다를 수 있으며, 수소, (C1-C3)알킬 및 -(C1-C3)알킬-(C1-C3)알콕시 중 어느 하나일 수 있다.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, and are one of (C1-C4)alkyl, (C1-C4)alkylene, (C1-C4)alkoxy, trifluoromethyl (CF ₃ ), 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 including 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 A 5 to 10-membered heteroaryl is a (C1-C5)alkyl substituted, 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 comprising at least one heteroatom selected from the group consisting of N, O and S, wherein the substituted (C5-C10)aryl or the substituted 5 to 10-membered heteroaryl is substituted at R ³ , wherein R ³ is -R ^3-1 or -(C1-C5)alkyl-R ^3-1 , wherein R ^3-1 is hydrogen, halogen, hydroxy, cyano, (C1-C5)alkyl, (C1-C5)alkoxy, -CONR ^31-1 R ^31-2 , -COOR ³² , -NHSO ₂ R ³³ , -SO ₂ R ³⁴ , -SO ₂ NR ^35-1 R ^35-2 , -COR ³⁶ , -NH-(C1-C3)alkyl-R ³⁷ ,

,

,

,

and

and wherein 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, -SO ₂ -(C1-C3)alkyl, -(C1-C3)alkyl-R ³⁰¹ and

and the above R ³⁰¹ is (C1-C4) alkylamino, di[(C1-C4) alkyl] amino, (C3-C8) cycloalkyl,

and

wherein R ³⁰⁰¹ is hydrogen or (C1-C5)alkyl, R ³⁰² is halogen, R 303 and R ³⁰⁴ may be the same or different, and are hydrogen or (C1-C3)alkyl, ^and R ³⁶ and R ³⁷ may be the same or different,

or

, wherein R ³⁰⁵ is hydrogen or (C1-C5)alkyl, wherein R ³⁰⁶ is any one of hydrogen, amino, (C1-C4)alkylamino and di[(C1-C4)alkyl]amino, wherein 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.

The corresponding features can be replaced by those described above.

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 so that, in addition to nutritional supply, it efficiently exhibits bioregulatory functions such as prevention of pulmonary fibrosis, biodefense, immunity, and recovery for the purpose of the present invention.

In the health functional food composition according to the present invention, the health functional food can 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 can take, and it can be formulated in the same manner as the pharmaceutical composition and used as a functional food or added to various foods.

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, beverages and various drinks, fruits and processed foods thereof (canned fruits, jams, etc.), fish, meat and processed foods thereof (ham, bacon, etc.), bread 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 feed for animals may also be included.

The health functional food composition according to the present invention can be manufactured by further including food additives (food additives) and other appropriate auxiliary ingredients that are commonly used in the art and are food-relatedly acceptable. Whether or not it is suitable as a food additive can be determined by the standards and criteria for the relevant item according to the general provisions and general test methods of the Food Additives Codex approved by the Ministry of Food and Drug Safety, unless otherwise specified. The items listed in the 'Food Additives Codex' include, for example, chemical synthetic substances such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; natural additives such as persimmon pigment, licorice extract, crystalline cellulose, calciphilic pigment, and guar gum; and mixed preparations such as sodium L-glutamate preparations, alkaline agents added to noodles, preservative preparations, and tar color preparations.

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 regulators, 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.

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

The above health functional food composition has the advantage of being made from food and having no side effects that may occur with long-term use of general drugs, and is highly portable, so it can be taken as a supplement for preventing or improving pulmonary fibrosis.

Hereinafter, in order to help understand the present invention, examples will be given and described in detail. However, the following examples are only intended to illustrate the content of the present invention, and the scope of the present invention is not limited to the following examples. The examples of the present invention are provided to more completely explain the present invention to a person having average knowledge in the art.

[NMR and MS data of the compound]

(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)

¹ H-NMR (400 MHz, MeOD-d ₄ ): δ 8.20-8.21 (1H, m), 8.07 (1H, d, J = 5.6 Hz), 7.70-7.72 (2H, m), 7.60-7.64 (1H, m), 7.36-7.44 (2H, m), 7.31 (2H, t, J = 7.8 Hz), 7.23-7.24 (1H, m), 6.60 (1H, dd, J = 6.0, 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 NH ₂ were not observed. MS Calcd.: 439.51; MS Found: 440.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.26 (1H, s), 8.11 (1H, d, J = 6.0 Hz), 8.03 (1H, s), 7.85-7.83 (2H, m), 7.72 (2H, d, J = 8.0 Hz), 7.37-7.35 (3H, m), 7.33-7.22 (3H, m), 7.17 (2H, s), 6.63 (1H, dd, J = 6.0, 2.4 Hz), 6.52 (1H, d, J = 2.4 Hz). MS Calcd.: 403.46; MS Found: 404.1 (M+H ⁺ ).

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

¹ H-NMR (400 MHz, MeOD-d ₄ ): δ 8.16 (1H, t, J = 1.8 Hz), 8.04 (1H, d, J = 6.0 Hz), 7.72-7.69 (3H, m), 7.58 (1H, d, J = 7.6 Hz), 7.35-7.29 (3H, m), 7.25-7.23 (1H, m), 6.58 (1H, dd, J = 6.2, 2.2 Hz), 6.48 (1H, d, J = 2.4 Hz), 3.88 (3H, s). * Three protons from NH and NH ₂ were not observed. MS Calcd.: 418.47; MS Found: 419.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.53 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 7.77 (2H, d, J = 8.4 Hz), 7.70-7.64 (4H, m), 7.32 (2H, t, J = 7.6 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.41 (1H, s), 8.15 (1H, d, J = 6.0 Hz), 7.77-7.67 (7H, m), 7.34 (2H, t, J = 7.6 Hz), 7.23 (1H, t, J = 7.2 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.30 (1H, s), 8.69 (1H, d, J = 2.8 Hz), 8.23 (1H, d, J = 9.2 Hz), 8.10 (1H, d, J = 2.0 Hz) 8.06 (1H, d, J = 3.6) Hz) 7.70 (2H, d, J = 7.6 Hz), 7.34 (2H, t, J = 8.0 Hz), 7.24-7.21 (2H, m), 7.15 (2H, s) 6.66 (1H, dd, J = 6.0, 2.4 Hz), 6.51 (1H, d, J = 2.4 Hz). MS Calcd.: 361.42 Found: 362.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.37 (1H, s), 8.41 (1H, s), 8.26 (1H, t, J = 8.8 Hz), 8.11 (1H, d, J = 6.0 Hz), 7.71 (2H, d, J = 7.6 Hz), 7.36 (2H, t, J = 7.6 Hz), 7.26 (1H, m), 7.22 (2H, s), 7.07 (1H, dd, J = 4.4 Hz), 6.68 (1H, dd, J = 2.0 Hz), 6.28 (1H, d, J = 2.0 Hz). MS Calcd.: 379.41 Found: 380.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.57 (1H, s), 8.26 (2H, d, J = 6.4 Hz), 8.18 (1H, d, J = 6.0 Hz), 7.69 (2H, d, J = 7.2 Hz), 7.59 (2H, d, J = 6.4) Hz), 7.34 (2H, t, J = 8.0 Hz), 7.23-7.19 (1H, t, J = 7.2 Hz), 7.17 (s, 2H), 6.75 (1H, dd, J = 6.0, 3.6 Hz), 6.58 (1H, d, J = 3.6 Hz). MS Calcd.: 361.42 Found: 362.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.1 (1H, s), 8.66 (1H, d, J = 2.4 Hz), 8.17 (1H, d, J = 6.0 Hz), 8.07 (1H, dd, J = 8.8, 2.4 Hz), 7.88 (1H, brs), 7.75 (1H, d, J = 8.8 Hz), 7.69 (2H, d, J = 7.2 Hz), 7.59 (1H, s), 7.33-7.29 (3H, m), 7.22 (1H, t, J = 7.6 Hz), 7.13 (2H, s), 6.71 (1H, dd, J = 6.0, 2.4 Hz). MS Calcd.: 404.45 Found: 405.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, MeOH-D ₄ ): δ 8.04 (1H, d, J = 6.0 Hz), 7.70 (3H, d, J = 7.6 Hz), 7.63 (1H, s), 7.50 (1H, d, J = 8.0 Hz), 7.32 (4H, t, J = 8.4 Hz), 7.24 (1H, d, J = 7.2 Hz), 6.95 (1H, d, J = 7.6 Hz), 6.57 (1H, dd, J = 10.0, 2.4 Hz), 6.47 (1H, d, J = 2.0 Hz), 3.08 (3H, s), 3.00 (3H, s). * one proton from NH was not observed. MS Calcd.: 431.51 Found: 432.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.66 (1H, s), 8.71 (1H, d, J = 2.0 Hz), 8.36 (1H, d, J = 8.8 Hz), 8.17 (1H, d, J = 5.6 Hz), 7.91 (1H, d, J = 8.8 Hz), 7.85 (1H, s), 7.69 (2H, d, J = 7.6 Hz), 7.37 (1H, s), 7.34 (2H, t, J = 7.2 Hz), 7.23 (1H, d, J = 7.2 Hz), 7.17 (2H, s), 7.74 (1H, d, J = 8.0 Hz), 6.57 (1H, s). MS Calcd.: 404.45 Found: 405.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.48 (1H, s), 8.14 (1H, s), 8.12 (1H, d, J = 5.6 Hz), 7.85 (1H, d, J = 7.6 Hz), 7.69 (2H, d, J = 8.0 Hz), 7.44 (1H, t, J = 8.0 Hz), 7.36-7.30 (3H, m), 7.23 (2H, d, J = 7.2 Hz), 7.16 (2H, s), 6.68 (1H, dd, J = 5.6, 2.0 Hz), 6.51 (1H, d, J = 2.0 Hz), 2.39 (3H, d, J = 5.2 Hz). MS Calcd.: 453.54 Found: 454.1 (M+H ⁺ ).

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.63 (1H, s), 9.18 (1H, s), 8.06 (1H, d, J = 6.0 Hz), 7.69 (2H, d, J = 7.2 Hz), 7.46-7.44 (2H, m), 7.34 (2H, t, J = 7.2 Hz), 7.23 (1H, t, J = 7.6 Hz), 7.15-7.11 (3H, m), 6.70 (1H, d, J = 9.2 Hz), 6.61 (1H, dd, J = 6.0, 2.4 Hz), 6.50 (1H, d, J = 1.6 Hz), 2.94 (3H, s). MS Calcd.: 453.54 Found: 454.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.55 (1H, s), 8.27 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 7.91 (1H, d, J = 9.2 Hz), 7.69 (2H, d, J = 7.2 Hz), 7.50 (1H, t, J = 8.0 Hz), 7.38-7.30 (3H, m), 7.23 (1H, t, J = 7.6 Hz), 7.16 (2H, s), 6.69 (1H, dd, J = 6.0, 2.4 Hz), 6.52 (1H, d, J = 2.0 Hz), 3.14 (3H, s). MS Calcd.: 438.52 Found: 439.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.60 (1H, s), 9.17 (1H, s), 8.06 (1H, d, J = 5.6 Hz), 7.69 (2H, d, J = 7.2 Hz), 7.52 (1H, s), 7.44 (1H, d, J = 8.4 Hz), 7.34 (2H, t, J = 7.2 Hz), 7.23 (1H, t, J = 7.6 Hz), 7.14-7.10 (3H, m), 6.72 (1H, d, J = 9.2 Hz), 6.60 (1H, dd, J = 5.6, 2.0 Hz), 6.50 (1H, d, J = 1.6 Hz), 2.57 (1H, q, J = 4.8 Hz), 0.93-0.83 (4H, m). MS Calcd.: 479.57 Found: 480.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.79 (1H, s), 8.64 (1H, s), 8.18 (1H, d, J = 6.0 Hz), 8.07 (1H, d, J = 7.2 Hz), 7.69-7.65 (3H, m), 7.55 (1H, d, J = 7.2 Hz), 7.34 (2H, t, J = 7.6 Hz), 7.23 (1H, d, J = 7.2 Hz), 7.18 (2H, s), 6.74 (1H, dd, J = 6.0, 4.0 Hz), 6.53 (1H, d, J = 5.6 Hz). MS Calcd.: 492.49 Found: 493.0 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.21 (1H, s), 8.07 (1H, d, J = 5.2 Hz), 7.69 (3H, d, J = 7.6 Hz), 7.57 (1H, s), 7.34 (2H, t, J = 7.2 Hz), 7.21-7.25 (2H, m), 7.14 (2H, s), 6.90 (1H, d, J = 8.0 Hz), 6.61 (1H, dd, J = 6.0, 3.6 Hz), 4.38 (2H, s), 2.88 (3H, s). MS Calcd.: 452.5 Found: 453.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.48 (1H, s), 8.19 (1H, s), 8.12 (1H, d, J = 5.6 Hz), 7.84 (2H, m), 7.69 (2H, d, J = 7.6 Hz), 7.42 (1H, t, J = 7.6 Hz), 7.34 (2H, t, J = 7.6 Hz), 7.27-7.21 (2H, m), 7.16 (2H, s), 6.67 (1H, d, J = 3.6 Hz), 6.51 (1H, s), 2.06 (1H, m), 0.45-0,44 (2H, m), 0.37 (2H, m). MS Calcd.: 479.11 Found: 480.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 7.84 (1H, d, J = 6.0 Hz), 7.62 (2H, d, J = 7.2 Hz), 7.30-7.22 (4H, m), 7.07 (1H, d, J = 7.6 Hz), 7.00 (1H, d, J = 9.6 Hz), 6.92 (1H, t, J = 7.6 Hz), 6.39 (1H, dd, J = 6.0, 2.0 Hz), 6.12 (1H, d, J = 2.0 Hz), 4.15 (2H, s). * Three protons from NH and NH ₂ were not observed. MS Calcd.:392.45 Found: 393.1 (M+H ⁺ ).

(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)

^1H -NMR (400 MHz, DMSO-d ₆ ): δ 9.92 (1H, s), 8.24 (1H, d, J = 5.2 Hz), 8.15 (1H, d, J = 5.6 Hz), 8.06 (2H, d, J = 6.4Hz), 7.69 (2H, d, J = 7.2 Hz), 7.60 (1H, s), 7.55 (1H, s), 7.33 (2H, t, J = 7.6 Hz), 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.25 (1H, s), 8.31-8.28 (1H, m), 8.09 (1H, d, J = 6.0 Hz), 7.98 (1H, s), 7.81 (1H, s), 7.69 (2H, d, J = 7.2 Hz), 7.32 (2H, t, J = 7.6 Hz), 7.27 (2H, d, J = 5.2 Hz), 7.22 (1H, t, J = 7.4 Hz), 7.15 (2H, s), 6.61 (1H, dd, J = 6.0, 2.4 Hz), 6.50 (1H, d, J = 2.0 Hz), 2.73 (3H, d, J = 4.4 Hz). MS Calcd.: 417.48; MS Found: 418.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.53 (1H, s), 8.17 (1H, d, J = 6.0 Hz), 7.86 (1H, d, J = 5.6 Hz), 7.68 (2H, d, J = 7.6 Hz), 7.32 (3H, t, J = 7.6) Hz), 7.22 (1H, t, J = 7.4 Hz), 7.17 (2H, s), 6.98 (1H, dd, J = 5.2, 2.0 Hz), 6.74 (1H, dd, J = 6.0, 2.0 Hz), 6.56 (1H, d, J = 2.4 Hz). 3.76 (3H, s). MS Calcd.: 391.45; MS Found: 392.1 (M+H ⁺ ).

(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)

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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.43 (2H, d, J = 5.6 Hz), 7.85 (1H, d, J = 5.6 Hz), 7.67 (2H, d, J = 7.2 Hz), 7.33-7.29 (3H, m), 7.23-7.21 (3H, m), 7.09 (2H, s), 6.34 (1H, dd, J = 5.6, 2.0 Hz), 6.22 (1H, d, J = 2.0 Hz), 4.44 (2H, d, J = 6.0 Hz). MS Calcd.: 375.45 Found: 376.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, MeOH-d ₄ ): δ 8.20 (1H, d, J = 5.6 Hz), 8.00 (1H, d, J = 6.0 Hz), 7.94 (1H, d, J = 1.6 Hz), 7.70 (2H, d, J = 8.0 Hz), 7.43 (1H, dd, J = 6.0, 2.0 Hz), 7.30 (2H, t, J = 7.6 Hz), 7.22 (1H, t, J = 7.6 Hz), 6.74 (1H, dd, J = 6.2, 2.2 Hz), 6.56 (1H, d, J = 2.0 Hz). * Three protons from NH and NH2 were not observed. MS Calcd.: 395.87; MS Found: 396.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, MeOH-d ₄ ): δ 8.46 (1H, s), 8.38 (1H, d, J = 4.4 Hz), 7.85 (1H, d, J = 5.6 Hz), 7.75 (1H, d, J = 7.6 Hz), 7.65 (2H, d, J = 7.6) Hz), 7.35 (1H, dd, J = 8.0, 5.2 Hz), 7.31 (2H, t, J = 8.8 Hz), 7.24 (1H, t, J = 10.0 Hz), 6.38 (1H, dd, J = 6.0, 2.4 Hz), 6.17 (1H, d, J = 2.4 Hz), 4.50 (2H, s). * Three protons from NH and NH ₂ were not observed. MS Calcd.: 375.45; MS Found: 376.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.21 (1H, brs), 8.06 (1H, d, J = 6.0 Hz), 7.69 (3H, d, J = 7.6 Hz), 7.51 (1H, s), 7.34 (2H, t, J = 7.2 Hz), 7.23-7.19 (2H, m), 7.14 (2H, brs), 6.87 (1H, d, J = 7.6 Hz), 6.80 (2H, s), 6.60 (1H, d, J = 6.0 Hz), 6.52 (1H, d, J = 2.0 Hz), 4.16 (2H, s). MS Calcd.: 453.54 Found: 454.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.91 (1H, s), 8.23 (1H, d, J = 6.0 Hz), 7.91 (1H, d, J = 5.6 Hz), 7.68 (2H, d, J = 7.6 Hz), 7.61 (1H, s), 7.33 (2H, t, J = 7.2 Hz), 7.23 (2H, d, J = 7.2 Hz), 7.17 (2H, s), 6.80 (1H, d, J = 6.0 Hz), 6.60 (1H, d, J = 2.4 Hz). MS Calcd.: 379.41 Found: 380.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.01 (1H, s), 8.31 (1H, d, J = 2.8 Hz), 8.02 (1H, d, J = 6.0 Hz), 7.94 (1H, dd, J = 8.8, 2.4 Hz), 7.69 (2H, d, J) = 7.2 Hz), 7.34 (2H, t, J = 7.2 Hz), 7.21 (1H, t, J = 7.2 Hz), 7.13 (2H, s), 6.72 (1H, d, J = 8.8 Hz), 6.56 (1H, d, J = 6.0 Hz), 6.39 (1H, s), 3.76 (3H, s). MS Calcd.: 391.45 Found: 392.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.46 (1H, s), 8.82 (1H, d, J = 2.4 Hz), 8.53 (2H, d, J = 9.2 Hz), 8.14 (1H, d, J = 6.0 Hz), 8.04 (1H, s), 7.70 (2H, d, J = 8.0 Hz), 7.51 (1H, s), 7.34 (2H, t, J = 7.2 Hz), 7.23 (1H, t, J = 7.6 Hz), 7.17 (2H, s), 6.69 (1H, dd, J = 6.0, 2.4 Hz), 6.53 (1H, d, J = 2.0 Hz). MS Calcd.: 404.45 Found: 405.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.89 (1H, s), 8.16 (1H, d, J = 5.6 Hz), 7.96 (1H, d, J = 8.4 Hz), 7.82 (1H, t, J = 7.2 Hz), 7.69 (2H, d, J = 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.55 (1H, s), 8.22 (1H, s), 8.14 (1H, d, J = 6.4 Hz), 7.93 (1H, d, J = 8.0 Hz), 7.69 (2H, d, J = 7.2 Hz), 7.50 (1H, t, J = 8.0 Hz), 7.34 (3H, t, J = 7.6 Hz), 7.23 (1H, t, J = 7.6 Hz), 7.15 (2H, s), 6.69 (1H, dd, J = 5.6, 2.4 Hz) , 6.52 (1H, d, J = 2.0 Hz), 3.22 (2H, q, J = 7.6 Hz), 1.90 (3H, t, J = 7.2 Hz). MS Calcd.: 425.55 Found: 453.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.46 (1H, s), 8.57 (1H, d, J = 2.8 Hz), 8.22 (1H, d, J = 8.4 Hz), 8.12, (1H, d, J = 5.6 Hz), 7.69 (2H, d, J = 7.2 Hz), 7.36-7.30 (3H, m), 7.21 (1H, m), 7.16 (2H, s), 6.70 (1H, dd, J = 8.4, 2.4 Hz), 6.50 (1H, d, J = 1.6 Hz). MS Calcd.: 395.87 Found: 396.0 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.35 (1H, brs), 8.08 (1H, d, J = 5.6 Hz), 7.68 (2H, d, J = 7.2 Hz), 7.63 (1H, s), 7.54 (1H, d, J = 8.0 Hz), 7.33 (2H, t, J = 7.8 Hz), 7.22-7.26 (3H, m), 6.76 (1H, d, J = 8.0 Hz), 6.65 (1H, d, J = 6.0 Hz), 6.52 (1H, s). * Two protons from NH were not observed. MS Calcd.: 507.51; MS Found: 508.1 (M+H+).

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

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.85 (1H, s), 8,01 (1H, d, J = 6.0 Hz), 7.84 (1H, s), 7.68 (2H, d, J = 7.2 Hz), 7.33-7.28 (3H, m), 7.22 (1H, t, J = 7.2 Hz), 7.12 (2H, s), 6.45 (1H, dd, J = 5.6, 2.0 Hz), 6.28 (1H, d, J = 2.4 Hz), 3.74 (3H, s). MS Calcd.: 364.42 Found: 365.1 (M+H ⁺ ).

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

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 12.4 (1H, brs), 8.94 (1H, s), 8.00 (1H, d, J = 6.0 Hz), 7.68 (3H, d, J = 7.2 Hz), 7.32 (3H, t, J = 7.6 Hz), 7.21 (1H, t, J = 7.2 Hz), 7.12 (2H, s), 6.44 (1H, dd, J = 6.0, 2.0 Hz), 6.28 (1H, d, J = 1.6 Hz). MS Calcd.: 350.40; MS Found: 351.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 12.4 (1H, brs), 9.55 (1H, s), 8.17 (1H, d, J = 5.6 Hz), 7.82 (2H, d, J = 8.4 Hz), 7.76-7.70 (4H, m), 7.35 (2H, t, J = 7.6 Hz), 7.26-7.22 (1H, m), 7.18 (2H, s), 6.72 (1H, dd, J = 6.0, 2.4 Hz), 6.59 (1H, d, J = 2.4 Hz). MS Calcd.: 404.44; MS Found: 405.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, MeOD-d ₄ ): δ 9.14 (1H, s), 8.09 (1H, d, J = 5.6 Hz), 7.78 (1H, d, J = 8.8 Hz), 7.71 (2H, d, J = 8.0 Hz), 7.40-7.33 (3H, m), 7.24 (2H, t, J = 7.6 Hz), 7.16 (2H, s), 6.59 (1H, d, J = 4.0 Hz), 6.51 (1H, d, J = 2.4 Hz). * Two protons from NH and OH were not observed. MS Calcd.: 404.44; MS Found: 405.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.08 (1H, d, J = 6.0 Hz), 7.74 (2H, d, J = 8.0 Hz), 7.38 (1H, s), 7.34-7.29 (3H, m), 7.26-7.25 (1H, m), 7.13 (1H, d, J = 8.0 Hz), 7.09 (1H, d, J = 8.0 Hz), 6.70 (1H, s), 6.59 (1H, d, J = 1.6 Hz), 6.54 (1H, dd, J = 5.4, 2.2 Hz), 4.83 (1H, s), 1.55 (6H, s). * A protons from OH was not observed. MS Calcd.: 418.51; MS Found: 419.2(M+H ⁺ ).

(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)

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

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.06 (1H, s), 8.17 (1H, d, J = 1.2 Hz), 8.08 (1H, d, J = 5.6 Hz), 7.73 (2H, dd, J = 8.4, 1.2 Hz), 7.64-7.62 (1H, m), 7.51 (1H, t, J = 2.0 Hz), 7.36 (2H, t, J = 7.6 Hz), 7.27-7.22 (1H, m), 7.15 (1H, t, J = 8.0 Hz), 6.97 (1H, d, J = 8.4 Hz), 6.59 (1H, dd, J = 5.8, 2.2 Hz), 6.51 (1H, d, J = 2.4 Hz), 4.92 (1H, s), 2.60-2.52 (1H, m), 0.75-0.73 (2H, m), 0.57-0.55 (2H, m). MS Calcd.: 458.58; MS Found: 459.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, CDCl ₃ ): δ 9.14 (1H, d, J = 5.6 Hz), 7.93 (1H, t, J = 1.6 Hz), 7.72 (2H, d, J = 8.0 Hz), 7.52-7.43 (1H, m), 7.42-7.39 (2H, m), 7.33-7.29 (2H, m), 7.26-7.23 (1H, m), 6.78 (1H, brs), 6.66 (1H, dd, J = 6.0, 2.0 Hz), 6.53 (1H, d, J = 2.0 Hz), 5.66 (1H, s), 4.94 (2H, s), 2.68-2.61 (1H, m), 0.82-0.73 (2H, m), 0.74-0.71 (2H, m). MS Calcd.: 479.57; MS Found: 480.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.24 (1H, s), 8.18 (1H, s), 8.12 (1H, d, J = 6.0 Hz), 8.02 (1H, s), 7.84-7.82 (2H, m), 7.73 (2H, d, J = 7.2 Hz), 7.38-7.34 (3H, m), 7.31-7.25 (3H, m), 6.64 (1H, dd, J = 5.6, 2.4 Hz), 6.52 (1H, d, J = 2.0 Hz), 2.60-2.52 (1H, m), 0.77-0.73 (2H, m), 0.58-0.54 (2H, m). MS Calcd.: 443.52; MS Found: 444.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.40 (1H, s), 8.19 (1H, d, J = 1.6 Hz), 8.16 (1H, d, J = 6.0 Hz), 7.80-7.73 (5H, m), 7.69 (2H, d, J = 8.4 Hz), 7.36 (2H, t, J = 7.4 Hz), 7.28-7.24 (1H, m), 7.11 (1H, brs), 6.70 (1H, dd, J = 5.8, 2.2 Hz), 6.56 (1H, d, J = 2.4 Hz), 2.60-2.55 (1H, m), 0.77-0.72 (2H, m), 0.58-0.55 (2H, m). MS Calcd.: 443.52; MS Found: 444.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.33 (1H, s), 8.24 (1H, s), 8.18 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 7.89 (1H, d, J = 9.2 Hz), 7.73 (1H, d, J = 8.0 Hz), 7.45 (1H, d, J = 8.0 Hz), 7.38-7.33 (2H, m), 7.28-7.24 (1H, m), 6.67 (1H, dd, J = 7.8, 1.0 Hz), 6.52 (1H, d, J = 1.6 Hz), 2.69-2.64 (1H, m), 0.77-0.71 (2H, m), 0.58-0.54 (2H, m). * Three protons from NH and OH were not observed. MS Calcd.: 444.51; MS Found: 445.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, MeOH-d ₄ ): 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 NH ₂ and OH were not observed. MS Calcd.: 444.51; MS Found: 445.2 (M+H ⁺ ).

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.45 (1H, s), 8.20 (1H, t, J = 2.0 Hz), 8.13 (1H, d, J = 6.0 Hz), 7.81 (1H, d, J = 8.0 Hz), 7.77-7.74 (2H, m), 7.69 (1H, d, J = 4.4 Hz), 7.43-7.36 (4H, m), 7.34-7.25 (2H, m), 6.69-6.67 (1H, m), 6.53 (1H, d, J = 2.4 Hz), 2.89 (3H, d, J = 4.8 Hz). * A proton form NH was not observed. MS Calcd.: 453.54; MS Found: 454.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.24 (s, 1H), 8.11 (d, J = 6.0 Hz, 1H), 8.02 (s, 1H), 7.83-7.81 (m, 2H), 7.76 (d, J = 7.2 Hz, 2H), 7.68-7.67 (m, 1H), 7.37-7.32 (m, 3H), 7.28-7.25 (m, 3H), 6.63 (dd, J = 1.6 Hz, 5.6 Hz, 1H), 6.51 (d, J = 2.0 Hz, 1H), 2.88 (d, J = 5.2 Hz, 3H). MS Calcd.: 417.48; MS Found: 418.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.53 (1H, s), 8.16 (1H, d, J = 5.6 Hz), 7.80-7.74 (4H, m), 7.69-7.65 (3H, s), 7.36 (2H, t, J = 7.2 Hz), 7.26-7.24 (1H, m), 7.12 (2H, m), 6.73-6.72 (1H, m), 6.57 (1H, s), 2.89 (3H, d, J = 4.8 Hz). MS Calcd.: 453.54; MS Found: 454.1 (M+H ⁺ ).

(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)

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

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 12.43 (1H, s), 9.51 (1H, s), 8.17 (1H, d, J = 5.6 Hz), 7.80 (2H, d, J = 8.8 Hz), 7.76-7.70 (4H, m), 7.69-7.67 (1H, m), 7.35 (2H, t, J = 7.6 Hz), 7.25 (1H, t, J = 7.6 Hz), 6.72 (1H, dd, J = 2.4 Hz, 5.8 Hz), 6.58 (1H, d, J = 2.4 Hz), 2.89 (3H, d, J = 4.8 Hz). MS Calcd.: 418.47; MS Found: 419.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.32 (1H, s), 8.25 (1H, s), 8.13 (1H, d, J = 5.2 Hz), 7.88 (1H, d, J = 8.4 Hz), 7.75 (2H, d, J = 7.6 Hz), 7.68 (1H, d, J = 4.8 Hz), 7.44 (1H, d, J = 8.0 Hz), 7.37-7.26 (3H, m), 7.25 (1H, t, J = 7.4 Hz), 6.66 (1H, dd, J = 2.4 Hz, 6.0 Hz), 6.51 (1H, d, J = 2.0 Hz), 2.89 (3H, d, J = 4.8 Hz). * A proton form OH was not observed. MS Calcd.: 418.47; MS Found: 419.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.45 (1H, s), 8.18 (1H, s), 8.16 (1H, d, J = 6.0 Hz), 7.84-7.79 (3H, m), 7.42 (3H, t, J = 7.8 Hz), 7.33 (2H, d, J = 7.6 Hz), 7.30 (2H, s), 6.70 (1H, dd, J = 6.0, 2.4 Hz), 6.47 (1H, d, J = 1.6 Hz), 2.71 (3H, s). MS Calcd.: 438.52; MS Found: 439.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.29 (1H, d, J = 5.6 Hz), 8.21 (1H, d, J = 6.0 Hz), 7.85 (2H, d, J = 7.6 Hz), 7.36 (2H, t, J = 7.6 Hz), 7.30-7.29 (2H, m), 7.17-7.16 (1H, m), 6.81 (1H, brs), 6.68 (1H, dd, J = 5.6, 2.0 Hz), 6.52 (1H, s), 2.70 (3H, s), 1.49 (6H, s). * A proton from OH was not observed. MS Calcd.: 418.51; MS Found: 419.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.23 (1H, s), 8.13 (1H, d, J = 5.2 Hz), 8.02 (1H, s), 7.85-7.79 (4H, m), 7.42 (2H, t, J = 7.6 Hz), 7.35 (1H, t, J = 7.8 Hz), 7.33-7.27 (3H, m), 6.65 (1H, dd, J = 5.8, 2.2 Hz), 6.45 (1H, d, J = 2.0 Hz), 2.70 (3H, s). MS Calcd.: 402.47; MS Found: 403.1 (M+H ⁺ ).

