Thiazolyl-pyrazolo[1,5-a]pyridine compound and use thereof as MYLK4 inhibitor

Abstract

The present invention provides a novel compound that inhibits MYLK4 activity, and a pharmaceutical use thereof.　Provided are a compound of formula (I) (wherein R1 to R5 are each independently hydrogen or a C1-3 chained aliphatic hydrocarbon, and R6 is an optionally substituted 5- to 10-membered aromatic hydrocarbon, an optionally substituted 5- to 10-membered heterocycle having 1 to 5 heteroatoms each independently selected from nitrogen, oxygen, and sulfur as a ring atom(s), or a fused ring in which any of the aromatic hydrocarbon and the heterocycle is fused with an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms each independently selected from nitrogen, oxygen, and sulfur as a ring atom(s)) or a pharmaceutically acceptable derivative thereof, and a pharmaceutical use of the compound or the derivative.

Description

Thiazolyl-pyrazolo[1,5-a]pyridine compounds and their use as MYLK4 inhibitors - Patent Application 20070122997

[0001] The present invention relates to thiazolyl-pyrazolo[1,5-a]pyridine compounds and uses thereof.

[0002] Myosin is a motor protein that moves along actin filaments while hydrolyzing ATP. It is a hexamer composed of two heavy chains, a regulatory light chain, and an essential light chain. The ATPase activity of myosin is regulated by phosphorylation and dephosphorylation of the regulatory light chain.

[0003] Myosin light chain kinase (MYLK) is involved in the phosphorylation of the regulatory light chain of myosin. Four isoforms of MYLK, MYLK1, MYLK2, MYLK3, and MYLK4, are known to exist, and all of them are thought to be involved in the phosphorylation of the regulatory light chain of myosin.

[0004] In addition to MYLK, myosin phosphatase (MLCP) is known as a protein that regulates the phosphorylation level of myosin regulatory light chain. MLCP dephosphorylates myosin light chain. MLCP activity is controlled by Rho-kinase, which reduces MLCP activity by phosphorylating MLCP. That is, Rho-kinase prevents the dephosphorylation of myosin light chain by phosphorylating MLCP, and inhibition of Rho-kinase induces a decrease in phosphorylated myosin light chain.

[0005] Many studies have been conducted on the in vivo roles of MYLK and Rho-kinase, and it has been reported that inhibition of MYLK or Rho-kinase (Rho-kinase inhibitors are also called ROCK inhibitors) is useful for the prevention, treatment, or alleviation of various symptoms or diseases (see Non-Patent Documents 1 to 13 and Patent Document 1, and the table at the end of this document).

[0006] Compounds having the following structure, called ML-7 and ML-9, have been reported as MYLK inhibitors (Non-Patent Documents 2, 3, 7, 10, 11, 12, and 13).

[0007] It has also been reported that a compound having the following structure has dual inhibitory activity against MYLK4 and Rho-kinase, and reduced intraocular pressure in an ocular hypertensive rabbit model (Patent Document 1 and Non-Patent Document 1).

[0008] Patent Publication No. 2021-113185

[0009] Invest. Ophthalmol. Vis. Sci. (2021) 62(13), 12. Exp. Eye Res. (2000) 71(6), 551-566. Exp. Eye Res. (2005) 80(6), 837-845. J. Ophthalmol. (2010) 175163. Invest. Ophthalmol. Vis. Sci. (2015) 56(2), 1335-1348. Invest. Ophthalmol. Vis. Sci. (2017) 58(12), 5584-5593. Invest. Ophthalmol. Vis. Sci. (2013) 54(4), 2705-2710. Curr. Opin. Cell Biol. (2008) 20(2), 242-248. Int. J. Mol. Sci. (2023) 24(13), 11219. Dig. Dis. Sci. (2013) 58(1), 107-114. J. Exp. Clin. Cancer Res. (2021) 40(1), 166. Mol. Med. Rep. (2015) 12(3), 4109-4116. J. Proteomics. (2012) 75(17), 5386-5395.

[0010] In light of the above-mentioned state of the art, the present invention provides a novel compound that inhibits MYLK4 activity and its pharmaceutical use. Specifically, it is as follows: [1] A compound of formula (I) or a pharmaceutically acceptable derivative thereof: (In the formula, R １ ~R ５ are each independently hydrogen or C １－３ A chain aliphatic hydrocarbon; R ６is an optionally substituted 5- to 10-membered aromatic hydrocarbon, an optionally substituted 5- to 10-membered heterocycle having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring-constituting atoms, or a fused ring of any of these with an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring-constituting atoms. ６ The 5- to 10-membered aromatic hydrocarbon, the 5- to 10-membered heterocycle, and the 4- to 10-membered heterocyclyl forming a condensed ring therewith are each independently unsubstituted or selected from the group consisting of: (1) halogen, nitro, cyano, hydroxy, difluoromethyl, trifluoromethyl, (2) -NR ３１ ２ , -N(R ３１ ) (CH ２ ) １－５ NR ３１ ２ , -N(R ３１ ) S (O) ２ R ３２ , -N(R ３１ ) C(O)R ３１ , -N(R ３１ )C(O)(CH ２ ) ０－３ NR ３１ ２ , -N(R ３１ )C(O)(CH ２ ) ０－３ R ３２ , (3) C １－６ Alkyl, -(CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ O (CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ R ３２ , -(CH ２ ) １－５ R ３３ , (4)-(CH ２ ) １－５ NR ３１ ２ , -(CH ２ ) １－５N(R ３１ )R ３２ 、-(CH ２ ) １－５ N(R ３１ )(CH ２ ) ０－５ R ３８ 、-(CH ２ ) １－５ N(R ３１ )C(O)R ３１ 、-(CH ２ ) １－５ N(R ３１ )C(O)(CH ２ ) １－５ OR ３１ 、-(CH ２ ) １－５ N(C(O)R ３１ )(CH ２ ) １－５ C(O)OR ３１ 、-(CH ２ ) １－５ N(R ３１ )C(O)(CH ２ ) ０－５ NR ３１ ２ 、-(CH ２ ) １－５ N(R ３１ )C(O)R ３２ 、 (5)-(CH ２ ) １－５ N(R ３１ )S(O) ２ R ３３ 、 (6)-C(R ３１ ) ２ C(O)R ３２ 、 (7)-C(R ３１ ) ２ C(O)NR ３１ ２ 、-C(R ３１ ) ２ C(O)N(R ３１ )OR ３１ 、 (8)-C(O)R ３１ 、-C(O)R ３２ 、 (9)-C(O)OR ３１ 、 (10)-C(O)NR ３１ ２ 、-C(O)N(R ３１ )(CH ２ )０－５ R ３２ , (11)-OC(R ３１ ) ２ C(O)N(R ３１ ) (CH ２ ) １－５ OR ３１ , -OC(R ３１ ) ２ C(O)OR ３１ , -OC(R ３１ ) ２ C(O)NR ３１ ２ , -OC(R ３１ ) ２ C(O)R ３２ , (12)-O(CH ２ ) １－６ R ３１ , -(O(CH ２ ) １－５ ) １－５ (CH ２ ) ０－３ NR ３１ ２ , -(O(CH ２ ) １－５ ) １－５ (CH ２ ) ０－３ NR ３１ C(O)R ３１ , -(O(CH ２ ) １－５ ) １－５ NR ３１ C(NH)NR ３１ ２ , -O((CH ２ ) １－５ O) １－５ R ３１ , (13)-OC(O)C(R ３１ ) ２ (O(CH ２ ) １－５ ) １－５ OR ３１ , and (14) optionally C １－３ a 5- or 6-membered heterocyclyl containing a nitrogen ring atom substituted with alkyl; ３１ are each independently hydrogen or C １－４ is a chain aliphatic hydrocarbon, R ３２is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen, sulfur, and oxygen as ring-constituting atoms, or a fused ring of the same with an optionally substituted 5- or 6-membered monocyclic aromatic hydrocarbon, and the 4- to 10-membered heterocyclyl forming the fused ring is optionally C １－５ substituted with a chain aliphatic hydrocarbon, R ３３ is a 3- to 10-membered alicyclic hydrocarbon or a 4- to 10-membered heterocyclyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring-constituting atoms; R ３８ is cyano, hydroxy, or S(O) ２ R ３１ [3] The compound according to [1], or a pharmaceutically acceptable derivative thereof, wherein R ６ teeth, wherein R ７ are each independently hydrogen, halogen, nitro, cyano, hydroxy, C １－６ Alkyl, C １－６ Alkoxyl, or -NR ３１ ２ and R ８ are each independently: (1) hydrogen, halogen, nitro, cyano, or hydroxy; (2) —NR ３１ ２ , -N(R ３１ ) S (O) ２ R ３２－１ (In the formula, R ３２－１ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring atoms. ３１ ) C(O)R ３１ , -N(R ３１ )C(O)(CH ２ ) ０－３ NR ３１ ２ , -N(R ３１ )C(O)(CH ２ ) ０－３ R ３２－２ (In the formula, R ３２－２is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring atoms.), (3) C １－６ Alkyl, -(CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ R ３２－３ (In the formula, R ３２―３ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring atoms.), (4) -(CH ２ ) １－５ NR ３１ ２ , -(CH ２ ) １－５ N (R ３１ ) R ３２－４ (In the formula, R ３２－４ is an optionally substituted 3- to 10-membered alicyclic hydrocarbon or an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-constituting atoms.), —(CH ２ ) １－５ N (R ３１ ) C(O)R ３１ , -(CH ２ ) １－５ N (R ３１ )C(O)(CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ N(C(O)R ３１ ) (CH ２ ) １－５ C(O)OR ３１ , -(CH ２ ) １－５ N (R ３１ )C(O)(CH ２ ) ０－５ NR ３１ ２ , -(CH ２ ) １－５ N (R ３１ ) C(O)R ３２－５ (In the formula, R ３２－５is an optionally substituted 3- to 10-membered alicyclic hydrocarbon or an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-constituting atoms.), (5) -(CH ２ ) １－５ N (R ３１ ) S (O) ２ R ３３－１ (In the formula, R ３３－１ is a 3- to 10-membered cycloalkyl.), (6) —C(R ３１ ) ２ C(O)R ３２－６ (In the formula, R ３２－６ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring atoms.), (7) -C(R ３１ ) ２ C(O)NR ３１ ２ , -C(R ３１ ) ２ C(O)N(R ３１ ) OR ３１ , (8)-C(O)R ３２－７ (In the formula, R ３２－７ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-constituting atoms, or a fused ring of the same with an optionally substituted 5- or 6-membered monocyclic aromatic hydrocarbon.), (9) -C(O)OR ３１ , (10)-C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) ０－５ R ３２－８ (In the formula, R ３２－８ is an optionally substituted 3- to 10-membered alicyclic hydrocarbon or an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-constituting atoms.), (11) -OC(R ３１ ) ２ C(O)N(R ３１ ) (CH ２ ) １－５ OR ３１ , -OC(R３１ ) ２ C(O)OR ３１ , -OC(R ３１ ) ２ C(O)NR ３１ ２ , -OC(R ３１ ) ２ C(O)R ３２－９ (In the formula, R ３２－９ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and sulfur as ring atoms.), (12) —O(CH ２ ) １－６ R ３１ , -(O(CH ２ ) １－５ ) １－５ (CH ２ ) ０－３ NR ３１ ２ , -(O(CH ２ ) １－５ ) １－５ (CH ２ ) ０－３ NR ３１ C(O)R ３１ , -(O(CH ２ ) １－５ ) １－５ NR ３１ C(NH)NR ３１ ２ , -O((CH ２ ) １－５ O) １－５ R ３１ , (13)-OC(O)C(R ３１ ) ２ (O(CH ２ ) １－５ ) １－５ OR ３１ , and (14) optionally C １－３ a 5- or 6-membered nitrogen-containing heterocycle substituted with alkyl; R ９ , R １０ , R １１ and R １２ are each independently hydrogen, halogen, cyano, hydroxy, C １－５ Alkyl, 3- to 6-membered cycloalkyl, C １－５ Alkoxyl, -N(R３１ ) C(O)R ３１ , -N(R ３１ )C(O)(CH ２ ) ０－３ NR ３１ ２ , -N(R ３１ ) (CH ２ ) １－５ NR ３１ ２ , -(CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ O (CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ R ３５ , -(CH ２ ) １－５ N (R ３１ ) C(O)R ３１ , -(CH ２ ) １－５ C(O)NR ３１ ２ , -C(R ３１ ) ２ NR ３１ ２ , -(CH ２ ) １－５ NR ３１ ２ , -C(O)R ３６ , -C(O)OR ３１ , —C(O)NR ３１ ２ , -NR ３１ ２ , -C(H) ２ R ３５ , -C(H)R ３５ ２ , and -CR ３５ ３ R is selected from the group consisting of ３１ are each independently hydrogen or C １－４ is a chain aliphatic hydrocarbon, R ３５ are each independently halogen, cyano, or optionally C １－５ a 3- to 10-membered alicyclic hydrocarbon substituted with alkyl, or —OR ３１ and R３６ has 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur as ring atoms, and optionally C １－５ R is a 4- to 10-membered heterocyclyl substituted with alkyl; １３ are each independently hydrogen, C １－５ Alkyl, -(CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ NR ３１ ２ , -(CH ２ ) １－５ N (R ３１ ) C(O)R ３１ , -(CH ２ ) １－５ N (R ３１ ) (CH ２ ) ０－５ R ３８ , -C(O)R ３１ , -C(O)R ３７ or -(CH ２ ) １－５ R ３７ and R ３７ is a 3- to 10-membered alicyclic hydrocarbon or a 3- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen, and R ３８ is cyano, hydroxy, or S(O) ２ R ３１ The heterocyclo rings in the structures shown in formulae (I-2), (I-3), and (I-27) to (I-32) and the benzene ring in the structure shown in (I-33) are each independently optionally represented by C １－５ The compound according to [1] or a pharmaceutically acceptable derivative thereof, which may be substituted with a chain aliphatic hydrocarbon. [4] R ６ but, The compound according to [1] or a pharmaceutically acceptable derivative thereof, selected from: [5] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (compound 3), 4-phenyl-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (compound 71), 2-methoxy-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (compound 79), 4-(3-fluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol (compound 112), 4-(2-fluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol (compound 122), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzene-1,3-diol (compound 120), 4-(2,4-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 121), 4-(3-methoxyphenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 83), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(o-tolyl)thiazole (Compound 132), 1-methyl-6-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-3,4-dihydroquinolin-2(1H)-one (Compound 131), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 12), 4-(4-Methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 7), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-3-yl)thiazole (Compound 15), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-4-yl)thiazole (Compound 92), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-2-yl)thiazole (Compound 93), 4-(2-chloropyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 94), 4-(2-methoxypyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 95), 4-(6-methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 96), 4-(5-methylpyridin-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 97), 6-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-[1,3]dioxolo[4,5-b]pyridine (Compound 98), 4-(2-methylpyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 99), 4-(2-fluoropyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 100), 4-(2-Bromopyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 101), 4-(5-chloropyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 125), 4-(4-chloropyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 135), 2'-Bromo-2-(pyrazolo[1,5-a]pyridin-3-yl)-4,5'-bithiazole (Compound 37), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline hydrochloride (Compound 1), 4-(3-nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 4), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline hydrochloride (Compound 10), 4-(2-nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiazole (Compound 133), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline hydrochloride (Compound 134), 2-methoxy-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline (Compound 90), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 118), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzonitrile (Compound 115), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzonitrile (Compound 116), 4-(3,5-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 119), 4-(2,6-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 123), 5-fluoro-2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 114), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isonicotinamide (Compound 126), 4-(5-Methoxypyridin-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 124), 4-(5-Methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 127), 4-(1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 107), 4-(4-Chloro-1-methyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 53), 4-(1,4-Dimethyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrobromide (Compound 54), 4-(1-Methyl-1H-pyrazol-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrobromide (Compound 106), 4-(1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 109), 5-methyl-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole hydrobromide (Compound 105), N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)oxetane-3-sulfonamide (Compound 69), N-methyl-N-(4-(2-(pyrazolo[1,N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 16), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-4-carboxamide (Compound 72), N-methyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanamine hydrochloride (Compound 74), N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-4-carboxamide (Compound 76), 2-methoxy-N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 78), 1,1-dimethyl-3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)urea (Compound 59), 1,1-dimethyl-3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)urea (Compound 75), 2-methoxy-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 77), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)cyclobutanesulfonamide (Compound 82), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)oxetane-3-carboxamide (Compound 85), 2-amino-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide hydrochloride (Compound 64), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)oxetane-3-carboxamide (Compound 66), 2-amino-N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide hydrochloride (Compound 65), 2-amino-N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide hydrochloride (Compound 81), 2-amino-N-(4-(2-(pyrazolo[1,2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide hydrochloride (Compound 80), sodium 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetic acid (Compound 5), N-acetyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)glycine (Compound 73), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetamide (Compound 26), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl-2-(2-(2-methoxyethoxy)ethoxy)acetate (Compound 13), 4-(3-(2-methoxyethoxy)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 14), 4-(3-(2-(2-methoxyethoxy)ethoxy)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 22), 4-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 108), 4-(1-ethyl-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 110), 4-(1-(2-Methoxyethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (Compound 111), 2-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethoxy)ethan-1-amine hydrochloride (Compound 32), 2-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethoxy)ethan-1-amine hydrochloride (Compound 20), N,N-dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-amine hydrochloride (Compound 47), 1-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethyl)guanidine hydrochloride (Compound 52), 1-(2-(4-(2-(pyrazolo[1,N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethyl)guanidine hydrochloride (Compound 51), N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethyl)acetamide (Compound 45), N-(2-hydroxyethyl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetamide (Compound 19), methyl 2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetate (Compound 18), methyl 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetate (Compound 25), 1-(piperazin-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one (Compound 31), 1-(1,4-diazepan-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one hydrochloride (Compound 55), 1-(4-methyl-1,4-diazepan-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one hydrochloride (Compound 102), 1-(2-(hydroxymethyl)pyrrolidin-1-yl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one (Compound 21), 1-(piperazin-1-yl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one (Compound 23), 1-(1,1-dioxidethiomorpholino)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one (Compound 24), (4-methylpiperazin-1-yl)(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazol-3-yl)methanone hydrochloride (Compound 103), piperazin-1-yl(5-(2-(pyrazolo[1,N-(4'-methyl-2-(pyrazolo[1,5-a]pyridin-3-yl)-[4,5'-bithiazol]-2'-yl)acetamide (Compound 46), N,N-dimethyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide (Compound 49), sodium 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoic acid (Compound 6), (3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)(2-oxa-6-azaspiro[3.3]heptan-6-yl)methanone (Compound 33), N,N-dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 87), N-(cyclopropylmethyl)-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoyl)azetidine-3-carboxamide (Compound 9), (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)(2-oxa-7-azaspiro[3.5]nonan-7-yl)methanone (Compound 40), (1,4-oxazepan-4-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 41), (4-(dimethylamino)piperidin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 48), (4-methylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 50), (4-ethylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 56), (3-methylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 58), N,N-dimethyl-3-(2-(pyrazolo[1,N-(2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide (Compound 61), 4-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoyl)piperazine-1-carbaldehyde (Compound 68), N-(2-morpholinoethyl)-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide (Compound 30), N-methyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 88), N-ethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 89), N-methoxy-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 91), (2,5-diazabicyclo[2.2.1]heptan-2-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 43), N-(2-(piperazin-1-yl)ethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide hydrochloride (Compound 11), (3-aminopyrrolidin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 42), N-methyl-N-(piperidin-4-yl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide hydrochloride (Compound 44), piperazin-1-yl(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 57), piperazin-1-yl(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 63), 1-(piperazin-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)ethan-1-one hydrochloride (Compound 86), N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)acetamide (Compound 60), 2-(hydroxymethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 8), (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanol (Compound 2), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)ethan-1-ol (Compound 84), 4-(3-(2,5-dihydro-1H-pyrrol-3-yl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol hydrochloride (Compound 17), 6-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)-2-oxa-6-azaspiro[3.3]heptane (Compound 29), N,N-dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanamine (Compound 27), 4-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 28), N,N-dimethyl-4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-2-carboxamide (Compound 38), N,2-dimethyl-4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-2-carboxamide (Compound 39), 1-morpholino-2-(4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)piperazin-1-yl)ethane-1,2-dione hydrochloride (Compound 36), 4-(4-((2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (Compound 34), N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)piperidin-4-amine hydrochloride (Compound 35), 4-(isoindolin-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)piperidin-4-amine hydrochloride (Compound 36),N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenethyl)acetamide (Compound 62), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)ethan-1-amine hydrochloride (Compound 113), N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 67), N-methyl-N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 70), N,N-dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 137), N,N-dimethyl-1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 128), N-methyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 136), N-((5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methyl)acetamide (Compound 129), N-methyl-1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 130), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrol-3-yl)thiazole (Compound 138), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrol-2-yl)thiazole (Compound 139), 4-(1H-imidazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 140), 4-(1H-imidazol-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 141), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,3-triazol-4-yl)thiazole (compound 142), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,4-triazol-3-yl)thiazole (Compound 143), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(thiophen-3-yl)thiazole (Compound 144), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(thiophen-2-yl)thiazole (Compound 145), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isothiazole (Compound 146), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isothiazole (Compound 147), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isothiazole (Compound 148), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4,4'-bithiazole (Compound 149), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4,5'-bithiazole (Compound 150), 2'-(pyrazolo[1,5-a]pyridin-3-yl)-2,4'-bithiazole (Compound 151), 4-(furan-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 152), 4-(furan-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 153), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole (Compound 154), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole (Compound 155), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole (Compound 156), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)oxazole (Compound 157), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)oxazole (Compound 158), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)oxazole (Compound 159), 4-(1-methyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 160), 4-(1-methyl-1H-pyrrol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 161), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1,2,4-thiadiazole (Compound 162), 4-(1-methyl-1H-pyrrol-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 163), 3-bromo-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole (Compound 164), 4-(1H-imidazol-1-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 165), 4-(1H-pyrazol-1-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 166), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrol-1-yl)thiazole (Compound 167), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,4-triazol-1-yl)thiazole (Compound 168), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(2H-1,2,3-triazol-2-yl)thiazole (Compound 169), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,3-triazol-1-yl)thiazole (Compound 170), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiophene-3-carboxamide (Compound 171), 2-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiophen-2-yl)acetamide (Compound 172), N,N-dimethyl-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiophene-3-carboxamide (Compound 173), N-(2-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiophen-2-yl)ethyl)acetamide (Compound 174), 4-(3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 178), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiophen-3-ol (Compound 175), 1-methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazole-3-carbonitrile (Compound 176), N-methyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-1-yl)ethan-1-amine (Compound 177), 4-(5-fluoro-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 179), 3-methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-5-amine (Compound 181), 4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-1-yl)butan-1-ol (Compound 180), 4-(1-(azetidin-2-ylmethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol (Compound 182), 2-((2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-1-yl)ethyl)amino)acetonitrile (Compound 183), 3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-1-yl)propan-1-amine (Compound 184), N-(3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-1-yl)propyl)methanesulfonamide (Compound 185), 5-methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-3-ol (Compound 186), N, １ , N １ -dimethyl-N ２N-(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazol]-2-yl)ethane-1,2-diamine (Compound 187), 2-(dimethylamino)-N-(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazol]-2-yl)acetamide (Compound 188), 2-amino-N-(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazol]-2-yl)acetamide hydrochloride (Compound 189), 2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazol]-2-ol (Compound 190), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)furan-2-carboxamide (Compound 191), 4-(2,5-dihydrofuran-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 192), (1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-4-yl)methanol (Compound 193), (1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-4-yl)methanamine hydrochloride (Compound 194), 3-((1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-4-yl)methoxy)propan-1-ol (Compound 195), 3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-1-yl)propan-1-ol (Compound 196), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-1-yl)ethan-1-amine (Compound 197), N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-1-yl)ethyl)acetamide (Compound 198), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyrimidin-5-yl)thiazole (compound 199), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyrimidin-2-yl)thiazole (compound 200), 4-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 201), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-yl)thiazole (compound 202), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazine (compound 203), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (compound 204), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-4,5,6,7-tetrahydrothiazolo[4,5-c]pyridine (Compound 205), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl)thiazole (Compound 206), 4-(1H-indazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 207), 4-(4-chloro-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 208), 2-(6-methylpyrazolo[1,5-a]pyridin-3-yl)-4-phenylthiazole (Compound 209), 2-(5-methylpyrazolo[1,5-a]pyridin-3-yl)-4-phenylthiazole (Compound 210), 2-(4-methylpyrazolo[1,5-a]pyridin-3-yl)-4-phenylthiazole (Compound 211), 4-(4-chloro-1-methyl-1H-pyrazol-3-yl)-2-(5-methylpyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 212), and N-((5-(2-(5-methylpyrazolo[1,[5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methyl)acetamide (Compound 213). [6] A composition comprising the compound according to any one of [1] to [5] or a pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable carrier. [7] A pharmaceutical composition comprising the compound according to any one of [1] to [5] or a pharmaceutically acceptable derivative thereof. [8] The pharmaceutical composition according to [7], for inhibiting myosin light chain kinase 4 (MYLK4) activity. [9] The pharmaceutical composition according to [7], for alleviating or treating a disease, disorder, or symptom associated with myosin light chain kinase 4 (MYLK4).