(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)

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

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

¹ H-NMR (400 MHz, MeOH-d ₄ ): δ 8.46 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.82 (1H, s), 7.70 (2H, d, J = 7.6 Hz), 7.30 (2H, t, J = 8.0 Hz), 7.22.7.20 (1H, m), 6.55 (1H, dd, J = 5.6, 2.0 Hz), 6.36 (1H, d, J = 2.0 Hz), 3.28 (3H, s). * Three protons from NH and NHBoc were not observed. MS Calcd.: 428.49 Found: 429.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, CDCl ₃ ): δ 9.38 (1H, s), 8.17 (1H, d, J = 5.6 Hz), 7.82 (2H, d, J = 6.8 Hz), 7.77-7.75 (3H, m), 7.67 (2H, d, J = 8.8 Hz), 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.52 (1H, s), 8.19 (1H, d, J = 6.0 Hz), 7.82 (2H, d, J = 6.8 Hz), 7.77 (2H, d, J = 8.8 Hz), 7.67 (2H, d, J = 9.2 Hz), 7.41 (2H, t, J = 7.2 Hz), 7.33-7.31 (1H, m), 7.13 (2H, s), 6.74 (1H, dd, J = 2.4 Hz, 6.0 Hz), 6.50 (1H, d, J = 2.4 Hz), 2.70 (3H, s). MS Calcd.: 438.52; MS Found: 439.1 (M+H ⁺ ).

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.14 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.81 (2H, d, J = 7.2 Hz), 7.65 (1H, d, J = 7.2 Hz), 7.42-7.39 (3H, m), 7.33-7.31 (1H, m), 7.18 (1H, t, J = 12.0 Hz), 6.87 (1H, d, J = 8.0 Hz), 6.63 (1H, dd, J = 2.4 Hz, 6.0 Hz), 6.43 (1H, d, J = 2.4 Hz), 2.69 (3H, s), 1.43 (6H, s). * A proton from OH was not observed. MS Calcd.: 445.53; MS Found: 446.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.22 (1H, s), 8.12 (1H, d, J = 5.6 Hz), 7.80 (2H, d, J = 6.8 Hz), 7.74 (1H, s), 7.54 (1H, d, J = 7.6 Hz), 7.39 (2H, t, J = 7.8 Hz), 7.31-7.24 (2H, m), 6.85 (1H, d, J = 7.2 Hz), 6.65 (1H, dd, J = 6.2, 2.2 Hz), 6.41 (1H, d, J = 2.0 Hz), 2.94 (3H, s), 2.88 (3H, s), 2.68 (3H, s). MS Calcd.: 430.52; MS Found: 431.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.15 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.81-7.78 (3H, m), 7.63 (1H, d, J = 8.4 Hz), 7.40 (2H, t, J = 7.8 Hz), 7.29 (1H, t, J = 7.4 Hz), 7.17-7.09 (2H, m), 6.60 (1H, dd, J = 6.0, 2.4 Hz), 6.42 (1H, d, J = 2.4 Hz), 2.68 (3H, s). * A proton from OH was not observed. MS Calcd.: 439.51; MS Found: 440.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.24 (1H, s), 8.32-8.28 (1H, m), 8.11 (1H, d, J = 5.2 Hz), 7.98 (1H, s), 7.81-7.78 (3H, m), 7.39 (2H, t, 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.53 (1H, s), 8.26 (1H, s), 8.17 (1H, d, J = 6.0 Hz), 7.88 (1H, d, J = 9.2 Hz), 7.80 (2H, d, J = 7.2 Hz), 7.49 (1H, d, J = 8.0 Hz), 7.41-7.37 (3H, m), 7.30 (1H, t, J = 7.4 Hz), 6.71 (1H, dd, J = 5.6, 2.0 Hz), 6.45 (1H, d, J = 2.4 Hz), 3.14 (3H, s), 2.69 (3H, s). MS Calcd.: 437.53; MS Found: 438.0 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.64 (1H, s), 9.16 (1H, s), 8.09 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.2 Hz), 7.45-7.41 (2H, m), 7.39 (2H, t, J = 7.8 Hz), 7.30 (1H, t, J = 5.2 Hz), 7.14 (1H, t, J = 8.4 Hz), 6.70 (1H, d, J = 8.0 Hz), 6.62 (1H, dd, J = 3.8, 1.8 Hz), 6.43 (1H, d, J = 2.4 Hz), 2.94 (3H, s), 2.68 (3H, s). MS Calcd.: 452.55; MS Found: 453.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.97 (1H, s), 8.83 (1H, s), 8.20 (1H, d, J = 5.6 Hz), 8.04 (1H, d, J = 8.8 Hz), 7.80 (2H, d, J = 8.0 Hz), 7.68 (1H, t, J = 8.0 Hz), 7.56 (1H, d, J = 7.6 Hz), 7.39 (2H, t, J = 7.8 Hz), 7.17 (1H, t, J = 7.8 Hz), 6.77 (1H, dd, J = 5.6, 2.4 Hz), 6.46 (1H, d, J) = 2.0 Hz), 2.69 (3H, s). MS Calcd.: 491.51; MS Found: 492.0 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.46 (1H, s), 8.15-8.14 (2H, m), 7.83-7.79 (3H, m), 7.45-7.35 (4H, m), 7.31 (1H, t, J = 3.8 Hz), 7.23 (1H, d, J = 8.4 Hz), 6.69 (1H, d, J = 6.0 Hz), 6.44 (1H, d, J = 2.4 Hz), 2.68 (3H, s), 2.39 (3H, d, J = 4.8 Hz). MS Calcd.: 452.55; MS Found: 453.1 (M+H ⁺ ).

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.61 (1H, s), 9.15 (1H, s), 8.09 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.50 (1H, s), 7.44-7.37 (3H, m), 7.29 (1H, t, J = 7.4 Hz), 7.13 (1H, t, J = 8.2 Hz), 6.72 (1H, d, J = 8.4 Hz), 6.62 (1H, dd, J = 5.8, 2.2 Hz), 6.43 (1H, d, J = 2.4 Hz), 2.68 (3H, s), 2.58-2.54 (1H, m), 0.93-0.89 (4H, m). MS Calcd.: 478.59; MS Found: 479.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.47 (1H, s), 8.18 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 7.84-7.79 (3H, m), 7.45-7.37 (3H, m), 7.31-7.26 (2H, m), 6.69 (1H, dd, J = 6.2, 2.2 Hz), 6.44 (1H, d, J = 2.0 Hz), 2.68 (3H, s), 2.10-2.06 (1H, m), 0.46-2.43 (2H, m), 0.39-0.37 (2H, m). * A proton from NH was not observed. MS Calcd.: 478.59; MS Found: 479.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.60 (1H, s), 8.38 (1H, s), 8.16 (1H, d, J = 5.2 Hz), 7.90 (1H, d, J = 9.6 Hz), 7.80 (2H, d, J = 7.2 Hz), 7.49 (1H, t, J = 8.0 Hz), 7.39 (2H, t, J = 7.4 Hz), 7.32 (2H, t, J = 9.2 Hz), 6.71 (1H, d, J = 5.6 Hz), 6.45 (1H, s), 3.22 (2H, q, J = 5.9 Hz), 2.69 (3H, s), 1.08 (3H, t, J = 7.4 Hz). MS Calcd.: 438.52 Found: 439.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.16 (1H, s), 8.09 (1H, d, J = 7.6 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.68 (1H, d, J = 8.4 Hz), 7.55 (1H, s), 7.39 (2H, t, J = 7.8 Hz), 7.30 (1H, t, J = 6.0 Hz), 7.21 (1H, t, J = 7.8 Hz), 6.90 (1H, d, J = 7.6 Hz), 6.62 (1H, dd, J = 6.0, 2.4 Hz) , 6.44 (1H, d, J) = 2.4 Hz), 4.17 (2H, s), 2.68 (3H, s). * Two protons from NH ₂ were not observed. MS Calcd.: 452.55; MS Found: 453.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.19 (1H, s), 8.09 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.67 (1H, d, J = 8.0 Hz), 7.59 (1H, s), 7.39 (2H, t, J = 7.8 Hz), 7.29 (1H, t, J = 7.8 Hz), 7.23 (1H, t, J = 7.8 Hz), 6.90 (1H, d, J = 7.6 Hz), 6.62 (1H, dd, J = 6.0, 2.4 Hz), 6.44 (1H, d, J) = 2.4 Hz), 4.39 (2H, s), 2.89 (3H, s), 2.68 (3H, s). MS Calcd.: 451.56; MS Found: 452.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.43 (2H, d, J = 5.6 Hz), 7.87 (1H, d, J = 6.0 Hz), 7.78 (2H, d, J = 7.2 Hz), 7.38 (2H, t, J = 7.4 Hz), 7.32-7.28 (2H, m), 7.22 (2H, d, J = 5.6 Hz), 6.35 (1H, dd, J = 6.0, 2.4 Hz), 6.16 (1H, d, J = 2.0 Hz), 4.44 (2H, d, J = 6.0 Hz), 2.65 (3H, s). MS Calcd.: 374.46; MS Found: 375.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.47 (1H, s), 8.40 (1H, d, J = 3.2 Hz), 7.91 (1H, d, J = 5.6 Hz), 7.78 (2H, d, J = 7.2 Hz), 7.64 (1H, d, J = 7.6) Hz), 7.38 (2H, t, J = 7.4 Hz), 7.29 (2H, t, J = 6.6 Hz), 7.24 (1H, t, J = 5.8 Hz), 6.35 (1H, dd, J = 6.0, 2.4 Hz), 6.14 (1H, d, J = 2.4 Hz), 4.43 (2H, d, J = 6.0 Hz), 2.65 (3H, s). MS Calcd.: 374.46; MS Found: 375.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.33 (1H, s), 8.39 (1H, s), 8.21 (1H, t, J = 6.6 Hz), 8.11 (1H, d, J = 5.2 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.39 (2H, t, J = 7.8 Hz), 7.30 (1H, t, J = 7.8 Hz), 7.06 (1H, dd, J = 9.2, 3.2 Hz), 6.68 (1H, dd, J = 5.8, 2.2 Hz), 6.39 (1H, d, J = 2.0 Hz), 2.68 (3H, s). MS Calcd.: 378.42; MS Found: 379.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.45 (1H, s), 8.57 (1H, d, J = 3.2 Hz), 8.19 (1H, dd, J = 8.6, 2.6 Hz), 8.14 (1H, d, J = 6.0 Hz), 7.80 (2H, 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.00 (1H, s), 8.30 (1H, d, J = 2.4 Hz), 8.04 (1H, d, J = 6.4 Hz), 7.93 (1H, dd, J = 9.0, 2.2 Hz), 7.80 (2H, d, J) = 8.0 Hz), 7.40 (2H, t, J = 7.8 Hz), 7.30 (1H, t, J = 7.4 Hz), 6.72 (1H, d, J = 8.8 Hz), 6.58 (1H, d, J = 5.6 Hz), 6.32 (1H, d, J = 1.6 Hz), 3.77 (3H, s), 2.67 (3H, s). MS Calcd.: 390.46; MS Found: 391.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.56 (1H, s), 8.26 (2H, brs), 8.21 (1H, d, J = 5.6 Hz), 7.79 (2H, d, J = 7.6 Hz), 7.59 (2H, s), 7.39 (2H, 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.89 (1H, s), 8.25 (1H, d, J = 5.6 Hz), 7.92 (1H, d, J = 6.0 Hz), 7.79 (2H, d, J = 8.0 Hz), 7.61 (1H, d, J = 1.6) Hz), 7.39 (2H, t, J = 7.6 Hz), 7.30 (1H, t, J = 8.0 Hz), 7.22 (1H, d, J = 6.0 Hz), 6.84 (1H, dd, J = 5.8, 2.2 Hz), 6.52 (1H, d, J = 2.0 Hz), 2.69 (3H, s). MS Calcd.: 378.42; MS Found: 379.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.51 (1H, s), 8.20 (1H, d, J = 5.6 Hz), 7.86 (1H, d, J = 6.0 Hz), 7.79 (2H, d, J = 7.6 Hz), 7.39 (2H, t, J = 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.83 (1H, s), 8.26 (1H, d, J = 6.0 Hz), 8.07 (1H, d, J = 5.2 Hz), 7.94 (1H, d, J = 1.6 Hz), 7.79 (2H, d, J = 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.1 (1H, s), 8.65 (1H, d, J = 2.4 Hz), 8.19 (1H, d, J = 6.0 Hz), 8.06 (1H, dd, J = 9.0, 2.2 Hz), 7.89 (1H, s), 7.80 (2H, d, J = 7.2 Hz), 7.69 (1H, d, J = 8.8 Hz), 7.62 (1H, d, J = 2.4 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.30-7.29 (2H, m), 6.71 (1H, dd, J) = 5.8, 2.2 Hz), 2.69 (3H, s). MS Calcd.: 403.46; MS Found: 404.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.64 (1H, s), 7.70 (1H, d, J = 2.8 Hz), 8.35 (1H, dd, J = 8.8, 2.4 Hz), 8.19 (1H, d, J = 6.0 Hz), 7.90 (1H, d, J) = 8.8 Hz), 7.86 (1H, s), 7.80 (2H, d, J = 7.2 Hz), 7.41-7.38 (3H, m), 7.31 (1H, d, J = 7.2 Hz), 6.76 (1H, dd, J = 7.4, 1.8 Hz), 6.49 (1H, d, J = 2.4 Hz), 2.69 (3H, s). MS Calcd.: 403.46; MS Found: 404.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.56 (1H, s), 8.80 (1H, d, J = 1.6 Hz), 8.52 (2H, s), 8.16 (1H, d, J = 5.2 Hz), 8.05 (1H, s), 7.80 (2H, d, J = 7.2 Hz), 7.52 (1H, s), 7.39 (2H, t, J = 7.8 Hz), 7.30 (1H, t, J = 7.2 Hz), 6.71 (1H, dd, J = 5.6, 2.0 Hz), 6.46 (1H, d, J = 1.6 Hz), 2.69 (3H, s). MS Calcd.: 403.46; MS Found: 404.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.94 (1H, s), 8.24 (1H, d, J = 4.8 Hz), 8.17 (1H, d, J = 6.0 Hz), 8.08 (1H, s), 8.01 (1H, s), 7.80 (2H, d, J = 6.8 Hz), 7.61-7.59 (2H, m), 7.39 (2H, t, J = 7.6 Hz), 7.28 (1H, t, J = 7.4 Hz), 7.20 (1H, d, J = 5.2 Hz), 6.67 (1H, dd, J = 5.6, 2.4 Hz), 2.68 (3H, s). MS Calcd.: 403.46; MS Found: 404.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 7.89 (1H, d, J = 5.6 Hz), 7.77 (2H, d, J = 7.2 Hz), 7.38 (2H, t, J = 7.6 Hz), 7.31-7.23 (5H, m), 7.20-7.17 (2H, m), 6.32 (1H, dd, J = 5.6, 2.0 Hz), 6.12 (1H, d, J = 2.4 Hz), 4.40 (2H, d, J = 6.0 Hz), 2.64 (3H, s). MS Calcd.: 373.47; MS Found: 374.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 7.24 (1H, d, J = 5.6 Hz), 7.77 (2H, d, J = 7.6 Hz), 7.38 (2H, t, J = 7.6 Hz), 7.31-7.26 (3H, m), 7.19 (1H, t, 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.00 (1H, d, J = 8.0 Hz), 7.90 (2H, d, J = 5.6 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.33-7.27 (3H, m), 7.09-6.99 (3H, m), 6.35 (1H, d, J = 4.8 Hz), 6.14 (1H, s), 4.42 (2H, d, J = 6.0 Hz), 2.69 (3H, s). MS Calcd.: 394.46; MS Found: 392.1 (M+H ⁺ ).

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

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.40 (1H, s), 8.43 (1H, s), 8.16 (1H, d, J = 5.6 Hz), 7.84 (1H, s), 7.79 (2H, d, J = 8.0 Hz), 7.39 (2H, t, 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 ⁺ ).

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

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.40 (1H, s), 8.42 (1H, s), 8.16 (1H, d, J = 6.0 Hz), 7.85 (1H, s), 7.79 (2H, d, J = 7.6 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.29 (1H, d, J = 7.4 Hz), 6.62 (1H, dd, J = 6.0, 2.0 Hz), 6.33 (1H, d, J = 2.0 Hz), 3.03-2.99 (1H, m), 2.68 (3H, s), 1.17-1.14 (2H, m), 1.12-1.10 (2H, m). MS Calcd.: 453.54; MS Found: 454.1 (M+H ⁺ ).

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

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.85 (1H, s), 8.03 (1H, d, J = 5.2 Hz), 7.85 (1H, s), 7.79 (2H, d, J = 7.6 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.31-7.27 (2H, m), 6.46 (1H, dd, J = 5.6, 2.0 Hz), 6.22 (1H, d, J = 2.4 Hz), 3.75 (3H, s), 2.66 (3H, s). MS Calcd.: 363.44; MS Found: 364.1 (M+H ⁺ ).

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

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 12.4 (1H, brs), 8.82 (1H, s), 8.02 (1H, d, J = 5.6 Hz), 7.83 (1H, s), 7.79 (2H, d, J = 7.6 Hz), 7.39 (3H, 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.89 (1H, s), 8.18 (1H, d, J = 5.6 Hz), 7.91 (1H, d, J = 8.8 Hz), 7.83-7.79 (3H, m), 7.63 (1H, s), 7.49 (1H, d, J = 6.8 Hz), 7.40 (1H, s), 7.38 (2H, t, J = 7.4 Hz), 7.30-7.28 (2H, m), 6.71 (1H, dd, J = 6.4, 3.4 Hz), 2.68 (3H, s). MS Calcd.: 403.46; MS Found: 404.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.79 (1H, s), 8.31 (1H, d, J = 5.2 Hz), 8.24-8.22 (2H, m), 7.99 (1H, s), 7.81-7.79 (3H, m), 7.54 (1H, s), 7.38 (2H, t, J = 6.8 Hz), 7.30 (1H, d, J = 6.8 Hz), 6.81 (1H, s), 6.53 (1H, d, J = 2.4 Hz), 2.69 (3H, s). MS Calcd.: 403.46; MS Found: 404.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.86 (1H, s), 8.03 (1H, d, J = 5.6 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.44 (2H, d, J = 9.6 Hz), 7.39 (2H, t, J = 7.6) Hz), 7.29 (1H, t, J = 7.4 Hz), 6.81 (2H, d, J = 8.8 Hz), 6.53 (1H, dd, J = 5.8, 2.2 Hz), 6.31 (1H, d, J = 2.4 Hz), 3.67 (3H, s), 2.67 (3H, s). MS Calcd.: 389.47; MS Found: 390.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.80 (1H, s), 8.01 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.2 Hz), 7.41-7.37 (4H, m), 7.30 (1H, d, J = 7.6 Hz), 6.81 (2H, d, J = 8.8 Hz), 6.50 (1H, dd, J = 5.6, 2.4 Hz), 6.30 (1H, d, J = 2.4 Hz), 2.98-2.93 (4H, m), 2.87-2.83 (4H, m), 2.67 (3H, s). * A proton from NH was not observed. MS Calcd.: 443.56; MS Found: 444.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.86 (1H, s), 8.03 (1H, d, J = 5.6 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.44-7.37 (4H, m), 7.30 (1H, d, J = 7.2 Hz), 6.81 (2H, d, J = 9.2 Hz), 6.53 (1H, dd, J = 5.8, 2.2 Hz), 6.31 (1H, d, J = 2.4 Hz), 3.97 (2H, t, J = 5.8 Hz), 2.67 (3H, s), 2.62-2.58 (2H, m), 2.39 (4H, s), 1.49-1.44 (4H, m), 1.38-1.32 (2H, m). MS Calcd.: 486.63; MS Found: 487.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.90 (1H, s), 8.05 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.29 (1H, t, J = 7.4 Hz), 7.18 (1H, d, J = 2.4 Hz), 7.06 (1H, dd, J = 8.6, 2.2 Hz), 6.74 (1H, d, J = 8.8 Hz), 6.54 (1H, dd, J = 5.8, 2.2 Hz), 6.34 (1H, d, J = 2.0 Hz), 3.69 (3H, s), 2.85 (4H, brs), 2.67 (3H, s), 2.40 (4H, brs), 2.18 (3H, s). MS Calcd.: 487.62; MS Found: 488.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.25 (1H, brs), 8.11 (1H, d, J = 5.6 Hz), 7.80 (2H, d, J = 8.0 Hz), 7.62 (1H, brs), 7.53 (1H, d, J = 8.4 Hz), 7.40 (2H, t, J = 7.6 Hz), 7.29-7.31 (1H, m), 7.22 (1H, t, J = 8.8 Hz), 6.74 (1H, d, J = 8.4 Hz), 6.45 (1H, d, J = 6.4 Hz), 6.43 (1H, s), 2.68 (3H, s). * A proton from NH was not observed. MS Calcd.: 506.07; MS Found: 507.1 (M+H ⁺ ).

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 12.8 (1H, brs), 9.31 (1H, s), 8.24 (1H, s), 8.16 (1H, d, J = 6.0 Hz), 7.87 (1H, d, J = 7.6 Hz), 7.83 (2H, 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.50 (1H, s), 8.19 (1H, d, J = 6.0 Hz), 7.83-7.82 (4H, m), 7.72 (2H, d, J = 8.8 Hz), 7.41 (2H, t, J = 6.8 Hz), 7.33-7.29 (1H, m), 6.74 (1H, dd, J = 1.6 Hz, 5.4 Hz), 6.51 (1H, d, J = 1.6 Hz), 2.70 (3H, s). *A proton from OH was not observed. MS Calcd.: 403.65; MS Found: 404.1 (M+H ⁺ ).

(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)

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

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

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.09 (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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.08 (1H, s), 8.09 (1H, d, J = 5.6 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.51 (1H, d, J = 8.0 Hz), 7.43-7.37 (3H, m), 7.30 (1H, t, J = 4.8 Hz), 7.17 (1H, t, J = 7.8 Hz), 6.80 (1H, d, J = 8.0 Hz), 6.61 (1H, dd, J = 6.0, 2.4 Hz), 6.43 (1H, d, J = 2.4 Hz), 2.79-2.74 (4H, m), 2.68 (3H, s). MS Calcd.: 412.5 Found: 413.2 (M+H ⁺ ).

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

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.03 (1H, s), 8.09 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.44-7.37 (4H, m), 7.30 (1H, t, J = 6.0 Hz), 7.11 (1H, t, J = 7.4 Hz), 6.72 (1H, d, J = 8.4 Hz), 6.60 (1H, dd, J = 6.0, 2.4 Hz), 6.41 (1H, s), 3.18-3.07 (2H, m), 2.96-2.91 (2H, m), 2.67 (3H, s). * A proton from NH was not observed. MS Calcd.: 455.53 Found: 456.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.09 (1H, dd, J = 5.0, 1.0 Hz), 7.83 (2H, dd, J = 8.2, 1.4 Hz), 7.37-7.33 (3H, m), 7.30-7.25 (2H, m), 7.17-7.11 (2H, m), 6.59 (1H, brs), 6.51-6.49 (2H, m), 2.24-2.20 (1H, m), 1.55 (6H, s), 1.14-1.10 (4H, m). * A proton from NH was not observed. MS Calcd.: 443.56 ; MS Found: 444.2 (M+H ⁺ ).

(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)

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

(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)

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.12 (1H, s), 7.86-7.84 (3H, m), 7.49-7.47 (1H, m), 7.43-7.41 (1H, m), 7.39-7.34 (3H, m), 7.29-7.26 (2H, m), 6.54-6.60 (2H, m), 6.45 (1H, s), 2.21-2.30 (1H, m), 1.56-1.13 (4H, m). * A proton from NH was not observed. MS Calcd.: 428.51 ; MS Found: 429.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.53 (1H, s), 8.19 (1H, d, J = 5.6 Hz), 7.81-7.77 (4H, m), 7.67 (2H, d, J = 9.2 Hz), 7.41 (2H, t, J = 8.0 Hz), 7.33-7.30 (1H, m), 7.14 (2H, s), 6.75 (1H, dd, J = 5.8, 2.2 Hz), 6.49 (1H, d, J = 2.4 Hz), 2.48-2.42 (1H, m), 1.18-1.15 (2H, m), 1.10-1.07 (2H, m). MS Calcd.: 464.56; MS Found: 465.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.39 (1H, s), 8.17 (1H, d, J = 5.6 Hz), 7.81-7.75 (5H, m), 7.68 (2H, d, J = 8.8 Hz), 7.41 (2H, t, J = 7.6 Hz), 7.31 (1H, t, J = 7.4 Hz), 7.12 (1H, brs), 6.71 (1H, dd, J = 6.0, 2.4 Hz), 6.48 (1H, d, J = 2.0 Hz), 2.50-2.42 (1H, m), 1.20-1.15 (2H, m), 1.10-1.07 (2H, m). MS Calcd.: 428.51; MS Found: 429.2 (M+H ⁺ ).

(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)

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

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.67 (1H, bs), 9.14 (1H, s), 8.08 (1H, d, J = 5.6 Hz), 7.77 (2H, d, J = 8.0 Hz), 7.44-7.45 (2H, m), 7.38 (2H, t, J = 7.4 Hz), 7.26-7.30 (1H, m), 7.13 (1H, t, J = 8.2 Hz), 6.70 (1H, d, J = 8.8 Hz), 6.61 (1H, dd, J = 8.5, 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 11.7 (1H, bs), 9.25 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.77 (2H, d, J = 7.6 Hz), 7.61 (1H, s), 7.53 (1H, d, J = 8.4 Hz), 7.38 (2H, t, J = 7.6 Hz), 7.29 (1H, t, J = 7.0 Hz), 7.21 (1H, t, J = 8.2 Hz), 6.73 (1H, d, J = 8.0 Hz), 6.34-6.66 (1H, m), 6.42 (1H, s), 2.39-2.45 (1H, m), 1.04-1.24 (4H, m). MS Calcd.: 532.09; MS Found: 533.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.86 (1H, s), 8.18 (1H, d, J = 6.0 Hz), 7.98 (1H, d, J = 8.0 Hz), 7.83-7.77 (3H, m), 7.59 (1H, s), 7.50 (1H, d, J = 7.6 Hz), 7.46 (1H, s), 7.39 (2H, t, J = 7.2 Hz), 7.29 (1H, t, J = 6.8 Hz), 7.21 (1H, d, J = 2.0 Hz), 6.71 (1H, dd, J = 6.0, 4.0 Hz), 2.40 (1H, m), 1.13-1.11 (2H, m), 1.06-1.05 (2H, m). MS Calcd.: 429.49 Found: 430.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.85 (1H, s), 8.18 (1H, d, J = 5.6 Hz), 8.02 (1H, d, J = 4.2 Hz), 7.95 (1H, d, J = 8.0 Hz), 7.82-7.77 (3H, m), 7.47 (1H, d, J = 7.2 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.30-7.25 (2H, m), 6.74 (1H, dd, J = 6.0, 2.4 Hz), 2.86 (3H, d, J = 5.2 Hz), 2.38-2.37 (1H, m), 1.14-1.10 (2H, m), 1.05-1.02 (2H, m). MS Calcd.: 443.52 Found: 444.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.34 (1H, s), 8.15 (2H, d, J = 6.0 Hz), 7.78 (2H, d, J = 8.0 Hz), 7.71 (4H, q, J = 9.2 Hz), 7.40 (2H, t, J = 7.6) Hz), 7.30 (1H, t, J = 7.6 Hz), 6.68 (1H, d, J = 6.0 Hz), 6.45 (1H, s), 2.73 (3H, d, J = 4.0), 2.40 (1H, m), 1.15-1.13 (2H, m), 1.05 (2H, m). MS Calcd.: 442.53 Found: 443.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.79 (1H, s), 9.46 (1H, s), 8.13 (1H, d, J = 6.0 Hz), 8.02 (1H, d, J = 2.4 Hz), 7.77 (2H, d, J = 7.2 Hz), 7.67 (1H, d, J = 9.2 Hz), 7.53-7.49 (2H, m), 7.37 (2H, t, J = 7.6 Hz), 7.28 (1H, t, J = 7.2 Hz), 6.64 (1H, dd, J = 6.0, 2.4 Hz), 2.93 (3H, s), 2.41-2.27 (1H, m), 1.15-1.13 (2H, m), 1.06-1.04 (2H, m). MS Calcd.: 479.57; MS Found: 480.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.33 (1H, s), 9.07 (1H, s), 8.07 (1H, d, J = 5.6 Hz), 7.78 (2H, d, J = 7.6 Hz), 7.54 (2H, d, J = 8.8 Hz), 7.40 (2H, t, J = 7.2 Hz), 7.30 (1H, t, J = 7.6 Hz), 7.08 (2H, d, J = 8.8 Hz), 6.60 (1H, dd, J = 6.0, 2.4 Hz), 6.36 (1H, d, J = 2.0 Hz), 2.86 (3H, s), 2.40 (1H, m), 1.14-1.12 (2H, m), 1.14 (2H, m). MS Calcd.: 478.59 Found: 479.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.09 (1H, s), 8.65 (1H, s), 8.19 (1H, d, J = 5.6 Hz), 8.07 (1H, d, J = 9.2 Hz), 7.78 (1H, brs), 7.76 (2H, d, J = 3.2 Hz), 7.73 (1H, d, J = 8.4 Hz), 7.56 (1H, s), 7.39 (2H, t, J = 7.6 Hz), 7.92 (2H, t, J = 7.2 Hz), 6.71 (1H, dd, J = 5.6, 2.4 Hz), 2.42 (1H, m), 1.15-1.11 (2H, m), 1.05-1.04 (2H, m). MS Calcd.: 429.49 Found: 430.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.32 (1H, brs), 8.69 (1H, s), 8.21 (1H, d, J = 5.6 Hz), 8.10-8.11 (1H, m), 7.78 (3H, t, J = 8.2 Hz), 7.58 (1H, s), 7.37 (2H, t, J = 7.6 Hz), 7.28 (1H, t, J = 7.2 Hz), 6.75-6.77 (1H, m), 3.81 (3H, s), 2.38-2.43 (1H, m), 1.15-1.21 (2H, m), 1.05-1.11 (2H, m). MS Calcd.: 444.13; MS Found: 445.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.16 (1H, s), 8.18 (1H, d, J = 5.6 Hz), 7.91 (1H, d, J = 8.8 Hz), 7.84-7.77 (3H, m), 7.72 (1H, s), 7.55 (1H, d, J = 7.2 Hz), 7.39 (2H, J = 7.6 Hz), 7.30 (1H, t, J = 7.2 Hz), 6.71 (1H, d, J = 5.6 Hz), 3.79 (3H, s), 2.39-2.38 (1H, m), 1.14-1.11 (2H, m), 1.10-1.03 (2H, m). MS Calcd.: 444.51 Found: 445.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.65 (1H, brs), 8.71 (1H, s), 8.25 (1H, d, J = 6.0 Hz), 8.14 (1H, d, J = 8.4 Hz), 7.76 (2H, d, J = 6.8 Hz), 7.61-7.63 (1H, m), 7.44 (1H, brs), 7.38 (2H, t, J = 7.6 Hz), 7.27-7.31 (1H, m), 6.87 (1H, brs), 2.34-2.44 (1H, m), 1.14-1.16 (2H, m), 1.06-1.14 (2H, m). * A proton from NH was not observed. MS Calcd.: 430.48; MS Found: 431.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.08 (1H, s), 8.60 (1H, s), 8.32-8.33 (1H, m), 8.17 (1H, d, J = 6.0 Hz), 8.00-8.02 (1H, m), 7.71-7.77 (3H, m), 7.54 (1H, s), 7.36 (2H, t, J = 7.6 Hz), 7.26 (1H, t, J = 7.0 Hz), 6.70 (1H, dd, J = 6.0, 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.06 (1H, s), 8.16 (1H, d, J = 5.6 Hz), 7.89 (1H, d, J = 8.0 Hz), 7.81-7.74 (4H, m), 7.53 (1H, d, J = 7.6 Hz), 7.39 (2H, t, J = 7.2 Hz), 7.29 (1H, t, J = 7.2 Hz), 6.64 (1H, d, J = 3.6 Hz), 2.39-2.37 (1H, m), 1.13-1.10 (2H, m), 1.05-1.04 (2H, m). * A proton from OH was not observed. MS Calcd.: 430.48 Found: 431.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 12.9 (1H, brs), 9.35 (1H, s), 8.23 (1H, t, J = 1.8 Hz), 8.15 (1H, d, J = 6.0 Hz), 7.87 (1H, dd, J = 7.6, 1.6 Hz), 7.80 (2H, d, J = 5.6 Hz), 4.47 (1H, d, J = 8.0 Hz), 7.43-7.31 (4H, m), 6.69 (1H, dd, J = 5.8, 2.2 Hz), 6.44 (1H, d, J = 2.4 Hz), 2.47-2.41 (1H, m), 1.17-1.13 (2H, m), 1.10-1.17 (2H, m). MS Calcd.: 429.49; MS Found: 430.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.52 (1H, s), 8.19 (1H, d, J = 6.0 Hz), 7.81 (3H, t, J = 9.0 Hz), 7.74 (2H, d, J = 8.4 Hz), 7.41 (2H, t, J = 7.6) Hz), 7.31 (1H, t, J = 8.6 Hz), 6.85 (1H, dd, J = 7.6, 2.4 Hz), 6.51 (1H, d, J = 2.4 Hz), 2.49-2.42 (1H, m), 1.19-1.14 (2H, m), 1.09-1.05 (2H, m). * Two protons from NH and OH were not observed. MS Calcd.: 429.49; MS Found: 430.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.40 (1H, s), 8.41 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 7.83 (1H, s), 7.68 (2H, d, J = 7.6 Hz), 7.33 (2H, t, J = 7.2 Hz), 7.23 (1H, t, J = 8.0 Hz), 7.14 (2H, s), 6.61 (1H, dd, J = 6.0, 2.4 Hz), 6.40 (1H, d, J = 2.4 Hz), 3.01 (1H, q, J = 3.6 Hz), 1.17-1.10 (4H, m). MS Calcd.: 454.53 Found: 455.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 11.1 (1H, s), 10.2 (1H, brs), 9.01 (1H, brs), 8.53 (1H, s), 8.19 (1H, d, J = 6.4 Hz), 7.97 (1H, d, J = 9.2 Hz), 7.77 (2H, d, J = 7.2 Hz), 7.70 (1H, d, J = 8.0 Hz), 7.54 (1H, s), 7.38 (2H, t, J = 7.4 Hz), 7.28 (1H, t, J = 8.0 Hz), 6.74 (1H, s), 2.48-2.38 (1H, m), 1.18-1.11 (2H, m), 1.09-1.02 (2H, m). MS Calcd.: 445.49; MS Found: 446.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 11.0 (1H, s), 9.36 (1H, s), 8.82 (1H, s), 8.15 (1H, d, J = 6.0 Hz), 7.77 (2H, d, J = 7.6 Hz), 7.64 (3H, q, J = 8.1 Hz), 7.38 (2H, t, J = 7.6 Hz), 7.29 (1H, t, J = 7.4 Hz), 6.69 (1H, dd, J = 8.4, 2.4 Hz), 6.45 (1H, d, J = 2.4 Hz), 2.44-2.38 (1H, m), 1.18-1.12 (2H, m), 1.08-1.03 (2H, m). * A proton from OH was not observed. MS Calcd.: 444.51; MS Found: 445.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.97 (1H, s), 8.45 (1H, s), 8.16 (1H, d, J = 5.2 Hz), 8.05 (1H, dd, J = 8.8, 2.0 Hz), 7.78 (2H, d, J = 7.6) Hz), 7.62 (1H, d, J = 8.8 Hz), 7.58 (1H, s), 7.38 (2H, t, J = 7.6 Hz), 7.27 (1H, t, J = 7.4 Hz), 6.84 (1H, d, J = 8.4 Hz), 6.68 (1H, d, J = 3.2 Hz), 2.86 (3H, s), 2.46-2.37 (1H, m), 1.18-1.12 (2H, m), 1.09-1.02 (2H, m). MS Calcd.: 507.58; MS Found: 508.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.10 (1H, d, J = 6.0 Hz), 7.82-7.80 (2H, m), 7.36-7.33 (3H, m), 7.30-7.26 (2H, m), 7.16 (1H, dd, J = 8.4, 1.2 Hz), 7.11 (1H, dd, J = 8.4, 1.2 Hz), 6.68 (1H, brs), 6.57 (1H, d, J = 2.4 Hz), 6.55 (1H, dd, J = 5.8, 2.2 Hz), 4.12 (3H, s), 1.55 (6H, s). * A proton from NH was not observed. MS Calcd.: 433.52 ; MS Found: 434.1 (M+H ⁺ ).

(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)

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

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 12.8 (1H, brs), 9.39 (1H, s), 8.23 (1H, s), 8.16 (1H, d, J = 6.0 Hz), 7.87 (1H, d, J = 6.8 Hz), 7.78 (2H, 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.46 (1H, s), 8.20 (1H, d, J = 6.0 Hz), 8.17 (1H, s), 7.87 (2H, d, J = 7.2 Hz), 7.81 (1H, d, J = 8.4 Hz), 7.49 (2H, t, J = 7.4 Hz), 7.45-7.41 (2H, m), 7.34 (1H, d, J = 7.6 Hz), 7.30 (2H, s), 6.80 (1H, dd, J = 5.8, 2.2 Hz), 6.52 (1H, d, J = 2.4 Hz). MS Calcd.: 492.49; MS Found: 493.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.15 (s, 1H), 8.66 (d, J = 2.1 Hz, 1H), 8.23 (d, J = 6.0 Hz, 1H), 8.07 (dd, J = 8.8, 2.4 Hz, 1H), 7.88-7.83 (m, 3H), 7.71 (d, J = 8.8 Hz, 1H), 7.64 (d, J = 2.4 Hz, 1H), 7.46 (t, J = 7.2 Hz, 2H), 7.39 (t, J = 7.6 Hz, 1H), 7.29 (s, 1H), 6.85 (dd, J = 5.2, 1.6 Hz, 1H). [M+H] ⁺ calcd for 457.43, found 458.15.(M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.37 (s, 1H), 8.19 (d, J = 5.6 Hz, 1H), 7.84 (d, J = 7.2 Hz, 2H), 7.77-7.75 (m, 3H), 7.66 (d, J = 9.2 Hz, 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.36 (s, 1H), 8.20-8.17 (m, 2H), 7.84 (d, J = 7.6 Hz, 2H), 7.71 (d, J = 8.0, 4.0 Hz, 2H), 7.66 (d, J = 9.2) Hz, 2H), 7.47 (t, J = 7.6 Hz, 2H), 7.40 (t, J = 6.8 Hz, 1H), 6.78 (dd, J = 6.0, 2.4 Hz, 1H), 6.51 (d, J = 2.4 Hz, 1H), 2.73 (d, J = 4.8 Hz, 3H). [M+H] ⁺ calcd for 470.47, found 471.22 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 11.50 (br s, 1H), 8.73 (s, 1H), 8.31 (d, J = 6.4 Hz, 1H), 8.19 (d, J = 8.8 Hz, 1H), 7.83 (d, J = 8.0 Hz, 2H), 7.58 (d, J = 8.8 Hz, 1H), 7.50-7.44 (m, 1H), 7.05 (d, J = 4.0 Hz, 1H). [M+H] ⁺ calcd for 458.42, found 459.20

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.15 (s, 1H), 8.61 (s, 1H), 8.34 (br s, 1H), 8.23 (d, J = 6.0 Hz, 1H), 8.03 (dd, J = 8.0, 1.6 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.62 (d, J = 2.0 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.40-7.39 (m, 1H), 6.85 (dd, J = 5.6, 2.8 Hz, 1H), 2.75 (d, J = 4.0 Hz, 3H). MS Calcd.: 471.46; Found: 472.21 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.34 (1H, s), 8.19 (2H, d, J = 6.0 Hz), 7.87 (2H, d, J = 6.8 Hz), 7.49-7.42 (4H, m), 7.36-7.30 (2H, m), 6.77 (1H, d, J = 4.8 Hz), 6.50 (1H, s). * A proton from OH was not observed. MS Calcd.: 457.43; Found: 458.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 12.4 (1H, brs), 9.52 (1H, s), 8.24 (1H, d, J = 6.0 Hz), 7.87-7.82 (4H, m), 7.74 (2H, d, J = 8.4 Hz), 7.49 (2H, t, J = 7.4 Hz), 7.42 (1H, t, J = 7.4 Hz), 6.84 (1H, dd, J = 6.0, 2.4 Hz), 6.57 (1H, d, J = 2.0 Hz). MS Calcd.: 457.43; Found: 458.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.07 (1H, d, J = 6.0 Hz), 7.83-7.80 (2H, m), 7.52-7.27 (3H, m), 7.25-7.21 (2H, m), 7.15-7.09 (2H, m), 6.72 (1H, brs), 6.58 (1H, d, J = 2.4 Hz), 6.56-6.54 (1H, m), 3.10 (6H, s), 1.55 (6H, s). * A proton form NH was not observed. MS Calcd.: 446.56; MS Found: 447.2 (M+H ⁺ ).

(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)

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

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.52 (1H, s), 8.17 (1H, d, J = 5.6 Hz), 7.80-7.77 (4H, m), 7.66 (2H, d, J = 9.2 Hz), 7.37 (2H, t, J = 7.2 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.38 (1H, s), 8.16 (1H, d, J = 6.0 Hz), 7.79-7.75 (4H, m), 7.68 (2H, d, J = 8.4 Hz), 7.37 (2H, t, J = 8.0 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 ⁺ ).

(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)

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

(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)

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

(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)

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

(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)

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

(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)

¹ H-(400 MHz, DMSO-d ₆ ): δ 10.1 (1H, s), 8.15 (1H, d, J = 5.2 Hz), 7.92 (1H, d, J = 8.4 Hz), 7.83-7.75 (4H, m), 7.54 (1H, d, J = 7.2 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 ⁺ ).

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): 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 ⁺ ).

(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)

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

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.38 (1H, s), 8.23 (1H, s), 8.13 (1H, d, J = 5.6 Hz), 7.86 (1H, d, J = 8.0 Hz), 7.78 (2H, d, J = 8.4 Hz), 7.47 (1H, d, J = 7.2 Hz), 7.39-7.33 (3H, m), 7.29-7.27 (1H, m), 6.68 (1H, dd, J = 2.4 Hz, 5.6 Hz), 6.52 (1H, d, J = 2.0 Hz), 3.08 (6H, s). * A proton from OH was not observed. MS Calcd.: 432.49; MS Found: 433.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.49 (1H, s), 8.16 (1H, d, J = 6.0 Hz), 7.79 (4H, t, J = 7.6 Hz), 7.69 (2H, d, J = 8.4 Hz), 7.37 (2H, t, J = 7.6) Hz), 7.27 (1H, t, J = 7.2 Hz), 6.71 (1H, d, J = 3.2 Hz), 6.56 (1H, d, J = 2.0 Hz), 3.08 (6H, s). * A protons from NH was not observed. MS Calcd.: 432.49; MS Found: 433.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.1 (1H, s), 8.14 (1H, d, J = 5.6 Hz), 7.89 (1H, d, J = 8.8 Hz), 7.82-7.74 (4H, m), 7.53 (1H, d, J = 6.8 Hz), 7.34 (2H, t, J = 7.6 Hz), 7.23 (1H, t, J = 8.0 Hz), 6.64 (1H, m), 3.05 (6H, s). * A proton from OH was not observed. MS Calcd.: 433.48; MS Found: 434.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.38 (1H, s), 8.26 (1H, s), 8.18 (1H, d, J = 5.6 Hz), 7.92 (1H, d, J = 8.0 Hz), 7.79 (2H, d, J = 8.4 Hz), 7.49-7.35 (5H, m), 6.74 (1H, dd, J = 5.8, 2.2 Hz), 6.49 (1H, d, J = 2.4 Hz), 3.84 (3H, s). MS Calcd.: 482.35; MS Found: 484.0 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, CDCl ₃ ): δ 9.85 (1H, s), 8.05-8.01 (2H, m), 7.85 (1H, d, J = 7.6 Hz), 7.78 (2H, d, J = 8.0 Hz), 7.52-7.29 (5H, m), 6.69 (1H, d, J = 2.0 Hz), 6.58 (1H, dd, J = 6.6, 2.2 Hz). * A proton from OH was not observed. MS Calcd.: 468.32; MS Found: 469.0 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, MeOD-d ₄ ): δ 8.15 (1H, d, J = 6.0 Hz), 7.89 (1H, d, J = 8.0 Hz), 7.74 (2H, d, J = 7.2 Hz), 7.61 (1H, d, J = 2.0 Hz), 7.50 (1H, t, J = 8.0 Hz), 7.44 (1H, s), 7.30 (2H, t, J = 7.2 Hz), 7.28-7.24 (1H, m), 7.12 (1H, d, J = 8.0 Hz), 6.98 (1H, dd, J = 5.8, 2.2 Hz). * Three protons from NH and NH ₂ were not observed. MS Calcd.:467.34; MS Found: 468.0 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.1 (1H, s), 8.64 (1H, d, J = 2.0 Hz), 8.19 (1H, d, J = 5.6 Hz), 8.60 (1H, dd, J = 9.0, 2.2 Hz), 7.88 (1H, s), 7.81 (2H, d, J = 7.2 Hz), 7.69 (1H, d, J = 8.8 Hz), 7.61 (1H, d, J = 2.0 Hz), 7.39 (2H, t, J = 7.4 Hz), 7.29 (2H, t, J = 7.4 Hz), 6.72 (1H, dd, J = 5.6, 2.4 Hz), 3.45 (1H, quint, J = 7.8 Hz), 2.20-2.09 (2H, m), 1.87-1.74 (4H, m), 1.71-1.65 (2H, m). MS Calcd.: 457.55; MS Found: 458.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.70 (1H, brs), 8.69 (1H, s), 8.25 (1H, d, J = 5.6 Hz), 8.13 (1H, d, J = 8.0 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.61 (1H, d, J = 7.6 Hz), 7.51 (1H, brs), 7.40 (2H, t, J = 7.6 Hz), 7.31 (1H, t, J = 7.2 Hz), 6.87 (1H, s), 3.37-3.44 (1H, t, J = 8.0 Hz), 2.15-2.13 (2H, m), 1.86-1.85 (2H, m), 1.86-1.83 (2H, m), 1.82-1.75 (2H, m), 1.68 -1.67 (2H, m). * A proton from OH was not observed. MS Calcd.: 458.53 Found: 459.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.52 (1H, s), 8.18 (1H, d, J = 6.0 Hz), 7.81-7.79 (4H, m), 7.22 (2H, d, J = 8.8 Hz), 7.41 (2H, t, J = 8.0 Hz), 7.31 (1H, t, J = 7.2 Hz), 6.73 (1H, dd, J = 5.6, 2.0 Hz), 6.50 (1H, d, J = 2.0 Hz), 3.46 (1H, t, J = 7.6 Hz), 2.14-2.12 (2H, m), 1.85-1.76 (4H, m), 1.68-1.66 (2H, m). * A proton from OH was not observed. MS Calcd.: 457.54 Found: 458.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.12 (1H, s), 8.59 (1H, s), 8.34 (1H, d, J = 4.0 Hz), 8.19 (1H, d, J = 5.6 Hz), 8.03 (1H, d, J = 10.8 Hz), 7.81 (2H, d, J = 7.6 Hz), 7.71 (1H, d, J = 9.6 Hz), 7.59 (1H, s), 7.40 (2H, t, J = 8.0 Hz), 7.30 (1H, t, J = 7.2 Hz), 6.73 (1H, dd, J = 5.6, 2.4 Hz), 3.44 (1H, t, J = 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.67 (1H, d, J = 2.0 Hz), 8.15 (1H, d, J = 6.0 Hz), 8.08 (1H, dd, J = 8.8, 2.4 Hz), 7.83 (2H, d, J = 7.6 Hz), 7.60 (1H, s), 7.56 (1H, d, J = 8.8 Hz), 7.36 (2H, t, J = 7.2 Hz), 7.28 (1H, t, J = 7.2 Hz), 6.68 (1H, dd, J = 5.2, 2.0 Hz), 3.03-2.97 (1H, m), 2.21-2.20 (2H, m), 1.91-1.88 (2H, m), 1.78-1.75 (1H, m), 1.61-1.32 (5H, m). * Three protons from NH and NH ₂ were not observed. MS Calcd.: 471.57; MS Found: 472.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 11.12 (1H, brs), 8.73 (1H, s), 8.30 (1H, d, J = 6.0 Hz), 8.20 (1H, d, J = 8.4 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.50 (1H, d, J = 8.4 Hz), 7.41-7.37 (3H, m), 7.32 (1H, t, J = 7.6 Hz), 6.97 (1H, s), 3.03 (1H, m), 2.12 (2H, m), 1.81-1.78 (2H, m), 1.69-1.66 (1H, m), 1.55-1.45 (2H, m), 1.42-1.36 (2H, m), 1.27-1.21 (1H, m).* A proton from OH was not observed. MS Calcd.: 472.56 Found: 473.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.51 (1H, s), 8.18 (1H, d, , J = 5.6 Hz), 7.81-7.78 (4H, m), 7.72 (2H, d, J = 8.8 Hz), 7.41 (2H, t, J = 8.0 Hz), 7.31 (1H, t, J = 7.2 Hz), 6.71 (1H, d, J = 4.4 Hz), 6.48 (1H, s), 2.97-2.91 (1H, m), 2.11-2.09 (2H, m), 1.77-1.75 (2H, m), 1.66-1.65 (1H, m), 2.53-1.38 (4H, m), 1.26-1.23 (1H, m). * A proton from OH was not observed. MS Calcd.: 471.57 Found: 472.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.13 (1H, s), 8.60 (1H, s), 8.33 (1H, s), 8.19 (1H, d, J = 5.6 Hz), 8.03 (1H, d, J = 8.8 Hz), 7.81 (2H, d, J = 8.0 Hz), 7.69 (1H, d, J = 9.6 Hz), 7.60 (1H, s), 7.40 (2H, t, J = 7.6 Hz), 7.30 (1H, t, J = 7.2 Hz), 6.72 (1H, d, J = 5.6 Hz), 2.98-2.91 (1H, m), 2.75 (3H, d, J = 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.44 (1H, s), 8.18-8.16 (2H, m), 7.84-7.79 (3H, m), 7.42 (3H, t, J = 7.4 Hz), 7.33 (2H, d, J = 7.2 Hz), 7.19 (2H, s), 6.70 (1H, dd, J = 6.0, 2.4 Hz), 6.47 (1H, d, J = 2.8 Hz), 3.03 (2H, q, J = 7.6 Hz), 1.36 (3H, t, J = 7.6 Hz). MS Calcd.: 452.55; MS Found: 453.1 (M+H ⁺ ).

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.24 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 8.02 (1H, s), 7.85-7.80 (4H, m), 7.42 (2H, t, J = 7.6 Hz), 7.36 (1H, t, J = 7.8 Hz), 7.32-7.27 (3H, m), 6.65 (1H, dd, J = 6.0, 1.6 Hz), 6.45 (1H, d, J = 2.0 Hz), 3.02 (2H, q, J = 7.5 Hz), 1.36 (3H, t, J = 7.4 Hz). MS Found: 417.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.53 (1H, s), 8.19 (1H, d, J = 6.0 Hz), 7.83 (2H, d, J = 7.2 Hz), 7.78 (2H, d, J = 8.8 Hz), 7.67 (2H, d, J = 8.8) Hz), 7.42 (2H, t, J = 7.6 Hz), 7.32 (1H, t, J = 8.0 Hz), 7.14 (2H, s), 6.75 (1H, dd, J = 5.8, 1.8 Hz), 6.50 (1H, d, J = 2.4 Hz), 3.03 (2H, q, J = 7.5 Hz), 1.36 (3H, t, J = 7.4 Hz). MS Calcd.: 452.55; MS Found: 453.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.39 (1H, s), 8.18 (1H, d, J = 5.6 Hz), 7.83 (2H, d, J = 7.2 Hz), 7.77 (3H, d, J = 8.8 Hz), 7.68 (2H, d, J = 8.8) Hz), 7.42 (2H, t, J = 7.6 Hz), 7.32 (1H, t, J = 7.8 Hz), 7.12 (1H, brs), 6.71 (1H, dd, J = 6.0, 2.4 Hz), 6.48 (1H, d, J = 2.0 Hz), 3.03 (2H, q, J = 7.6 Hz), 1.36 (3H, t, J = 7.4 Hz). MS Calcd.: 416.50; MS Found: 417.2 (M+H ⁺ ).

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.21 (1H, s), 8.59 (1H, d, J = 2.4 Hz), 8.12 (1H, d, J = 6.0 Hz), 8.08 (1H, dd, J = 8.8, 2.4 Hz), 7.84 (2H, d, J) = 8.0 Hz), 7.51 (1H, d, J = 9.2 Hz), 7.42 (2H, t, J = 7.6 Hz), 7.32 (1H, t, J = 7.6 Hz), 6.66 (1H, d , 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.66 (1H, brs), 9.14 (1H, s), 8.08 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.2 Hz), 7.37-7.45 (4H, m), 7.29 (1H, t, J = 7.4 Hz), 7.13 (1H, t, J = 8.2 Hz), 6.70 (1H, d, J = 7.6 Hz), 6.62 (1H, dd, J = 6.0 and 2.4 Hz), 6.42 (1H, s), 2.97-3.07 (4H, m), 1.33 (3H, t, J = 7.8 Hz), 1.16 (3H, t, J = 7.4 Hz). MS Calcd.: 480.13; MS Found: 481.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.35 (1H, s), 8.16 (2H, d, J = 5.6 Hz), 7.82 (2H, d, J = 7.6 Hz), 7.71 (4H, q, J = 8.8 Hz), 7.41 (2H, t, J = 8.0 Hz), 7.31 (1H, t, J = 7.6 Hz), 6.69 (1H, dd, J = 5.6, 2.4 Hz), 6.46 (1H, d, J = 2.4 Hz), 3.03 (2H, q, J = 7.6 Hz), 2.73 (3H, d, J = 5.6 Hz), 1.35 (3H, t, J = 7.6 Hz). MS Calcd.: 430.52 Found: 431.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.1 (1H, s), 8.65 (1H, d, J = 2.4 Hz), 8.19 (1H, d, J = 6.0 Hz), 8.06 (1H, d, J = 10.8 Hz), 7.88 (1H, s), 7.81 (2H, d, J = 7.6 Hz), 7.69 (1H, d, J = 8.4 Hz), 7.63 (1H, s), 7.39 (2H, t, J = 7.6 Hz), 7.29 (2H, t, J = 8.0 Hz), 6.72 (1H, d, J = 5.2 Hz), 3.00 (2H, q, J = 7.0 Hz), 1.34 (3H, t, J = 7.4 Hz). MS Calcd.: 432.50 Found: 433.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.33 (1H, s), 8.69 (1H, s), 8.21 (1H, d, J = 6.0 Hz), 8.09-8.12 (1H, m), 7.76-7.81 (3H, m), 7.58 (1H, s), 7.62 (1H, s), 7.42 (1H, t, J = 5.0 Hz), 7.29 (1H, t, J = 7.2 Hz), 6.75-6.77 (1H, m), 3.81 (3H, s), 2.98-3.03 (2H, m), 1.34 (3H, t, J) = 7.4 Hz). MS Calcd.: 432.13; MS Found: 433.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.75 (1H, s), 8.30 (1H, d, J = 6.8 Hz), 8.21 (1H, d, J = 8.8 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.49-7.51 (1H, m), 7.39 (2H, t, J = 7.8 Hz), 7.29-7.34 (2H, m), 7.00 (1H, brs), 3.00-3.05 (2H, m), 1.35 (3H, t, J = 7.6 Hz m). * Two protons from NH and OH were not observed. MS Calcd.: 418.11; MS Found: 419.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.11 (1H, s), 8.60 (1H, s), 8.34 (1H, brs), 8.19 (1H, d, J = 6.0 Hz), 8.01-8.04 (1H, m), 7.81 (2H, d, J = 7.2 Hz), 7.70 (1H, d, J = 9.2 Hz), 7.60 (1H, s), 7.37-7.39 (2H, m), 7.29-7.30 (1H, m), 6.71-6.72 (1H, m), 2.98-3.04 (2H, m), 2.75 (3H, d, J = 4.4 Hz), 1.34 (3H, t, J = 7.4 Hz). MS Calcd.: 431.14; MS Found: 432.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.36 (1H, s), 8.23 (1H, s), 8.15 (1H, d, J = 6.0 Hz), 7.88-7.83 (3H, m), 7.48-7.40 (3H, m), 7.38-7.30 (2H, m), 6.69 (1H, dd, J = 5.8, 2.2 Hz), 6.45 (1H, d, J = 2.0 Hz), 3.03 (2H, q, J = 7.5 Hz), 1.36 (3H, t, J = 7.4 Hz). * A proton from OH was not observed. MS Calcd.: 417.48; MS Found: 418.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.54 (1H, s), 8.20 (1H, d, J = 6.0 Hz), 7.84-7.81 (4H, m), 7.74 (2H, d, J = 8.4 Hz), 7.42 (2H, t, J = 7.6 Hz), 7.32 (1H, t, J = 7.8 Hz), 6.75 (1H, dd, J = 6.0, 2.4 Hz), 6.52 (1H, d, J = 2.4 Hz), 3.03 (2H, q, J = 7.5 Hz), 1.36 (3H, t, J = 7.6 Hz). * A proton form OH was not observed. MS Calcd.: 417.48; MS Found: 418.1 (M+H ⁺ ).

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.1 (1H, s), 8.20-8.17 (2H, m), 7.81 (2H, d, J = 6.8 Hz), 7.68-7.64 (3H, m), 7.39-7.34 (2H, m), 7.30-7.23 (1H, m), 6.69 (1H, s), 3.48 (4H, s), 3.00 (2H, q, J = 8.0 Hz), 2.29 (4H, s), 2.06 (3H, s), 1.33 (3H, t, J = 7.0 Hz). MS Calcd.: 500.62; MS Found: 501.3 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.1 (1H, s), 8.34 (1H, s), 8.18 (1H, d, J = 6.0 Hz), 7.81 (3H, d, J = 7.6 Hz), 7.69 (1H, d, J = 8.4 Hz), 7.63 (1H, s), 7.39 (2H, t, J = 7.6 Hz), 7.29 (1H, t, J = 7.4 Hz), 6.70 (1H, d, J = 5.2 Hz), 3.70-3.52 (3H, m), 3.38-3.24 (2H, m), 3.00 (2H, q, J = 7.5 Hz), 1.98 (1H, brs), 1.88 (1H, brs), 1.33 (3H, t, J = 7.4 Hz). * Two protons from NH ₂ were not observed. MS Calcd.:486.59; MS Found: 487.2 (M+H ⁺ ).

(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)

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

(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)

¹ H-NMR (400 MHz, MeOH-d ₄ ): δ 8.39 (1H, d, J = 3.2 Hz), 8.13 (1H, d, J = 6.0 Hz), 7.82 (3H, d, J = 8.0 Hz), 7.61 (1H, s), 7.57 (1H, d, J = 8.8 Hz), 7.35 (2H, t, J = 7.8 Hz), 7.27 (1H, t, J = 7.4 Hz), 6.66 (1H, dd, J = 6.0, 2.0 Hz), 3.78-3.71 (2H, m), 3.70-3.57 (2H, m), 3.50-3.45 (1H, m), 3.40-3.33 (1H, m), 3.03 (2H, q, J = 7.5 Hz), 2.42 (1.5H, s), 2.32 (1.5H, s), 1.91-1.80 (1H, m), 1.42 (3H, t, J = 7.6 Hz). * A proton from NH was not observed. MS Calcd.: 500.62; MS Found: 501.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.1 (1H, s), 8.60 (1H, d, J = 2.0 Hz), 8.34 (1H, t, J = 5.4 Hz), 8.19 (1H, d, J = 6.0 Hz), 8.02 (1H, dd, J = 8.6, 2.2 Hz), 7.81 (2H, d, J = 7.6 Hz), 7.70 (1H, d, J = 8.8 Hz), 7.61 (1H, d, J = 2.4 Hz), 7.41-7.37 (2H, m), 7.30-7.27 (1H, m), 6.72 (1H, dd, J = 5.6, 2.4 Hz), 3.34 (2H, s), 3.00 (2H, q, J = 7.5 Hz), 2.48-2.41 (3H, m), 2.39-2.11 (7H, m), 1.97 (3H, s), 1.33 (3H, t, J = 7.8 Hz). MS Calcd.: 543.68; MS Found: 544.3 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.15 (1H, s), 8.61 (1H, s), 8.34 (1H, s), 8.19 (1H, d, J = 5.6 Hz), 8.03 (1H, d, J = 8.8 Hz), 7.81 (2H, d, J = 7.6 Hz), 7.70 (1H, d, J = 8.8 Hz), 7.61 (1H, s), 7.38 (2H, t, J = 7.4 Hz), 7.28 (1H, t, J = 7.2 Hz), 6.71 (1H, d, J = 5.2 Hz), 3.32 (2H, s), 3.00 (2H, q, J = 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.16 (1H, s), 8.60 (1H, d, J = 1.6 Hz), 8.34 (1H, t, J = 5.4 Hz), 8.19 (1H, d, J = 5.6 Hz), 8.02 (1H, dd, J = 8.4, 2.0 Hz), 7.81 (2H, d, J = 7.6 Hz), 7.70 (1H, d, J = 8.8 Hz), 7.61 (1H, d, J = 2.0 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.29 (1H, d, J = 6.8 Hz), 6.72 (1H, dd, J = 5.4, 2.2 Hz), 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 ⁺ ).

(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)

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

(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)

¹ H-NMR (400 MHz, MeOH-d ₄ ): δ 7.88 (1H, d, J = 6.0 Hz), 7.78 (2H, d, J = 8.0 Hz), 7.35 (2H, t, J = 7.6 Hz), 7.28 (1H, d, J = 7.2 Hz), 7.01 (2H, d, J = 8.4 Hz), 6.60 (2H, d, J = 8.8 Hz), 6.39-6.37 (1H, m), 6.17 (1H, s), 3.19 (2H, t, J = 6.4 Hz), 2.97 (2H, dd, J = 15.0, 7.8 Hz), 2.70-2.58 (11H, m), 1.37 (3H, t, J = 7.4 Hz), 1.08 (6H, d, J = 6.8 Hz). * Two protons from NH were not observed. MS Calcd.: 542.74; MS Found: 543.4 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.58 (1H, s), 7.97 (1H, d, J = 6.0 Hz), 7.8 (2H, d, J = 7.2 Hz), 7.39-7.37 (2H, m), 7.31-7.29 (1H, m), 7.16 (2H, d, J = 8.0 Hz), 6.49-6.43 (3H, m), 6.22 (1H, s), 5.04 (1H, s), 3.04-2.97 (4H, m), 2.46-2.30 (10H, m), 2.12 (3H, s), 1.32 (3H, t, J = 7.2 Hz), MS Calcd.: 514.68; MS Found: 515.3 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, MeOH-d ₄ ): δ 7.87 (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 ⁺ ).