[10] The pharmaceutical composition according to [9], wherein the disease, disorder, or symptom associated with myosin light chain kinase 4 (MYLK4) is arteriosclerosis, inflammatory bowel disease, osteosarcoma, ischemic heart disease, glaucoma, ocular hypertension, aqueous humor outflow disorder, dry eye, uveitis, age-related macular degeneration, or diabetic retinopathy.

[11] The pharmaceutical composition according to [7], for alleviating or treating dry eye, uveitis, age-related macular degeneration, or diabetic retinopathy.

[12] The pharmaceutical composition according to [7], for alleviating or treating glaucoma, ocular hypertension, or aqueous humor outflow disorder.

[0011]

[13] The compound according to any one of [1] to [5] or a pharmaceutically acceptable derivative thereof for use as a pharmaceutical.

[14] The compound according to

[13] or a pharmaceutically acceptable derivative thereof for use in inhibiting myosin light chain kinase 4 (MYLK4) activity.

[15] The compound according to

[13] or a pharmaceutically acceptable derivative thereof for use in alleviating or treating a disease, disorder, or symptom associated with myosin light chain kinase 4 (MYLK4).

[16] The compound according to

[15] or a pharmaceutically acceptable derivative thereof, wherein the disease, disorder, or symptom associated with myosin light chain kinase 4 (MYLK4) is arteriosclerosis, inflammatory bowel disease, osteosarcoma, ischemic heart disease, glaucoma, ocular hypertension, aqueous humor outflow obstruction, dry eye, uveitis, age-related macular degeneration, or diabetic retinopathy.

[17] The compound according to

[13] or a pharmaceutically acceptable derivative thereof for use in alleviating or treating dry eye, uveitis, age-related macular degeneration, or diabetic retinopathy.

[18] The compound according to

[13] or a pharmaceutically acceptable derivative thereof, which is used for alleviating or treating glaucoma, ocular hypertension, or aqueous humor outflow disorder.

[19] Use of the compound according to any one of [1] to [5] or a pharmaceutically acceptable derivative thereof for preparing a medicament.

[20] The use according to

[19] for preparing a medicament for inhibiting myosin light chain kinase 4 (MYLK4) activity.

[21] The use according to

[19] for preparing a medicament for alleviating or treating a disease, disorder, or symptom associated with myosin light chain kinase 4 (MYLK4).

[22] The use according to

[21] , wherein the disease, disorder, or symptom associated with myosin light chain kinase 4 (MYLK4) is arteriosclerosis, inflammatory bowel disease, osteosarcoma, ischemic heart disease, glaucoma, ocular hypertension, aqueous humor outflow disorder, dry eye, uveitis, age-related macular degeneration, or diabetic retinopathy.

[23] The use according to

[19] for preparing a medicament for alleviating or treating dry eye, uveitis, age-related macular degeneration, or diabetic retinopathy.

[24] The use according to

[19] for preparing a medicament for alleviating or treating glaucoma, ocular hypertension, or aqueous humor outflow disorder.

[25] A method for inhibiting myosin light chain kinase 4 (MYLK4) activity, comprising administering to a patient an amount of the compound according to any one of [1] to [5] or a pharmaceutically acceptable derivative thereof effective for inhibiting MYLK4 activity.

[26] A method for alleviating or treating a disease, disorder, or symptom associated with myosin light chain kinase 4 (MYLK4), comprising administering to a patient a therapeutically effective amount of the compound according to any one of [1] to [5] or a pharmaceutically acceptable derivative thereof.

[27] The method according to

[26] , wherein the disease, disorder, or symptom associated with myosin light chain kinase 4 (MYLK4) is arteriosclerosis, inflammatory bowel disease, osteosarcoma, ischemic heart disease, glaucoma, ocular hypertension, aqueous humor outflow obstruction, dry eye, uveitis, age-related macular degeneration, or diabetic retinopathy.

[28] A method for alleviating or treating dry eye, uveitis, age-related macular degeneration, or diabetic retinopathy, comprising administering to a patient a therapeutically effective amount of the compound according to any one of [1] to [5] or a pharmaceutically acceptable derivative thereof.

[29] A method for alleviating or treating glaucoma, ocular hypertension, or aqueous humor outflow disorder, comprising administering to a patient a therapeutically effective amount of the compound according to any one of [1] to [5] or a pharmaceutically acceptable derivative thereof.

[0012] Here, the terms relating to structures or substituents used in the present specification are defined. Unless otherwise specified in the present specification, the terms relating to each substituent have the following meanings.