(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)

^1H -NMR (400 MHz, DMSO-d ₆ ): δ 8.58 (1H, s), 7.97 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 7.6 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.29 (1H, t, J = 7.4 Hz), 7.16 (2H, d, J = 8.4 Hz), 6.48 (2H, d, J = 8.8 Hz), 6.43 (1H, dd, J = 6.0, 2.0 Hz), 6.22 (1H, d, J = 2.0 Hz), 5.12 (1H, t, J = 5.4 Hz), 3.05 (2H, m), 2.97 (2H, q, J = 7.5 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.30 (1H, s), 8.04 (1H, d, J = 6.0 Hz), 7.80 (2H, d, J = 8.0 Hz), 7.56 (1H, s), 7.37-7.41 (4H, m), 7.28 (1H, t, J = 7.2 Hz), 6.99 (1H, d, J = 6.0 Hz), 6.50 (1H, d, J = 5.6 Hz), 5.15 (1H, t, J = 5.4 Hz), 3.02-3.06 (2H, m), 2.99 (2H, q, J = 6.4 Hz), 2.43-4.48 (2H, m), 2.00-2.42 (8H, m), 1.33 (3H, t, J = 7.6 Hz). MS Calcd.: 516.3; MS Found: 515.25 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.29 (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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.29 (1H, s), 8.04 (1H, d, J = 6.0 Hz), 7.81 (2H, d, J = 7.6 Hz), 7.56 (1H, d, J = 3.2 Hz), 7.37-7.41 (4H, m), 7.27-7.30 (1H, m), 6.98-7.00 (1H, m), 6.49-6.51 (1H, m), 5.10-5.20 (1H, m), 3.02-3.06 (2H, m), 2.99 (2H, q, J = 7.3 Hz), 2.38-2.48 (10H, m), 2.27 (2H, q, J = 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 ⁺ ).

(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)

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

(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)

^1H -NMR (400 MHz, DMSO-d ₆ ): δ 12.9 (1H, s), 9.80 (1H, s), 8.44 (1H, s), 8.14 (2H, d, J = 6.0 Hz), 7.88-7.81 (4H, m), 7.67 (1H, d, J = 8.8 Hz), 7.58 (1H, s), 7.39 (2H, t, J = 7.8 Hz), 7.29 (1H, t, J = 7.4 Hz), 6.63 (1H, dd, J = 5.6, 1.6 Hz), 3.00 (2H, q, J = 7.6 Hz), 1.34 (3H, t, J = 7.6 Hz). MS Calcd.: 440.52; MS Found: 441.2 (M+H ⁺ ).

(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)

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

(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)

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

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.31 (1H, brs), 8.17 (1H, d, J = 6.0 Hz), 7.83-7.76 (4H, m), 7.52 (1H, d, J = 7.6 Hz), 7.41 (2H, t, J = 7.6) Hz), 7.30 (2H, t, J = 7.2 Hz), 6.62 (1H, s), 3.28-3.23 (1H, m), 1.37 (6H, d, J = 7.2 Hz) * A proton from OH was not observed. MS Calcd.: 432.49 Found: 433.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.44 (1H, s), 8.16 (2H, d, J = 6.0 Hz), 7.85-7.80 (3H, m), 7.44-7.39 (3H, m), 7.33-7.29 (4H, m), 6.69 (1H, 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.05 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.83 (2H, d, J = 7.6 Hz), 7.61 (1H, d, J = 8.0 Hz), 7.49 (1H, s), 7.41 (2H, t, J = 7.6 Hz), 7.31 (1H, t, J = 7.2 Hz), 7.15 (1H, t, J = 7.6 Hz), 6.97 (1H, d, J = 8.0 Hz), 6.59 (1H, dd, J = 2.0 Hz, 5.8 Hz), 6.43 (1H, d, J = 2.4 Hz), 4.91 (1H, s), 3.32-3.25 (1H, m), 1.39-1.38 (12H, m). MS Calcd.: 445.58; MS Found: 446.2 (M+H ⁺ ).

(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)

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

(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)

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

(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)

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

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.55 (1H, s), 8.21 (2H, t, J = 5.6 Hz), 7.83 (2H, d, J = 7.2 Hz), 7.68-7.65 (2H, m), 7.42 (2H, t, J = 7.2 Hz), 7.32 (1H, t, J = 7.2 Hz), 6.75 (1H, dd, J = 6.0 Hz), 6.54 (1H, d, J = 2.4 Hz), 5.09 (1H, s), 3.32-3.28 (1H, m), 1.39 (12H, d, J = 9.2 Hz). MS Calcd.: 446.56; MS Found: 447.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.19 (1H, s), 8.56 (1H, d, J = 2.4 Hz), 8.09 (1H, d, J = 6.0 Hz), 8.04 (1H, dd, J = 2.4 Hz, 9.0 Hz), 7.81 (2H, d, J = 6.8 Hz), 7.48 (1H, d, J = 8.8 Hz), 7.40 (2H, t, J = 8.0 Hz), 7.30 (1H, t, J = 7.2 Hz), 6.64 (1H, dd, J = 2.4 Hz, 5.6 Hz), 6.39 (1H, d, J = 2.4 Hz), 5.04 (1H, s), 3.29-3.27 (1H, m), 1.37 (12H, d, J = 6.8 Hz). MS Calcd.: 446.56; MS Found: 447.3 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.87 (1H, s), 8.19 (1H, d, J = 6.0 Hz), 8.02 (1H, s), 7.93 (1H, d, J = 8.4 Hz), 7.83-7.78 (3H, m), 7.47 (1H, d, J = 6.8 Hz), 7.41 (2H, t, J = 7.6 Hz), 7.31-7.28 (2H, m), 6.74 (1H, d, J = 3.6 Hz), 3.25-3.23 (1H, m), 2.76 (3H, d, J = 4.4 Hz), 1.35 (6H, d, J = 6.8 Hz). MS Calcd.: 445.54 Found: 446.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.87 (1H, s), 8.19 (1H, d, J = 6.0 Hz), 7.96 (1H, d, J = 8.4 Hz), 7.83-7.79 (3H, m), 7.59 (1H, s), 7.50-7.44 (2H, m), 7.40 (2H, t, J = 7.6 Hz), 7.30-7.24 (2H, m), 6.72 (1H, dd, J = 5.6, 2.4 Hz), 3.27-3.26 (1H, m), 1.37 (6H, d, J = 6.4 Hz). MS Calcd.: 431.51 Found: 432.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.14 (1H, s), 8.64 (1H, s), 8.20 (1H, d, J = 4.2 Hz), 8.06 (1H, d, J = 8.4 Hz), 7.88 (1H, s), 7.82 (2H, d, J = 6.8 Hz), 7.69 (1H, d, J = 8.8 Hz), 7.61 (1H, s), 7.41 (2H, t, J = 7.2 Hz), 7.30 (2H, t, J = 7.6 Hz), 6.72 (1H, d, J = 4.2 Hz), 3.28-3.26 (1H, m), 1.38 (6H, d, J = 6.8 Hz). MS Calcd.: 431.51 Found: 432.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.12 (1H, s), 8.59 (1H, s), 8.34 (1H, brs), 8.20 (1H, d, J = 6.4 Hz), 8.01 (1H, m), 7.82 (2H, d, J = 8.0 Hz), 7.70 (1H, d, J = 9.2 Hz), 7.60 (1H, s), 7.39-7.37 (2H, m), 7.30 (1H, d, J = 7.2 Hz), 6.72-6.70 (1H, m), 2.75 (3H, d, J = 4.4 Hz), 1.38 (6H, d, J = 7.2 Hz). MS Calcd.: 445.54; MS Found: 446.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.35 (1H, s), 8.17 (2H, t, J = 4.2 Hz), 7.82 (2H, d, J = 7.6 Hz), 7.22 (4H, q, J = 8.8 Hz), 7.81 (2H, t, J = 7.2 Hz), 7.31 (1H, t, J = 8.0 Hz), 6.68 (1H, dd, J = 5.6, 2.4 Hz), 6.46 (1H, d, J = 2.0 Hz), 3.27-3.25 (1H, m), 2.73 (3H, d, J = 4.4 Hz), 1.38 (6H, d, J = 7.2 Hz). MS Calcd.: 444.16 Found: 445.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 12.85 (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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 12.43 (1H, s), 9.52 (1H, s), 8.20 (1H, d, J = 6.0 Hz), 7.84-7.81 (4H, m), 7.73 (2H, d, J = 8.4 Hz), 7.42 (2H, t, J = 7.2 Hz), 7.34-7.30 (1H, m), 6.73 (1H, dd, J = 2.0 Hz, 5.6 Hz), 6.51 (1H, d, J = 2.0 Hz), 3.32-3.26 (1H, m), 1.39 (6H, d, J = 7.2 Hz). MS Calcd.: 431.51; MS Found: 432.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 12.79 (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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.43 (1H, s), 8.30 (1H, s), 8.18 (1H, s), 8.14 (1H, d, J = 5.6 Hz), 7.91-7.83 (4H, m), 7.80 (1H, d, J = 8.0 Hz), 7.74 (1H, d, J = 5.2 Hz), 7.49-7.47 (2H, m), 7.39 (1H, t, J = 7.6 Hz), 7.30 (1H, d, J = 6.4 Hz), 7.26 (2H, s), 6.75 (1H, dd, J = 2.4 Hz, 5.6 Hz), 6.57 (1H, d, J = 2.0 Hz), 2.94 (3H, d, J = 4.4 Hz). MS Calcd.: 503.6; MS Found: 504.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.47 (1H, s), 8.26 (1H, s), 8.17-8.13 (2H, m), 7.85-7.79 (4H, m), 7.49-7.47 (2H, m), 7.42 (1H, t, J = 8.0 Hz), 7.38-7.24 (4H, m), 6.75 (1H, dd, J = 2.0 Hz, 5.8 Hz), 6.58 (1H, s). * Two proton form NH ₂ were not observed. MS Calcd.: 489.57; MS Found: 490.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.43 (1H, s), 8.33 (1H, s), 8.18 (1H, s), 8.15 (1H, d, J = 6.0 Hz), 7.93-7.84 (4H, m), 7.78 (1H, d, J = 8.0 Hz), 7.50-7.48 (2H, m), 7.39 (1H, t, J = 8.0 Hz), 7.31-7.27 (3H, m), 6.75 (1H, dd, J = 2.4 Hz, 6.0 Hz) 6.56 (1H, d, J = 2.0 Hz), 3.12 (6H, s). MS Calcd.: 517.62; MS Found: 518.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, MeOD-d ₄ ): δ 7.98-7.97 (2H, m), 7.61 (1H, d, J = 7.6 Hz), 7.54 (1H, d, J = 8.0 Hz), 7.49-7.42 (3H, m), 7.37-7.30 (3H, m), 7.22-7.18 (1H, m), 7.13 (1H, d, J = 8.0 Hz), 6.83 (1H, d, J = 8.0 Hz), 5.77 (1H, s). * Two protons from NH ₂ were not observed. MS Calcd.: 440.50; MS Found: 441.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.75 (1H, s), 8.26 (1H, s), 7.83 (1H, s), 7.59-7.57 (1H, m), 7.57-7.48 (4H, m), 7.47-7.32 (5H, m), 5.67 (1H, s), 2.72 (3H, s). MS Calcd.: 439.51; MS Found: 440.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.0 (1H, s), 8.47 (1H, d, J = 6.0 Hz), 8.11 (1H, s), 7.82 (3H, d, J = 8.4 Hz), 7.39 (4H, t, J = 7.4 Hz), 7.29 (3H, s), 6.75 (1H, d, J = 4.8 Hz), 2.67 (3H, s). MS Calcd.: 439.51; MS Found: 440.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.1 (1H, s), 8.43 (1H, d, J = 5.2 Hz), 8.09 (1H, s), 7.97 (1H, s), 7.68 (1H, d, J = 8.0 Hz), 7.38 (1H, d, J = 4.8 Hz), 7.33 (2H, d, J = 7.2 Hz), 7.25-7.20 (1H, m), 6.99 (2H, s), 6.65 (1H, d, J = 5.2 Hz), 6.55 (1H, s). * Three protons from NH and NH ₂ were not observed. MS Calcd.: 440.50; MS Found: 441.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.06 (1H, s), 8.48 (1H, d, J = 5.6 Hz), 8.08 (1H, brs), 7.83 (3H, d, J = 8.0 Hz), 7.42-7.35 (4H, m), 7.31-7.28 (3H, m), 6.75 (1H, d, J = 5.6 Hz), 3.00 (2H, q, J = 7.3 Hz), 1.33 (3H, t, J = 7.6 Hz). MS Calcd.: 453.09; MS Found: 454.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.95 (1H, s), 8.54 (1H, d, J = 6.0 Hz), 8.02 (1H, d, J = 8.4 Hz), 7.83-7.77 (4H, m), 7.65 (1H, s), 7.58 (1H, d, J = 7.2 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.31-7.29 (1H, m), 6.86 (1H, d, J = 5.6 Hz), 3.01 (2H, q, J = 7.6 Hz), 1.34 (3H, t, J = 7.8 Hz). MS Calcd.: 418.12; MS Found: 419.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.23 (1H, s), 8.53 (1H, d, J = 5.6 Hz), 8.36 (1H, d, J = 5.2 Hz), 8.31 (1H, s), 8.08 (1H, s), 7.85 (2H, d, J = 7.2 Hz), 7.65 (1H, s), 7.41 (2H, t, J = 7.6 Hz), 7.35-7.30 (2H, m), 6.81 (1H, d, J = 5.2 Hz), 2.96 (2H, q, J = 7.6 Hz), 1.30 (3H, t, J = 7.6 Hz). MS Calcd.: 418.12; MS Found: 419.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.86 (1H, s), 8.45 (1H, d, J = 5.6 Hz), 7.99 (1H, s), 7.83 (3H, d, J = 7.6 Hz), 7.71 (1H, d, J = 9.6 Hz), 7.42-7.38 (3H, m), 7.29-7.22 (3H, m), 6.70 (1H, d, J = 5.6 Hz), 2.98 (2H, q, J = 7.5 Hz), 1.32 (3H, t, J = 7.4 Hz). MS Calcd.: 417.13; MS Found: 418.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.9 (1H, brs), 8.77 (1H, s), 8.58 (1H, d, J = 6.0 Hz), 8.09 (1H, d, J = 8.8 Hz), 7.90 (1H, d, J = 8.8 Hz), 7.82 (2H, d, J = 7.2 Hz), 7.39 (3H, t, J = 7.6 Hz), 7.30-7.27 (1H, m), 6.94 (1H, d, J = 5.6 Hz), 3.01 (2H, q, J = 7.5 Hz), 1.34 (3H, t, J = 7.4 Hz). MS Calcd.: 419.11; MS Found: 420.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.44 (1H, s), 8.73 (1H, s), 8.54 (1H, d, J = 5.6 Hz), 8.02-8.01 (2H, m), 7.90-7.87 (1H, m), 7.83 (2H, d, 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 12.57 (1H, s), 10.16 (1H, s), 8.50 (1H, d, J = 5.2 Hz), 7.81 (2H, d, J = 7.6 Hz), 7.75 (2H, d, J = 8.8 Hz), 7.64 (2H, d, J = 8.0 Hz), 7.39 (2H, t, J = 7.4 Hz), 7.30-7.27 (1H, m), 6.79 (1H, d, J = 5.6 Hz), 3.01 (2H, q, J = 7.3 Hz), 1.35 (3H, t, J = 7.4 Hz). MS Calcd.: 418.11; MS Found: 419.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.35 (1H, s), 8.22 (1H, s), 8.09 (1H, d, J = 5.6 Hz), 7.80 (1H, d, J = 8.4 Hz), 7.65 (1H, t, J = 7.6 Hz), 7.54 (1H, d, J = 8.0 Hz), 7.39 (1H, t, J = 7.8 Hz), 7.30 (1H, d, J = 7.6 Hz), 7.27 (2H, s), 7.16 (2H, s), 7.03 (1H, d, J = 7.6 Hz), 6.60 (1H, dd, J = 5.6, 2.4 Hz), 6.47 (1H, d, J = 2.0 Hz), 2.20 (3H, s). MS Calcd.: 454.53; MS Found: 455.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.50 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 7.81 (2H, d, J = 9.2 Hz), 7.72 (3H, d, J = 8.8 Hz), 7.59 (1H, d, J = 7.6) Hz), 7.31 (2H, s), 7.13 (1H, d, J = 7.2 Hz), 6.68 (1H, d, J = 6.4 Hz), 6.55 (1H, d, J = 2.0 Hz), 2.28 (3H, s). * Two protons from OH and TFA were not observed. MS Calcd.: 419.46; MS Found: 420.1(M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.38 (1H, s), 8.21 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.85 (1H, d, J = 8.4 Hz), 7.76 (1H, t, J = 7.6 Hz), 7.59 (1H, d, J = 8.4 Hz), 7.48 (1H, d, J = 6.8 Hz), 7.36 (1H, t, J = 8.0 Hz), 7.34 (2H, s), 7.14 (1H, d, J = 7.6 Hz), 6.65 (1H, d, J = 3.2 Hz), 6.50 (1H, d, J = 2.0 Hz), 2.30 (3H, s). * Two protons from OH and TFA were not observed. MS Calcd.: 419.46; MS Found: 420.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.33 (1H, s), 8.18 (1H, s), 8.09 (1H, d, J = 6.0 Hz), 7.77 (1H, d, J = 8.0 Hz), 7.71-7.69 (2H, m), 7.39 (1H, t, J = 8.0 Hz), 7.28 (1H, d, J = 7.6 Hz), 7.27 (2H, s), 7.09 (1H, d, J = 6.8 Hz), 6.60 (1H, dd, J = 5.6, 4.0 Hz), 6.36 (1H, d, J = 2.0 Hz), 3.04 (2H, q, J = 8.0 Hz), 2.20 (3H, s), 1.36 (3H, t, J = 7.2 Hz). MS Calcd.: 467.56 Found: 468.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.0 (1H, s), 8.63 (1H, d, J = 2.4 Hz), 8.13 (1H, d, J = 6.0 Hz), 8.05 (1H, dd, J = 9.0, 2.2 Hz), 7.87 (1H, s), 7.72-7.66 (3H, m), 7.51 (1H, d, J = 2.4 Hz), 7.26 (1H, s), 7.07 (1H, d, J = 6.4 Hz), 6.61 (1H, dd, J = 6.0, 2.4 Hz), 3.02 (2H, q, J = 7.5 Hz), 2.19 (3H, s), 1.35 (3H, t, J = 7.4 Hz). MS Calcd.: 432.50; MS Found: 433.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 12.5 (1H, s), 8.84 (1H, d, J = 2.4 Hz), 8.39 (1H, d, J = 7.6 Hz), 8.30 (1H, dd, J = 8.6, 2.2 Hz), 7.89-7.78 (2H, m), 7.32 (1H, d, J = 8.4 Hz), 7.18-7.15 (3H, m), 3.05 (2H, q, J = 7.6 Hz), 2.19 (3H, s), 1.36 (3H, t, J = 7.6 Hz). * A proton from OH was not observed. MS Calcd.: 433.48; MS Found: 434.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.0 (1H, s), 8.59 (1H, s), 8.32 (1H, s), 8.13 (1H, d, J = 5.2 Hz), 8.02 (1H, d, J = 9.6 Hz), 7.70-7.65 (3H, m), 7.48 (1H, s), 7.07 (1H, d, J = 7.2 Hz), 6.63 (1H, s), 3.02 (2H, q, J = 7.6 Hz), 2.75 (3H, d, J = 4.4 Hz), 2.19 (3H, s), 1.35 (3H, t, J = 7.6 Hz). MS Calcd.: 446.52; MS Found: 447.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.97 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.86 (1H, d, J = 8.0 Hz), 7.78 (1H, t, J = 7.8 Hz), 7.71-7.65 (3H, m), 7.50 (1H, d, J = 6.8 Hz), 7.06 (1H, d, J = 5.6 Hz), 6.56 (1H, dd, J = 5.6, 2.4 Hz), 3.01 (2H, q, J = 7.6 Hz), 2.19 (3H, s), 1.34 (3H, t, J = 7.6 Hz). * A proton from OH was not observed. MS Calcd.: 433.48; MS Found: 434.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.77 (1H, s), 8.13 (1H, d, J = 6.0 Hz), 7.93 (1H, d, J = 8.4 Hz), 7.80 (1H, t, J = 7.6 Hz), 7.70-7.57 (2H, m), 7.60 (1H, s), 7.47 (1H, d, J = 7.2 Hz), 7.38 (1H, s), 7.15 (1H, d, J = 2.4 Hz), 7.07 (1H, d, J = 7.2 Hz), 6.64 (1H, d, J = 5.6 Hz), 3.02 (2H, q, J = 7.6 Hz), 2.18 (3H, s), 1.35 (3H, t, J = 7.6 Hz). MS Calcd.: 432.50 Found: 433.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.75 (1H, s), 8.13 (1H, d, J = 5.6 Hz), 8.00 (1H, s), 7.94 (1H, d, J = 6.8 Hz), 7.79 (1H, t, J = 8.0 Hz), 7.70-7.67 (2H, m), 7.45 (1H, d, J = 7.2 Hz), 7.12 (1H, s), 7.08 (1H, d, J = 8.8 Hz), 6.66 (1H, s), 3.00 (2H, q, J = 7.5 Hz), 2.78 (3H, d, J) = 5.2 Hz), 2.19 (3H, s), 1.33 (3H, t, J = 7.4 Hz). 446.52; MS Found: 447.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.18 (1H, s), 8.21 (1H, s), 8.08 (1H, d, J = 6.0 Hz), 7.83 (1H, d, J = 8.0 Hz), 7.72-7.68 (2H, m), 7.41 (1H, d, J = 7.2 Hz), 7.30 (1H, t, J = 7.8 Hz), 7.08 (1H, d, J = 7.6 Hz), 6.56 (1H, d, J = 6.0 Hz), 6.34 (1H, d, J = 1.6 Hz), 3.01 (2H, q, J = 7.6 Hz), 2.22 (3H, s), 1.34 (3H, t, J = 7.4 Hz). * A proton from OH was not observed. MS Calcd.: 432.49; MS Found: 433.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.10 (1H, s), 8.07 (1H, d, J = 5.6 Hz), 7.99 (1H, s), 7.80-7.78 (2H, m), 7.70-7.69 (2H, m), 7.32 (1H, d, J = 8.4 Hz), 7.26-7.23 (2H, m), 7.09 (1H, dd, J = 6.0, 2.4 Hz), 6.55 (1H, dd, J = 5.6, 3.2 Hz), 6.35 (1H, d, J = 2.0 Hz), 3.03 (2H, q, J = 8.0 Hz), 2.22 (3H, s), 1.36 (3H, t, J = 7.2 Hz). MS Calcd.: 431.52 Found: 432.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.12 (1H, s), 8.27 (1H, d, J = 4.4 Hz), 8.07 (1H, d, J = 5.6 Hz), 7.97 (1H, s), 7.77 (1H, s), 7.70-7.69 (2H, m), 7.26 (2H, d, J = 5.6 Hz), 7.08 (1H, dd, J = 8.8, 2.4 Hz), 6.55 (1H, dd, J = 5.2, 3.2 Hz), 6.35 (1H, d, J = 2.4 Hz), 3.03 (2H, q, J = 7.6 Hz), 2.73 (3H, d, J = 4.4 Hz), 2.22 (3H, s), 1.36 (3H, t, J = 7.2 Hz). MS Calcd.: 445.16 Found: 446.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.42 (1H, s), 8.84 (1H, d, J = 2.8 Hz), 8.73 (1H, s), 8.54 (1H, s), 8.14 (1H, d, J = 6.0 Hz), 7.72-7.67 (2H, m), 7.09 (1H, d, J = 6.8 Hz), 6.64 (1H, dd, J = 6.0, 1.8 Hz), 6.37 (1H, d, J = 1.6 Hz), 3.09 (2H, q, J = 7.7 Hz), 2.20 (3H, s), 1.35 (3H, t, J = 7.6 Hz). * A proton from OH was not observed. MS Calcd.: 433.48; MS Found: 434.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.32 (1H, s), 8.79 (1H, d, J = 2.4 Hz), 8.53 (1H, s), 8.49 (1H, s), 8.12 (1H, d, J = 4.2 Hz), 8.03 (1H, s), 7.73-7.67 (2H, m), 7.48 (1H, s), 7.09 (1H, d, J = 8.0 Hz), 6.63 (1H, dd, J = 6.0, 3.6 Hz), 6.63 (1H, dd, J = 6.0, 4.6 Hz), 6.37 (1H, d, J = 2.0 Hz), 3.04 (2H, q, J = 7.6 Hz), 2.30 (3H, s), 1.36 (3H, t, J = 7.2 Hz). MS Calcd.: 432.50 Found: 433.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.34 (1H, s), 8.79 (1H, d, J = 2.8 Hz), 8.52-8.49 (2H, m), 8.44 (1H, s), 8.12 (1H, d, J = 5.6 Hz), 7.65-7.58 (2H, m), 7.09 (1H, d, J = 7.2 Hz), 6.63 (1H, dd, J = 5.6, 1.8 Hz), 6.37 (1H, d, J = 1.6 Hz), 3.02 (2H, q, J = 7.5 Hz), 2.76 (3H, d, J = 4.4 Hz), 2.21 (3H, s), 1.35 (3H, t, J = 7.4 Hz). MS Calcd.: 446.52; MS Found: 447.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.2 (1H, s), 8.29-8.25 (3H, m), 7.93 (1H, s), 7.75-7.68 (2H, m), 7.08 (1H, d, J = 7.2 Hz), 6.81 (1H, d, J = 5.2 Hz), 6.523 (1H, s), 3.02 (2H, q, J = 7.5 Hz), 2.16 (3H, s), 1.35 (3H, t, J = 7.4 Hz). * A proton from OH was not observed. MS Calcd.: 433.48; MS Found: 434.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.69 (1H, s), 8.29 (1H, d, J = 5.6 Hz), 8.22-8.19 (2H, m), 7.97 (1H, s), 7.80 (1H, d, J = 4.0 Hz), 7.74-7.67 (2H, m), 7.51 (1H, s), 7.07 (1H, d, J = 7.2 Hz), 6.71 (1H, d, J = 4.0 Hz), 6.44 (1H, s), 3.01 (2H, q, J = 7.6 Hz), 2.18 (3H, s), 1.34 (3H, t, J = 7.4 Hz). MS Calcd.: 432.50; MS Found: 433.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.72 (1H, s), 8.64 (1H, s), 8.30 (1H, d, J = 5.6 Hz), 8.20 (1H, d, J = 5.6 Hz), 8.16 (1H, s), 7.86 (1H, d, J = 4.0 Hz), 7.74-7.68 (2H, m), 7.08 (1H, d, J = 7.2 Hz), 6.71 (1H, d, J = 5.6 Hz), 6.45 (1H, d, J = 1.2 Hz), 3.02 (2H, q, J = 7.5 Hz) , 2.77 (3H, d, J = 4.8 Hz), 2.18 (3H, s), 1.35 (3H, t, J = 7.6 Hz). MS Calcd.: 446.52; MS Found: 447.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.35 (1H, d, J = 5.6 Hz), 8.25 (1H, d, J = 6.4 Hz), 7.78 (1H, d, J = 7.6 Hz), 7.71-7.66 (2H, m), 7.53 (1H, d, J = 5.6 Hz), 7.09 (1H, d, J = 8.0 Hz), 6.97-6.93 (2H, m), 3.07 (2H, q, J = 7.5 Hz), 2.29 (3H, s), 1.44 (3H, t, J = 7.4 Hz). * Two protons from NH and OH were not observed. MS Calcd.: 433.48; MS Found: 434.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.82 (1H, s), 8.21 (1H, d, J = 5.2 Hz), 8.11 (1H, d, J = 5.6 Hz), 8.05-8.02 (2H, m), 7.69-7.67 (2H, m), 7.58 (1H, s), 7.49 (1H, s), 7.17 ( 1H , d, J = 4.0 Hz), 7.07 (1H, d, J = 6.8 Hz), 6.57 (1H, d, J = 4.4 Hz), 3.04 (2H, q, J = 7.6 Hz), 2.19 (3H, s), 1.36 (3H, t, J = 7.6 Hz). MS Calcd.: 432.50; Found: 433.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.23 (1H, d, J = 5.2 Hz), 8.09 (1H, d, J = 6.0 Hz), 7.86 (1H, s), 7.67-7.66 (2H, m), 7.44 (1H, s), 7.14 (1H, d, J = 5.6 Hz), 7.10 (1H, t, J = 4.0 Hz), 6.63 (1H, dd, J = 6.0, 2.0 Hz), 3.07 (2H, q, J = 7.8 Hz), 2.91 (3H, s), 2.38 (3H, s), 1.44 (3H, t, J = 7.6 Hz). * Two protons from NH were not observed. MS Calcd.: 446.52; MS Found: 447.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.2 (1H, s), 9.25 (1H, s), 8.63 (1H, s), 8.58-8.57 (1H, m), 8.14 (1H, d, J = 6.0 Hz), 8.04 (1H, d, J = 11.2 Hz), 7.78 (1H, d, J = 8.4 Hz), 7.74-7.67 (1H, m), 7.58 (1H, s), 7.14 (1H, d, J = 17.6 Hz), 6.63 (1H, d, J = 3.2 Hz), 3.61-3.51 (2H, m), 3.26-3.19 (2H, m), 3.02 (2H, q, J = 7.6 Hz), 2.82 (6H, s), 2.19 (3H, s), 1.35 (3H, t, J = 7.4 Hz). MS Calcd.: 503.62; MS Found: 504.3 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.2 (1H, s), 8.68 (1H, d, J = 2.0 Hz), 8.15 (1H, d, J = 5.2 Hz), 8.09 (1H, d, J = 9.6 Hz), 7.77 (1H, d, J = 8.8 Hz), 7.73-7.66 (2H, m), 7.54 (1H, s), 7.06 (1H, d, J = 6.8 Hz), 6.66 (1H, d, J = 6.0 Hz), 4.07 (2H, d, J = 7.2 Hz), 3.01 (2H, q, J = 7.5 Hz), 1.33 (3H, t, J = 7.6 Hz), 0.77-0.89 (1H, m), 0.56-0.52 (2H, m), 0.35-0.31 (2H, m). MS Calcd.: 487.57; MS Found: 488.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.78 (1H, d, J = 2.0 Hz), 8.16 (1H, dd, J = 8.4, 2.4 Hz), 8.12 (1H, d, J = 6.0 Hz), 7.69-7.64 (2H, m), 7.59 (1H, d, J = 2.0 Hz), 7.56 (1H, d, J = 8.8 Hz), 7.10 (1H, dd, J = 8.4, 2.0 Hz), 6.67 (1H, dd, J = 5.8, 1.8 Hz), 4.44 (2H, t, J = 5.6 Hz), 3.07 (2H, q, J = 7.6 Hz), 2.81 (2H, t, J = 5.6 Hz), 2.39 (6H, s), 2.37 (3H, s), 1.44 (3H, t, J = 7.6 Hz). * A proton from NH was not observed. MS Calcd.: 504.60; MS Found: 505.3 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.63 (1H, s), 9.06 (1H, s), 8.04 (1H, d, J = 6.0 Hz), 7.70-7.69 (2H, m), 7.43 (2H, s), 7.14-7.09 (2H, m), 6.68 (1H, d, J = 6.8 Hz), 6.54 (1H, d, J = 3.6 Hz), 6.33 (1H, s), 3.03 (2H, q, J = 8.0 Hz), 2.89 (3H, s), 2.30 (3H, s), 1.35 (3H, t, J = 7.2 Hz). MS Calcd.: 481.59; Found: 482.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.76 (1H, s), 8.17-8.13 (3H, m), 7.95 (1H, d, J = 10.4 Hz), 7.70-7.62 (2H, m), 7.61 (2H, d, J = 8.4 Hz), 7.54 (1H, d, J = 8.8 Hz), 7.11 (1H, d, J = 6.0 Hz), 6.67 (1H, d, J = 4.0 Hz), 4.49 (2H, t, J = 5.4 Hz), 3.08 (2H, q, J = 7.6 Hz), 2.70-2.60 (2H, m), 2.42 (3H, s), 2.37 (6H, d, J = 8.4 Hz), 1.45 (3H, t, J = 7.4 Hz). * Two protons from NH were not observed. MS Calcd.: 641.72; MS Found: 642.3 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.12 (1H, s), 8.06 (1H, d, J = 6.0 Hz), 8.00 (1H, s), 7.83-7.78 (2H, m), 7.71-7.66 (2H, m), 7.32 (1H, d, J = 8.0 Hz), 7.27-7.23 (2H, m), 7.07 (1 H, dd, J = 6.4, 2.0 Hz), 6.85 (1H, dd, J = 5.6, 2.0 Hz), 6.34 (1H, d, J = 2.0 Hz), 2.45-2.40 (1 H, m), 2.21 (3 H, s), 1.66-1.13 (2 H, m), 1.07-1.03 (2 H, m). MS Calcd.: 443.53; MS Found: 444.28 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.01 (1H, s), 8.64 (1H, d, J = 1.6 Hz), 8.12 (1H, d, J = 5.6 Hz), 8.05 (1H, dd, J = 9.2, 2.4 Hz), 7.88 (1H, s), 7.75 (1H, d, J = 9.2 Hz), 7.68-7.67 (2H, m), 7.46 (1H, d, J = 1.6 Hz), 7.28 (1H, s), 7.05 (1H, t, J = 4.0 Hz), 6.61 (1H, dd, J = 5.6, 2.4 Hz), 2.44-2.40 (1H, m), 2.17 (3H, s), 1.17-1.13 (2H, m), 1.07-1.04 (2H, m). MS Calcd.: 444.51; MS Found: 445.27 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.81 (s, 1H), 8.21 (d, J = 4.8 Hz, 1H), 8.10 (d, J = 6.0 Hz, 1H), 8.05 (s, 1H), 7.44 (d, J = 2.4 Hz, 1H), 7.18 (d, J = 5.2 Hz, 1H), 7.06 (t, J = 4.4 Hz, 1H), 6.57 (dd, J = 6.0, 2.4 Hz, 1H), 2.44-2.30 (m, 2H), 2.18 (s, 3H), 1.21-1.12 (m, 2H), 1.09-1.03 (m, 2H). MS Calcd.: 444.51; MS Found: 445.27 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.33 (1H, s), 8.19 (1H, s), 8.09 (1H, d, J = 6.0 Hz), 7.76 (1H, d, J = 7.6 Hz), 7.70-7.68 (2H, m), 7.34 (1H, t, J = 8.0 Hz), 7.29-7.27 (3H, m), 7.09-7.07 (1H, m), 6.65 (1H, dd, J = 5.6, 2.4 Hz), 6.36 (1H, d, J = 2.0 Hz), 2.45-2.40 (1H, m), 2.20 (3H, s), 1.18-1.13 (2H, m), 1.08-1.04 (2H, m). MS Calcd.: 479.57; MS Found: 480.29 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.76 (1H, s), 8.12 (1H, d, J = 5.6 Hz), 7.79 (1H, t, J = 7.6 Hz), 7.68-7.65 (2H, m), 7.59 (1H, br s), 7.47 (1H, d, J = 7.2 Hz), 7.41 (1H, br s), 7.10 (1H, d, J = 2.4 Hz), 7.05 (1H, dd, J = 6.0, 2.4 Hz), 6.63 (1H, dd, J = 5.6, 2.4 Hz), 2.47-2.41 (1H, m), 2.17 (3H, s), 1.16-1.12 (2H, m), 1.10-1.05 (2H, m). MS Calcd.: 444.51; MS Found: 445.32 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.75 (1H, s), 8.13 (1H, d, J = 5.2 Hz), 8.01-7.95 (2H, m), 7.79 (1H, t, J = 7.2 Hz), 7.68-7.65 (2H, m), 7.45 (1H, d, J = 7.6 Hz), 7.09 (1H, d, J = 4.4 Hz), 6.65 (1H, dd, J = 5.6, 2.4 Hz), 2.78 (3 H, d, J = 5.2 Hz), 2.44-2.38 (1H, m), 2.18 (3H, s), 1.66-1.12 (2H, m), 1.05-1.01 (2H, m). MS Calcd.: 458.54; MS Found: 459.31 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.84 (1H, s), 8.56 (1H, d, J = 4.8 Hz), 8.22 (1H, d, J = 5.2 Hz), 8.11 (1H, d, J = 6.1 Hz), 8.04 (1H, s), 7.63 (2H, d, J = 4.8 Hz), 7.44 (1H, d, J = 2.4 Hz), 7.14 (1H, d, J = 1.6 Hz), 7.06 (1H, t, J = 4.4 Hz), 6.57 (1H, dd, J = 6.0, 2.4 Hz), 2.75 (3H, d, J) = 4.2 Hz), 2.46-2.31 (1H, m), 2.07 (3H, s), 1.21-1.27 (2H, m), 1.07-1.03 (2H, m). MS Calcd.: 458.54; MS Found: 459.37 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.14 (1H, s), 8.30 (1H, d, J = 4.9 Hz), 8.06 (1H, d, J = 5.7 Hz), 7.98 (1H, s), 7.78 (1H, dd, J = 6.7, 3.0 Hz), 7.73-7.63 (2H, m), 7.25 (2H, d, J = 4.7 Hz), 7.07 (1H, dd, J = 5.6, 2.7 Hz), 6.55 (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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.01 (1H, s), 8.59 (1H, d, J = 2.2 Hz), 8.35 (1H, d, J = 4.3 Hz), 8.12 (1H, d, J = 5.7 Hz), 8.01 (1H, dd, J = 9.1, 2.4 Hz), 7.76 (1H, d, J = 8.6 Hz), 7.68 (2H, dd, J = 6.3, 2.3 Hz), 7.44 (1H, d, J = 1.9 Hz), 7.09-7.02 (1H, m), 6.65-6.57 (1H, m), 2.74 (2H, d, J = 4.4 Hz), 2.41 (1H, dd, J = 13.2, 1.0 Hz), 2.17 (2H, s), 1.19-1.11 (2H, m), 1.06-1.03 (2H, m). MS Calcd.: 458.54; MS Found: 459.25 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.32 (1H, s), 8.22 (1H, s), 8.09 (1H, d, J = 5.6 Hz), 7.78 (1H, d, J = 8.4 Hz), 7.70-7.65 (2H, m), 7.39 (1H, t, J = 8.0 Hz), 7.30-7.26 (3H, m), 7.07-7.04 (1H, m), 6.61 (1H, dd, J = 2.0 Hz, 5.8 Hz), 6.45 (1H, d, J = 2.0 Hz), 3.08 (6H, s), 2.08 (3H, s). MS Calcd.: 482.58; MS Found: 483.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.98 (1H, s), 8.64 (1H, d, J = 2.0 Hz), 8.11 (1H, d, J = 6.0 Hz), 8.05 (1H, dd, J = 8.8, 2.4 Hz), 7.87 (1H, s), 7.76 (1H, d, J = 8.8 Hz), 7.65 (2H, d, J = 4.4 Hz), 7.48 (1H, d, J = 2.0 Hz), 7.27 (1H, s), 7.01 (1H, t, J = 4.2 Hz), 6.61 (1H, dd, J = 6.0, 2.4 Hz), 3.07 (6H, s), 2.16 (3H, s). MS Calcd.: 447.51; MS Found: 448.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.79 (1H, s), 8.31 (1H, d, J = 6.8 Hz), 8.24 (1H, d, J = 8.8 Hz), 7.72 (2H, s), 7.33 (1H, s), 7.14-7.03 (3H, m), 3.09 (6H, s), 2.16 (3H, s). * Two protons from NH and OH were not observed. MS Calcd.: 448.50; MS Found: 449.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.96 (1H, s), 8.60 (1H, s), 8.32 (1H, d, J = 4.0 Hz), 8.11 (1H, d, J = 5.6 Hz), 8.01 (1H, dd, J = 9.2, 2.4 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.33 (1H, s), 8.18 (1H, s), 8.09 (1H, d, J = 6.0 Hz), 7.78-7.68 (3H, m), 7.38 (1H, t, J = 7.8 Hz), 7.28 (1H, d, J = 7.8 Hz), 7.26 (2H, s), 7.08 (1H, d, J = 6.0 Hz), 6.59 (1H, dd, J = 5.6, 2.4 Hz), 6.36 (1H, d, J = 2.4 Hz), 3.31-3.27 (1H, m), 2.21 (3H, s), 1.38 (6H, d, J = 7.2 Hz). MS Calcd.: 481.59 Found: 482.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.01 (1H, s), 8.62 (1H, s), 8.13 (1H, d, J = 6.4 Hz), 8.05 (1H, d, J = 9.2 Hz), 7.86 (1H, s), 7.71-7.68 (3H, m), 7.50 (1H, s), 7.25 (1H, s), 7.07 (1H, d, J = 6.4 Hz), 6.62 (1H, d, J = 6.4 Hz), 3.32-3.25 (1H, m), 2.06 (3H, s), 1.39 (6H, d, J = 7.2 Hz). MS Calcd.: 446.52 Found: 447.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.34 (1H, s), 8.17 (1H, s), 8.13 (1H, d, J = 6.0 Hz), 7.79-7.76 (3H, m), 7.39 (1H, t, J = 8.0 Hz), 7.30 (1H, d, J = 9.2 Hz), 7.27 (2H, s), 7.19 (1H, dd, J = 6.4, 2.8 Hz), 6.69 (1H, dd, J = 6.0, 2.4 Hz), 6.41 (1H, d, J = 2.0 Hz), 2.25 (3H, s). MS Calcd.: 507.51 Found: 508.1 (M+H ⁺ ).

(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)

^1H NMR (400 MHz, CDCl ₃ ): δ 8.63 (s, 1H), 8.17 (d, J = 5.8 Hz, 1H), 8.05 (d, J = 8.6 Hz, 1H), 7.82 (d, J = 8.4 Hz, 2H), 7.62 (t, J = 7.7 Hz, 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 ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.14 (s, 1H), 8.10 (d, J = 6.0 Hz, 1H), 7.99 (br s, 1H), 7.83 (br s, 1H), 7.80-7.74 (m, 3H), 7.33 (d, J = 7.2 Hz, 1H), 7.28-7.24 (m, 2H), 7.19 (dd, J = 6.4, 2.0 Hz, 1H), 6.64 (dd, J = 6.0, 2.0 Hz, 1H), 6.39 (d, J = 2.0 Hz, 1H), 2.26 (s, 3H). MS Calcd.: 471.46 Found: 472.28 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.33 (1H, s), 8.22 (1H, s), 8.09 (1H, d, J = 5.6 Hz), 7.79 (1H, d, J = 8.0 Hz), 7.69-7.67 (2H, m), 7.65-7.62 (1H, m), 7.39 (1H, t, J = 8.0 Hz), 7.30 (1H, d, J = 6.0 Hz), 7.27 (2H, s), 7.04 (1H, d, J = 7.2 Hz), 6.61 (1H, dd, J = 5.6, 2.4 Hz), 6.46 (1H, d, J = 2.4 Hz), 2.89 (3H, d, J = 4.8 Hz), 2.20 (3H, s). MS Calcd.: 468.55 Found: 469.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.4 (1H, brs), 8.68 (1H, s), 8.25 (1H, d, J = 5.2 Hz), 8.10 (1H, d, J = 9.2 Hz), 7.71 (1H, d, J = 8.8 Hz), 7.63-7.61 (3H, m), 7.38 (2H, t, J = 7.6 Hz), 7.26 (1H, t, J = 7.6 Hz), 6.80 (1H, d, J = 5.6 Hz), 2.17-2.13 (1H, m), 1.08-0.99 (4H, m). * A proton from NH was not observed. MS Calcd.: 414.41; MS Found: 415.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.2 (1H, s), 8.66 (1H, s), 8.23 (1H, d, J = 5.6 Hz), 8.08 (1H, d, J = 8.4 Hz), 7.92 (1H, s), 7.70 (1H, d, J = 8.8 Hz), 7.63-7.58 (3H, m), 7.38 (2H, t, J = 7.4 Hz), 7.31 (1H, s), 7.26 (1H, t, J = 7.6 Hz), 6.74 (1H, d, J = 6.0 Hz), 2.19-2.10 (1H, m), 1.10-1.00 (4H, m). MS Calcd.: 446.52; MS Found: 414.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.54 (1H, s), 8.21 (1H, d, J = 6.0 Hz), 7.81 (2H, d, J = 8.4 Hz), 7.72 (2H, d, J = 8.4 Hz), 7.61 (2H, d, J = 7.6) Hz), 7.39 (2H, t, J = 7.6 Hz), 7.25 (1H, t, J = 7.2 Hz), 6.73 (1H, d, J = 6.0 Hz), 6.46 (1H, s), 2.18-2.11 (1H, m), 1.08-1.01 (4H, m). * A proton from OH was not observed. MS Calcd.: 413.43; MS Found: 414.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.28 (s, 1H), 8.17 (d, J = 5.8 Hz, 1H), 8.02 (s, 1H), 788-7.83 (m, 2H), 7.64 (d, J = 7.4 Hz, 2H), 7.44-7.37 (m, 3H), 7.32-7.28 (m, 3H), 6.66 (d, J = 5.8, 2.0 Hz, 1H), 6.41 (d, J = 2.0 Hz, 1H), 2.19-2.15 (m, 1H), 1.10-1.03 (m, 4H). (M+H ⁺ ).MS Calcd.: 412.45; MS Found: 413.30 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.28 (s, 1H), 8.32 (d, J = 5.5 Hz, 1H), 8.15 (d, J = 5.8 Hz, 1H), 7.97 (s, 1H), 7.86-7.76 (m, 1H), 7.61 (d, J = 7.4 Hz, 2H), 7.39 (t, J = 7.5 Hz, 2H), 7.28 (d, J = 10.6 Hz, 3H), 6.64 (dd, J = 5.8, 2.2 Hz, 1H), 6.38 (d, J = 2.3 Hz, 1H), 2.73 (d, J = 4.4 Hz, 3H), 2.14 (s, 1H), 1.11-0.96 (m, 4H). MS Calcd.: 426.48; MS Found: 427.29 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.47 (s, 1H), 8.21-8.13 (m, 2H), 7.80 (d, J = 7.5 Hz, 1H), 7.62 (d, J = 8.0 Hz, 2H), 7.43-7.37 (m, 3H), 7.32-7.30 (m, 4H), 6.69 (d, J = 4.4 Hz, 1H), 6.40 (s, 1H), 2.17-2.11 (m, 1H), 1.13-0.95 (m, 4H). MS Calcd.: 448.50; MS Found: 449.23 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 10.19 (s, 1H), 8.66 (d, J = 2.1 Hz, 1H), 8.23 (d, J = 5.7 Hz, 1H), 8.07 (dd, J = 8.8, 2.3 Hz, 1H), 7.91 (s, 1H), 7.70 (d, J = 8.8 Hz, 1H), 7.62 (d, J = 7.6 Hz, 2H), 7.58 (d, J = 2.2 Hz, 1H), 7.39 (t, J = 7.7 Hz, 2H), 7.32 (s, 1H) , 7.27 (t, J = 7.3 Hz, 1H), 6.75 (dd, J = 5.8, 2.4 Hz, 1H), 2.20-2.09 (m, 1H), 1.13-0.97 (m, 4H). MS Calcd.: 413.15; MS Found: 414.31 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 12.85 (s, 1H), 9.34 (s, 1H), 8.22 (s, 1H), 8.18 (d, J = 5.7 Hz, 1H), 7.87 (d, J = 8.9 Hz, 1H), 7.62 (d, J = 7.7 Hz, 2H), 7.45 (d, J = 7.9 Hz, 1H), 7.40 (t, J = 7.6 Hz, 2H), 7.34 (t, J = 7.9 Hz, 1H), 7.27 (t, J = 7.3 Hz, 1H), 6.67 (d, J = 5.5 Hz, 1H), 6.38 (s, 1H), 2.15 (d, J = 4.9 Hz, 1H), 1.12-0.97 (m, 4H). MS Calcd.: 413.14; MS Found: 414.25 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 13.05 (br s, 1H), 10.99 (br s, 1H), 8.73 (d, J = 2.1 Hz, 1H), 8.32 (d, J = 6.1 Hz, 1H), 8.18 (dd, J = 8.7, 2.0 Hz, 1H), 7.67 - 7.56 (m, 3H), 7.40 (dd, J = 15.6, 8.1 Hz, 3H), 7.28 (t, J = 7.4 Hz, 1H), 6.95 (d, J = 4.5 Hz, 1H), 2.16 (m, 1H), 1.14 - 0.99 (m, 4H). MS Calcd.: 414.42; MS Found: 415.26 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 11.04 (s, 1H), 8.70 (s, 1H), 8.55 (d, J = 4.9 Hz, 1H), 8.34 (d, J = 6.4 Hz, 1H), 8.20 (d, J = 8.7 Hz, 1H), 7.63 (d, J = 7.8 Hz, 2H), 7.53-7.35 (m, 3H), 7.29 (t, J = 7.4 Hz, 1H), 7.20 (s, 1H), 7.03 (s, 1H), 2.77 (d, J = 4.4 Hz, 3H), 2.20-2.13 (m, 1H), 1.13-0.99 (m, 4H). MS Calcd.: 427.46; MS Found: 428.24 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.47 (1H, s), 8.18 (1H, s), 8.09 (1H, d, J = 6.0 Hz), 7.76 (1H, d, J = 8.0 Hz), 7.70-7.67 (2H, m), 7.37 (1H, t, J = 8.0 Hz), 7.29-7.27 (3H, m), 7.09-7.05 (1H, m), 6.59 (1H, dd, J = 7.6, 2.0 Hz), 6.36 (1H, d, J = 2.0 Hz), 2.69 (3H, s), 2.21 (3H, s). MS Calcd.: 453.54 Found: 454.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.10 (1H, s), 8.06 (1H, d, J = 6.0 Hz), 7.70-7.69 (2H, m), 7.61 (1H, s), 7.55 (1H, d, J = 8.4 Hz), 7.20 (1H, t, J = 7.8 Hz), 7.08 (1H, t, J = 4.6 Hz), 6.79 (1H, d, J = 8.0 Hz), 6.55 (1H, dd, J = 5.8, 2.2 Hz), 6.34 (1H, d, J = 2.4 Hz), 3.96 (2H, s), 2.68 (3H, s), 2.21 (3H, s). MS Calcd.: 413.49 Found: 414.2 (M+H ⁺ ).

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

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.99 (1H, s), 8.03 (1H, d, J = 5.6 Hz), 7.69 (2H, d, J = 4.4 Hz), 7.55 (1H, d, J = 7.6 Hz), 7.37 (1H, s), 7.15 (1H, t, J = 7.8 Hz), 7.08 (1H, t, J = 4.4 Hz), 6.72 (1H, d, J = 7.6 Hz), 6.53 (1H, d, J = 5.6 Hz), 6.31 (1H, d, J = 2.0 Hz), 4.18 (2H, s), 2.68 (3H, s), 2.21 (3H, s). * A proton from NH was not observed. MS Calcd.: 456.52; Found: 457.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.98 (1H, s), 8.05 (1H, d, J = 6.0 Hz), 7.69 (2H, d, J = 4.8 Hz), 7.49 (1H, d, J = 8.0 Hz), 7.41 (1H, s), 7.15 (1H, t, J = 8.0 Hz), 7.08 (1H, t, J = 4.4 Hz), 6.77 (1H, d, J = 6.8 Hz), 6.53 (1H, dd, J = 6.0, 2.0 Hz), 6.34 (1H, d, J = 2.4 Hz), 2.78-2.73 (4H, m), 2.68 (3H, s), 2.22 (3H, s). MS Calcd.: 427.52; Found: 428.2 (M+H ⁺ ).

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

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.92 (1H, s), 8.06 (1H, d, J = 5.6 Hz), 7.69 (2H, d, J = 4.0 Hz), 7.43-7.39 (2H, m), 7.20-7.06 (2H, m), 6.71 (1H, d, J = 7.6 Hz), 6.52 (1H, d, J = 6.4 Hz), 6.33 (1H, s), 2.92-2.88 (2H, m), 2.87-2.80 (2H, m), 2.65 (3H, s), 2.23 (3H, s). * A proton from NH was not observed. MS Calcd.: 470.55; Found: 471.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, CDCl ₃ ): δ 9.00 (1H, s), 8.06 (1H, d, J = 6.0 Hz), 7.12 (2H, d, J =4.4 Hz), 7.63 (1H, d, J = 8.0 Hz), 7.40 (1H, s), 7.17 (1H, t, J = 7.6 Hz), 7.10 (1H, t, J = 4.8 Hz), 6.80 (1H, d, J = 8.4 Hz), 6.55-6.54 (1H, m), 6.33 (1H, d, J =1.6 Hz), 3.58 (3H, s), 2.70 (3H, s), 2.24 (3H, s), 1.45 (6H, s). MS Calcd.: 474.57; MS Found: 475.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.06 (1H, d, J = 6.8 Hz), 7.80-7.78 (2H, m), 7.41 (1H, brs), 7.31-7.25 (2H, m), 7.19 (1H, d, J = 6.8 Hz), 7.04 (1H, brs), 6.73 (1H, brs), 6.45 (1H, s), 2.71 (3H, s), 2.28 (3H, s), 1.43 (6H, s). * Two protons from OH, NH were not observed. MS Calcd.: 460.55; MS Found: 461.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.39 (1H, s), 8.15 (1H, d, J = 5.6 Hz), 7.77-7.74 (4H, m), 7.69-7.67 (3H, m), 7.35 (2H, t, J = 7.6 Hz), 7.25 (1H, t, J = 7.2 Hz), 7.10 (1H, s), 6.69 (1H, dd, J = 2.0 Hz, 5.6 Hz), 6.55 (1H, d, J = 2.4 Hz), 2.89 (3H, d, J = 4.8 Hz). * A proton from NH was not observed. MS Calcd.: 417.48; MS Found: 418.2 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.23 (1H, brs), 8.11 (1H, d, J = 5.6 Hz), 7.81 (2H, d, J = 7.2 Hz), 7.59 (1H, brs), 7.51 (1H, brs), 7.40 (2H, t, J = 7.6 Hz), 7.29-7.31 (1H, m), 7.19-7.21 (1H, m), 6.72 (1H, d, J = 9.2 Hz), 6.64 (1H, d, J = 3.2 Hz), 6.43 (1H, s), 3.00 (2H, t, J = 7.5 Hz), 1.33 (3H, t, J = 7.6 Hz). * A proton from NH was not observed. MS Calcd.: 520.55; MS Found: 521.1 (M+H ⁺ ).

(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)

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.04 (1H, d, J = 5.2 Hz), 7.87 (2H, d, J = 8.4 Hz), 7.58 (1H, s), 7.35 (2H, t, J = 7.2 Hz), 7.26-7.20 (3H, m), 6.88 (1H, d, J = 10.4 Hz), 6.48 (1H, dd, J = 5.6 Hz), 3.46-3.41 (3H, m), 3.27-3.18 (2H, m), 3.01 (2H, q, J = 7.2 Hz), 2.52 (3H, s), 2.24-1.94 (2H, m), 1.42 (3H, t, J = 7.6 Hz). * Two protons from NH were not observed. MS Calcd.: 472.61; MS Found: 473.3 (M+H ⁺ ).

[Example] Synthesis of novel thiazole derivative compounds

1. Preparation of intermediates 1-6 & 1-6'

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

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 K ₂ CO ₃ (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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 2:1) to give compound 1-3 (6.00 g, 63%) as a yellow solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.21 (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).

(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)

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

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.38 (1H, t, J = 5.4 Hz), 8.16 (2H, t, J = 7.2 Hz), 7.68 (1H, t, J = 7.4 Hz), 7.55 (2H, t, J = 7.6 Hz), 7.21 (1H, dd, J = 14.8, 2.0 Hz), 7.13 (1H, dd, J = 5.4, 1.8 Hz), 7.08 (1H, s).

(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)

A mixture of compounds 1-4 (4.70 g, 14.4 mmol) and thiourea (2.19 g, 28.8 mmol) was heated in EtOH (144 mL) 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-SiO ₂ (DCM:MeOH = 100:1) to give compound 1-5 (2.72 g, 62%) as a pale yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 7.55 (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).

(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')

Compound 1-5 (2.72 g, 8.95 mmol) was dissolved in THF (90 mL) and Boc ₂ O (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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (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 a pale yellow solid.

¹ H-NMR (400 MHz, DMSO- d ₆ ): δ 8.34-8.31 (1H, m), 7.71-7.69 (2H, m), 7.40-7.38 (2H, m), 7.34-7.32 (1H, m), 7.32-7.25 (1H, m), 7.22-7.19 (1H, m), 1.51 (18H, s).

2. A-1 Synthesis

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

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 K ₂ CO ₃ (205 mg, 1.49 mmol) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 3:2) to give compound 1-7 (140 mg, 52%) as a brown solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 9.80 (1H, brs), 8.14 (1H, d, J = 6.0 Hz), 7.76-7.72 (3H, m), 7.72-7.42 (1H, m), 7.34-7.21 (5H, m), 6.63 (1H, dd, J = 2.0 Hz, 6.0 Hz), 6.51 (1H, d, J = 2.0 Hz), 5.18 (2H, brs), 1.47 (9H, s). * A proton form NH was not observed.

(2) Manufacturing of A-1

To DCM (dichloromethane; 3 mL) containing compound 1-7 was added TFA (0.2 mL, 2.60 mmol), and the mixture was stirred at room temperature for 18 h. The reaction mixture was extracted with saturated NaHCO ₃ aqueous solution and EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 3:2 to 1:1) to give A-1 (52 mg, 45%) as a white solid.

A-2 to A-38 were synthesized using the procedure described for the synthesis of A-1 above.

3. A-39 Synthesis

(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)

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) at room temperature. LIOH ^. H ₂ O (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.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 11.8 (1H, s), 9.66 (1H, s), 8.18 (1H, d, J = 6.0 Hz), 7.83 (2H, d, J = 7.2 Hz), 7.76 (2H, d, J = 8.0 Hz), 7.72 (2H, d, J = 8.8 Hz), 7.40 (2H, t, J = 7.0 Hz), 7.32-7.28 (1H, m), 6.79 (1H, dd, J = 6.0, 2.0 Hz), 6.59 (1H, d , J = 2.4 Hz), 1.50 (9H, s). * A proton from NH was not observed.

(2) A-39 Preparation

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.

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

4. A-41 Synthesis

(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)

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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 3:1) to give compound 1-10 (358 mg, 64%) as a yellow solid.

(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)

Diphenylmethanimine (0.07 mL, 0.41 mmol), Xantphos (16.0 mg, 0.03 mmol), and Cs ₂ CO ₃ (266 mg, 0.82 mmol) were added to a solution of compounds 1-10 in dioxane (2.7 mL) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After Pd ₂ (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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 5:1) to give compound 1-11 (62.0 mg, 49%) as a yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.33 (1H, d, J = 6.0 Hz), 7.79 (2H, d, J = 7.6 Hz), 7.75-7.70 (4H, m), 7.67-7.63 (4H, m), 7.42-7.38 (4H, m), 7.33-7.30 (1H, m), 7.16 (1H, d, J = 2.4 Hz), 7.07 (1H, dd, J = 6.0, 2.4 Hz).

(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)

2-(3-aminophenyl)propan-2-ol (30.0 mg, 0.20 mmol) and K ₂ CO ₃ (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 addition of 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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 1:1) to give compound 1-12 (15.4 mg, 20%) as a yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.04 (1H, s), 8.06 (1H, d, J = 6.0 Hz), 7.79-7.74 (4H, m), 7.64-7.59 (1H, m), 7.59-7.55 (6H, m), 7.53 (1H, s), 7.53-7.42 (4H, m), 7.33-7.29 (1H, m), 7.16 (1H, t, J = 7.8 Hz), 6.98 (1H, d, J = 8.4 Hz), 6.45 (1H, dd, J = 6.2, 2.2 Hz), 6.37 (1H, d, J = 2.0 Hz), 4.93 (1H, s), 1.38 (6H, s).

(4) Manufacturing of A-41

To a methanol solution containing compound 1-12 (15.0 mg, 0.03 mmol) was added NH ₂ OH ^. HCl (3.58 mg, 0.05 mmol) at room temperature. After stirring at room temperature for 3 h, the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (DCM:MeOH = 100:1 to 50:1) to give A-41 (2.20 mg, 20%) as a white solid.

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

5. A-44 Synthesis

(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)

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 SiO ₂ (hexane:EtOAc = 2:1) to give compound 2-1 (74.0 mg, 35%) as a yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.34 (1H, d, J = 5.2 Hz), 8.24 (1H, d, J = 1.6 Hz), 7.69 (2H, d, J = 7.6 Hz), 7.36 (2H, t, J = 7.6 Hz), 7.31 (1H, d, J = 2.0 Hz), 7.27 (1H, d, J = 7.6 Hz), 7.20 (1H, dd, J = 5.8, 2.2 Hz), 2.60-2.54 (1H, m), 0.76-0.71 (2H, m), 0.59-0.57 (2H, m).

(2) Manufacturing of A-44

2-(3-aminophenyl)propan-2-ol (46.0 mg, 0.31 mmol) and K 2 CO 3 (84.0 mg, 0.61 mmol) were added to a solution of compound _2-1 (70.0 mg, 0.20 mmol) in _DMF (4.1 mL) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After BrettPhos Pd G3 (37.0 mg, 0.04 mmol) was added, 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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (only DCM) to give A-44 (19.6 mg, 21%) as an ivory solid.

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

6. A-48 Synthesis

(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)

Compound 2-1 (200 mg, 0.58 mmol) was dissolved in DMF (12 mL) at room temperature, to which 3-aminobenzoate (132 mg, 0.87 mmol) and K ₂ CO ₃ (241 mg, 1.75 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After addition of 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 4:1) to give methyl compound 2-2 (103 mg, 39%) as a yellow solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.12 (1H, d, J = 5.6 Hz), 7.94 (1H, t, J = 1.8 Hz), 7.75 (2H, d, J = 8.0 Hz), 7.69 (1H, d, J = 7.2 Hz), 7.55 (1H, dd, J = 8.0, 2.0 Hz), 7.37-7.32 (3H, m), 7.26-7.24 (1H, m), 6.71 (1H, s), 6.59 (1H, dd, J = 5.6, 2.0 Hz), 6.52 (1H, d, J = 2.4 Hz), 3.90 (3H, s), 2.62-2.57 (1H, m), 0.79-0.77 (2H, m), 0.72-0.68 (2H, m). * A proton from NH was not observed.

(2) Manufacturing of A-48

LiOH ^. H ₂ O (55.0 mg, 1.31 mmol) was added to a solution of THF (2.0 mL) and water (0.65 mL) containing compound 2-2 (60.0 mg, 0.13 mmol) at room temperature. 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 solid.