[0013] The terms "halogen" and "halo" refer to fluorine, chlorine, bromine, or iodine and are used alone to represent a substituent or as part of a larger substituent or structure. "Halide" and "halide" refer to a compound to which a halogen is attached, such as fluoride, chloride, bromide, or iodide. The terms "hydroxy" and "hydroxy group" refer to the -OH group and are used alone to represent a substituent or as part of a larger substituent or structure. The terms "cyano" and "cyano group" refer to the -CN group and are used alone to represent a substituent or as part of a larger substituent or structure. The terms "difluoromethyl" and "difluoromethyl group" refer to the -CHF ２ The term "trifluoromethyl" refers to a group, and may be used alone to represent a substituent or as a part of a larger substituent or structure. The terms "trifluoromethyl" and "trifluoromethyl group" also refer to -CF ３ The term "acetyl" and "acetyl group" refers to a group that is a substituent or is used alone to represent a substituent or as a part of a larger substituent or structure. ３ It refers to the group —C(O)— and is used to represent a substituent by itself or as a part of a larger substituent or structure.

[0014] The terms "amino" and "amino group" refer to -NR ２ "Amine" refers to a group (wherein R is hydrogen or a substituent, including cases where two Rs form a ring structure together with N) (a functional group excluding one H bonded to N in ammonia or amine), and is used to represent a substituent by itself or as a part of a larger substituent or structure. Also, "amine" refers to a compound having an "amino group." The terms "nitro" and "nitro group" refer to -NO ２The terms "carbonyl" and "carbonyl group" refer to the divalent group -C(O)- and are used to represent a substituent alone or as a part of a larger substituent or structure. The term "thiocarbonyl" refers to the divalent group -C(S)- and are used to represent a substituent alone or as a part of a larger substituent or structure. The term "nitro compound" refers to a compound having "nitro". The terms "aldehyde", "aldehyde group", "formyl", and "formyl group" refer to the -CHO group and are used to represent a substituent alone or as a part of a larger substituent or structure. The term "aldehyde compound" refers to a compound having an "aldehyde". The terms "carbonyl" and "carbonyl group" refer to the divalent group -C(O)- and are used to represent a substituent alone or as a part of a larger substituent or structure. The term "thiocarbonyl" refers to the divalent group -C(S)- and are used to represent a substituent alone or as a part of a larger substituent or structure.

[0015] The terms "alkyl" and "alkyl group" refer to a straight or branched chain saturated hydrocarbon group (a monovalent group having the general formula: -C ｎ H ２ｎ＋１ and is used either alone to represent a substituent or as part of a larger substituent or structure. The terms "alkyl" and "alkyl group" refer to a monovalent group when used alone to represent a substituent, but when used as a term to represent a part of a larger substituent or structure, they may refer to a divalent or higher valent group, in which case they have the same meaning as "alkylene." As used herein, "C ｘ－ｙ The term "alkyl" means an alkyl having x to y carbon atoms. Examples of alkyl include methyl, ethyl, propyl (e.g., propan-1-yl, propan-2-yl (or isopropyl)), butyl (e.g., 2-methylpropan-2-yl (or tert-butyl), butan-1-yl, butan-2-yl), pentyl (e.g., pentan-1-yl, pentan-2-yl, pentan-3-yl), 2-methylbutan-1-yl, 3-methylbutan-1-yl, hexyl (e.g., hexan-1-yl), and the like.

[0016] The terms "alkenyl" and "alkenyl group" refer to a straight or branched chain unsaturated hydrocarbon group having at least one double bond (a monovalent group having the general formula: -C ｎ H ２ｎ－１ and is used to represent a substituent alone or as part of a larger substituent or structure. The terms "alkenyl" and "alkenyl group" represent a monovalent group when used to represent a substituent alone, but when used as a term to represent a part of a larger substituent or structure, they may refer to a divalent or higher valent group, in which case they have the same meaning as "alkenylene." As used herein, "C ｘ－ｙ The term "alkenyl" means an alkenyl having x to y carbon atoms. Examples of alkenyl include vinyl, 1-propenyl, 2-propenyl, iso-propenyl, 1,3-butadienyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-methyl-1-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 3-methyl-2-butenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 2,4-hexadienyl, 5-hexenyl, and the like.

[0017] The terms "alkynyl" and "alkynyl group" refer to a straight or branched chain unsaturated hydrocarbon radical (monovalent radicals of the general formula: -C) having at least one triple bond. ｎ H ２ｎ－３ and is used to represent a substituent alone or as part of a larger substituent or structure. The terms "alkynyl" and "alkynyl group" represent a monovalent group when used to represent a substituent alone, but when used as a term to represent a part of a larger substituent or structure, they may refer to a divalent or higher valent group, in which case they have the same meaning as "alkynylene." As used herein, "C ｘ－ｙ The term "alkynyl" means an alkynyl having x to y carbon atoms. Examples of alkynyl include 2-propynyl, 2-butynyl, 1,3-hexadien-5-ynyl, and the like.

[0018] The terms "chain aliphatic hydrocarbon" and "chain aliphatic hydrocarbon group" refer to straight-chain or branched-chain non-aromatic hydrocarbon groups. Thus, "chain aliphatic hydrocarbon" and "chain aliphatic hydrocarbon group" include saturated or unsaturated hydrocarbon groups, and more specifically, straight-chain or branched-chain alkyl, alkenyl, or alkynyl. As used herein, "C ｘ－ｙ The term "chain aliphatic hydrocarbon" means a chain aliphatic hydrocarbon having x to y carbon atoms. Examples of alkyl, alkenyl, and alkynyl are as described above.

[0019] The terms "alicyclic hydrocarbon" and "alicyclic hydrocarbon group" refer to monocyclic or polycyclic non-aromatic cyclic hydrocarbon groups, including monocyclic or polycyclic cycloalkyl or cycloalkenyl groups. Furthermore, the terms "alicyclic hydrocarbon" and "alicyclic hydrocarbon group" refer to a monovalent group when used alone as a substituent or as part of a larger substituent or structure, but may refer to a divalent or higher group when used as part of a larger substituent or structure. The term "x- to y-membered alicyclic hydrocarbon" refers to a monocyclic or polycyclic non-aromatic cyclic hydrocarbon whose ring is composed of x to y carbon atoms, including a monocyclic or polycyclic cycloalkyl or cycloalkenyl whose ring is composed of x to y carbon atoms. Polycyclic non-aromatic cyclic hydrocarbon groups include bicyclic or tricyclic non-aromatic cyclic hydrocarbon groups. Polycyclic non-aromatic cyclic hydrocarbon groups include bridged ring hydrocarbons and spiro hydrocarbons. Examples of alicyclic hydrocarbons include cyclopropyl, cyclopropenyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, cyclooctadienyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[3.2.1]octyl, and adamantyl.

[0020] The terms "cycloalkyl" and "cycloalkyl group" refer to a monocyclic or polycyclic saturated hydrocarbon group, whether used alone as a substituent or as part of a larger substituent or structure. When used alone as a substituent, the terms "cycloalkyl" and "cycloalkyl group" refer to a monovalent group, but when used as part of a larger substituent or structure, they can refer to a divalent or higher valent group, in which case they have the same meaning as "cycloalkylene." The term "x to y-membered cycloalkyl" refers to a monocyclic or polycyclic cycloalkyl ring composed of x to y carbon atoms. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[3.2.1]octyl, and the like.

[0021] The terms "cycloalkenyl" and "cycloalkenyl group" refer to a monocyclic or polycyclic non-aromatic cyclic hydrocarbon group containing at least one carbon-carbon double bond, and are used alone as a substituent or as part of a larger substituent or structure. When used alone as a substituent, the terms "cycloalkenyl" and "cycloalkenyl group" refer to a monovalent group, but when used as part of a larger substituent or structure, they can refer to a divalent or higher valent group, in which case they have the same meaning as "cycloalkenylene." The term "x to y-membered cycloalkenyl" refers to a monocyclic or polycyclic cycloalkenyl whose ring is composed of x to y carbon atoms. Examples of cycloalkenyl include cyclopentenyl, cyclohexenyl, cycloheptenyl, and the like.

[0022] The terms "aromatic hydrocarbon" and "aromatic hydrocarbon group", which are used interchangeably with the term "aryl", refer to hydrocarbon groups having a monocyclic or polycyclic ring structure composed of carbon atoms with alternating single and double bonds and delocalized electrons, either alone as a substituent or as part of a larger substituent or structure. The terms "aromatic hydrocarbon" and "aromatic hydrocarbon group", when used alone as a substituent, refer to a monovalent group, but when used as part of a larger substituent or structure, may refer to a divalent or higher valent group. The term "x to y-membered aromatic hydrocarbon" refers to an aromatic hydrocarbon whose ring is composed of x to y carbon atoms. Examples of aromatic hydrocarbons include phenyl, 1-naphthyl, 2-naphthyl, 1-anthryl, 2-anthryl, 9-anthryl, and the like.

[0023] The terms "heterocycle" and "heterocyclic group" refer to a monocyclic or polycyclic group having a ring structure containing heteroatoms other than carbon atoms as ring-constituting atoms, and are used alone to represent a substituent or as part of a larger substituent or structure. The terms "heterocycle" and "heterocyclic group" refer to a monovalent group when used alone to represent a substituent, but can refer to a divalent or higher valent group when used as part of a larger substituent or structure. The term "x to y-membered heterocycle" refers to a heterocycle whose ring is composed of x to y atoms (including carbon and heteroatoms other than carbon atoms). Heterocycles include aromatic heterocycles, heterocyclyls, and heterocycloalkenyls.

[0024] The terms "aromatic heterocycle" and "aromatic heterocyclic group", which are used interchangeably with the term "heteroaryl", refer to a monocyclic or polycyclic group having a ring structure with alternating single and double bonds resulting in electron delocalization and containing heteroatoms other than carbon atoms as ring constituent atoms, either used alone as a substituent or as part of a larger substituent or structure. The terms "aromatic heterocycle" and "aromatic heterocyclic group", when used alone as a substituent, refer to a monovalent group, but when used as part of a larger substituent or structure, may refer to a divalent or higher valent group. The term "x- to y-membered aromatic heterocycle" refers to an aromatic heterocycle whose ring is composed of x to y atoms (including carbon and heteroatoms other than carbon atoms). Examples of aromatic heterocycles include 5- or 6-membered monocyclic aromatic heterocycles such as thiophene, furan, pyrrole, imidazole, pyrazole, thiazole, isothiazole, oxazole, isoxazole, pyridine, pyrazine, pyrimidine, pyridazine, 1,2,4-oxadiazole, 1,3,4-oxadiazole, 1,2,4-thiadiazole, 1,3,4-thiadiazole, triazole, tetrazole, and triazine; and benzothiophene, benzofuran, benzimidazole, benzoxazole, benzisoxazole, benzothiazole, benzisothiazole, benzotriazole, imidazopyridine, thienopyridine, furopyridine, pyrrolopyridine, pyrazolopyridine, oxazolopyridine, thiazolopyridine, imidazopyrazine, imidazopyrimidine, thienopyrimidine, furopyrimidine, pyrrolopyrimidine, pyrazolopyrimidine, oxazolopyrimidine, thiazolopyridine, and 8- to 14-membered fused polycyclic (preferably bi- or tricyclic) aromatic heterocycles such as pyrimidine, pyrazolopyrimidine, pyrazolotriazine, naphtho[2,3-b]thiophene, phenoxathiin, indole, isoindole, 1H-indazole, purine, isoquinoline, quinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, carbazole, β-carboline, phenanthridine, acridine, phenazine, phenothiazine, and phenoxazine.

[0025] The terms "heterocyclyl" and "heterocyclyl group" refer to monocyclic or polycyclic groups having saturated ring structures containing heteroatoms other than carbon atoms as ring constituent atoms, and are used alone as a substituent or as part of a larger substituent or structure. When used alone as a substituent, the terms "heterocyclyl" and "heterocyclyl group" refer to monovalent groups, but when used as part of a larger substituent or structure, they can refer to divalent or higher valent groups. The term "x- to y-membered heterocyclyl" refers to a heterocyclyl whose ring consists of x to y atoms (including heteroatoms other than carbon and carbon atoms). Polycyclic heterocyclyls include bicyclic and tricyclic heterocyclyls. Polycyclic heterocyclyls also include bridged rings and spirocyclic rings. Heterocyclyls typically include saturated heterocycles containing one or more (e.g., 1 to 3) heteroatoms selected from nitrogen, oxygen, and sulfur atoms.

[0026] The terms "heterocycloalkenyl" and "heterocycloalkenyl group" refer to a monocyclic or polycyclic non-aromatic heterocyclic group containing at least one carbon-carbon double bond and containing heteroatoms other than carbon atoms as ring-constituting atoms, and are used alone as a substituent or as part of a larger substituent or structure. The terms "heterocycloalkenyl" and "heterocycloalkenyl group" refer to a monovalent group when used alone as a substituent, but can refer to a divalent or higher valent group when used as part of a larger substituent or structure, in which case they have the same meaning as "heterocycloalkenylene." The term "x to y-membered heterocycloalkenyl" refers to a monocyclic or polycyclic cycloalkenyl whose ring consists of x to y carbon atoms. Examples of heterocycloalkenyls include dihydrofuran, pyran, pyrroline, and pyrazoline.

[0027] The terms "aralkyl" and "aralkyl group" refer to an alkyl substituted with phenyl, and may represent a substituent alone or may represent a part of a larger substituent or structure. When the terms "aralkyl" and "aralkyl group" represent a substituent alone, they represent a monovalent group, but when used as part of a larger substituent or structure, they may refer to a divalent or higher valent group. ｘ－ｙ The term "aralkyl" means an aralkyl in which the alkyl portion has x to y carbon atoms. Examples of aralkyl include benzyl, phenethyl, naphthylmethyl, phenylpropyl, and the like.

[0028] The terms "alkoxy" and "alkoxy group" refer to a group of the formula: -OR, where R is alkyl, either alone as a substituent or as part of a larger substituent or structure. When alone as a substituent, the terms "alkoxy" and "alkoxy group" refer to a monovalent group, but when used as part of a larger substituent or structure, they can refer to a divalent or higher valent group. ｘ－ｙ The term "alkoxy" means an alkoxy having x to y carbon atoms. Examples of alkoxy include methoxy, ethoxy, propoxy (e.g., 1-propoxy, 2-propoxy), butoxy (e.g., 1-butoxy, 2-butoxy, 2-methyl-2-propoxy), pentyloxy (1-pentyloxy, 2-pentyloxy), hexyloxy (1-hexyloxy, 3-hexyloxy), and the like.

[0029] The terms "cycloalkoxy" and "cycloalkoxy group" refer to a group of the formula: -OR, where R is cycloalkyl, either alone as a substituent or as part of a larger substituent or structure. The terms "cycloalkoxy" and "cycloalkoxy group", when alone as a substituent, refer to a monovalent group, but when used as part of a larger substituent or structure, can refer to a divalent or higher valent group. Additionally, the term "x to y-membered cycloalkoxy" refers to a cycloalkoxy in which the cycloalkyl ring is made up of x to y carbon atoms. Examples of cycloalkoxy include cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, and cyclooctyloxy.