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

7. A-50 Synthesis

(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)

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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 4:1) to give compound 3-1 (58.0 mg, 20%) as a yellow oil.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.24 (1H, d, J = 5.6 Hz), 7.74-7.71 (2H, m), 7.33-7.29 (2H, m), 7.26-7.24 (1H, m), 7.04 (1H, d, J = 2.4 Hz), 6.96 (1H, dd, J = 5.9 Hz, 2.0 Hz), 2.97 (3H, d, J = 4.8 Hz). * A proton form NH was not observed.

(2) Manufacturing of A-50

2-(3-aminophenyl)propan-2-ol (41.0 mg, 0.27 mmol) and K 2 CO 3 (74.0 mg, 0.54 mmol) were added to a solution of compound _3-1 (57.0 mg, 0.18 mmol) in _DMF (2.0 mL) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After 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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 1:1) to give A-50 (3.4 mg, 4%) as an ivory solid.

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

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

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

Methyl 4-aminobenzoate (570 mg, 3.78 mmol) and K ₂ CO ₃ (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 addition of 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 Na ₂ SO ₄ , 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.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.15 (1H, d, J = 5.6 Hz), 7.96-7.93 (2H, m), 7.79-7.77 (2H, m), 7.38-7.32 (2H, m), 7.28-7.22 (2H, m), 6.94 (1H, s), 6.64 (1H, dd, J = 2.0 Hz, 5.6 Hz), 6.58 (1H, d, J = 2.4 Hz), 3.88 (3H, s), 2.99 (3H, d, J = 6.4 Hz). * Two protons from two NH were not observed.

(2) Manufacturing of A-56

Compound 3-2 (630 mg, 1.46 mmol) was dissolved in THF/H ₂ O ( v/v = 1/1, 30.0 mL) at room temperature, LiOH ^. H ₂ O (1.22 g, 29.1 mmol) was added, and the mixture was stirred at 50°C for 5 days. After cooling to room temperature, the reaction mixture was poured into 1 N aq. HCl solution, and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 2:3) and triturated with DCM to give A-56 (180 mg, 30%) as an ivory solid.

(3) Manufacturing of A-56_salt

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 EtO ₂ to give A- 56_Salt (17.0 mg, 52%) as a yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.70 (1H, s), 8.16 (1H, d, J = 6.4 Hz), 7.83 (2H,d, J = 8.8 Hz), 7.75-7.70 (5H, m), 7.36 (2H, t, J = 7.6 Hz), 7.26 (1H, t, J = 7.6 Hz), 6.76 (1H, dd, J = 2.4 Hz, 6.2 Hz), 6.62 (1H, d, J = 2.4 Hz), 2.83 (3H, s). * A proton from NH was not observed. MS Calcd.: 418.47; MS Found: 419.1 (M+H ⁺ ).

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

9. A-58 Synthesis

(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)

Methylboronic acid (733 mg, 12.2 mmol), Sphos (837 mg, 2.04 mmol), and K 2 CO 3 (1.69 mg, 12.2 mmol) were added to a mixture of dioxane (37 mL) and water (3.7 mL) containing _{compound 1-10 (} 1.50 g, 4.08 mmol) at room temperature. After addition of 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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography over SiO ₂ (hexane:EtOAc = 10:1 to 7:1) to give compound 4-1 (403 mg, 33%) as a yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.35 (1H, d, J = 5.6 Hz), 7.79 (2H, d, J = 8.0 Hz), 7.41 (2H, t, J = 7.8 Hz), 7.35 (1H, d, J = 2.0 Hz), 7.32 (1H, t, J = 7.6 Hz), 7.21 (1H, dd, J = 5.4, 2.2 Hz), 2.69 (3H, s).

(2) Manufacturing of A-58

3-Aminobenzenesulfonamide (15.0 mg, 0.09 mmol) and K ₂ CO ₃ (25.0 mg, 0.18 mmol) were added to a solution of compound 4-1 (18.0 mg, 0.06 mmol) in DMF (1.2 mL) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After BrettPhos Pd G3 (10.8 mg, 0.01 mmol) was added, 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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (hexane:EtOAc = 1:1) to give A-58 (6.6 mg, 25%) as an ivory solid.

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

10. A-109 Synthesis

(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)

Methyl 3-aminobenzoate (37.0 mg, 0.25 mmol) and K ₂ CO ₃ (68.0 mg, 0.50 mmol) were added to DMF (3.3 mL) containing compound 4-1 (50.0 mg, 0.17 mmol) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After 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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 3:1) to give methyl compound 4-2 (61.0 mg, 88%) as a yellow oil.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.37 (1H, s), 8.26 (1H, s), 8.16 (1H, d, J = 6.0 Hz), 7.92 (1H, d, J = 8.0 Hz), 7.83 (2H, d, J = 7.6 Hz), 7.48-7.30 (5H, m), 6.69 (1H, d, J = 4.4 Hz), 6.45 (1H, d, J = 1.6 Hz), 3.84 (3H , s), 2.71 (3H, s).

(2) Manufacturing of A-109

LiOH ^. H ₂ O (61.0 mg, 1.46 mmol) was added to a solution of THF/water ( v / v = 1/1, 3 mL) containing compound 4-2 (61.0 mg, 0.15 mmol) at room temperature. 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 solid.

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

11. A-111 and A-112 synthesis

(1) Manufacturing of A-111

2-(3-aminophenyl)acetonitrile (196 mg, 1.49 mmol) and K ₂ CO ₃ (411 mg, 2.97 mmol) were added to DMF (9.9 mL) containing compound 4-1 (300 mg, 0.99 mmol) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 1:4) to give A-111 (343 mg, 87%) as a pale yellow solid.

(2) Manufacturing of A-112

A-111 (150 mg, 0.376 mmol) was dissolved in dioxane (4.7 mL) at room temperature, Bu ₂ SnO (187 mg, 0.75 mmol) and Me ₃ SiN ₃ (0.25 mL, 1.88 mmol) were added. 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (only EtOAc) to give A-112 (23.5 mg, 14%) as an ivory solid.

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

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

12. A-115 Synthesis

(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)

Cyclopropylboronic acid (335 mg, 3.90 mmol) and K ₂ CO ₃ (404 mg, 2.92 mmol) were added to a mixture of dioxane (7.3 mL) and water (2.4 mL) containing compound 1-10 (358 mg, 0.97 mmol) at room temperature. The mixture was purged to degas and backfilled with argon several times, and PdCl ₂ (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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by SiO ₂ (hexane:EtOAc = 1:1) column chromatography to obtain compound 5-1 (92.0 mg, 29%) as a white solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.32 (1H, dd, J = 6.0 Hz), 7.73 (2H, d, J = 7.2 Hz), 7.39-7.33 (3H, m), 7.31-7.27 (1H, m), 7.17 (1H, dd, J = 5.8, 2.2 Hz), 2.42-2.37 (1H, m), 1.15-1.11 (2H, m), 1.09-1.03 (2H, m).

(2) Manufacturing of A-115

2-(3-aminophenyl)propan-2-ol (14.0 mg, 0.09 mmol) and K 2 CO 3 (25.0 mg, 0.18 mmol) were added to _DMF (1.2 mL) containing compound _5-1 (20 mg, 0.06 mmol) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After 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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 2:1) to give A-115 (10.7 mg, 40%) as a yellow solid.

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

13. A-132 and A-133 synthesis

(1) Manufacturing of A-132

LiOH H ₂ O (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 purified by adding 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.

(2) Manufacturing of A-133

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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (DCM:MeOH = 10:1) to give A-133 (35.0 mg, 85%) as a white solid.

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

14. A-138 Synthesis

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. NH ₂ OH (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.

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

15. A-140 Synthesis

A-132 (35.0 mg, 0.08 mmol) was dissolved in DMF (1.6 mL) methanesulfonamide (9.28 mg, 0.10 mmol), DMAP (10.9 mg, 0.09 mmol), 2-chloro-1-methylpyridinium iodide (31.0 mg, 0.12 mmol), and TEA (34.0 μL, 0.24 mmol). The mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was triturated with DCM and hexanes, 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.

16. A-141 Synthesis

(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)

To a solution of compound 1-10 (60.0 mg, 0.16 mmol) in MeOH (1.6 mL) was added sodium methoxide (25 wt% in MeOH, 0.15 mL, 0.65 mmol) at room temperature. After stirring for 4 h, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtAOc = 3:1) to give compound 6-1 (13.0 mg, 25%) as a yellow solid.

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

(2) Manufacturing of A-141

2-(3-aminophenyl)propan-2-ol (9.3 mg, 0.0610 mmol) and K 2 CO 3 (17.0 mg, 0.122 mmol) were added to _DMF (1.0 mL) containing compound _6-1 (13 mg, 0.0410 mmol) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After 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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 3:1) to give A-141 (1.1 mg, 6%) as a yellow solid.

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

17. A-145 Synthesis

(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)

Compound 1-10 (200 mg, 0.54 mmol) was dissolved in DMF (11 mL) at room temperature, to which were added methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (0.35 mL, 2.72 mmol), CuI (518 mg, 2.72 mmol), and AsPh ₃ (67.0 mg, 0.22 mmol). The mixture was degassed by purging and backfilled with argon several times. After Pd ₂ (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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 20:1) to give compound 7-1 (95.0 mg, 49%) as a yellow solid.

(2) Manufacturing of A-145

3-Aminobenzenesulfonamide (72.0 mg, 0.14 mmol) and K ₂ CO ₃ (116 mg, 0.84 mmol) were added to a solution of compound 7-1 (100 mg, 0.28 mmol) in DMF (2.8 mL) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After 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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 1:1) to give A-145 (10.0 mg, 7%) as a white solid.

A-146 to A-148 were synthesized using the above A-145 synthesis procedure.

18. A-149 and A-150 composite

(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)

Methyl 6-aminonicotinate (86.0 mg, 0.57 mmol) and K ₂ CO ₃ (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 addition of 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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 1:1) to give compound 7-2 (127.6 mg, 52%) as a yellow crude solid.

[M+H] ⁺ calcd for 472.44, found 473.14 (M+H ⁺ ).

(2) Manufacturing of A-149

LiOH H ₂ O (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.

(3) Manufacturing of A-150

A-149 (30.0 mg, 0.07 mmol) was dissolved in DMF (4.0 mL) at room temperature, HATU (37.3 mg, 0.11 mmol), DIPEA (0.02 mL, 0.11 mmol) and 2 M methyl amine (0.05 mL, 0.11 mmol) dissolved in THF solution were added. The mixture was stirred at room temperature for 17 h. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (DCM:MeOH = 10:1) to give A-150 (3.1 mg, 10%) as a white solid.

A-151 and A-152 were synthesized using the above A-149 synthesis procedure.

19. A-153 Synthesis

(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)

Compound 1-10 (100 mg, 0.27 mmol) was dissolved in DMF (5.50 mL), dimethyl amine (2 M in THF, 0.20 mL, 0.41 mmol) was added, 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc: = 3:2) to give compound 8-1 (32 mg, 36%) as a yellow oil.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.23 (1H, d, J = 6.0 Hz), 7.81-7.78 (2H, m), 7.40-7.32 (3H, m), 7.03 (1H, m), 7.00-6.99 (1H, m), 3.12 (6H, s).

(2) Manufacturing of A-153

2-(3-aminophenyl)propan-2-ol (21.0 mg, 0.14 mmol) and K 2 CO 3 (37.0 mg, 0.27 mmol) were added to _DMF (1.0 mL) containing compound _8-1 (30.0 mg, 0.09 mmol) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After 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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 1:1) to give A-153 (1.3 mg, 3%) as a white solid.

A-154 to A-164 were synthesized using the above A-153 synthesis procedure.

20. A-165 and A-166 composite

(1) Manufacturing of A-165

LiOH H ₂ O (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.

(2) Manufacturing of A-166

A-165 (60.0 mg, 0.14 mmol) was dissolved in DMF (1.4 mL) at room temperature, HATU (79.0 mg, 0.21 mmol), MeNH ₂ (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 Na ₂ SO ₄ , 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.

A-167 to A-169 were synthesized using the above A-165 synthesis procedure.

21. A-170 and A-171 composite

(1) Manufacturing of A-170

A-3 (104 mg, 0.25 mmol) was dissolved in acetonitrile (ACN; 2.5 mL) at 0 °C, copper (Ⅱ) bromide (56.0 mg, 0.25 mmol) and tert -butyl nitrite (38.0 mg, 0.37 mmol). 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 3:1) to give methyl A-170 (47.8 mg, 40%) as a pale yellow solid.

(2) Manufacturing of A-171

Methyl 3-(4-(2-bromo-4-phenylthiazol-5-yloxy)pyridin-2-ylamino)benzoate (7.50 mg, 0.02 mmol) was dissolved in a mixture of THF (0.23 mL) and water (0.08 mL) at room temperature, followed by addition of 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.

22. A-172 Synthesis

Compound 1-13 (15.0 mg, 0.03 mol) was dissolved in a mixture of water (0.24 mL) and EtOH (1.4 mL), and 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) were added at room temperature. After stirring at room temperature for 30 min, the reaction mixture was quenched with ammonia water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (DCM:EtOAc = 1:1) to give A-172 (11.0 mg, 71%) as a yellow solid.

23. A-173 Synthesis

(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)

Cyclopentenylboronic acid (100 mg, 0.90 mmol) and K ₂ CO ₃ (189 mg, 1.37 mmol) were added to a mixture of dioxane (6.1 mL) and water (2.0 mL) containing compound 1-10 (300 mg, 0.82 mmol). The mixture was degassed by purging and backfilled with argon several times. After PdCl ₂ (dppf) (119 mg, 0.16 mmol) was added, 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 10:1) to give compound 9-1 (125 mg, 42%) as a brown oil.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.33 (1H, d, J = 5.6 Hz), 7.79 (2H, d, J = 7.2 Hz), 7.42-7.39 (3H, m), 7.32 (1H, t, J = 7.4 Hz), 7.22 (1H, dd, J = 6.0, 2.4 Hz), 6.67 (1H, s), 2.78 (2H, t, J = 6.4 Hz), 2.54-2.51 (2H, m), 1.99 (2H, quint. J = 7.6 Hz)

(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)

Compound 9-1 (125 mg, 0.35 mmol) was dissolved in MeOH (3.5 mL) and PtO ₂ (96.0 mg, 0.42 mmol) was added. The mixture was stirred at room temperature for 2 h under H ₂ 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.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.33 (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).

(3) Manufacturing of A-173

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 K ₂ CO ₃ (131 mg, 0.95 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After addition of 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (only EtOAc) to give A- 173 (39.0 mg, 27%) as a white solid.

A-174 to A-176 were synthesized using the above A-173 synthesis procedure.

24. A-177 Synthesis

(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)

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), K ₂ CO ₃ (1.12 g, 8.16 mmol) and PdCl ₂ (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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (EtOAc:hexane = 1:10) to give compound 10-1 (728 mg, 72%) as a yellow solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.27 (1H, d, J = 6.0 Hz), 7.85 (2H, d, J = 7.2 Hz), 7.37 (2H, t, J = 6.8 Hz), 7.30 (1H, d, J = 7.2 Hz), 7.02 (1H, d, J) = 2.4 Hz), 6.95 (1H, dd, J = 6.0, 2.4 Hz), 6.63 (1H, s), 2.58 (2H, m), 2.27-2.26 (2H, m), 1.81-1.78 (2H, m), 1.73-1.69 (2H, m).

(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)

Compound 10-1 (710 mg, 1.92 mmol) was mixed with PtO ₂ (524 mg, 2.3 mmol) in MeOH (19 mL) and left to stand at room temperature for 1 h under a H ₂ 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.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.27 (1H, d, J = 6.0 Hz), 7.82 (2H, 7.2 Hz), 7.37 (2H, t, J = 6.8 Hz), 7.27 (1H, d, J = 8.8 Hz), 7.00 (1H, d, J = 2.0 Hz), 6.93 (1H, dd, J = 6.0, 2.4 Hz), 2.96 (1H, m), 2.21-2.18 (2H, m), 2.09 (1H, s), 1.89-1.86 (2H, m), 1.77-1.74 (1H, m), 1.48-1.45 (2H, m), 0.82-0.80 (2H, m).

(3) Manufacturing of A-177

Compound 10-2 (50.0 mg, 0.13 mmol) was dissolved in DMF (1.3 mL) at room temperature, 6-aminonicotinamide (22 mg, 0.16 mmol) and K ₂ CO ₃ (55 mg, 0.4 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After addition of 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (DCM:MeOH = 9:1) to give A-177 (1.8 mg, 2%) as a pink solid.

A-178 to A-180 were synthesized using the above A-177 synthesis procedure.

25. A-181 Synthesis

(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)

To a mixture of 1,4-dioxane (22 mL) and water (2.2 mL) containing compound 1-10 (900 mg, 2.45 mmol) was added 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (754 mg, 4.90 mmol) and Na ₂ CO ₃ (778 mg, 7.34 mmol) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After addition of PdCl ₂ (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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 10:1) to give compound 11-1 (443 mg, 58%) as a yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.37 (1H, d, J = 5.6 Hz), 7.81 (2H, d, J = 7.6 Hz), 7.45-7.41 (3H, m), 7.37-7.33 (1H, m), 7.27 (1H, dd, J = 5.4, 1.8 Hz), 6.96 (1H, dd, J = 17.6, 11.2 Hz), 6.11 (1H, d, J = 17.2 Hz), 5.70 (1H, d, J = 10.8 Hz).

(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)

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 H ₂ 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. It was used in the next synthesis without further purification.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.33 (1H, d, J = 5.6 Hz), 7.77 (2H, d, J = 8.0 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.33-7.38 (2H, m), 7.18 (1H, dd, J = 5.6, 1.6 Hz), 2.99 (2H, q, J = 7.7 Hz), 1.32 (3H, t, J = 7.6 Hz).

(3) Manufacturing of A-181

Compound 11-2 (30.0 mg, 0.0950 mmol) was dissolved in DMF (1.9 mL) at room temperature, 3-aminobenzenesulfonamide (24.0 mg, 0.14 mmol) and K ₂ CO ₃ (39.0 mg, 0.284 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After addition of 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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 1:1) to give A-181 (21 mg, 49%) as a white solid.

A-182 to A-190 were synthesized using the above A-181 synthesis procedure.

26. A-191 to A-193 Synthesis

(1) Manufacturing of A-191

Compound 11-2 (200 mg, 0.63 mmol), methyl 6-aminonicotinate (96.0 mg, 0.63 mmol) and K ₂ CO ₃ (87.0 mg, 0.63 mmol) were dissolved in DMF (6.31 mL), which was purged to degassed and backfilled with argon several times. After BrettPhos Pd G3 (572 mg, 0.63 mmol) was added, 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 MgSO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 1:1) to give A-191 (120 mg, 44%) as a yellow solid.

(2) Manufacturing of A-192

Methyl 6-(4-(2-ethyl-4-phenylthiazol-5-yloxy)pyridin-2-ylamino)nicotinate (70.0 mg, 0.16 mmol) was dissolved in a mixture of THF (1.29 mL) and water (0.32 mL) at 0 °C, to which was added LiOH H ₂ O (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.

(3) Manufacturing of A-193

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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (DCM:MeOH = 10:1) to give A-193 (43.0 mg, 83%) as a white solid.

A-194 and A-195 were synthesized using the above A-192 synthesis procedure.

A-196 to A-215 were synthesized using the above A-191 or A-193 synthetic procedure.

27. Synthesis of A-216 and A-217

(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)

A solution of compound 1-10 (40.0 mg, 0.11 mmol), potassium isopropenyltrifluoroborat (24.0 mg, 0.16 mmol), Na ₂ CO ₃ (81.0 mg, 0.76 mmol) and PdCl ₂ (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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (EtOAc:hexane = 1:4) to give compound 12-1 (24.0 mg, 67%) as a yellow oil.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.26 (1H, d, J = 6.0 Hz), 7.88-7.85 (2H, m), 7.39-7.35 (2H, m), 7.39-7.25 (1H, m), 7.02 (1H, d, J = 2.0 Hz), 6.95-6.93 (1H, m), 5.77 (1H, s), 5.37 (1H, d, J = 1.2 Hz), 2.26 (3H, s).

(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)

Compound 12-1 (300 mg, 0.91 mmol) was dissolved in DCM (10 mL), to which 10% Pd/C (97.0 mg, 0.09 mmol) was added, and the mixture was stirred at room temperature for 30 min under a H ₂ 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.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.26 (1H, d, J = 8.8 Hz), 7.83 (2H, d, J = 8.4 Hz), 7.35 (2H, t, J = 6.0 Hz), 7.27 (1H, t, J = 4.8 Hz), 7.00 (1H, d, J) = 2.4 Hz), 6.92 (1H, dd, J = 2.4 Hz, 6.0 Hz), 3.31-3.24 (1H, m), 1.42 (6H, 5.2 Hz).

(3) Manufacturing of A-216

Methyl 6-aminopicolinate (55.0 mg, 0.36 mmol) and K ₂ CO ₃ (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 addition of 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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 3:1) to give methyl A- 216 (41.0 mg, 38%) as a yellow solid.

(4) Manufacturing of A-217

LiOH H ₂ O (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 give A-217 (24.0 mg, 60%) as a yellow solid.

A-218 to A-229 were synthesized using the above A-216 synthesis procedure.

A-230 to A-232 were synthesized using the above A-217 synthetic procedure.

28. A-233 Synthesis

(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)

Compound 13-1 (1.50 g, 11.58 mmol), 2-bromo-1-(naphthalene-2-yl)ethanone (3.46 g, 13.89 mmol) and K ₂ CO ₃ (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 Na ₂ SO ₄ , filtered and concentrated in vacuo to give compound 13-2 (2.77 g, 80%) as a yellow foam.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.49 (1H, s), 8.21 (1H, d, J = 5.6 Hz), 8.01-7.86 (4H, m), 7.67-7.58 (2H, m), 6.88 (1H, d, J = 2.4 Hz), 6.82 (1H, dd, J = 2.4 Hz, 5.6 Hz), 5.49 (2H, s).

(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)

Compound 13-2 (230 mg, 0.77 mmol) was dissolved in CHCl ₃ (8.0 mL) at 0 °C, Br ₂ (0.06 mL, 1.16 mmol) and AlCl ₃ (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. NaHCO ₃ solution at 0 °C, and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo to give compound 13-3 (300 mg) as a yellow foam.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.73 (1H, s), 8.40 (1H, d, J = 5.6 Hz), 8.14 (1H, d, J = 8.8 Hz), 8.03 -7.90 (3H, m), 7.69-7.59 (2H, m), 7.27 (1H, s), 7.16 (1H, s).

(3) 5-((2-chloropyridin-4-yl)oxy)- N -Methyl-4-(naphthalen-2-yl)thiazol-2-amine (5-((2-chloropyridin-4-yl)oxy)- N -Manufacture of methyl-4-(naphthalen-2-yl)thiazol-2-amine (hereinafter referred to as compound 13-4)

A mixture of compound 13-3 (480 mg, 1.27 mmol) and 1-methylthiourea (115 mg, 1.27 mmol) was dissolved in EtOH (13.0 mL) and 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (DCM) to give compound 13-4 (160 mg, 34%) as a yellow solid.

^1H -NMR (400 MHz, CDCl ₃ ): δ 8.25 (2H, d, J = 5.2 Hz), 7.85-7.76 (4H, m), 7.47-7.43 (2H, m), 7.08 (1H, d, J = 2.0 Hz), 7.00 (1H, dd, J = 2.4 Hz, 5.6 Hz), 5.59-5.57 (1H, m), 3.00 (3H, d, J = 4.8 Hz).

(4) Manufacturing of A-233

Compound 13-4 (80.0 mg, 0.22 mmol) was dissolved in DMF (5.0 mL) at room temperature, to which were added K ₂ CO ₃ (90.0 mg, 0.65 mmol) and 3-aminobenzenesulfonamide (56.0 mg, 0.33 mmol). The mixture was degassed by purging and backfilled with argon several times. After 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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (DCM:MeOH = 98:2) to give A-233 (8.2 mg, 7%) as a beige solid.

29. A-234 Synthesis

(1) Preparation of 5-(2-chloropyridin-4-yloxy)-4-(naphthalen-2-yl)thiazol-2-amine (hereinafter referred to as compound 13-5)

A mixture of compound 13-2 and thiourea (61.0 mg, 0.80 mmol) was dissolved in EtOH (7.9 mL) and 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (only DCM) to give compound 13-5 (120 mg, 42%) as a yellow solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.49 (1H, S), 8.21 (1H, d, J = 5.6 Hz), 7.90-8.02 (4H, m), 7.59-7.68 (2H, m), 6.89 (1H, d, J = 2.4 Hz), 6.82 (1H, dd, J = 2.4 Hz, 5.6 Hz), 5.50 (2H, s).

(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)

A mixture of compound 13-5 (300 mg, 0.85 mmol), Boc ₂ O (2.34 mL, 1.02 mmol), TEA (0.14 mL, 1.02 mmol), and DMAP (10.4 mg, 0.08 mmol) was dissolved in DCM (30 mL) and stirred at room temperature for 18 h. The reaction mixture was quenched with water and extracted with DCM. The organic layer was dried over Na ₂ SO ₄ , 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.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.29 (1H, s), 8.26 (1H, d, J = 5.6 Hz), 7.89 (1H, dd, J = 1.6 Hz, 8.4 Hz), 7.80-7.75 (3H, m), 7.45 (2H, dd, J = 2.8 Hz, 6.2 Hz), 7.06 (1H, d, J = 2.0 Hz), 7.06-6.99 (1H, m), 1.60 (18H, s).

(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)

Compound 13-6 (200 mg, 0.36 mmol) was dissolved in DMF (8 mL) at room temperature, and K ₂ CO ₃ (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 addition of 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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 4:1) to give compound 13-7 (120 mg, 56%) as a dark brown solid.

MS Calcd.: 689.8; MS Found: 690.12 (M+H ⁺ ).

(4) Manufacturing of A-234

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 stirred at room temperature for 18 h. The reaction mixture was neutralized with saturated aq. NaHCO ₃ solution and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (DCM:MeOH = 95:5) to give A-234 (10.0 mg, 10%) as a beige solid.

30. A-235 Synthesis

(1) Preparation of 2-bromo-5-(2-chloropyridin-4-yloxy)-4-(naphtalen-2-yl)thiazole (2-bromo-5-(2-chloropyridin-4-yloxy)-4-(naphtalen-2-yl)thiazole; hereinafter referred to as compound 13-8)

5-(2-chloropyridin-4-yloxy)-4-(naphthalene-2-yl)thiazol-2-amine was dissolved in ACN (90 mL) and CuBr ₂ (5.99 g, 26.8 mmol) and isopentyl nitrite (5.40 mL, 40.2 mmol) were added at 0 °C. The reaction mixture was stirred at 0 °C for 90 min. The reaction mixture was quenched with NH ₄ OH and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 1:4) to give compound 13-8 (5.40 g, 48%) as a brown solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.33 (1H, s), 8.29 (1H, dd, J = 6.0 Hz), 7.88-7.78 (4H, m), 7.50-7.45 (2H, m), 7.06 (1H, d, J = 2.5 Hz), 6.98-6.96 (1H, m).

(2) Preparation of 5-(2-chloropyridin-4-yloxy)-N,N-dimethyl-4-(naphthalen-2-yl)thiazol-2-amine (5-(2-chloropyridin-4-yloxy)-N,N-dimethyl-4-(naphthalen-2-yl)thiazol-2-amine; hereinafter referred to as compound 13-9)

A mixture of compound 13-8 (100 mg, 0.24 mmol) and dimethyl amine (2 M in THF, 0.18 mL, 0.36 mmol) dissolved in DMF (5 mL) was stirred from room temperature to 50 °C for 2 days. After cooling to room temperature, the reaction mixture was washed with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 3:2) to give compound 13-9 (23.0 mg, 25%) as a yellow oil.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.30 (1H, s), 8.25 (1H, d, J = 6.0 Hz), 7.90 (1H, dd, J = 1.6 Hz, 8.6 Hz), 7.82-7.71 (3H, m), 7.46-7.41 (2H, m), 7.08 (1H, d, J = 2.0 Hz), 7.00 (1H, dd, J = 2.4 Hz, 6.0 Hz), 3.16 (6H, s).

(3) Manufacturing of A-235

Compound 13-9 (23.0 mg, 0.06 mmol) was dissolved in DMF (2 mL) at room temperature, to which were added K ₂ CO ₃ (33.0 mg, 0.24 mmol) and 3-aminobenzenesulfonamide (16.0 mg, 0.09 mmol). The mixture was degassed by purging and backfilled with argon several times. After addition of BrettPhos Pd G3 (11.0 mg, 0.01 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 Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 1:1) to give A-235 (5.8 mg, 18%) as a pale yellow solid.

31. A-236 Synthesis

(1) Preparation of 2-(6-chloropyrimidin-4-yloxy)-1-phenylethanone (hereinafter referred to as compound 14-1)

Compound 1-1 (5.03 g, 25.3 mmol) was dissolved in acetone (46 mL) at room temperature, 6-chloropyrimidin-4-ol (3.00 g, 23.0 mmol) and K ₂ CO ₃ (4.76 g, 34.5 mmol) were added. 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 1:2) to give compound 14-1 (5.55 g, 97%) as a white solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.01 (2H, d, J = 8.0 Hz), 7.96 (1H, s), 7.68 (1H, t, J = 7.4 Hz), 7.54 (2H, t, J = 7.8 Hz), 6.59 (1H, s), 5.36 (2H, s).

(2) Preparation of 2-bromo-2-(6-chloropyrimidin-4-yloxy)-1-phenylethanone (hereinafter referred to as compound 14-2)

Compound 14-1 (5.55 g, 22.3 mmol) was slowly added to CHCl ₃ (74 mL) at room temperature, AlCl ₃ (1.19 g, 8.93 mmol) and Br ₂ (1.73 mL, 33.5 mmol). The mixture was stirred at room temperature for 18 h. The reaction mixture was quenched with saturated NaHCO ₃ solution and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 5:1) to give compound 14-2 (4.71 g, 64%) as a white solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.53 (1H, s), 8.14 (1H, s), 8.08 (2H, d, J = 8.08 Hz), 7.70 (1H, t, J = 7.8 Hz), 7.56 (2H, t, J = 7.6 Hz), 6.53 (1H, s).

(3) Preparation of 5-(6-chloropyrimidin-4-yloxy)-4-phenylthiazol-2-amine (hereinafter referred to as compound 14-3)

A mixture of compound 14-2 (4.70 g, 14.4 mmol) and thiourea (1.20 g, 15.8 mmol) was dissolved in ACN (48 mL) and heated at 80 °C for 30 min. After cooling to room temperature, the reaction mixture was quenched with saturated NaHCO ₃ solution and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo to give compound 14-3 (4.03 g, 92%) as a yellow solid. It was used in the next step without further purification.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.44 (1H, d, J = 14.4 Hz), 8.06 (1H, d, J = 8.0 Hz), 7.60 (1H, t, J = 7.6 Hz), 7.43 (1H, s), 7.34-7.30 (3H, m). Two protons from NH ₂ were not observed.

(4) Preparation of tert-butyl (tert-butoxycarbonyl)(5-((6-chloropyrimidin-4-yl)oxy)-4-phenylthiazol-2-yl)carbamate (hereinafter referred to as compound 14-4)

Compound 14-3 (1.00 g, 3.28 mmol) was dissolved in THF (33 mL) at room temperature, Boc ₂ O (2.15 g, 9.84 mmol), TEA (1.37 mL, 9.84 mmol) and DMAP (80.0 mg, 0.67 mmol) were added. 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 5:1 to 3:1) to give compound 14-4 (1.14 g, 69%) as a yellow solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 7.84 (1H, s), 7.44-7.41 (2H, m), 7.36-7.32 (3H, m), 6.67 (1H, s), 1.58 (18H, s).