[0030] The terms "alkylthio" and "alkylthio group" refer to a group of the formula: -SR, where R is alkyl, either alone as a substituent or as part of a larger substituent or structure. When alone as a substituent, the terms "alkylthio" and "alkylthio group" refer to a monovalent group, but when used as part of a larger substituent or structure, they can refer to a divalent or higher valent group. ｘ－ｙ The term "alkylthio" means an alkylthio having x to y carbon atoms. Examples of alkylthio include methylthio, difluoromethylthio, trifluoromethylthio, ethylthio, propylthio, isopropylthio, butylthio, 4,4,4-trifluorobutylthio, pentylthio, hexylthio, and the like.

[0031] The terms "cycloalkylthio" and "cycloalkylthio group" refer to a group of the formula: -SR, where R is cycloalkyl, either alone as a substituent or as part of a larger substituent or structure. The terms "cycloalkylthio" and "cycloalkylthio group" refer to a monovalent group when alone as a substituent, but can refer to a divalent or higher valent group when used as part of a larger substituent or structure. Additionally, the term "x to y-membered cycloalkylthio" refers to a cycloalkylthio in which the cycloalkyl ring is made up of x to y carbon atoms.

[0032] The terms "alkylsulfonyl" and "alkylsulfonyl group," "cycloalkylsulfonyl" and "cycloalkylsulfonyl group," and "heterocyclosulfonyl" and "heterocyclosulfonyl group" refer to groups of the formula: -S(O) ２ -R (wherein R is alkyl, cycloalkyl, or heterocyclyl, respectively), and represents a substituent alone or as part of a larger substituent or structure. The terms "alkylsulfonyl" and "alkylsulfonyl group," "cycloalkylsulfonyl" and "cycloalkylsulfonyl group," and "heterocyclosulfonyl" and "heterocyclosulfonyl group" represent a monovalent group when representing a substituent alone, but may refer to a divalent or higher valent group when used as part of a larger substituent or structure. ｘ－ｙThe term "alkylsulfonyl" means an alkylsulfonyl in which the alkyl has x to y carbon atoms, the term "x to y-membered cycloalkylsulfonyl" means a cycloalkylsulfonyl in which the cycloalkyl ring consists of x to y carbon atoms, and the term "x to y-membered heterocyclosulfonyl" means a heterocyclosulfonyl in which the heterocyclo ring consists of x to y atoms (including carbon and heteroatoms other than carbon atoms). Examples of alkylsulfonyl include methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, etc. The terms "arylsulfonyl" and "arylsulfonyl group" are used in the same manner as above, and examples of arylsulfonyl include phenylsulfonyl, 1-naphthylsulfonyl, 2-naphthylsulfonyl, etc.

[0033] The terms "alkylcarbonyl" and "alkylcarbonyl group," "cycloalkylcarbonyl" and "cycloalkylcarbonyl group," and "heterocyclocarbonyl" and "heterocyclocarbonyl group" mean a group of the formula -C(O)-R, where R is alkyl, cycloalkyl, or heterocyclyl, respectively, and represent a substituent alone or as part of a larger substituent or structure. The terms "alkylcarbonyl" and "alkylcarbonyl group," "cycloalkylcarbonyl" and "cycloalkylcarbonyl group," and "heterocyclocarbonyl" and "heterocyclocarbonyl group," when used alone as a substituent, represent a monovalent group, but can refer to a divalent or higher valent group when used as part of a larger substituent or structure. In addition, "C ｘ－ｙThe term "alkylcarbonyl" means an alkylcarbonyl in which the alkyl has x to y carbon atoms, the term "x to y-membered cycloalkylcarbonyl" means a cycloalkylcarbonyl in which the cycloalkyl ring is composed of x to y carbon atoms, and the term "x to y-membered heterocyclocarbonyl" means a heterocyclocarbonyl in which the heterocyclo ring is composed of x to y atoms (including heteroatoms other than carbon and carbon atoms). Examples of alkylcarbonyl include acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 3-methylbutanoyl, 2-methylbutanoyl, 2,2-dimethylpropanoyl, hexanoyl, heptanoyl, and the like.

[0034] The terms "alkoxycarbonyl" and "alkoxycarbonyl group", as well as "cycloalkoxycarbonyl" and "cycloalkoxycarbonyl group", mean a group of the formula: -C(O)-R (wherein R is alkoxyl and cycloalkoxyl, respectively), and represent a substituent alone or a part of a larger substituent or structure. The terms "alkoxycarbonyl" and "alkoxycarbonyl group", as well as "cycloalkoxycarbonyl" and "cycloalkoxycarbonyl group", when representing a substituent alone, represent a monovalent group, but when used as part of a larger substituent or structure, may refer to a divalent or higher valent group. In addition, "C ｘ－ｙ The term "alkoxycarbonyl" means an alkoxycarbonyl where the alkoxyl has x to y carbon atoms, and the term "x to y-membered cycloalkoxycarbonyl" means a cycloalkoxycarbonyl where the cycloalkyl ring is made up of x to y carbon atoms. Examples of alkoxycarbonyl include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, and the like.

[0035] The terms "arylcarbonyl", "arylcarbonyl group", "aralkylcarbonyl", "aralkylcarbonyl group", "aromatic heterocyclylcarbonyl", "aromatic heterocyclylcarbonyl group", and "heterocyclylcarbonyl" and "heterocyclylcarbonyl group" are used in the same manner as above. Examples of arylcarbonyl include benzoyl, 1-naphthoyl, and 2-naphthoyl. Examples of aralkylcarbonyl include phenylacetyl and phenylpropionyl. Examples of aromatic heterocyclylcarbonyl include nicotinoyl, isonicotinoyl, thenoyl, and furoyl. Examples of heterocyclylcarbonyl include morpholinylcarbonyl, piperidinylcarbonyl, and pyrrolidinylcarbonyl. The terms "amide" and "amide group", as well as "carboxylic acid amide" and "carboxylic acid amide group" mean a compound having a structure represented by the formula: R-C(O)-NR'R'' (wherein R is an arbitrary substituent or structure, and R, R', and R'' are each independently hydrogen or an arbitrary substituent or structure, including cases where R' and R'' form a cyclic structure together with N). Furthermore, the terms "thioamide" and "thioamide group", as well as "thioacid amide" and "thioacid amide group" mean a compound having a structure represented by the formula: R-C(S)-NR'R'' (wherein R is an arbitrary substituent or structure, and R, R', and R'' are each independently hydrogen or an arbitrary substituent or structure). The terms "acetamide" and "acetamide group", as well as the symbol "-NHAc" mean a compound having a structure represented by the formula: R-C(S)-NR'R'' (wherein R is an arbitrary substituent or structure, and R, R', and R'' are each independently hydrogen or an arbitrary substituent or structure). ３ It means a monovalent substituent represented by C(O)NH-.

[0036] The terms "alkylcarbamoyl" and "alkylcarbamoyl group," "cycloalkylcarbamoyl" and "cycloalkylcarbamoyl group," and "heterocyclocarbamoyl" and "heterocyclocarbamoyl group" mean a group of the formula: -C(O)-NR'R" (where R' and R" are hydrogen atoms or alkyl, cycloalkyl, and heterocyclyl, respectively, and at least one of R' and R" is alkyl, cycloalkyl, and heterocyclyl, respectively), either alone as a substituent or as part of a larger substituent or structure. The terms "alkylcarbamoyl" and "alkylcarbamoyl group," "cycloalkylcarbamoyl" and "cycloalkylcarbamoyl group," and "heterocyclocarbamoyl" and "heterocyclocarbamoyl group," when used alone as a substituent, refer to a monovalent group, but may refer to a divalent or higher valent group when used as part of a larger substituent or structure. In addition, "C ｘ－ｙ The term "alkylcarbamoyl" means an alkylcarbamoyl in which the alkyl has x to y carbon atoms, the term "x to y-membered cycloalkylcarbamoyl" means a cycloalkylcarbamoyl in which the cycloalkyl ring is composed of x to y carbon atoms, and the term "x to y-membered heterocyclocarbamoyl" means a heterocyclocarbamoyl in which the heterocyclo ring is composed of x to y atoms (including carbon and heteroatoms other than carbon atoms). Examples of alkylcarbamoyl include methylcarbamoyl, ethylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl, N-ethyl-N-methylcarbamoyl, etc. The terms "aralkylcarbamoyl" and "aralkylcarbamoyl group" are used in the same manner as above, and examples of "aralkylcarbamoyl" include benzylcarbamoyl and phenethylcarbamoyl. The term "ester" refers to a group of the formula: R-C(O)O-R' (R is C １－３The term "ether" refers to a structure represented by the formula R-O-R' (R and R' are each substituents such as alkyl, aromatic hydrocarbon, etc.), and "ether compound" refers to a compound having an ether.

[0037] The embodiments of the present invention will be described in detail below, but the present invention is not limited to the following embodiments.

[0038] 1. Novel Thiazolyl-Pyrazolopyridine Compound The novel thiazolyl-pyrazolopyridine compound provided by the present invention (hereinafter referred to as "the compound") is represented by the following formula (I): or a pharmaceutically acceptable derivative thereof. １ ~R ５ are each independently hydrogen or C １－３ A chain aliphatic hydrocarbon; R ６ is an optionally substituted 5- to 10-membered aromatic hydrocarbon, an optionally substituted 5- to 10-membered heterocycle having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring-constituting atoms, or a fused ring of either of these with an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring-constituting atoms.

[0039] R in formula (I) １ ~R ５ are each independently hydrogen or a chain C １－３ Alkyl groups are preferred, and hydrogen or straight chain C １－３ An alkyl group is preferred, hydrogen or a methyl group is more preferred, and hydrogen is particularly preferred. １ , R ２ and R ４ is preferably hydrogen, and R １ , R ２ , R ４ , and R ５ is more preferably hydrogen.

[0040] R in formula (I) ６ The "5- to 10-membered aromatic hydrocarbon" in the formula (I) is preferably a 5- or 6-membered monocyclic aromatic hydrocarbon or an 8- to 10-membered bicyclic or tricyclic aromatic hydrocarbon, more preferably phenyl, 1-naphthyl, or 2-naphthyl, and particularly preferably phenyl.

[0041] R in formula (I) ６ The "5- to 10-membered heterocycle" in the above formula (I) includes, for example, a 5- to 10-membered aromatic heterocycle and a 5- or 6-membered heterocycloalkenyl, preferably a 5- or 6-membered monocyclic aromatic heterocycle, an 8- to 10-membered bicyclic or tricyclic aromatic heterocycle, or a 5-membered heterocycloalkenyl, more preferably a 5- or 6-membered monocyclic aromatic heterocycle or an 8- to 10-membered bicyclic aromatic heterocycle, and particularly preferably a 5- or 6-membered monocyclic aromatic heterocycle. Among these, pyridine, pyrazole, thiazole, isoxazole, pyrrole, imidazole, triazole, thiophene, furan, and isothiazole are preferred.

[0042] R in formula (I) ６Examples of the "4- to 10-membered heterocyclyl" that forms a "fused ring" with the "5- to 10-membered aromatic hydrocarbon" or "5- to 10-membered heterocycle" (preferably, "5- to 10-membered aromatic heterocycle") in the above formula (I) include a 4- to 10-membered saturated heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur atoms. Examples of such a "4- to 10-membered heterocyclyl" include dioxolanes such as 1,3-dioxolane, dihydropyridin-2(1H)-one, oxetanyl, azetidinyl, piperazinyl, piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, tetrahydropyranyl, tetrahydrofuranyl, oxazolidinyl, thiazolidinyl, imidazolidinyl, pyrazolidinyl, thianyl, oxanyl, thioxanyl, azepinyl, and tropanyl. Among these, 5- or 6-membered monocyclic heterocyclyls containing one or two oxygen or nitrogen ring atoms are preferred, and 5- or 6-membered monocyclic heterocyclyls containing one or two nitrogen ring atoms are more preferred. Examples of such monocyclic heterocyclyls include dioxolanes such as 1,3-dioxolane, dihydropyridin-2(1H)-one, and pyrrolidinyl.

[0043] Therefore, R in formula (I) ６ The "fused ring" in (I) is preferably a fused ring of a 5- or 6-membered monocyclic aromatic hydrocarbon and a 5- or 6-membered monocyclic heterocyclyl, in which the aromatic hydrocarbon is linked to the thiazole of formula (I), or a fused ring of a 5- or 6-membered monocyclic nitrogen-containing aromatic heterocycle containing one or two nitrogen atoms as ring-constituting atoms and a 5- or 6-membered monocyclic heterocyclyl, in which the aromatic heterocycle is linked to the thiazole of formula (I), and or a bicyclic fused ring with a 6-membered monocyclic nitrogen-containing heterocyclyl, wherein the phenyl is linked to the thiazole of formula (I); or a fused ring with a 5- or 6-membered monocyclic nitrogen- or oxygen-containing heterocyclyl, wherein the pyridine is linked to the thiazole of formula (I), is more preferred, and a bicyclic fused ring with a 6-membered monocyclic nitrogen-containing heterocyclyl, wherein the phenyl is linked to the thiazole of formula (I), is particularly preferred.

[0044] R in formula (I) ６ The "5- to 10-membered aromatic hydrocarbon", "5- to 10-membered heterocyclic ring", and "4- to 10-membered heterocyclyl" forming a condensed ring therewith in the above formula (I) may be optionally substituted. Here, "optionally substituted" means unsubstituted or substituted with a predetermined substituent. The substituent is bonded to an appropriate position of these ring structures in a chemically possible form, and is selected depending on the bonding position to these ring structures. Examples of the substituent of the "5- to 10-membered aromatic hydrocarbon" or "5- to 10-membered heterocyclic ring" include: (1) halogen, nitro, cyano, hydroxy, difluoromethyl, trifluoromethyl, (2) -NR ３１ ２ , -N(R ３１ ) (CH ２ ) １－５ NR ３１ ２ , -N(R ３１ ) S (O) ２ R ３２ , -N(R ３１ ) C(O)R ３１ , -N(R ３１ )C(O)(CH ２ ) ０－３ NR ３１ ２ , -N(R ３１ )C(O)(CH ２ ) ０－３ R ３２ , (3) C １－６ Alkyl, -(CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ O (CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ R ３２ , -(CH ２ ) １－５ R ３３ , (4)-(CH ２ ) １－５ NR ３１ ２ , -(CH ２ ) １－５ N (R ３１ ) R３２ 、-(CH ２ ) １－５ N(R ３１ )(CH ２ ) ０－５ R ３８ 、-(CH ２ ) １－５ N(R ３１ )C(O)R ３１ 、-(CH ２ ) １－５ N(R ３１ )C(O)(CH ２ ) １－５ OR ３１ 、-(CH ２ ) １－５ N(C(O)R ３１ )(CH ２ ) １－５ C(O)OR ３１ 、-(CH ２ ) １－５ N(R ３１ )C(O)(CH ２ ) ０－５ NR ３１ ２ 、-(CH ２ ) １－５ N(R ３１ )C(O)R ３２ 、 (5)-(CH ２ ) １－５ N(R ３１ )S(O) ２ R ３３ 、 (6)-C(R ３１ ) ２ C(O)R ３２ 、 (7)-C(R ３１ ) ２ C(O)NR ３１ ２ 、-C(R ３１ ) ２ C(O)N(R ３１ )OR ３１ 、 (8)-C(O)R ３１ 、-C(O)R ３２ 、 (9)-C(O)OR ３１ 、 (10)-C(O)NR ３１ ２ 、-C(O)N(R ３１ )(CH ２ ) ０－５ R ３２, (11)-OC(R ３１ ) ２ C(O)N(R ３１ ) (CH ２ ) １－５ OR ３１ , -OC(R ３１ ) ２ C(O)OR ３１ , -OC(R ３１ ) ２ C(O)NR ３１ ２ , -OC(R ３１ ) ２ C(O)R ３２ , (12)-O(CH ２ ) １－６ R ３１ , -(O(CH ２ ) １－５ ) １－５ (CH ２ ) ０－３ NR ３１ ２ , -(O(CH ２ ) １－５ ) １－５ (CH ２ ) ０－３ NR ３１ C(O)R ３１ , -(O(CH ２ ) １－５ ) １－５ NR ３１ C(NH)NR ３１ ２ , -O((CH ２ ) １－５ O) １－５ R ３１ , (13)-OC(O)C(R ３１ ) ２ (O(CH ２ ) １－５ ) １－５ OR ３１ , and (14) optionally C １－３ and n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 39, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 69, 69, 68, 69, 70, 71, 72, 73, 74, 75, 7

[0045] R ３１ are each independently hydrogen or C １－４ A chain aliphatic hydrocarbon, preferably hydrogen or a chain C １－４alkyl, more preferably hydrogen, or linear C １－４ It is preferably alkyl, more preferably hydrogen, methyl, or ethyl, and particularly preferably hydrogen.