(5) Preparation of tert-butyl 4-phenyl-5-(6-(3-sulfamoylphenylamino) pyrimidin-4-yloxy)thizol-2-ylcarbamate (hereinafter referred to as compound 14-5)

Compound 14-4 (300 mg, 0.60 mmol) was dissolved in DMF (6.0 mL) at room temperature, 3-aminobenzenesulfonamide (113 mg, 0.65 mmol) and K ₂ CO ₃ (246 mg, 1.78 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After addition of BrettPhos Pd G3 (162 mg, 0.18 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 1:3) to give compound 14-5 (106 mg, 28%) as a yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.78 (1H, s), 8.30 (1H, s), 7.84 (1H, s), 7.59-7.57 (1H, m), 7.51-7.49 (2H, m), 7.36-7.33 (3H, m), 7.15 (2H, s), 6.98 (1H, s), 6.90 (1H, d, J = 7.6 Hz), 6.68 (1H, d, J = 6.8 Hz), 1.53 (9H, s).

* A proton from NH was not observed.

(6) Manufacturing of A-236

Compound 14-5 (106 mg, 0.17 mmol) was dissolved in DCM (1.7 mL) at room temperature, and TFA (0.13 mL, 1.65 mmol) was added at 0 °C. The mixture was stirred for 18 h. The reaction mixture was quenched with saturated NaHCO ₃ solution and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (DCM:MeOH = 20:1) to give A-236 (7.6 mg, 10%) as a pale yellow solid.

32. A-237 Synthesis

(1) Preparation of 2-bromo-5-(6-chloropyrimidin-4-yloxy)-4-phenylthiazole (hereinafter referred to as compound 14-6)

Compound 14-3 (400 mg, 1.31 mmol) was dissolved in ACN (6.6 mL) and CuBr ₂ (293 mg, 1.31 mmol) and isopentyl nitrite (0.26 mL, 1.97 mmol) were added at 0 °C. After stirring at room temperature for 1 h, the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 5:1) to give compound 14-6 (284 mg, 59%) as a pale yellow solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 7.81 (1H, s), 7.45-7.40 (5H, m), 6.69 (1H, s).

(2) Preparation of 5-(6-chloropyrimidin-4-yloxy)-2-methyl-4-phenylthiazole (hereinafter referred to as compound 14-7)

Compound 14-6 (284 mg, 0.77 mmol) was dissolved in THF (7.7 mL) at room temperature, MeZnCl (2 M in THF, 0.96 mL, 1.93 mmol) and CuI (103 mg, 0.54 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After PdCl ₂ (dppf) (113 mg, 0.15 mmol) was added, and the reaction mixture was refluxed 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 1:1) to give compound 14-7 (111 mg, 47%) as a yellow solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 7.82 (1H, s), 7.45-7.43 (2H, m), 7.41-7.37 (3H, m), 6.67 (1H, s), 2.79 (3H, s).

(3) Manufacturing of A-237

Compound 14-7 (111 mg, 0.37 mmol) was dissolved in DMF (3.7 mL) at room temperature, 3-aminobenzenesulfonamide (69.0 mg, 0.40 mmol) and K ₂ CO ₃ (152 mg, 1.10 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After addition of Brettphos Pd G3 (99.0 mg, 0.11 mmol), the reaction mixture was heated at 80 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 1:3) to give A-237 (38 mg, 24%) as a yellow solid.

33. A-238 Synthesis

(1) Preparation of 2-(2-chloropyrimidin-4-yloxy)-1-phenylethanone (hereinafter referred to as compound 15-1)

Compound 1-1 (1.68 g, 8.43 mmol) was dissolved in acetone (15 mL) at room temperature, 2-chloropyrimidin-4-ol (1.00 g, 7.66 mmol) and K ₂ CO ₃ (1.59 g, 11.5 mmol) were added. 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 1:2) to give compound 15-1 (1.69 g, 89%) as a white solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.37 (1H, d, J = 5.2 Hz), 7.97 (2H, d, J = 8.0 Hz), 7.65 (1H, t, J = 7.2 Hz), 7.53 (2H, t, J = 7.8 Hz), 6.89 (1H, d, J) = 5.6 Hz), 5.71 (2H, s).

(2) Preparation of 2-bromo-2-(2-chloropyrimidin-4-yloxy)-1-phenylethanone (hereinafter referred to as compound 15-2)

Compound 15-1 (1.69 g, 6.80 mmol) was dissolved in CHCl ₃ (23 mL) at 0 °C, AlCl ₃ (362 mg, 2.72 mmol) and Br ₂ (0.525 mL, 10.2 mmol) were slowly added. The mixture was stirred at room temperature for 18 h. The reaction mixture was quenched with saturated NaHCO ₃ solution and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 3:1) to give compound 15-2 (1.55 g, 70%) as a white solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.50 (1H, d, J = 5.6 Hz), 8.11 (2H, d, J = 7.6 Hz), 8.06 (1H, s), 7.66 (1H, t, J = 7.4 Hz), 7.54 (2H, t, J = 7.8 Hz), 6.99 (1H, d, J = 5.6 Hz).

(3) Preparation of 5-(2-chloropyrimidin-4-yloxy)-4-phenylthiazol-2-amine (hereinafter referred to as compound 15-3)

A mixture of compound 15-2 (1.55 g, 4.73 mmol) and thiourea (396 mg, 5.21 mmol) was dissolved in ACN (16 mL) and heated at 80 °C for 30 min. After cooling to room temperature, the reaction mixture was quenched with saturated NaHCO ₃ solution and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo to give compound 15-3 (1.13 g, 78%) as a yellow solid. It was used in the next step without further purification.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.67 (1H, d, J = 5.6 Hz), 7.67 (2H, d, J = 8.0 Hz), 7.37 (2H, d, J = 6.0 Hz), 7.32 (2H, d, J = 7.6 Hz), 7.12 (2H, s).

(4) Preparation of 2-bromo-5-(2-chloropyrimidin-4-yloxy)-4-phenylthiazole (hereinafter referred to as compound 15-4)

Compound 15-3 (400 mg, 1.31 mmol) was dissolved in ACN (6.6 mL) and CuBr ₂ (293 mg, 1.31 mmol) and isopentyl nitrite (0.26 mL, 1.97 mmol) were added at 0 °C. The mixture was stirred at 0 °C for 1 h. The reaction mixture was poured into water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 3:1) to give compound 15-4 (159 mg, 33%) as a yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.76 (1H, d, J = 6.0 Hz), 7.86 (2H, d, J = 7.2 Hz), 7.56 (1H, d, J = 6.0 Hz), 7.46 (2H, t, J = 7.4 Hz), 7.38 (1H, t, J = 7.4 Hz).

(5) Preparation of 5-(2-chloropyrimidin-4-yloxy)-2-methyl-4-phenylthiazole (hereinafter referred to as compound 15-5)

Compound 15-4 (159 mg, 0.43 mmol) was dissolved in THF (4.3 mL) at room temperature, MeZnCl (2 M in THF, 0.54 mL, 1.08 mmol) and CuI (63.0 mg, 0.30 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After Pd(dppf)Cl ₂ (63.0 mg, 0.09 mmol) was added, and the reaction mixture was refluxed 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 3:1) to give compound 15-5 (57.0 mg, 44%) as a yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.72 (1H, d, J = 5.2 Hz), 7.81 (2H, d, J = 7.2 Hz), 7.47 (1H, d, J = 5.6 Hz), 7.41 (2H, t, J = 7.6 Hz), 7.31 (1H, t, J = 7.4 Hz), 2.67 (3H, s).

(6) Manufacturing of A-238

Compound 15-5 (57.0 mg, 0.19 mmol) was dissolved in DMF (1.9 mL) at room temperature, 3-aminobenzenesulfonamide (36.0 mg, 0.21 mmol) and K ₂ CO ₃ (78.0 mg, 0.56 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After addition of Brettphos Pd G3 (51.0 mg, 0.06 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (DCM:MeOH = 20:1) to give A-238 (8.8 mg, 11%) as a white solid.

34. A-239 Synthesis

(1) Preparation of tert-butyl (tert-butoxycarbonyl)(5-((2-chloropyrimidin-4-yl)oxy)-4-phenylthiazol-2-yl)carbamate (hereinafter referred to as compound 15-6)

Compound 15-3 (700 mg, 3.28 mmol) was dissolved in THF (23 mL) at room temperature, Boc ₂ O (1.50 g, 6.89 mmol), TEA (0.96 mL, 6.89 mmol) and DMAP (56.0 mg, 0.46 mmol) were added. 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 5:1 to 3:1) to give compound 15-6 (339 mg, 29%) as a yellow solid.

Compound 15-6: MS Calcd.: 504.99; MS Found: 504.78 (M+H ⁺ )

(2) Preparation of tert-butyl 4-phenyl-5-(2-(3-sulfamoylphenylamino)pyrimidin-4-yloxy)thiazol-2-ylcarbamate (hereinafter referred to as compound 15-7)

Compound 15-6 (339 mg, 0.67 mmol) was dissolved in DMF (6.0 mL) at room temperature, 3-aminobenzenesulfonamide (127 mg, 0.74 mmol) and K ₂ CO ₃ (278 mg, 2.01 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After addition of Brettphos Pd G3 (183 mg, 0.20 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 1:1) to give compound 15-7 (144 mg, 40%) as a beige solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 11.6 (1H, s), 10.0 (1H, s), 8.45 (1H, d, J = 6.0 Hz), 8.08 (1H, s), 7.91 (1H, d, J = 6.8 Hz), 7.74 (2H, d, J = 7.06 Hz), 7.41-7.32 (4H, m), 7.31-7.25 (3H, m), 6.72 (1H, d, J = 5.2 Hz), 1.48 (9H, s).

(3) Manufacturing of A-239

Compound 15-7 (144 mg, 0.27 mmol) was dissolved in DCM (2.7 mL) and TFA (0.31 mL, 4.00 mmol) was added at 0 °C. The mixture was stirred at room temperature for 18 h. The reaction mixture was quenched with saturated NaHCO ₃ solution and extracted with DCM. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (DCM:MeOH = 10:1) to give A-239 (5.0 mg, 4%) as a white solid.

35. A-240 Synthesis

(1) Preparation of 5-(2-chloropyrimidin-4-yloxy)-4-phenyl-2-vinylthiazole (hereinafter referred to as compound 15-8)

To a solution of compound 15-4 (170 mg, 0.46 mmol) dissolved in dioxane (2.1 mL) and water (0.21 mL) at room temperature were added 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (107 mg, 0.69 mmol) and Na ₂ CO ₃ (147 mg, 1.38 mmol). The mixture was degassed by purging and backfilled with argon several times. After addition of Pd(dppf)Cl ₂ (67.5 mg, 0.09 mmol), the reaction mixture was heated at 80 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 9:1) to give compound 15-8 (59.0 mg, 41%) as an ivory oil.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.53 (1H, d, J = 6.0 Hz), 7.87 (2H, d, J = 7.6 Hz), 7.44-7.40 (2H, m), 7.35-7.33 (1H, m), 7.01 (1H, d, J = 5.6 Hz), 6.92-6.85 (1H, m), 6.07-6.02 (1H, m), 5.61-5.58 (1H, m).

(2) Preparation of 5-(2-chloropyrimidin-4-yloxy)-2-ethyl-4-phenylthiazole (hereinafter referred to as compound 15-9)

A mixture of compound 15-8 (59.0 mg, 0.19 mmol) and Pd/C (5 wt%, 9.94 mg, 0.09 mmol) dissolved in MeOH (3.7 mL) was stirred under H ₂ atmosphere at room temperature for 3 h. After filtration through a pad of Celite, the filtrate was concentrated in vacuo to give compound 15-9 (51.0 mg, 86%) as a brown oil. It was used in the next step without further purification.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.51 (1H, d, J = 5.2 Hz), 7.85 (1H, d, J = 7.2 Hz), 7.42-7.38 (2H, m), 7.33-7.29 (1H, m), 6.97 (1H, d, J = 5.2 Hz), 3.04 (2H, q, J = 7.6 Hz), 1.44 (3H, t, J = 7.4 Hz).

(3) Manufacturing of A-240

Compound 15-9 (51.0 mg, 0.16 mmol) was dissolved in DMF (2.0 mL) at room temperature, 3-aminobenzenesulfonamide (33.2 mg, 0.19 mmol) and K ₂ CO ₃ (66.5 mg, 0.48 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After addition of BrettPhos Pd G3 (43.6 mg, 0.05 mmol), the reaction mixture was heated at 100 °C for 4 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (only EtOAc) to give A-240 (8.5 mg, 12%) as an ivory solid.

A-241 to A-246 were synthesized using the procedure described above for A-240.

36. Synthesis of tert-butyl (5-((2-chloropyridin-4-yl)oxy)-4-(6-methylpyridin-2-yl)thiazol-2-yl)carbamate (hereinafter referred to as compound 16-6)

(1) Preparation of 2-bromo-1-(6-methylpyridin-2-yl)ethanone (hereinafter referred to as compound 16-2)

1-(6-methylpyridin-2-yl)ethanone (1-(6-methylpyridin-2-yl)ethanone; hereinafter referred to as compound 16-1) (10.0 g, 74.0 mmol) was dissolved in DCM (148 mL) at 0 °C, HBr (33 wt% in AcOH, 24.35 mL, 148 mmol) and Br ₂ (4.58 mL, 89.0 mmol) were added. The mixture was stirred at room temperature for 3 h. The reaction mixture was neutralized with NaHCO ₃ (aq) at 0 °C and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo to give compound 16-2 (15.52 g, 98%) as a yellow oil. It was used for the next step without further purification.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 7.90 (1H, t, J = 7.6 Hz), 7.81 (1H, d, J = 7.6 Hz), 7.55 (1H, d, J = 7.6 Hz), 4.99 (2H, s), 2.55 (3H, s).

(2) Preparation of 4-(6-methylpyridin-2-yl)thiazol-2-amine (4-(6-methylpyridin-2-yl)thiazol-2-amine; hereinafter referred to as compound 16-3)

Compound 16-2 (15.52 g, 72.5 mmol) was dissolved in ACN (145 mL) at room temperature, and thiourea (6.07 g, 80.0 mmol) was added. The mixture was heated at 80 °C for 2 h. After cooling to room temperature, the reaction mixture was neutralized with saturated NaHCO ₃ (aq) at 0 °C and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo to give compound 16-3 (12.3 g, 89%) as a yellow solid. It was used in the next step without further purification.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 7.66 (1H, t, J = 7.8 Hz), 7.59 (1H, d, J = 7.6 Hz), 7.16 (1H, s), 7.09 (1H, d, J = 7.2 Hz), 7.05 (2H, s), 2.45 (3H, s).

(3) Preparation of tert-butyl (tert-butoxycarbonyl)(4-(6-methylpyridin-2-yl)thiazol-2-yl)carbamate (hereinafter referred to as compound 16-4)

Compound 16-3 (12.3 g, 64.3 mmol) was dissolved in THF (19 mL) at room temperature, Boc ₂ O (42.1 g, 193 mmol), DMAP (2.35 g, 19.29 mmol) and TEA (26.7 mL, 193 mmol) were added. 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 5:1) to give compound 16-4 (15.78 g, 62%) as a pale yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 7.90 (1H, s, J = 7.6 Hz), 7.78 (1H, d, J = 8.0 Hz), 7.62 (1H, t, J = 8.0 Hz), 7.06 (1H, d, J = 7.6 Hz), 2.57 (3H, s), 1.53 (18H, s).

(4) Preparation of tert-butyl (5-bromo-4-(6-methylpyridin-2-yl)thiazol-2-yl)(tert-butoxycarbonyl)carbamate (hereinafter referred to as compound 16-5)

Compound 16-4 (15.7 g, 40.1 mmol) was dissolved in DMF (201 mL) at 0 °C, to which NBS (7.85 g, 44.1 mmol) was slowly added. The mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with saturated NaHCO ₃ (aq) and extracted with EtOAc. The organic layer was washed several times with brine, dried over Na ₂ SO ₄ , filtered and concentrated in vacuo to give compound 16-5 (16.3 g, 86%) as a brown oil. This was used in the next step without further purification.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 7.77 (1H, t, J = 7.6 Hz), 7.61 (1H, d, J = 8.0 Hz), 7.24 (1H, d, J = 7.2 Hz), 2.51 (3H, s), 1.51 (18H, s).

(5) Preparation of compound 16-6

A mixture of compound 16-5 (15.5 g, 33.0 mmol), 2-chloropyridin-4-ol (4.70 g, 36.2 mmol) and K ₂ CO ₃ (9.11 g, 65.9 mmol) was dissolved in DMF (165 mL) and stirred at 100 °C for 150 min. The reaction was followed by consumption of compound 16-5 by LC-MS once every 1 h. The mixture was poured into water and extracted with EtOAc. The organic layer was washed several times with brine, dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (hexane:EtOAc = 2:1) to give compound 16-6 (6.4 g, 37%) as a yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.24 (1H, d, J = 5.6 Hz), 7.68 (1H, t, J = 7.6 Hz), 7.60 (1H, d, J = 7.2 Hz), 7.16 (1H, s), 7.08-7.04 (2H, m), 2.09 (3H, s), 1.47 (9H, s). * A proton from NH was not observed.

37. A-247 Synthesis

(1) Preparation of tert-butyl 4-(6-methylpyridin-2-yl)-5-(2-(3-sulfamoylphenylamino)pyridin-4-yloxy)thiazol-2-ylcarbamate (hereinafter referred to as compound 16-7)

Compound 16-6 (150 mg, 0.36 mmol) was dissolved in DMF (7.2 mL) at room temperature, 3-aminobenzenesulfonamide (92.0 mg, 0.54 mmol) and Cs ₂ CO ₃ (350 mg, 1.07 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After addition of Brettphos Pd G3 (97.0 mg, 0.11 mmol), the reaction mixture was heated at 100 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (only EtOAc to EtOAc:MeOH = 50:1) to give compound 16-7 (44.0 mg, 22%) as a yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 9.31 (1H, s), 8.20 (1H, s), 8.10 (1H, d, J = 6.0 Hz), 7.80 (1H, d, J = 8.4 Hz), 7.70 (1H, t, J = 7.8 Hz), 7.60 (1H, d, J = 8.0 Hz), 7.40 (1H, t, J = 8.0 Hz), 7.30 (1H, d, J = 7.6 Hz), 7.27 (2H, s), 7.08 (1H, d, J = 7.6 Hz), 6.64 (1H, dd, J = 5.8, 2.2 Hz), 6.43 (1H, d, J = 2.0 Hz), 2.25 (3H, s), 1.50 (9H, s). * A proton from NH was not observed.

(2) Manufacturing of A-247

Compound 16-7 (44.0 mg, 0.08 mmol) was dissolved in DCM (1.6 mL) at 0 °C, TFA (0.122 mL, 1.59 mmol). After stirring at room temperature for 1 h, the reaction mixture was quenched with saturated NaHCO ₃ and extracted with 5% MeOH/DCM. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (only EtOAc and EtOAc:MeOH = 10:1) to give A-247 (7.0 mg, 19%) as a pale orange solid.

A-248 and A-249 were synthesized using the above A-247 synthesis procedure.

38. A-250 Synthesis

(1) Preparation of 5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)thiazol-2-amine (5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)thiazol-2-amine; hereinafter referred to as compound 16-8)

Compound 16-6 (6.4 g, 15.28 mmol) was dissolved in DCM (153 mL) at 0 °C, TFA (23.54 mL, 306 mmol) was added. After stirring at room temperature for 5 h, the reaction mixture was neutralized with saturated NaHCO ₃ (aq) at 0 °C and extracted with DCM. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo to give compound 16-8 (4.3 g, 88%) as a red solid. It was used in the next step without further purification.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.25 (1H, d, J = 5.6 Hz), 7.64 (1H, d, , J = 6.8 Hz), 7.54 (1H, d, , J = 8.0 Hz), 7.22 (2H, s), 7.11 (1H, s), 7.06 (1H, d, , J = 6.0 Hz), 7.01 (1H, d, , J = 7.6 Hz), 2.05 (3H, s).

(2) Preparation of 2-bromo-5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)thiazole (2-bromo-5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)thiazole; hereinafter referred to as compound 16-9)

Compound 16-8 (4.3 g, 13.49 mmol) was added to ACN (100 mL) containing CuBr ₂ (3.01 g, 13.49 mmol) and isopentyl nitrite (2.72 mL, 20.23 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 2 h, quenched with NH ₄ OH (100 mL) and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 5:1 to 3:1) to give compound 16-9 (1.57 g, 30%) as a yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.28 (1H, d, J = 5.6 Hz), 7.75 -7.68 (2H, m), 7.30 (1H, d, J = 2.0 Hz), 7.16 (1H, dd, J = 5.6, 2.4 Hz), 7.12 (1H, d, J = 7.2 Hz), 2.08 (3H, s).

(3) Preparation of 5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)-2-vinylthiazole (5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)-2-vinylthiazole; hereinafter referred to as compound 17-1)

At room temperature, tributyl(vinyl)stannane (1.91 mL, 6.56 mmol) was added to THF (41 mL) to which compound 16-9 (1.57 g, 4.10 mmol) was dissolved. The mixture was degassed with argon and PdCl ₂ (PPh ₃ ) ₂ (576 mg, 0.82 mmol) was added. The mixture was heated at 80 °C for 4 h. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 7:1 to 5:1) to give compound 17-1 (510 mg, 37%) as a yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.27 (1H, d, J = 6.0 Hz), 7.78-7.70 (2H, m), 7.23 (1H, d, J = 2.0 Hz), 7.10 (2H, d, J = 6.4 Hz), 6.10 (1H, d, J = 17.6 Hz), 5.70 (1H, d, J = 10.8 Hz), 2.10 (3H, s).

(4) Preparation of 5-(2-chloropyridin-4-yloxy)-2-ethyl-4-(6-methylpyridin-2-yl)thiazole (5-(2-chloropyridin-4-yloxy)-2-ethyl-4-(6-methylpyridin-2-yl)thiazole; hereinafter referred to as compound 17-2)

A mixture of compound 17-1 and PtO ₂ (70.0 mg, 0.31 mmol) dissolved in MeOH (18 mL) was stirred under H ₂ atmosphere at room temperature for 3 h. After filtration through a pad of Celite, the filtrate was concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (EA only) to give compound 17-2 (456 mg, 89%) as a yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.26 (1H, d, J = 6.0 Hz), 7.76-7.68 (2H, m), 7.16 (1H, d, J = 1.6 Hz), 7.08 (1H, d, J = 7.2 Hz), 7.05 (1H, dd, J = 6.0, 2.4 Hz), 3.01 (2H, q, J = 7.6 Hz), 2.09 (3H, s), 1.34 (3H, t, J = 7.8 Hz).

(5) Manufacturing of A-250

Compound 17-2 (456 mg, 1.37 mmol) was dissolved in DMF (13 mL) at room temperature, 3-aminobenzenesulfonamide (355 mg, 2.06 mmol) and Cs ₂ CO ₃ (1.3 g, 4.12 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After BrettPhos Pd G3 (374 mg, 0.41 mmol) was added, the reaction mixture was heated at 80 °C for 2 h. After cooling to room temperature, the reaction mixture was quenched with water and EA was extracted. The organic layer was purified by NH-SiO ₂ (hexane:EA = 1:2 to 1:4) column chromatography to give A-250 (151 mg, 23%) as a white solid.

A-251 and A-273 were synthesized using the above A-250 synthesis procedure.

39. A-274 Synthesis

(1) Preparation of 5-((2-chloropyridin-4-yl)oxy)-2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazole (5-((2-chloropyridin-4-yl)oxy)-2-cyclopropyl-4-(6-methylpyridin-2-yl)thiazole; hereinafter referred to as compound 18-1)

Compound 16-9 (50 mg, 0.13 mmol) was dissolved in dioxane (3 mL) at room temperature, and cyclopropyltributylstane (86.5 mg, 0.26 mmol) and PdCl ₂ (PPh ₃ ) ₂ (18.3 mg, 0.03 mmol) were added. The mixture was heated at 100 °C for 4 h. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 3:1) to give compound 18-1 (20.0 mg, 44.5%) as a yellow liquid.

MS Calcd.: 343.83; MS Found: 344.26 (M+H ⁺ ).

(2) Manufacturing of A-274

Compound 18-1 (20.0 mg, 0.06 mmol) was dissolved in DMF (1.0 mL) at room temperature, 3-aminobenzamide (10.0 mg, 0.07 mmol) and K ₂ CO ₃ (24.1 mg, 0.18 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After addition of Brettphos Pd G3 (21.0 mg, 0.02 mmol), the reaction mixture was heated at 100 °C for 2 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (DCM:MeOH = 10:1) to give A-274 (3.4 mg, 13.0%) as an ivory solid.

A-275 and A-282 were synthesized using the above A-274 synthesis procedure.

40. A-283 Synthesis

(1) 5-(2-chloropyridin-4-yloxy)- N , N -Dimethyl-4-(6-methylpyridin-2-yloxy)thiazol-2-amine (5-(2-chloropyridin-4-yloxy)- N , N - Preparation of dimethyl-4-(6-methylpyridin-2-yloxy)thiazol-2-amine (hereinafter referred to as compound 19-1)

Dimethylamine (2.0 M in THF, 0.57 mL, 1.14 mmol) was added to DMF (3.0 mL) containing compound 16-9 (290 mg, 0.76 mmol). The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was washed with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo to give compound 19-1 (100 mg, 38%) as a yellow oil.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.19 (1H, d, J = 5.6 Hz), 7.95 (1H, d, J = 6.0 Hz), 7.87 (1H, d, J = 7.6 Hz), 7.52 (1H, t, J = 8.0 Hz), 6.46 (1H, d, J) = 2.4 Hz), 6.40-6.38 (1H, m), 3.11 (6H, s), 2.25 (3H, s).

(2) Manufacturing of A-283

Compound 19-1 (100 mg, 0.29 mmol) was dissolved in DMF (3.0 mL) at room temperature, 3-aminobenzenesulfonamide (74.0 mg, 0.43 mmol) and K ₂ CO ₃ (120 mg, 0.87 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After addition of BrettPhos Pd G3 (52.0 mg, 0.06 mmol), the reaction mixture was heated at 100 °C for 2 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (DCM:MeOH = 98:2) to give A-283 (55.4 mg, 40%) as an ivory solid.

A-284 and A-286 were synthesized using the above A-283 synthesis procedure.

41. A-287 Synthesis

(1) Preparation of 5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)-2-(prop-1-en-2yl)thiazole (5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)-2-(prop-1-en-2yl)thiazole; hereinafter referred to as compound 20-1)

Potassium isopropenyltrifluoroborate (232 mg, 1.57 mmol) and Na ₂ CO ₃ (776 mg, 7.32 mmol) were added to a mixture of THF (5.2 mL) and water (5.2 mL) containing compound 16-9 (400 mg, 1.05 mmol) at room temperature. The mixture was degassed by purging and backfilled with argon several times. After PdCl ₂ (dppf) (86.0 mg, 0.11 mmol) was added, the reaction mixture was heated at 60 °C for 18 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 4:1) to give compound 20-1 (133 mg, 37%) as a yellow oil.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.27 (1H, d, J = 8.27 Hz), 7.80 (1H, d, J = 8.0 Hz), 7.73 (1H, t, J = 7.8 Hz), 7.22 (1H, s), 7.10 (2H, d, J = 7.6) Hz), 5.84 (1H, s), 5.50 (1H, s), 2.20 (3H, s), 2.09 (3H, s).

(2) Preparation of 5-(2-chloropyridin-4-yloxy)-2-isopropyl-4-(6-methylpyridin-2-yl)thiazole (5-(2-chloropyridin-4-yloxy)-2-isopropyl-4-(6-methylpyridin-2-yl)thiazole; hereinafter referred to as compound 20-2)

Compound 20-1 (173 mg, 0.503 mmol) was dissolved in a mixture of DCM (2.5 mL) and MeOH (2.5 mL) at room temperature, to which Pd/C (10 wt%, 54.0 mg, 0.05 mmol) was added. The mixture was stirred at room temperature for 18 h under H ₂ atmosphere. After filtering through a pad of Celite, the filtrate was concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (Heaxanes:EtOAc = 3:1) to give compound 20-2 (60.0 mg, 35%) as a colorless oil.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.23 (1H, d, J = 5.6 Hz), 7.76 (1H, d, J = 7.6 Hz), 7.58 (1H, t, J = 7.6 Hz), 6.98-6.96 (2H, m), 6.90 (1H, dd, J = 5.8, 2.2 Hz), 3.31 (1H, sep., J = 6.8 Hz), 2.28 (3H, s), 1.45 (6H, d, J = 6.4 Hz).

(3) Manufacturing of A-287

Compound 20-2 (60.0 mg, 0.17 mmol) was dissolved in DMF (3.5 mL) at room temperature, 3-aminobenzenesulfonamide (45.0 mg, 0.26 mmol) and Cs ₂ CO ₃ (170 mg, 0.52 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After addition of Brettphos Pd G3 (47.0 mg, 0.05 mmol), the reaction mixture was heated at 80 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by NH-SiO ₂ (hexane:EtOAc = 1:2) column chromatography to give A-287 (22.2 mg, 27%) as a white solid.

A-288 was synthesized using the above A-287 synthesis procedure.

42. A-289 Synthesis

(1) Preparation of 5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)-2-(trifluoromethyl)thiazole (5-(2-chloropyridin-4-yloxy)-4-(6-methylpyridin-2-yl)-2- (trifluoromethyl)thiazole; hereinafter referred to as compound 21-1)

Compound 16-9 (0.45 g, 1.18 mmol) was dissolved in DMF (3 mL) at room temperature, and CuI (403.1 mg, 2.12 mmol), HMPA (0.41 mL, 2.35 mmol) and methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (0.45 mL, 3.53 mmol) were added. The mixture was heated at 90 °C for 0.5 h. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 5:1) to give compound 21-1 (50.0 mg, 11%) as a yellow liquid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.32 (1H, d, J = 6.0 Hz), 7.80 (2H, s), 7.43 (1H, d, J = 28.8 Hz), 7.21 (2H, dd, J = 20.2, 3.0 Hz), 2.14 (3H, s).

(2) Manufacturing of A-289

Compound 21-1 (38.0 mg, 0.10 mmol) was dissolved in DMF (2.0 mL) at room temperature, 3-aminobenzenesulfonamide (26.0 mg, 0.15 mmol) and Cs ₂ CO ₃ (100 mg, 0.31 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After addition of BrettPhos Pd G3 (26.0 mg, 0.15 mmol), the reaction mixture was heated at 80 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (hexane:EtOAc = 1:4) to give A-289 (12.0 mg, 23%) as a white solid.

A-290 and A-291 were synthesized using the above A-289 synthesis procedure.

43. A-292 Synthesis

(1) Preparation of N-methyl-4-(6-methylpyridin-2-yl)thiazole-2-amine (hereinafter referred to as compound 22-1)

Compound 16-2 (2.00 g, 9.34 mmol) was dissolved in EtOH (31 mL) at room temperature, and 1-methylthiourea (842 mg, 9.34 mmol) was added. The mixture was heated at 80 °C for 1 h. After cooling to room temperature, the reaction mixture was concentrated in vacuo to give compound 22-1 (1.70 g, 89%) as a yellow solid. It was used in the next step without further purification.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 7.66 (1H, d, J = 7.4 Hz), 7.61 (1H, t, J = 7.8 Hz), 7.26 (1H, d, J = 8.4 Hz), 7.05 (1H, d, J = 7.6 Hz), 3.00 (3H, s), 2.58 (3H, s). * A proton from NH was not observed.