[0046] R ３２ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen, sulfur, and oxygen as ring-constituting atoms, or a fused ring thereof with an optionally substituted 5- or 6-membered monocyclic aromatic hydrocarbon, and the substituents are preferably C １－１２ Chain aliphatic hydrocarbons, -(CH ２ ) １－５ OH, halogen, nitro, hydroxy, cyano, -(CH ２ ) ０－５ NR ３１ ２ , -(CH ２ ) ０－５ N (R ３１ ) R ３３ , -(CH ２ ) ０－５ NC(O)R ３３ , -OR ３１ , -SR ３１ , -S(O) ２ R ３１ , -C(O)R ３１ , -C(O)OR ３１ , -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ R ３３ , -N(R ３１ ) SO ２ R ３１ , -N(R ３１ ) C(O)R ３１ , -N(R ３１ )C(O)OR ３１ , -N(R ３１ )C(O)NR ３１ ２ , and -N(R ３１ ) S (O) ２ NR ３１ ２ and more preferably selected from the group consisting of C１－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ When the ring contains sulfur, the sulfur atom is selected from the group consisting of 3 to 10-membered alicyclic hydrocarbons and acetyl, and the sulfur atom is —S(O) ２ - forms.

[0047] R ３３ is a 3- to 10-membered alicyclic hydrocarbon or a 4- to 10-membered heterocyclyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring members.

[0048] R ３８ is cyano, hydroxy, or S(O) ２ R ３１ In addition, R ３１ , R ３２ , R ３３ , and R ３８ In the present specification, unless otherwise specified, the same groups or structures are also represented in the following description.

[0049] Substituents of the "4- to 10-membered heterocyclyl" that form a fused ring include C １－５ A chain aliphatic hydrocarbon is exemplified, and preferably C １－３ It is alkyl.

[0050] As used herein, the substituents of "alicyclic hydrocarbons," "aromatic hydrocarbons," "aromatic heterocycles," "heterocycloalkenyls," "heterocyclyls," or fused rings formed from any two of these may be introduced at chemically appropriate positions in any chemically possible number, but in the case of halogens, nitro, hydroxy, cyano, and amino, the number of substituents is usually 4 or less, preferably 3 or less, and more preferably 2 or less. In addition, in the case of substituents other than halogens, nitro, hydroxy, cyano, and amino, the number of substituents is usually 2 or less, preferably 1. When the number of substituents is 2 or more, the respective substituents may be the same or different.

[0051] In a preferred embodiment, R ６ teeth, and more preferably selected from the group consisting of: is selected from the group consisting of:

[0052] In each formula, R ７ are each independently hydrogen, halogen, nitro, cyano, hydroxy, C １－６ Alkyl, C １－６ Alkoxyl, or -NR ３１ ２ and R ８ are each independently: (1) hydrogen, halogen, nitro, cyano, hydroxy; (2) (i) —NR ３１ ２ , (ii) -N(R ３１ ) S (O) ２ R ３２－１ (In the formula, R ３２－１ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring atoms, and the heterocyclyl is preferably optionally C １－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH２ ) １－５ 3- to 10-membered alicyclic hydrocarbon or acetyl-substituted, R ３２－１ is preferably of the formula: (In the formula, R ２０ and R ２１ are each independently hydrogen, C １－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ (iii) -N(R ３１ ) C(O)R ３１ , (iv) -N(R ３１ )C(O)(CH ２ ) ０－３ NR ３１ ２ , (v)-N(R ３１ )C(O)(CH ２ ) ０－３ R ３２－２ (In the formula, R ３２－２ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring atoms, and the heterocyclyl is preferably optionally C １－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ 3- to 10-membered alicyclic hydrocarbon or acetyl-substituted, R ３２－２is preferably of the formula: (In the formula, R ２０ and R ２１ are each independently hydrogen, C １－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ (i) a heterocyclyl selected from the group consisting of a 3- to 10-membered alicyclic hydrocarbon and acetyl, preferably hydrogen or methyl, and m and n are each independently an integer of 1 to 4, preferably an integer of 1 to 2. １－６ alkyl, (ii) —(CH ２ ) １－５ OR ３１ , (iii) -(CH ２ ) １－５ R ３２－３ (In the formula, R ３２－３ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring atoms, and the heterocyclyl is preferably optionally C １－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ 3- to 10-membered alicyclic hydrocarbon or acetyl-substituted, R ３２－３ is preferably of the formula: (In the formula, R ２０ and R ２１ are each independently hydrogen, C １－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ is selected from the group consisting of 3- to 10-membered alicyclic hydrocarbons and acetyl, and is preferably hydrogen, methyl, -(CH ２ ) １－３ OH, -C(O)C(O)R ３３ and —C(O)NR ３１ ２ R is selected from the group consisting of ２３ and R ２４ are each independently hydrogen, and C １－１２ R is selected from the group consisting of linear aliphatic hydrocarbons, preferably hydrogen or methyl; ２２ , O, SO ２ , C.R. ３１ ２ , and N.R. ２２－１ (R ２２－１ is C １－１２ Chain aliphatic hydrocarbons, -(CH ２ ) １－５ OH, —C(O)R ３１ , -C(O)OR ３１ , -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , and —C(O)N(R ３１ ) (CH ２ ) １－５ R ３３ and more preferably selected from the group consisting of C １－３ Alkyl, -(CH ２ ) １－３ OH, -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ 3- to 10-membered alicyclic hydrocarbons, and acetyl. ３１ ２ , or NR ２２－２ (R２２－２ is C １－３ Alkyl, and —C(O)C(O)R ３３ is selected from the group consisting of ２５ , O, SO ２ , C.R. ３１ ２ , and N.R. ３１ and preferably selected from the group consisting of NR ３１ and R ３１ is preferably hydrogen or methyl, more preferably hydrogen, and m, n, p and q are each independently an integer of 1 to 4.) heterocyclyl.), (4) (i) -(CH ２ ) １－５ NR ３１ ２ , (ii) -(CH ２ ) １－５ N (R ３１ ) R ３２－４ (In the formula, R ３２－４ is an optionally substituted 3- to 10-membered alicyclic hydrocarbon or an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-constituting atoms, and the alicyclic hydrocarbon and heterocyclyl are preferably each independently optionally selected from C １－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ 3- to 10-membered alicyclic hydrocarbon or acetyl-substituted, R ３２－４ is preferably of the formula: (In the formula, R ２０ and R ２１ are each independently hydrogen, C １－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３, —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ R is selected from the group consisting of 3- to 10-membered alicyclic hydrocarbons and acetyl, and is preferably hydrogen or methyl; ２２ , O, SO ２ , C.R. ３１ ２ , and N.R. ３１ and preferably selected from the group consisting of NR ３１ and R ３１ is preferably hydrogen or methyl, and m and n are each independently an integer of 1 to 4.) is an alicyclic hydrocarbon or heterocyclyl of the formula (iii) -(CH ２ ) １－５ N (R ３１ ) C(O)R ３１ (iv) -(CH ２ ) １－５ N (R ３１ )C(O)(CH ２ ) １－５ OR ３１ , (v) -(CH ２ ) １－５ N(C(O)R ３１ ) (CH ２ ) １－５ C(O)OR ３１ (vi) -(CH ２ ) １－５ N (R ３１ )C(O)(CH ２ ) ０－５ NR ３１ ２ , (vii)-(CH ２ ) １－５ N (R ３１ ) C(O)R ３２－５ (In the formula, R ３２－５ is an optionally substituted 3- to 10-membered alicyclic hydrocarbon or an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-constituting atoms, and the alicyclic hydrocarbon and heterocyclyl are preferably each independently optionally selected from C １－３ Alkyl, -(CH２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ 3- to 10-membered alicyclic hydrocarbon or acetyl-substituted, R ３２－５ is preferably of the formula: (In the formula, R ２０ and R ２１ are each independently hydrogen, C １－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ R is selected from the group consisting of 3- to 10-membered alicyclic hydrocarbons and acetyl, and is preferably hydrogen or methyl; ２２ , O, SO ２ , C.R. ３１ ２ , and N.R. ３１ is selected from the group consisting of, preferably O; ３１ is preferably hydrogen or methyl, and m and n are each independently an integer of 1 to 4.) is an alicyclic hydrocarbon or heterocyclyl of the formula (5) -(CH ２ ) １－５ N (R ３１ ) S (O) ２ R ３３－１ (In the formula, R ３３－１ is a 3- to 10-membered cycloalkyl.), (6) —C(R ３１ ) ２ C(O)R ３２－６ (In the formula, R ３２－６is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring atoms, and the heterocyclyl is preferably optionally C １－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ 3- to 10-membered alicyclic hydrocarbon or acetyl-substituted, R ３２－６ is preferably of the formula: (In the formula, R ２０ and R ２１ are each independently hydrogen, C １－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ R is selected from the group consisting of 3- to 10-membered alicyclic hydrocarbons and acetyl, and is preferably hydrogen or methyl; ２２ , O, SO ２ , C.R. ３１ ２ , and N.R. ３１ and preferably selected from the group consisting of NR ３１ and R ３１ is preferably hydrogen or methyl, and m and n are each independently an integer of 1 to 4.), (7) (i) -C(R ３１ ) ２ C(O)NR ３１ ２ , (ii) -C(R ３１ ) ２ C(O)N(R ３１ ) OR ３１, (8)-C(O)R ３２－７ (In the formula, R ３２－７ has 1 to 3 heteroatoms selected from nitrogen and oxygen as ring atoms, and optionally C １－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ a 3- to 10-membered alicyclic hydrocarbon, or a 4- to 10-membered heterocyclyl substituted by acetyl, or optionally C １－１２ a condensed ring with a chain aliphatic hydrocarbon, acetamide (-NHAc), or a 5- or 6-membered monocyclic aromatic hydrocarbon substituted with acetyl, R ３２－７ is preferably of the formula: (In the formula, R ２０ and R ２１ are each independently hydrogen, C １－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ is selected from the group consisting of 3- to 10-membered alicyclic hydrocarbons and acetyl, preferably hydrogen, C １－３ Alkyl, —NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ R is selected from the group consisting of 3- to 10-membered alicyclic hydrocarbons and acetyl; ２３ and R ２４ are each independently hydrogen, C １－１２ is selected from the group consisting of a chain aliphatic hydrocarbon, an acetamide group (-NHAc), and an acetyl group; R ２２, O, SO ２ , C.R. ３１ ２ , C.R. ３１ C(O)N(R ３１ ) (CH ２ ) １－５ 3- to 10-membered alicyclic hydrocarbon, NR ３１ and NCHO, preferably O, CR ３１ ２ , N.R. ３１ or NCHO, and R ３１ is preferably hydrogen, C １－３ alkyl, R ２５ , O, SO ２ , C.R. ３１ ２ , and N.R. ３１ and preferably selected from the group consisting of NR ３１ and R ３１ is preferably hydrogen or methyl, more preferably hydrogen; m, n, p, and q are each independently an integer of 1 to 4; and (9) -C(O)OR ３１ , (10) (i)-C(O)NR ３１ ２ , (ii)-C(O)N(R ３１ ) (CH ２ ) ０－５ R ３２－８ (In the formula, R ３２－８ is an optionally substituted 3- to 10-membered alicyclic hydrocarbon or an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-constituting atoms, and the alicyclic hydrocarbon or heterocyclyl is preferably each independently optionally C １－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５3- to 10-membered alicyclic hydrocarbon or acetyl-substituted, preferably R ３２－８ is the formula: (In the formula, R ２０ and R ２１ are each independently hydrogen, C １－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ R is selected from the group consisting of 3- to 10-membered alicyclic hydrocarbons and acetyl, and is preferably hydrogen or methyl; ２２ , O, SO ２ , C.R. ３１ ２ , and N.R. ３１ and preferably O, or NR ３１ and R ３１ is preferably hydrogen or methyl, and m and n are each independently an integer of 1 to 4.) is an alicyclic hydrocarbon or heterocyclyl of the formula (11). ３１ ) ２ C(O)N(R ３１ ) (CH ２ ) １―５ OR ３１ , (ii)-OC(R ３１ ) ２ C(O)OR ３１ , (iii)-OC(R ３１ ) ２ C(O)NR ３１ ２ , (iv)-OC(R ３１ ) ２ C(O)R ３２－９ (In the formula, R ３２－９ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and sulfur as ring atoms, and the heterocyclyl is preferably optionally C １－３ Alkyl, -(CH２ ) １－３ OH, -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ 3- to 10-membered alicyclic hydrocarbon or acetyl-substituted, R ３２－９ is preferably of the formula: (In the formula, R ２０ and R ２１ are each independently hydrogen, C １－３ Alkyl, -(CH ２ ) １－３ OH, -NR ３１ ２ , -CHO, -C(O)C(O)R ３３ , —C(O)NR ３１ ２ , -C(O)N(R ３１ ) (CH ２ ) １－５ is selected from the group consisting of 3- to 10-membered alicyclic hydrocarbons and acetyl, preferably hydrogen, C １－３ Alkyl, and -(CH ２ ) １－３ OH; R ２２ , O, SO ２ , C.R. ３１ ２ , and N.R. ３１ and preferably selected from the group consisting of SO ２ , C.R. ３１ ２ , and N.R. ３１ R is selected from the group consisting of ３１ is preferably hydrogen or methyl, and m and n are each independently an integer of 1 to 4.) heterocyclyl.), (12) (i) —O(CH ２ ) １－６ R ３１ , (ii) -(O(CH ２ ) １－５ ) １―５ (CH ２ ) ０－３ NR ３１ ２ , (iii)-(O(CH２ ) １－５ ) １－５ (CH ２ ) ０－３ NR ３１ C(O)R ３１ , (iv)-(O(CH ２ ) １－５ ) １－５ NR ３１ C(NH)NR ３１ ２ , (v)-O((CH ２ ) １－５ O) １－５ R ３１ , (13)-OC(O)C(R ３１ ) ２ (O(CH ２ ) １－５ ) １－５ OR ３１ , and (14) optionally C １－３ Alkyl-substituted 5- or 6-membered nitrogen-containing heterocycles, preferably of the formula: (In the formula, R ２０ and R ２１ are each independently hydrogen, and C １－３ alkyl, preferably hydrogen, or methyl; R ２２ is NR ３１ The nitrogen-containing heterocycle is selected from the group consisting of:

[0053] R ９ , R １０ , R １１ and R １２ are each independently hydrogen, halogen, cyano, hydroxy, C １－５ Alkyl, 3- to 6-membered cycloalkyl, C １－５ Alkoxyl, -N(R ３１ ) C(O)R ３１ , -N(R ３１ )C(O)(CH ２ ) ０－３ NR ３１ ２ , -N(R ３１ ) (CH ２ ) １－５ NR ３１ ２ , -(CH ２ )１－５ OR ３１ , -(CH ２ ) １－５ O (CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ R ３５ , -(CH ２ ) １－５ N (R ３１ ) C(O)R ３１ , -(CH ２ ) １－５ C(O)NR ３１ ２ , -C(R ３１ ) ２ NR ３１ ２ , -(CH ２ ) １－５ NR ３１ ２ , -C(O)R ３６ , -C(O)OR ３１ , —C(O)NR ３１ ２ , -NR ３１ ２ , -C(H) ２ R ３５ , -C(H)R ３５ ２ , and -CR ３５ ３ R is selected from the group consisting of ３１ are each independently hydrogen or C １－４ is a chain aliphatic hydrocarbon, R ３５ are each independently halogen, cyano, or optionally C １－５ an alkyl-substituted 3- to 10-membered alicyclic hydrocarbon (preferably an unsubstituted 3- to 5-membered alicyclic hydrocarbon), or —OR ３１ and R ３６ has 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur as ring atoms, and optionally C １－５ and 4-10 membered heterocyclyl substituted with alkyl, preferably of the formula: (In the formula, R ２０ and R ２１ are each independently hydrogen, and C １－３alkyl, preferably hydrogen; R ２２ , O, SO ２ , C.R. ３１ ２ , and N.R. ３１ and preferably selected from the group consisting of NR ３１ and R ３１ is preferably hydrogen, and C １－３ alkyl, more preferably hydrogen, or methyl; and m and n are each independently an integer of 1 to 4, preferably an integer of 1 to 2.

[0054] R １３ are each independently hydrogen, C １－５ Alkyl, -(CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ NR ３１ ２ , -(CH ２ ) １－５ N (R ３１ ) C(O)R ３１ , -(CH ２ ) １－５ N (R ３１ ) (CH ２ ) ０－５ R ３８ , -C(O)R ３１ , -C(O)R ３７ or -(CH ２ ) １－５ R ３７ and R ３７ is a 3- to 10-membered alicyclic hydrocarbon or a 3- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen, and R ３８ is cyano, hydroxy, or S(O) ２ R ３１ is.

[0055] The heterocyclo rings in the structures shown in formulae (I-2), (I-3), and (I-27) to (I-32), and the benzene ring in the structure shown in (I-33) may each independently optionally be C １－５It may be substituted with a chain aliphatic hydrocarbon, preferably optionally C １－３ It may be substituted with alkyl, but is particularly preferably unsubstituted.

[0056] In certain embodiments of the present invention, R ６ Specific examples of the structure include the following:

[0057] Specific examples of the present compound include the following compounds: 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 3), 4-phenyl-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 71), 2-methoxy-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 79), 4-(3-fluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol (Compound 112), 4-(2-fluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol (Compound 122), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzene-1,3-diol (Compound 120), 4-(2,4-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 121), 4-(3-methoxyphenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 83), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(o-tolyl)thiazole (Compound 132), 1-methyl-6-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-3,4-dihydroquinolin-2(1H)-one (Compound 131), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 12), 4-(4-Methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 7), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-3-yl)thiazole (Compound 15), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-4-yl)thiazole (Compound 92), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-2-yl)thiazole (Compound 93), 4-(2-chloropyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 94), 4-(2-methoxypyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 95), 4-(6-methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 96), 4-(5-methylpyridin-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 97), 6-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-[1,3]dioxolo[4,5-b]pyridine (Compound 98), 4-(2-methylpyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 99), 4-(2-fluoropyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 100), 4-(2-Bromopyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 101), 4-(5-chloropyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 125), 4-(4-chloropyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 135), 2'-Bromo-2-(pyrazolo[1,5-a]pyridin-3-yl)-4,5'-bithiazole (Compound 37), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline hydrochloride (Compound 1), 4-(3-nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 4), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline hydrochloride (Compound 10), 4-(2-nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiazole (Compound 133), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline hydrochloride (Compound 134), 2-methoxy-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline (Compound 90), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 118), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzonitrile (Compound 115), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzonitrile (Compound 116), 4-(3,5-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 119), 4-(2,6-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 123), 5-fluoro-2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 114), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isonicotinamide (Compound 126), 4-(5-Methoxypyridin-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 124), 4-(5-Methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 127), 4-(1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 107), 4-(4-Chloro-1-methyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 53), 4-(1,4-Dimethyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrobromide (Compound 54), 4-(1-Methyl-1H-pyrazol-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrobromide (Compound 106), 4-(1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 109), 5-methyl-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole hydrobromide (Compound 105), N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)oxetane-3-sulfonamide (Compound 69), N-methyl-N-(4-(2-(pyrazolo[1,N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 16), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-4-carboxamide (Compound 72), N-methyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanamine hydrochloride (Compound 74), N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-4-carboxamide (Compound 76), 2-methoxy-N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 78), 1,1-dimethyl-3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)urea (Compound 59), 1,1-dimethyl-3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)urea (Compound 75), 2-methoxy-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 77), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)cyclobutanesulfonamide (Compound 82), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)oxetane-3-carboxamide (Compound 85), 2-amino-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide hydrochloride (Compound 64), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)oxetane-3-carboxamide (Compound 66), 2-amino-N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide hydrochloride (Compound 65), 2-amino-N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide hydrochloride (Compound 81), 2-amino-N-(4-(2-(pyrazolo[1,2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide hydrochloride (Compound 80), sodium 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetic acid (Compound 5), N-acetyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)glycine (Compound 73), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetamide (Compound 26), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl-2-(2-(2-methoxyethoxy)ethoxy)acetate (Compound 13), 4-(3-(2-methoxyethoxy)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 14), 4-(3-(2-(2-methoxyethoxy)ethoxy)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 22), 4-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 108), 4-(1-ethyl-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 110), 4-(1-(2-Methoxyethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (Compound 111), 2-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethoxy)ethan-1-amine hydrochloride (Compound 32), 2-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethoxy)ethan-1-amine hydrochloride (Compound 20), N,N-dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-amine hydrochloride (Compound 47), 1-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethyl)guanidine hydrochloride (Compound 52), 1-(2-(4-(2-(pyrazolo[1,N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethyl)guanidine hydrochloride (Compound 51), N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethyl)acetamide (Compound 45), N-(2-hydroxyethyl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetamide (Compound 19), methyl 2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetate (Compound 18), methyl 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetate (Compound 25), 1-(piperazin-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one (Compound 31), 1-(1,4-diazepan-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one hydrochloride (Compound 55), 1-(4-methyl-1,4-diazepan-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one hydrochloride (Compound 102), 1-(2-(hydroxymethyl)pyrrolidin-1-yl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one (Compound 21), 1-(piperazin-1-yl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one (Compound 23), 1-(1,1-dioxidethiomorpholino)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one (Compound 24), (4-methylpiperazin-1-yl)(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazol-3-yl)methanone hydrochloride (Compound 103), piperazin-1-yl(5-(2-(pyrazolo[1,N-(4'-methyl-2-(pyrazolo[1,5-a]pyridin-3-yl)-[4,5'-bithiazol]-2'-yl)acetamide (Compound 46), N,N-dimethyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide (Compound 49), sodium 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoic acid (Compound 6), (3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)(2-oxa-6-azaspiro[3.3]heptan-6-yl)methanone (Compound 33), N,N-dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 87), N-(cyclopropylmethyl)-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoyl)azetidine-3-carboxamide (Compound 9), (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)(2-oxa-7-azaspiro[3.5]nonan-7-yl)methanone (Compound 40), (1,4-oxazepan-4-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 41), (4-(dimethylamino)piperidin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 48), (4-methylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 50), (4-ethylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 56), (3-methylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 58), N,N-dimethyl-3-(2-(pyrazolo[1,N-(2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide (Compound 61), 4-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoyl)piperazine-1-carbaldehyde (Compound 68), N-(2-morpholinoethyl)-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide (Compound 30), N-methyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 88), N-ethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 89), N-methoxy-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 91), (2,5-diazabicyclo[2.2.1]heptan-2-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 43), N-(2-(piperazin-1-yl)ethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide hydrochloride (Compound 11), (3-aminopyrrolidin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 42), N-methyl-N-(piperidin-4-yl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide hydrochloride (Compound 44), piperazin-1-yl(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 57), piperazin-1-yl(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 63), 1-(piperazin-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)ethan-1-one hydrochloride (Compound 86), N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)acetamide (Compound 60), 2-(hydroxymethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 8), (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanol (Compound 2), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)ethan-1-ol (Compound 84), 4-(3-(2,5-dihydro-1H-pyrrol-3-yl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol hydrochloride (Compound 17), 6-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)-2-oxa-6-azaspiro[3.3]heptane (Compound 29), N,N-dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanamine (Compound 27), 4-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 28), N,N-dimethyl-4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-2-carboxamide (Compound 38), N,2-dimethyl-4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-2-carboxamide (Compound 39), 1-morpholino-2-(4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)piperazin-1-yl)ethane-1,2-dione hydrochloride (Compound 36), 4-(4-((2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (Compound 34), N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)piperidin-4-amine hydrochloride (Compound 35), 4-(isoindolin-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)piperidin-4-amine hydrochloride (Compound 36),N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenethyl)acetamide (Compound 62), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)ethan-1-amine hydrochloride (Compound 113), N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 67), N-methyl-N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 70), N,N-dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 137), N,N-dimethyl-1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 128), N-methyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 136), N-((5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methyl)acetamide (Compound 129), N-methyl-1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 130), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrol-3-yl)thiazole (Compound 138), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrol-2-yl)thiazole (Compound 139), 4-(1H-imidazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 140), 4-(1H-imidazol-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 141), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,3-triazol-4-yl)thiazole (compound 142), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,4-triazol-3-yl)thiazole (Compound 143), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(thiophen-3-yl)thiazole (Compound 144), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(thiophen-2-yl)thiazole (Compound 145), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isothiazole (Compound 146), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isothiazole (Compound 147), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isothiazole (Compound 148), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4,4'-bithiazole (Compound 149), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4,5'-bithiazole (Compound 150), 2'-(pyrazolo[1,5-a]pyridin-3-yl)-2,4'-bithiazole (Compound 151), 4-(furan-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 152), 4-(furan-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 153), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole (Compound 154), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole (Compound 155), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole (Compound 156), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)oxazole (Compound 157), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)oxazole (Compound 158), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)oxazole (Compound 159), 4-(1-methyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 160), 4-(1-methyl-1H-pyrrol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 161), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1,2,4-thiadiazole (Compound 162), 4-(1-methyl-1H-pyrrol-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 163), 3-bromo-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole (Compound 164), 4-(1H-imidazol-1-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 165), 4-(1H-pyrazol-1-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 166), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrol-1-yl)thiazole (Compound 167), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,4-triazol-1-yl)thiazole (Compound 168), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(2H-1,2,3-triazol-2-yl)thiazole (Compound 169), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,3-triazol-1-yl)thiazole (Compound 170), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiophene-3-carboxamide (Compound 171), 2-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiophen-2-yl)acetamide (Compound 172), N,N-dimethyl-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiophene-3-carboxamide (Compound 173), N-(2-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiophen-2-yl)ethyl)acetamide (Compound 174), 4-(3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 178), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiophen-3-ol (Compound 175), 1-methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazole-3-carbonitrile (Compound 176), N-methyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-1-yl)ethan-1-amine (Compound 177), 4-(5-fluoro-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 179), 3-methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-5-amine (Compound 181), 4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-1-yl)butan-1-ol (Compound 180), 4-(1-(azetidin-2-ylmethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol (Compound 182), 2-((2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-1-yl)ethyl)amino)acetonitrile (Compound 183), 3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-1-yl)propan-1-amine (Compound 184), N-(3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-1-yl)propyl)methanesulfonamide (Compound 185), 5-methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-3-ol (Compound 186), N, １ , N １ -dimethyl-N ２N-(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazol]-2-yl)ethane-1,2-diamine (Compound 187), 2-(dimethylamino)-N-(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazol]-2-yl)acetamide (Compound 188), 2-amino-N-(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazol]-2-yl)acetamide hydrochloride (Compound 189), 2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazol]-2-ol (Compound 190), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)furan-2-carboxamide (Compound 191), 4-(2,5-dihydrofuran-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 192), (1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-4-yl)methanol (Compound 193), (1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-4-yl)methanamine hydrochloride (Compound 194), 3-((1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-4-yl)methoxy)propan-1-ol (Compound 195), 3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-1-yl)propan-1-ol (Compound 196), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-1-yl)ethan-1-amine (Compound 197), N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-1-yl)ethyl)acetamide (Compound 198), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyrimidin-5-yl)thiazole (compound 199), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyrimidin-2-yl)thiazole (compound 200), 4-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 201), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-yl)thiazole (compound 202), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazine (compound 203), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (compound 204), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-4,5,6,7-tetrahydrothiazolo[4,5-c]pyridine (Compound 205), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl)thiazole (Compound 206), 4-(1H-indazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 207), 4-(4-chloro-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 208), 2-(6-methylpyrazolo[1,5-a]pyridin-3-yl)-4-phenylthiazole (Compound 209), 2-(5-methylpyrazolo[1,5-a]pyridin-3-yl)-4-phenylthiazole (Compound 210), 2-(4-methylpyrazolo[1,5-a]pyridin-3-yl)-4-phenylthiazole (Compound 211), 4-(4-chloro-1-methyl-1H-pyrazol-3-yl)-2-(5-methylpyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 212), and N-((5-(2-(5-methylpyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methyl)acetamide (Compound 213).

[0058] 2. Method for Producing the Present Compound The present compound can be produced by combining known reactions. Illustrative examples of synthesis of the compounds of the present invention are shown below. Those skilled in the art can synthesize compounds of formula (I) and derivatives thereof other than the exemplified compounds in accordance with the following description and the description of the Examples. (Abbreviations) The meanings of the abbreviated symbols in the following reaction schemes are as follows: Δ: Heating Halo: Halogen DME: Dimethoxyethane EtOH: Ethanol DMF: Dimethylformamide TEA: Triethylamine DIPEA: Diisopropylethylamine CH ３ CN: Acetonitrile Boc ２ O: Di-tert-butyl dicarbonate Boc-ON: 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile aq.: Aqueous solution N-BocGlycine: N-butoxycarbonyl-glycine BrCH ２ CO ２ tBu: tert-butyl bromoacetate BrCH ２ COOBn: benzyl bromoacetate Boc: tert-butoxycarbonyl DCM: dichloromethane EDC.HCl: N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride DCC: N,N'-dicyclohexylcarbodiimide HOBt: 1-hydroxybenzotriazole (condensation auxiliary) HOAt: 1-hydroxy-7-azabenzotriazole (condensation auxiliary) BOP: 1H-benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate HATU: 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate TATU: 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-Oxidotetrafluoroborate COMU: 1-[bis(cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholino]uronium hexafluorophosphate Ac ２O: Acetic anhydride DBU: 1,8-diazabicyclo[5.4.0]-7-undecene DBN: 1,5-diazabicyclo[4.3.0]non-5-ene THF: Tetrahydrofuran Me: Methyl Et: Ethyl MeOH: Methanol LAH: Lithium aluminum hydride DIBAL: Diisobutylaluminum hydride LiBH ４ : Lithium borohydride LiBEt ３ : Lithium triethylborohydride AcOEt: Ethyl acetate Pd(PPh ３ ) ４ : tetrakis(triphenylphosphine)palladium(0) Pd(OAc) ２ : Palladium acetate PdCl ２ (PPh ３ ) ２ : Bis(triphenylphosphine)palladium(II) dichloride PdCl ２ (dppf): [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) Pd(acac) ２ : Palladium (II) acetylacetonate Pd ２ (dba) ３ : Tris(dibenzylideneacetone)dipalladium(0) DMAP: 4-dimethylaminopyridine BocPiperazine: Butoxycarbonylpiperazine NaBH(OAc) ３ : Sodium triacetoxyborohydride NaBH ３ CN: Sodium cyanoborohydride AcOH: Acetic acid rt: Room temperature XPhos: 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl Tf: Trifluoromethanesulfonyl DMSO: Dimethyl sulfoxide TBS: tert-butyldimethylsilyl TBAF: Tetrabutylammonium fluoride TFA: Trifluoroacetic acid t-BuOH: tert-butanol

[0059] (1) Main Reactions The compound of formula (I) can be synthesized, for example, by the following reaction. (In the formula, R １ ~R ６ is as defined in formula (I) above.

[0060] Step A: In this reaction, a thioamide of formula (II) and a halide of formula (III) having corresponding substituents or structures can be selected depending on the structure of the compound of formula (I) to be synthesized. The reaction can be carried out by dissolving the thioamide in a solvent such as DME, acetone, toluene, hexane, xylene, ethyl acetate, dioxane, THF, ethanol, methanol, dichloroethane, DMF, or water, adding a halide to the resulting mixture, distilling off the solvent from the reaction mixture, adding a solvent such as ethanol and an excess of a base such as potassium carbonate, sodium hydroxide, potassium hydroxide, sodium carbonate, triethylamine, DBU, DBN, or pyridine to the residue, and distilling off the solvent from the reaction mixture. If necessary, the resulting crude product may be purified. R １ ~R ６ By modifying the group with a protecting group or the like or by replacing it with a different group, a derivative of the compound of formula (I) can also be obtained, and the compound of formula (I) can also be synthesized from this derivative by an additional reaction described below.

[0061] The compound of formula (I) is R ６ is an optionally substituted 5- to 10-membered aromatic heterocycle having at least one nitrogen atom, or a fused ring of the same with an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring-constituting atoms, the compound can also be synthesized by the following reaction (Goldberg amination reaction): (In the formula, R １ ~R ５ is as defined in formula (I) above, and R ６’ is an optionally substituted 5- to 10-membered heterocycle having at least one nitrogen atom (preferably a 5- to 10-membered aromatic heterocycle or a 5- or 6-membered heterocycloalkenyl), or a fused ring of such a heterocycle (preferably a 5- to 10-membered aromatic heterocycle) and an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring-constituting atoms; R ６’The nitrogen atom constituting the aromatic heterocycle is linked to a carbon atom constituting the thiazole ring, and Halo is a halogen atom such as iodine, bromine, or chlorine, preferably bromine.

[0062] Step A: The aryl halide compound represented by formula (IV) is heated with a nitrogen-containing heterocycle such as imidazole or pyrazole in the presence of a copper catalyst such as copper(I) iodide for a predetermined time to induce a Goldberg reaction, thereby obtaining the corresponding condensation product. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Preferred solvents include toluene, hexane, xylene, methanol, ethanol, isopropanol, ethylene glycol, acetonitrile, dioxane, THF, dichloromethane, dichloroethane, DME, DMF, and dimethylacetamide. Examples of bases used include potassium carbonate, sodium carbonate, sodium bicarbonate, potassium phosphate, potassium acetate, cesium carbonate, potassium phosphate, sodium hydride, sodium methoxide, sodium ethoxide, sodium butoxide, sodium hydroxide, potassium hydroxide, DBU, and DBN. Examples of copper catalysts that can be used include copper(I) chloride, copper(I) bromide, copper(I) iodide, copper, and copper oxide. Furthermore, trans-1,2-cyclohexanediamine, N,N'-dimethyl-trans-1,2-cyclohexanediamine, 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, and 3,4,7,8-tetramethyl-1,10-phenanthroline can also be used as reaction additives. The reaction temperature is usually 40 to 200°C, and the reaction time is 1 to 24 hours, preferably 1 hour at 180°C. In this reaction, the R １ ~R ６’ By modifying the group with a protecting group or the like or by replacing it with a different group, a derivative of the compound of formula (I') above can also be obtained, and the compound of formula (I') above can also be synthesized from this derivative by an additional reaction described below.

[0063] The compound of formula (I) can also be synthesized, for example, by the following reaction. (In the formula, R １ ~R ６ is as defined in formula (I) above, Tf represents triflate, R ’ and R ’ ’ represents a hydrogen atom, or R ’ and R ’ ’ form an alkylenedioxy group together with the two adjacent oxygen atoms.) Step A: A triflate compound of formula (V) and a boronic acid compound of formula (VI) are heated for a predetermined time in the presence of a palladium catalyst to cause a Suzuki-Miyaura coupling reaction, thereby producing a compound of formula (I). Examples of palladium catalysts include palladium acetate, palladium chloride, bis(triphenylphosphine)palladium(II) dichloride, tetrakis(triphenylphosphine)palladium(0), tris(dibenzylideneacetone)dipalladium(0), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride. The catalyst is used in the presence of a base such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, tripotassium phosphate, sodium methoxide, or potassium tert-butoxide, with the addition of water. Examples of reaction solvents that can be used include toluene, hexane, xylene, dioxane, tetrahydrofuran, dimethoxyethane, dichloroethane, and N,N-dimethylformamide. The reaction may be carried out at a temperature of 50 to 200°C for about 5 minutes to 20 hours. １ ~R ６ By modifying the group with a protecting group or the like or by replacing it with a different group, a derivative of the compound of formula (I) can be obtained, and the compound of formula (I) can be synthesized from this derivative by the additional reaction described below. The compound of formula (I) can also be synthesized, for example, by the following reaction. (In the formula, R １ ~R ６ is as defined in formula (I) above, and R ’ and R ’ ’ represents a hydrogen atom, or R ’ and R ’ ’form an alkylenedioxy group together with the two adjacent oxygen atoms, and Halo is a halogen such as iodine, bromine, or chlorine. Step A: A boronic acid compound of formula (VII) and a halogen compound of formula (VIII) are heated for a predetermined time in the presence of a palladium catalyst to cause a Suzuki-Miyaura coupling reaction, thereby producing a compound of formula (I). This reaction can be carried out in the same manner as the reaction between formula (V) and formula (VI). R １ ~R ６ By modifying the group with a protecting group or the like or by replacing it with a different group, a derivative of the compound of formula (I) can also be obtained, and the compound of formula (I) can also be synthesized from this derivative by an additional reaction described below.

[0064] (2) Additional Reactions: The substituents of the compound of formula (I) or its derivatives obtained in the above main reaction can be replaced by known reactions to produce a compound of formula (I) or its derivatives having different substituents. Applicable known reactions are described in general laboratory textbooks, such as Maruzen's Fourth Edition Experimental Chemistry Lectures (30 volumes in total), and each reaction can be carried out in accordance with these. The contents of these documents are incorporated herein by reference. Exemplary additional reactions are shown below. In the following reaction schemes, the double circle structures represent 5- to 10-membered aromatic hydrocarbons, 5- to 10-membered aromatic heterocycles having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or fused rings of either of these with 4- to 10-membered heterocyclyls having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0065] (Reduction of nitro group with metal, and protection and deprotection of the resulting amino group) When a compound having a nitro group is synthesized in the main reaction or in another additional reaction, the nitro group can be converted to an amino group by an additional reaction represented by the following reaction formula. (where n is an integer of 0 or greater (e.g., an integer from 0 to 3).) Step A: In this reaction, a nitro compound is dissolved in a solvent such as acetonitrile, and an additive such as zinc powder or calcium chloride is added together with water. The resulting mixture is heated to produce an amino compound. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Preferred solvents include acetone, toluene, hexane, xylene, dioxane, THF, ethanol, methanol, DME, and DMF. The reaction temperature is typically 80 to 120°C, and the reaction time is 0.5 to 6 hours, preferably 1 hour at 100°C. While Step A demonstrates the reduction of a nitro group under neutral conditions, the reaction conditions are not limited to these. Alternatively, reduction using metals such as zinc, iron, and tin under acidic conditions can also be used. Step B: To protect the less stable amino group, the Boc group is used. The obtained amino compound is dissolved in a solvent such as acetonitrile, an excess of a Boc-containing agent is added, and the mixture is stirred to react, followed by purification as necessary, to synthesize a carbamate compound in which the amino group is protected with a Boc group. The solvent to be used varies depending on the starting materials and reagents, and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Preferred solvents include acetonitrile, acetone, toluene, hexane, xylene, dioxane, THF, ethanol, methanol, DME, and DMF. Examples of the Boc-containing agent include Boc ２Examples of suitable protecting groups include Boc-O and Boc-ON. The reaction temperature is typically −20 to 80° C., and the reaction time is 1 to 48 hours, preferably 24 hours at room temperature. In Step B, a Boc group was used as the protecting group; however, this is not limiting; other protecting groups, such as a benzoyl group, can also be used. Step C: A carbamate compound in which the amino group is protected with a Boc group is added to a solution of hydrochloric acid in dioxane to remove the protecting group, thereby synthesizing the amine hydrochloride. This reaction can also be carried out by dissolving the carbamate compound in a solvent and adding an acid thereto. The solvent used will vary depending on the starting materials and reagents, and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Preferred solvents include acetonitrile, acetone, toluene, hexane, xylene, dioxane, dichloromethane, ethanol, methanol, DME, DMF, and water. Examples of suitable acids include nitric acid, sulfuric acid, acetic acid, and trifluoroacetic acid. Usually, the reaction temperature is −20 to 80° C. and the reaction time is 0.5 to 12 hours, preferably 0° C. for 1 hour.

[0066] (Reaction of Amine with Halide) When an amine is synthesized in the main reaction or in other additional reactions, it can be subjected to additional reactions represented by the following reaction formula to add a desired substituent (R ’ ) can be synthesized. (wherein n is an integer of 0 or more (for example, an integer of 0 to 3), and R is a hydrogen atom or an arbitrary substituent (for example, C １－３ alkyl group), and R ’ is any structure or group to be introduced (e.g., R ３１ , R ３２ , —C(O)(CH ２ ) ０－３ NR ３１ ２ , -(CH ２ ) １－３ CN, -(CH ２ ) １－３ R ３２ or —C(O)NR ３２ )

[0067] Step A: In this reaction, an amine hydrochloride is suspended in dichloromethane, to which a halide is added, followed by the addition of a base such as triethylamine to convert the amino group to the desired substituent (R ’ ) can be introduced into the resulting compound. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Preferred solvents include acetonitrile, acetone, toluene, hexane, xylene, dioxane, THF, dichloromethane, DME, DMF, and mixtures thereof. Acid scavengers include an equivalent to excess amount of a base such as triethylamine, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium hydride, sodium methoxide, sodium ethoxide, sodium hydroxide, potassium hydroxide, DBU, DBN, or pyridine. The reaction temperature is typically −20 to 80°C, and the reaction time is 1 to 48 hours, preferably 1 hour at 0°C.

[0068] (Condensation reaction of amine and carboxylic acid) When an amine is synthesized in the main reaction or in the additional reaction, it is subjected to an additional reaction represented by the following reaction formula to add a desired substituent (R ’ A compound having a carbonyl group having the formula (I) can be synthesized. (wherein n is an integer of 0 or more (for example, an integer of 0 to 3), and R is a hydrogen atom or an arbitrary substituent (for example, C １－３ alkyl group), and R ’ is any structure or group to be introduced (e.g., R ３１ , R ３２ , -(CH ２ ) １－５ C(O)OR ３１ , -(CH ２ ) １－５ NR ３１ ２ )

[0069] Step A: In this condensation reaction, an amine hydrochloride, the desired substituent (R ’Various amides can be synthesized by adding a carboxylic acid having a carboxylic acid group having a carboxylic acid group (C1) and a condensing agent such as EDC·HCl, and then adding an equal to excess amount of a base such as triethylamine as an acid scavenger. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. However, preferred solvents include anhydrous solvents such as dichloromethane, acetonitrile, acetone, toluene, hexane, xylene, dioxane, THF, DME, and DMF. Acid scavenger agents include an equal to excess amount of triethylamine, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium hydride, sodium methoxide, sodium ethoxide, sodium hydroxide, potassium hydroxide, DBU, DBN, or pyridine. The reaction temperature is typically −20 to 80°C, and the reaction time is 1 to 48 hours, preferably 24 hours at room temperature. If necessary, a reaction catalyst such as DMAP can be used. Here, EDC was used as the condensing agent, but DCC and other solvents can also be used. In addition, HOBt or HOAt may be added to prevent epimerization. Furthermore, BOP-based reagents can also be used as condensation agents, and HATU, TATU, COMU, etc. can also be used.