(2) Preparation of 5-bromo-N-methyl-4-(6-methylpyridin-2-yl)thiazol-2-amine (5-bromo-N-methyl-4-(6-methylpyridin-2-yl)thiazol-2-amine; hereinafter referred to as compound 22-2)

Compound 22-1 (2.00 g, 9.74 mmol) was dissolved in DMF (49 mL) at 0 °C, to which NBS (1.73 g, 9.74 mmol) was slowly added. The mixture was stirred at room temperature for 1 h. The reaction mixture was quenched with saturated NaHCO ₃ solution and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was triturated with diethyl ether and hexane. The solid was filtered and diluted to give compound 22-2 (1.60 g, 58%) as a yellow solid.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 7.68-7.55 (2H, m), 7.11 (1H, dd, J = 7.2, 1.6 Hz), 2.75 (3H, s), 2.64 (3H, s). * A proton from NH was not observed.

(3) Preparation of 5-(2-chloropyridin-4-yloxy)-N-methyl-4-(6-methylpyridin-2-yl)thiazol-2-amine (5-(2-chloropyridin-4-yloxy)-N-methyl-4-(6-methylpyridin-2-yl)thiazol-2-amine; hereinafter referred to as compound 22-3)

A mixture of compound 22-2 (1.00 g, 3.52 mmol), 2-chloropyridin-4-ol (501 mg, 3.87 mmol) and K ₂ CO ₃ (501 mg, 3.87 mmol) was dissolved in DMF (35 mL) and stirred at 100 °C for 1 h. The reaction mixture was poured into water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on NH-SiO ₂ (hexane:EtOAc = 1:1) to give compound 22-3 (542 mg, 46%) as a yellow solid.

MS Calcd.: 332.81; MS Found: 333.20 (M+H ⁺ ).

(4) Manufacturing of A-292

Compound 22-3 (250 mg, 0.75 mmol) was dissolved in DMF (15 mL) at room temperature, 3-aminobenzenesulfonamide (194 mg, 1.13 mmol) and Cs ₂ CO ₃ (734 mg, 2.25 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After addition of BrettPhos Pd G3 (204 mg, 0.22 mmol), the reaction mixture was heated at 80 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (DCM:MeOH = 10:1) to give A-292 (4.0 mg, 1%) as a pale yellow solid.

44. Synthesis of A-293 and A-294

(1) Preparation of 5-(2-chloropyridin-4-yloxy)-2-cyclopropyl-4-phenyloxazole (hereinafter referred to as compound 23-1)

Cyclopropanecarboxamide (1.00 g, 11.8 mmol) was added to EtCN (20 mL) containing compound 1-4 (700 mg, 2.14 mmol) at room temperature. The mixture was heated at 120 °C for 18 h. After cooling to room temperature, the reaction mixture was quenched with saturated NaHCO ₃ solution and extracted with EtOAc. The organic layer was washed with brine, dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 4:1) to give compound 23-1 (180 mg, 27%) as a colorless oil.

¹ H-NMR (400 MHz, CDCl ₃ ): δ 8.32 (1H, d, J = 5.6 Hz), 7.67 (2H, d, J = 7.2 Hz), 7.36 (2H, t, J = 7.4 Hz), 7.28-7.25 (1H, m), 6.99 (1H, d, J = 2.0 Hz), 6.90 (1H, dd, J = 5.6, 2.0 Hz), 2.08-2.02 (1H, m), 1.14-1.05 (4H, m).

(2) Preparation of methyl 6-(4-(2-cyclopropyl-4-phenyloxazol-5-yloxy)pyridin-2-ylamino)nicotinate (hereinafter referred to as compound 23-2)

Compound 23-1 (40.0 mg, 0.13 mmol) was dissolved in DMF (5.0 mL) at room temperature, to which was added methyl 6-aminonicotinate (40.0 mg, 0.26 mmol) and K ₂ CO ₃ (60.0 mg, 0.43 mmol). The mixture was degassed by purging and backfilled with argon several times. After addition of Brettphos Pd G3 (40.0 mg, 44.0 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 4:1) to give methyl compound 23-2 (30.0 mg, 55%) as a yellow solid.

MS Calcd.: 428.15; MS Found: 429.2 (M+H ⁺ ).

(3) Manufacturing of A-293

Compound 23-2 (30.0 mg, 0.07 mmol) was dissolved in a mixture of THF (5.0 mL) and water (5.0 mL) at room temperature, and LiOH H ₂ O (50.0 mg, 2.09 mmol) was added. 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-293 (21.0 mg, 72%) as an ivory solid.

(4) Manufacturing of A-294

A-293 (15.0 mg, 36.0 μmol) was dissolved in DMF (5.0 mL) at room temperature, HATU (30.0 mg, 79.0 μmol), NH ₄ Cl (50.0 mg, 0.94 mmol) and DIPEA (0.20 mL, 1.15 mmol) were added. The mixture was stirred at room temperature for 18 h. The reaction mixture was poured into water. The resulting solid was filtered and triturated with DCM and hexane. The precipitated solid was collected by filtration and dried in vacuo to give A-294 (4.0 mg, 19%) as a white solid.

A-295 to A-302 were synthesized using the above A-293 synthesis procedure.

45. A-303 Synthesis

(1) Preparation of 5-(2-chloropyridin-4-yloxy)-2-methyl-4-(6-methylpyridin-2-yl)thiazole (5-(2-chloropyridin-4-yloxy)-2-methyl-4-(6-methylpyridin-2-yl)thiazole; hereinafter referred to as compound 24-1)

Compound 16-9 (200 mg, 0.52 mmol) was dissolved in THF (5.2 mL) at room temperature, to which were added CuI (70.0 mg, 0.37 mmol) and Pd(dppf)Cl ₂ (76.0 mg, 0.11 mmol). The mixture was degassed by purging and backfilled with argon several times. After addition of MeZnCl ₂ (2 M in THF, 0.65 mL, 1.31 mmol), the reaction mixture was refluxed 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 Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 2:1) to give compound 24-1 (90.0 mg, 54%) as a beige solid.

¹ H-NMR (400 MHz, DMSO-d ₆ ): δ 8.26 (1H, d, J = 5.8 Hz), 7.74-7.68 (2H, m), 7.16 (1H, d, J = 1.6 Hz), 7.08-7.04 (2H, m), 2.68 (3H, s), 2.08 (3H, s).

(2) Manufacturing of A-303

Compound 24-1 (90.0 mg, 0.28 mmol) was dissolved in DMF (5.7 mL) at room temperature, 3-aminobenzenesulfonamide (73.0 mg, 0.42 mmol) and Cs ₂ CO ₃ (277 mg, 0.85 mmol) were added. The mixture was degassed by purging and backfilled with argon several times. After addition of Brettphos Pd G3 (77.0 mg, 0.08 mmol), the reaction mixture was heated at 80 °C for 3 h. After cooling to room temperature, the reaction mixture was quenched with water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO ₂ (hexane:EtOAc = 2:1) to give A-303 (5.0 mg, 4%) as a white solid.

A-304 to A-309 were synthesized using the above A-303 synthesis procedure.

A-62 and A-137 were synthesized using the above A-1 synthetic procedure.

A-310 was synthesized using the above A-50 synthesis procedure.

A-311 was synthesized using the above A-191 synthetic procedure.

A-312 was synthesized using the above A-193 synthetic procedure.

[Experimental Example 1] Kinase binding analysis

4 μL of 4X novel compounds synthesized in the above examples in 4% DMSO and 4 μL of 4X Kinase in Kinase buffer were added to the wells (low volume, white 384-well plate (Greiner Cat. #784207)). The plate was shaken for 30 seconds, centrifuged at 1000 rpm for 10 seconds, and incubated for 30 minutes at RT (room temperature). Then, 4 μL of 4X Eu-anti-GST antibody and 4 μL of 4X Kinase Tracer 178 were added to the wells. The plate was shaken for 30 seconds, centrifuged at 1000 rpm for 10 seconds, and incubated for 60 minutes at RT. Fluorescence was measured under the following conditions by a plate reader Biotek Synergy H1 (Vermont, USA). The results are shown in Table 1.

- Excitation: 340 nm (30 nm bandpass)

- Kinase tracer emission: 665 nm (10 nm band pass)

- Eu Ab emission: 615 nm (10 nm bandpass)

- Emission ratio = 665 nm (tracer) / 615 nm (Eu Ab)

*The higher the binding affinity of a compound for ALK5 kinase, the lower the release ratio.

IC50 < 100 nM (**) > 100 nM (*) Enzyme A-1, A-2, A-3, A-4, A-5, A-9, A-10, A-14, A-39, A-40, A-41, A-42, A-43, A-44, A-45, A-46, A-48, A-49, A-50, A-51, A-52, A-53, A-54, A-55, A-56, A-57, A-58, A-59, A-60, A-61, A-63, A-64, A-65, A-66, A-68, A-69, A-70, A-71, A-91, A-92, A-93, A-104, A-105, A-107, A-109, A-110, A-111, A-112, A-113, A-114, A-115, A-116, A-117, A-118, A-119, A-120, A-121, A-122, A-124, A-125, A-126, A-127, A-128, A-129, A-132, A-133, A-134, A-135, A-136, A-138, A-139, A-140, A-141, A-142, A-143, A-144, A-145, A-146, A-147, A-148, A-149, A-150, A-151, A-152, A-153, A-154, A-155,A-156, A-157, A-158, A-159, A-160, A-161, A-163, A-164, A-165, A-166, A-167, A-168, A-169, A-170, A-171, A-174, A-175, A-181, A-182, A-183, A-184, A-185, A-186, A-187, A-188, A-189, A-190, A-192, A-193, A-194, A-195, A-220, A-221, A-223, A-224, A-225, A-226, A-227, A-228, A-229, A-230, A-231, A-232, A-238, A-247, A-248, A-249, A-250, A-251, A-252, A-253, A-255, A-256, A-257, A-258, A-259, A-260, A-261, A-262, A-263, A-264, A-265, A-266, A-267, A-268, A-269, A-270, A-271, A-274, A-275, A-276, A-277, A-278, A-279, A-280, A-283, A-284, A-285, A-286, A-287, A-288, A-289, A-290, A-291, A-292, A-293, A-294, A-295, A-303, A-304, A-309, A-310 A-47, A-72, A-172, A-173, A-176, A-177, A-178, A-179, A-180, A-217, A-218, A-219, A-222, A-233, A-234, A-235, A-254

[Experimental Example 2] Analysis for evaluating cell inhibition of TGF-β signaling

4T1 (SBE-luc2P) transient pool or HEK293 (SBE reporter) stable cells (BPS bioscience) harboring SBE-luc2P (hygro) expression plasmid were seeded at 6× ¹⁰³ cells/well or 2.5× ¹⁰⁴ cells/well, respectively, in 96-well plates. 4T1 (SBE-luc2P) transient pool was pretreated with the novel compound synthesized in the above example in 0.2% FBS (approximately 60% confluence at 37°C, 5% _CO2 ), and HEK293 (SBE reporter) stable cells were pretreated with the novel compound synthesized in the above synthesis example in 0.5% FBS (approximately 80% confluence at 37°C, 5% _CO2 ). After 2 h, each cell was treated with TGF-β1 (2 ng/mL) for 24 h at 37°C, 5% CO _2. Cell lysates were prepared using Luciferase Assay (Promega) according to the manufacturer's instructions, and luminescence was measured using a plate reader, Biotek Synergy H1 (Vermont, USA), and the results are shown in Table 2.

IC50 < 100 nM (**) > 100 nM (*) 4T1 Cell A-1, A-2, A-9, A-12, A-13, A-14, A-15, A-16, A-19, A-20, A-22, A-23, A-24, A-29, A-33, A-34, A-36, A-51, A-58, A-60, A-61, A-66, A-67, A-69, A-70, A-71, A-73, A-74, A-75, A-76, A-77, A-78, A-79, A-88, A-89, A-90, A-92, A-93, A-99, A-100, A-101, A-104, A-105, A-106, A-107, A-108, A-111, A-112, A-113, A-114, A-116, A-117, A-119, A-122, A-123, A-124, A-125, A-126, A-127, A-128, A-129, A-130, A-132, A-133, A-134, A-135, A-136, A-138, A-146, A-147, A-148, A-149, A-150, A-152, A-155, A-157, A-160, A-161, A-162, A-163, A-165, A-166, A-168, A-181, A-183, A-186, A-188, A-189, A-190, A-191, A-192, A-193, A-195, A-225, A-227, A-228, A-231, A-232, A-238, A-239, A-249, A-250, A-251, A-252, A-253, A-254, A-255, A-256, A-257, A-258, A-259, A-261, A-262, A-265, A-267, A-268, A-274, A-275, A-283, A-284, A-285, A-286, A-287, A-288, A-289, A-290, A-291, A-292, A-303, A-304, A-306, A-307, A-308, A-309, A-311 A-3, A-4, A-5, A-6, A-7, A-8, A-10, A-11, A-17, A-18, A-21, A-25, A-26, A-27, A-28, A-30, A-31, A-32, A-35, A-37, A-38, A-39, A-40, A-41, A-42, A-43, A-44, A-45, A-6, A-47, A-48, A-49, A-50, A-52, A-3, A-4, A-5, A-56, A-57, A-59, A-62, A-63, A-64, A-65, A-68, A-72, A-80, A-81, A-82, A-83, A-84, A-5, A-6, A-87, A-91, A-94, A-95, A-96, A-97, A-98, A-102, A-103, A-109, A-110, A-115, A-118, A-120, A-121, A-131, A-137, A-139, A-140, A-141, A-142, A-143, A-144, A-145, A-151, A-153, A-154, A-156, A-158, A-159, A-164, A-167, A-169, A-170, A-171, A-172, A-17, A-174, A-175, A-176, A-177, A-178, A-179, A-180, A-182, A-184, A-185, A-187, A-194, A-216, A-217, A-218, A-219, A-220, A-221, A-222, A-223, A-224, A-226, A-229, A-230, A-233, A-234, A-235, A-236, A-237, A-248, A-249, A-260, A-263, A-266, A-305, A-310 HEK 293 Cell A-196, A-197, A-198, A-199, A-200, A-201, A-202, A-203, A-204, A-205, A-206, A-207, A-208, A-209, A-210, A-211, A-212, A-213, A-214, A-215, A-240, A-241, A-243, A-246, A-264, A-269, A-270, A-271, A-272, A-276, A-277, A-278, A-279, A-280, A-281, A-282, A-293, A-294, A-295, A-296, A-297, A-298, A-299, A-300, A-301, A-302, A-312 A-242, A-244, A-245, A-273

[Experimental Example 3] Compound in vitro evaluation

3-1. Confirmation of anti-fibrotic activity

The antifibrotic activity of compounds A-136, A-58, A-195, and A-250 was confirmed through protein analysis of Collagen I, a-SMA, E-cadherin, and N-cadherin using human lung fibroblast MRC-5 and idiopathic pulmonary fibrosis (IPF) patient-derived human lung fibroblast LL97A cell lines. As shown in Fig. 1, the protein expression levels of Collagen I, a-SMA, and N-cadherin, whose expression increases when lung fibrosis is induced, decreased when treated with the compounds, whereas E-cadherin, whose expression decreased when lung fibrosis was induced, was restored.

3-2. Analysis of protein expression in human fibroblasts

As a result of analyzing the mRNA expression levels of Collagen I, a-SMA, E-cadherin, and N-cadherin according to treatment with A-136, A-58, A-195, and A-250 compounds using MRC-5 and LL97A cell lines, as shown in Fig. 2, it was confirmed that the protein expression levels decreased when the compounds were treated, and it was confirmed that E-cadherin, whose expression was decreased when pulmonary fibrosis was induced, was restored.

3-3. Analysis of collagen changes in human fibroblasts

After cell experiments, collagen accumulation in the cell culture medium was measured using a collagen assay kit (Biocolor, Sircol ^TM Soluble collagen assay), and absorbance was measured at 555 nm.

As a result, as shown in Fig. 3, the increase in collagen induced by TGF-β1 in MRC-5 and LL97A cell lines was decreased by treatment with A-136, A-58, A-195, and A-250 compounds. In particular, it was confirmed that A-195 and A-250 had an effect similar to that of Nintedanib, a conventional therapeutic agent.

[Experimental Example 4] Compound in vivo evaluation

4-1. Mouse model

As shown in Fig. 4, a BLM-induced idiopathic pulmonary fibrosis mouse model was prepared by administering bleomycin (BLM) to C57BL/6 female mice (IT treatment, 10 mice/group). The mice were treated as shown in Table 3 below.

4-2. Confirmation of changes in mouse body weight and lung weight according to treatment with compound A-192 or A-250

As shown in Fig. 5, the body weights of mice were measured before, 1, 7, and 12 days after bleomycin (BLM) administration. Compared to the PBS group, the BLM treatment group showed a significant decrease in body weight. However, body weight was recovered by treatment with the existing treatment agent, nintedanib, and it was confirmed that the body weight recovery rate was also good by treatment with compounds A-192 or A-250.

After the experiment on the mice was completed, the lungs were removed and the weight was measured. As shown in Fig. 5, the BLM-administered group showed lung swelling and an increase in lung weight, whereas the groups treated with the existing treatment agent nintedanib or compounds A-192 or A-250 showed a decrease in lung weight due to a decrease in the swelling phenomenon.

4-3. Analysis of protein expression levels in lung tissue

After the experiment on the mice was completed, the results of analyzing the proteins in the tissues showed that, as shown in Fig. 6, TGF-β1, SMAD2, SMAD3, Collagen I, PAI-1, a-SMA, and N-cadherin, which were increased by BLM, were also decreased by nintedanib, A-192, or A-250, and E-cadherin, which was decreased by cadherin-switching, was increased in the groups treated with A-192 or A-250.

4-4. Analysis of cytokines in lung lavage fluid and lung tissue

After the experiment, the alveolar lavage fluid of the mice was collected, centrifuged, and the inflammatory cytokines TNF-α, IL-1b, IL-6, and TGF-β1 were measured in the supernatant. As shown in Fig. 7, it was confirmed that each cytokine increased in the BLM group was suppressed to a level similar to that of nintedanib, an anti-pulmonary fibrosis drug, in the A-192 or A-250 administration groups.

4-5. Analysis of lung damage/Analysis of collagen I formation inhibition ability

As a result of analyzing lung damage using hematoxylin & eosin (H&E) staining, as shown in Figure 8, it was confirmed that lung damage and inflammation were significantly reduced in the A-192 or A-250 administration group compared to the control group, which was administered the existing treatment, nintedanib.

As a result of analyzing the accumulation of collagen I using Masson's Trichrome staining, as shown in Fig. 9, the accumulation of collagen I induced by BLM was reduced in the group administered A-192 or A-250 compared to the group administered nintedanib, confirming that compound A-192 or A-250 can inhibit pulmonary fibrosis caused by collagen I fiber accumulation.

[Experimental Example 5] Compound A-250 in vivo evaluation

5-1. Mouse model

As shown in Figure 10, a BLM-induced idiopathic pulmonary fibrosis mouse model was created by administering bleomycin (BLM) to C57BL/6 female mice, and changes were observed for 21 days (IT treatment, 10 mice/group).

5-2. Analysis of fibrosis markers using Western blot

To identify pulmonary fibrosis-related markers (a-SMA, collagen I, PAI-1, E-cadherin, N-cadherin) and Acetylated H3 in the tissue, western blot was performed. After sacrifice, the lungs were removed by thoracotomy and stored frozen for one day. The mouse tissues were ground to prepare protein samples. These were analyzed by SDS-polyacrylamide gel electrophoresis, and the fractionated proteins were transferred to a polyvinylidene difluoride (PVDF) membrane. The PVDF membrane with the transferred proteins was blocked by shaking for 1 hour in a blocking buffer solution diluted with 5% skim milk in 1X TBST, and then a rabbit-derived polyclonal primary antibody was diluted 1000-fold in the blocking buffer and reacted overnight. After the reaction, the membrane was washed with a buffer solution and the secondary antibody for rabbit conjugated with HRP was diluted 2000-fold in a blocking buffer solution and reacted for 1 hour. After the reaction, the membrane was washed with a buffer solution and the washed membrane was confirmed by reacting with ECL.

As a result, as shown in Fig. 11, it was confirmed that TGF-β1, SMAD2, SMAD3, Collagen I, PAI-1, a-SMA, and N-cadherin, which were increased by BLM, were decreased by A-250 treatment, and E-cadherin, which was decreased by cadherin-switching, was increased in the group treated with A-250.

5-3. ELISA analysis

1) Analysis of inflammatory cells in alveolar lavage fluid

After the experiment, the alveolar lavage fluid of the mice was collected, centrifuged, and the sedimented cells were collected on a slide, stained using Diff-Quick solution, and the number of macrophages, lymphocytes, and neutrophils was confirmed, and the total cells were counted. As a result, as shown in Fig. 12, it was confirmed that the increase in inflammatory cells in the BLM group was suppressed in the A-250 administration group.

2) Analysis of cytokines in alveolar lavage fluid and lung tissue

After the experiment, the alveolar lavage fluid of the mice was collected, centrifuged, and the inflammatory cytokines TNF-α, IL-1b, IL-6, and TGF-β1 were measured in the supernatant. As shown in Figures 13 and 14, it was confirmed that each cytokine that was increased in the BLM group was suppressed in the A-250 administration group.

5-4. Analysis of the degree of fibrosis

The morphology of cells can be confirmed by H&E staining. As a result of observing the degree of inflammatory cell infiltration, as shown in Fig. 15, it was confirmed that the degree of inflammatory cell infiltration was reduced by A-250, and this was expressed as the Ashcroft score, which numerically indicates the level of pulmonary fibrosis.

In addition, after the end of the animal experiment, the lungs were separated and observed using Masson's trichrome stain to stain collagen and muscle fibers. As shown in Fig. 16, it was confirmed that the increased collagen and muscle fibers in the BLM treatment group were reduced by A-250 administration.

[Experimental Example 6] Aerosol-induced bleomycin-induced mouse model in vivo Efficacy Evaluation

6-1. Mouse model

As shown in Fig. 17, a BLM-induced idiopathic pulmonary fibrosis mouse model was prepared by administering bleomycin (BLM) to C57BL/6 female mice (Aerosol, 5 mice/group). Compound A-250 was inhaled as an aerosol at three doses as follows. [LD (low dose): 0.03 mg/kg, MD (medium dose): 0.08 mg/kg, HD (high dose): 0.244 mg/kg (n=5)]

6-2. Confirmation of mouse weight change due to inhalation of compound A-250

As shown in Fig. 18, the body weights of mice were measured before BLM administration and on days 7, 14, and 21 after administration. Compared to the PBS group, the body weights of the BLM treatment group were significantly reduced, but it was confirmed that the body weights were restored by compound A-250.

6-3. Confirmation of collagen production and pSMAD2/3 changes in lung tissue

After the end of the mouse experiment, the results of analyzing the proteins in the tissues showed that, as shown in Fig. 19, the expression of Collagen I, pSMAD2, and pSMAD3, which had been increased by BLM, was dose-dependently reduced by A-250, and a better inhibitory effect was shown when the low dose of the drug was administered 5 times a week compared to 3 times a week.

While the specific parts of the present invention have been described in detail above, it is obvious to those skilled in the art that such specific description is merely a preferred embodiment and that the scope of the present invention is not limited thereby. In other words, the actual scope of the present invention is defined by the appended claims and their equivalents.

Claims (7)

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 and are one of (C1-C4)alkyl, (C1-C4)alkylene, (C1-C4)alkoxy, trifluoromethyl (CF ₃ ), halo, NR ¹¹ R ¹² , unsubstituted or substituted (C3-C8)cycloalkyl, unsubstituted or substituted (C5-C10)aryl and unsubstituted or substituted heteroaryl of 5 to 10 members containing one or more heteroatoms selected from the group consisting of N, O and S, wherein said 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 wherein said substituted (C3-C8)cycloalkyl, substituted (C5-C10)aryl or substituted heteroaryl of 5 to 10 members is (C1-C5)alkyl substituted, n is one of 0 to 3, Ar is an unsubstituted or substituted (C5-C10)aryl or an unsubstituted or substituted heteroaryl of 5 to 10 atoms containing one or more heteroatoms selected from the group consisting of N, O and S, wherein said substituted (C5-C10)aryl or substituted heteroaryl of 5 to 10 atoms is substituted with R ³ , wherein R ³ is -R ^3-1 or -(C1-C5)alkyl-R ^3-1 , The above R ^3-1 is hydrogen, halogen, hydroxy, cyano, (C1-C5)alkyl, (C1-C5)alkoxy, -CONR ^31-1 R ^31-2 , -COOR ³² , -NHSO ₂ R ³³ , -SO ₂ R ³⁴ , -SO ₂ NR ^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, -SO ₂ -(C1-C3)alkyl, -(C1-C3)alkyl-R ³⁰¹ and

And, The above R ³⁰¹ is (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. In claim 1, In the above chemical formula 1, R ¹ is any one of (C1-C3) alkyl, (C1-C3) alkylene, methoxy, trifluoromethyl (CF ₃ ), bromine (Br), (C3-C6) cycloalkyl and NR ¹¹ R ¹² , and 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, wherein A ³ is CH or N, and wherein R ²¹ is hydrogen or methyl, n is one of 0 to 2, Ar is

,

and

One of them, wherein R ³ is -R ^3-1 or -(C1-C3)alkyl-R ^3-1 , 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 , -NHSO ₂ R ³³ , -SO ₂ R ³⁴ , -SO ₂ NR ^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, -SO ₂ CH ₃ , -(C1-C3)alkyl-R ³⁰¹ and

And, The above R ³⁰¹ is 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, A pharmaceutical composition, wherein the above R ³⁸ and R ³⁹ may be the same or different and are each selected from the group consisting of hydrogen, (C1-C3)alkyl and -(C1-C3)alkyl-methoxy. In claim 1, In the above chemical formula 1, R ¹ is any one of methyl, ethyl, isopropyl, methoxy, ethylene, trifluoromethyl (CF ₃ ), bromine (Br), cyclopropyl, cyclopentyl, cyclohexyl and NR ¹¹ R ¹² , and 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, wherein R ³ is -R ^3-1 or -(C1-C3)alkyl-R ^3-1 , The above R ^3-1 is hydrogen, fluorine, chlorine, hydroxy, cyano, methyl, methoxy, -CONR ^31-1 R ^31-2 , -COOR ³² , -NHSO ₂ R ³³ , -SO ₂ R ³⁴ , -SO ₂ NR ^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, -SO ₂ CH ₃ , -(C1-C2)alkyl-R ³⁰¹ and

And, The above R ³⁰¹ is dimethylamino, cyclopropyl,

and

One of them, The above R ³⁰⁰¹ is one of methyl, ethyl and isopropyl, The above R ³⁰² is fluorine, wherein R ³⁰³ and R ³⁰⁴ are methyl, wherein R ³² is one of hydrogen, methyl and -(C1-C2)alkyl-dimethylamino, wherein R ³³ is one of methyl, ethyl, cyclopropyl and trifluoromethyl, wherein 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 is

or

And, wherein R ³⁰⁵ is methyl, and R ³⁰⁶ is amino or methylamino, The above R ³⁷ is

or

And, The above R ³⁸ is methyl or -CH ₂ CH ₂ OCH ₃ , A pharmaceutical composition, characterized in that the above R ³⁹ is hydrogen or methyl. 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-1 H -pyrazol-4-yl)amino)pyridin-4-yl)oxy)-4-phenylthiazol-2-amine ; ( 38) 5-((2-((1 H -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)-1 H -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)-1 H -pyrazol-4-yl)pyridin-2-amine; (98) N -(1-(Cyclopropylsulfonyl)-1 H -pyrazol-4-yl) -4 -((2-methyl-4-phenylthiazol-5-yl)oxy)pyridin - 2-amine; (99) N -(1-Methyl-1 H -pyrazol-4-yl) -4 -((2-methyl-4 - phenylthiazol-5-yl)oxy)pyridin-2-amine; (100) 4-((2-Methyl-4-phenylthiazol-5-yl)oxy)- N - (1 H -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-((1 H -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-(2 H -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); (201) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)- N -(2-( 4 -methylpiperazin-1-yl)ethyl)nicotinamide; (202) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)- N -(2-( 4 -isopropylpiperazin-1-yl)ethyl)nicotinamide; (203) 6-((4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)amino)- N -(2-( 4 -ethylpiperazin-1-yl)ethyl)nicotinamide; (204) 5-(3-aminopyrrolidin-1-yl)- N -(4-((2-ethyl-4 - phenylthiazol-5-yl)oxy)pyridin-2-yl)pyridin-2-amine; (205) N ¹ -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)- N ^{4 -} (2-(4 - isopropylpiperazin-1- yl )ethyl)benzene-1,4- ^diamine (206) N ¹ -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)- N ^{4 -} ( ^2- (4 - methylpiperazin-1- yl )ethyl)benzene-1,4-diamine (207) N ¹ -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)- N ⁴ -( ^2- (4 - ^{ethylpropylpiperazin} -1- yl )ethyl)benzene-1,4-diamine (208) N ¹ -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)- N ⁴ -(2-(pyrrolidin ^- 1-yl ) ethyl)benzene- ^1,4 - diamine (209) N ² -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)- N ^{5 -} ( ^2- (4 - methylpiperazin-1- yl )ethyl)pyridine-2,5-diamine (210) N ² -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2- yl )- N ⁵ -(2-(pyrrolidin ^- 1-yl)ethyl)pyridine- ^2,5 - diamine (211) N ² -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)- N ⁵ -( ^2- (4 - ethylpiperazin-1-yl)ethyl)pyridine-2,5 - ^diamine (212) N ² -(4-((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-yl)- N ^{5 -} (2-(4 - isopropylpiperazin-1- yl )ethyl)pyridine ^- 2,5-diamine (213) N -(5-(1H-pyrazol-4-yl)pyridin-2-yl) -4 -((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (214) N -(4-(3-aminopyrrolidin-1-yl)phenyl) -4 -((2-ethyl-4-phenylthiazol-5-yl)oxy)pyridin-2-amine; (215) 4-((2-ethyl-4-phenylthiazol-5-yl)oxy)- N -( 4- (3-(methylamino)pyrrolidin-1-yl)phenyl)pyridin-2-amine; (216) 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)- 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-((1 H -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-(2 H -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. 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. In claim 1, The above composition, A pharmaceutical composition characterized in that it reduces 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. 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-chemically 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 and are one of (C1-C4)alkyl, (C1-C4)alkylene, (C1-C4)alkoxy, trifluoromethyl (CF ₃ ), halo, NR ¹¹ R ¹² , unsubstituted or substituted (C3-C8)cycloalkyl, unsubstituted or substituted (C5-C10)aryl and unsubstituted or substituted heteroaryl of 5 to 10 members containing one or more heteroatoms selected from the group consisting of N, O and S, wherein said 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 wherein said substituted (C3-C8)cycloalkyl, substituted (C5-C10)aryl or substituted heteroaryl of 5 to 10 members is (C1-C5)alkyl substituted, n is one of 0 to 3, Ar is an unsubstituted or substituted (C5-C10)aryl or an unsubstituted or substituted heteroaryl of 5 to 10 atoms containing one or more heteroatoms selected from the group consisting of N, O and S, wherein said substituted (C5-C10)aryl or substituted heteroaryl of 5 to 10 atoms is substituted with R ³ , The above R ³ is -R ^3-1 or -(C1-C5)alkyl-R ^3-1 , The above R ^3-1 is hydrogen, halogen, hydroxy, cyano, (C1-C5)alkyl, (C1-C5)alkoxy, -CONR ^31-1 R ^31-2 , -COOR ³² , -NHSO ₂ R ³³ , -SO ₂ R ³⁴ , -SO ₂ NR ^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, -SO ₂ -(C1-C3)alkyl, -(C1-C3)alkyl-R ³⁰¹ and

And, The above R ³⁰¹ is (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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