[0070] (Introduction Reaction of an Amino Group Protected by a Boc Group) By utilizing the reaction between an amine and a carboxylic acid, for example, an amino group having a protecting group (Boc) that can be converted into an amino group (hydrochloride thereof) can be added to a side chain by a reaction represented by the following exemplary reaction formula: wherein R and A are a bond or any structure, such as C １－５ Alkylene, —C(O)—, —(CH ２ ) ０－５ N (R ３１ )C(O)(CH ２ ) ０－５ -, -C(R ３１ ) ２ C(O)-,-(CH ２ ) １－５ O (CH ２ ) １－５ -, -O(CH ２ ) １－５ -, -(OCH ２ ) １－５-, etc.) Step A: This reaction is carried out under the same conditions as in Step B described above (reduction of the nitro group with a metal, and protection and deprotection of the resulting amino group).

[0071] (Removal reaction of protecting group (Boc)) When a compound having an amino group protected with Boc is synthesized in the main reaction or in an additional reaction, the Boc group can be removed by an additional reaction represented by the following exemplary reaction formula. wherein R and A are a bond or any structure, such as C １－５ Alkylene, —C(O)—, —(CH ２ ) ０－５ N (R ３１ )C(O)(CH ２ ) ０－５ -, -C(R ３１ ) ２ C(O)-,-(CH ２ ) １－５ O (CH ２ ) １－５ -, -O(CH ２ ) １－５ -, -(OCH ２ ) １－５ - etc.)

[0072] Step A: This reaction is carried out under the same conditions as in Step C described above (reduction of the nitro group with a metal, and protection and deprotection of the resulting amino group).

[0073] (Acetylation Reaction) When a compound having an amino group is synthesized in the main reaction or in the additional reaction, an amide in which the amino group is protected with an acetyl group can be synthesized by subjecting the compound to an additional reaction represented by the following reaction formula. (wherein n is an integer of 0 or more (for example, an integer of 0 to 3), and R is a hydrogen atom or an arbitrary substituent (for example, C １－３ alkyl group).

[0074] Step A: In these reactions, an amine is added to a solvent such as acetonitrile, and then an acetylating agent and a catalytic amount of a base such as DMAP or TEA are added to the resulting mixture to synthesize the acetylated product. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Preferred solvents include acetonitrile, acetone, toluene, hexane, xylene, dioxane, THF, dichloromethane, DME, and DMF. Furthermore, examples of acid scavengers include bases such as TEA, DIPEA, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium hydride, sodium methoxide, sodium ethoxide, sodium hydroxide, potassium hydroxide, DBU, DBN, and pyridine. Examples of acetylating agents include acetic anhydride and acetyl chloride. The reaction temperature is typically −20 to 80°C, and the reaction time is 1 to 48 hours, with 24 hours at room temperature being preferred.

[0075] (Removal reaction of protecting group (acetyl group)) When a compound in which the amino group is protected with an acetyl group is synthesized in the main reaction or in an additional reaction, the acetyl group can be removed by an additional reaction represented by the following exemplary reaction formula. (wherein n is an integer of 0 or more (for example, an integer of 0 to 3), and R is a hydrogen atom or an arbitrary substituent (for example, C １－３ alkyl group).

[0076] Step A: In these reactions, a compound in which the amino group is protected with an acetyl group is suspended in a solvent and heated under acidic or basic conditions for a predetermined period of time to deprotect the acetyl group. The solvent used will vary depending on the starting materials and reagents, and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Preferred solvents include methanol, ethanol, dioxane, DME, DMF, water, and the like. Examples of acids include hydrochloric acid, nitric acid, sulfuric acid, trifluoroacetic acid, and hydrobromic acid. Examples of bases include sodium hydroxide, potassium hydroxide, and lithium hydroxide. The reaction temperature is usually 50 to 160°C, and the reaction time is 0.5 to 24 hours, with a preferred reaction time being 1 hour at 100°C.

[0077] (Removal reaction of protecting group (phthalimide)) When a compound in which an amino group is protected with phthalic anhydride is synthesized in the main reaction, the compound can be removed by subjecting it to an additional reaction (deprotection) represented by the following exemplary reaction formula. Step A: In this reaction, a phthalimide derivative and hydrazine monohydrate are added to a solvent such as ethanol, and the mixture is heated for a predetermined period of time to react and deprotect, thereby obtaining an amine derivative. The solvent used will vary depending on the starting materials, reagents, etc., and is not particularly limited as long as it does not inhibit the reaction and can dissolve the starting materials to some extent. Preferred solvents include ethanol, methanol, water, dichloromethane, THF, DMF, toluene, chloroform, acetonitrile, diethyl ether, 1-butanol, isopropanol, acetic acid, acetone, benzene, tert-butanol, and DMSO.

[0078] (Alkylation Reaction) When a compound having an amino functional group such as an acetamide group is synthesized in the main reaction or in an additional reaction, an alkyl group can be introduced to the amino group by an additional reaction represented by the following reaction formula: (In the formula, R ’ is a bond or any structure (e.g., C １－３ alkylene), and R ’’ is any group (e.g., C １－３ Alkyl, C(O)C １－３ alkyl), and R ’’’ is an alkyl group (e.g., C １－３ alkyl), etc.

[0079] Step A: In this reaction, a compound having an amino functional group such as an acetamide group is added to a suspension of sodium hydride in a solvent such as DMF, and an alkyl halide (Halo-R ’’’) is added dropwise and reacted to obtain an N-alkylamide. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. However, preferred examples include THF, DME, and DMF. Furthermore, examples of strong bases include sodium hydride, sodium methoxide, sodium ethoxide, sodium butoxide, sodium hydroxide, potassium hydroxide, DBU, and DBN. The reaction temperature is usually −20 to 50°C, and the reaction time is 1 to 24 hours, preferably 1 hour at 0°C.

[0080] (Reductive Amination Reaction) When a compound having an amino group is synthesized in the main reaction or in the additional reaction, an alkyl group can be introduced into the amino group by subjecting it to an additional reaction represented by the following reaction formula. (In the formula, n is an integer of 0 or more (e.g., an integer of 0 to 3).)

[0081] Step A: In this reaction, an amine derivative and an aldehyde are added to a dry solvent such as methanol, stirred, and then added to NaBH(OAc) ３ and reacting for a predetermined time to obtain an alkylamine derivative. The reaction is carried out in a solvent in the presence or absence of an acid. The solvent used varies depending on the starting materials, reagents, etc., and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Preferred examples include methanol, ethanol, toluene, benzene, hexane, xylene, dioxane, THF, dichloromethane, dichloroethane, DME, and DMF. The acid used varies depending on the starting materials, solvent, etc., and is not particularly limited as long as it does not inhibit the reaction. Preferred examples include acetic acid and formic acid. Furthermore, as a reducing agent, NaBH(OAc) ３ , NaBH ３ CN can be used, and the reaction temperature is usually −20 to 100° C. for 1 to 24 hours, preferably 25° C. for 3 hours.

[0082] (N-Alkylation Reaction of Amide Group) When a compound having an amino group is synthesized in the main reaction or in the additional reaction, it can be converted into an amide group and further N-alkylated by subjecting it to the following additional reaction. (In the formula, n is an integer of 0 or more (e.g., an integer of 0 to 3).) Step A: In this reaction, the solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it does not inhibit the reaction and can dissolve the starting materials to some extent. However, preferred examples include THF, DME, and DMF. Examples of strong bases include an equivalent to excess amounts of sodium hydride, sodium methoxide, sodium ethoxide, sodium hydroxide, and potassium hydroxide. The reaction temperature is usually −20 to 80°C, and the reaction time is 1 to 48 hours, preferably 24 hours at 0°C. This reaction is similar to Step A in the above-described (Alkylation Reaction). Step B: An N-alkylamide can be synthesized by reacting a compound having an amide group with a strong base in a dry DMF solution and then reacting with an alkyl halide.

[0083] (Reaction of Hydroxyl Group with Halide) When a derivative having a hydroxyl group is synthesized in the main reaction or in the additional reaction, the derivative is subjected to an additional reaction represented by the following reaction formula to convert the hydroxyl group into a desired substituent (R ’ ) can be used to synthesize ether (phenoxy ether) compounds. (wherein n is an integer of 0 or more (for example, an integer of 0 to 3), and R ’ is an optional substituent (e.g., —C(R ３１ ) ２ C(O)(CH ２ ) ０―３ OH, -C(R ３１ ) ２ C(O)NR ３１ ２ , -C １―６ Alkyl group, -((CH ２ ) １―５ O) １―５ R ３１ , -C(O)C(R ３１ ) ２ (O(CH ２ ) １―５ ) １―５ OR ３１etc.)

[0084] Step A: In this reaction, a compound having a hydroxyl group (mainly a phenol derivative) is reacted with a base in DMF, and then a halide (Halo-R ’ ) can be used to synthesize an ether (phenoxy ether) derivative. The solvent used will vary depending on the starting materials, reagents, etc., and is not particularly limited as long as it does not inhibit the reaction and can dissolve the starting materials to some extent. Preferred solvents include THF, DME, DMF, and dichloromethane. Examples of bases include an equivalent to excess amount of sodium hydride, sodium methoxide, sodium ethoxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, DBU, DBN, and pyridine. The reaction temperature is typically −20 to 80°C, and the reaction time is 1 to 48 hours, preferably 24 hours at 0°C.

[0085] (Alkaline Hydrolysis Reaction) When an ester is synthesized in the main reaction or in the additional reaction, it can be subjected to an additional reaction represented by the following reaction formula to be subjected to alkaline hydrolysis. (In the formula, R ’ is a bond, any structure (e.g., C １－３ alkylene, —O—C—, etc.), and R ’’ is an optional substituent (e.g., a chain alkyl group, an aromatic hydrocarbon, etc.).

[0086] Step A: In this reaction, an ester compound is added to a solvent such as a mixed solvent of aqueous sodium hydroxide and ethanol, and the mixture is heated and stirred for a predetermined time to react, followed by an acid-base treatment to obtain a carboxylic acid. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Preferred solvents include methanol, ethanol, dioxane, DME, DMF, and water. Furthermore, strong bases include sodium hydroxide, potassium hydroxide, sodium hydride, sodium methoxide, sodium ethoxide, sodium butoxide, DBU, and DBN. The reaction temperature is typically 30 to 140°C, and the reaction time is 1 to 24 hours, with 1 hour at 100°C being preferred.

[0087] (Reaction of Esters (and Carboxylic Acids) with Amines) When an ester compound is synthesized in the main reaction or in an additional reaction, the ester can be converted to an aminocarbonyl by an additional reaction represented by the following reaction scheme. (In the formula, R ’ is a bond, any structure (e.g., C １－３ alkylene, —O—C—, etc.), and R ’’ is hydrogen or an arbitrary substituent (e.g., a chain alkyl group, an aromatic hydrocarbon, etc.), and R is O, SO ２ , C.R. ３１ ２ , and N.R. ３１ wherein m and n are each independently an integer from 1 to 4.

[0088] Step A: In these reactions, a predetermined amine is added to an ester compound in an equivalent amount to a large excess, preferably in a large excess, and the reaction is carried out using either no solvent or DME, acetone, toluene, hexane, xylene, dioxane, THF, chloroform, dichloromethane, dichloroethane, etc., preferably without a solvent. The reaction solution can be reacted at room temperature or under reflux for 1 to 48 hours, preferably under reflux for 12 hours, to obtain the target product.

[0089] (Transesterification Reaction) When an ester compound is synthesized in the main reaction or in the additional reaction, the ester substituent can be exchanged by subjecting it to an additional reaction represented by the following reaction formula. (In the formula, R ’ is a bond, any structure (e.g., C １－３ alkylene, —O—C—, etc.), and R ’’ is an optional substituent (e.g., a chain alkyl group, an aromatic hydrocarbon, etc.), and Alkyl is an alkyl group (e.g., C １－３ alkyl group).

[0090] Step A: In these reactions, an equivalent to a large excess amount of a specific alkyl alcohol is added to an ester compound, preferably in a large excess amount, and the reaction is carried out using either no solvent or DME, acetone, toluene, hexane, xylene, dioxane, THF, chloroform, dichloromethane, dichloroethane, DMF, or the like. The base that can be used is piperazine, sodium hydride, piperidine, pyrrolidine, sodium hydroxide, potassium hydroxide, DBU, DBN, or the like, preferably piperazine. The reaction solution can be reacted at room temperature or under reflux for 1 to 48 hours, preferably under reflux for 12 hours, to obtain the target product.

[0091] (Reduction Reaction of Ester) When an ester compound is synthesized in the main reaction or in the additional reaction, the ester can be reduced to an alcohol derivative by subjecting it to an additional reaction represented by the following reaction formula. (In the formula, R' is a bond or any structure (e.g., C1-3 alkylene, -O-C-, etc.), and R'' is any substituent (e.g., a chain alkyl group, aromatic hydrocarbon).)

[0092] Step A: In this reaction, a reducing agent such as LAH is added to a solvent such as diethyl ether, and then an ester compound is added to the solvent and reacted for a predetermined time. The dry solvent used varies depending on the starting materials, reagents, etc., and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Preferred examples include diethyl ether, THF, toluene, and hexane. Furthermore, examples of reducing agents include LAH, DIBAL, and LiBH. ４ , LiBEt ３ The reaction temperature is usually −20 to 50° C., and the reaction time is 1 to 24 hours, preferably 2 hours at 0° C. In addition to hydride reduction, diborane or the like can also be used for the reduction of the ester.

[0093] (Condensation Reaction of Carboxylic Acid and Amine) When a carboxylic acid compound is synthesized in the main reaction or in an additional reaction, the carboxylic acid can be converted to an amide compound by subjecting it to an additional reaction represented by the following reaction formula. (In the formula, R ’is a bond, any structure (e.g., C １－３ alkylene, -O-C-, etc.), and R is O, SO ２ , C.R. ３１ ２ , and N.R. ３１ wherein m and n each independently represent an integer of 1 to 4. Step A: Details are the same as in Step A described above (condensation reaction of an amine with a carboxylic acid).

[0094] (Alkyl Metal Salt of Carboxylic Acid) When a carboxylic acid is synthesized in the main reaction or in an additional reaction, it can be subjected to an additional reaction represented by the following reaction formula to convert it into an alkyl metal salt of the carboxylic acid. (In the formula, R ’ is a bond or any structure (e.g., C １－３ alkyl, —O—C—, etc.)

[0095] Step A: In this reaction, carboxylic acid and sodium carbonate are added to purified water and reacted. Examples of purified water used here include tap water, ion-exchanged water, and distilled water. Examples of alkali metal salts include sodium, potassium, calcium, and barium. In particular, when preparing sodium salts, sodium hydroxide, sodium bicarbonate, and the like can be used in addition to sodium carbonate. The reaction temperature is typically −20 to 50°C, and the reaction time is typically 1 to 24 hours, preferably 6 hours at room temperature.

[0096] (Reductive Alkylamination Reaction of Formyl Group) When an aldehyde is synthesized in the main reaction or in the additional reaction, the desired amino group can be introduced by subjecting it to an additional reaction represented by the following reaction formula. (In the formula, R ’ is a bond, any structure (e.g., C １－３ alkylene, —O—C—, etc.), and Alkyl is an alkyl group (e.g., C １－３ alkyl group), and R is O, SO ２ , C(R ３１ ) R ３１’ , and N.R. ３１’ and R ３１’are each independently hydrogen or an optional substituent (e.g., C １－３ Alkyl, CHO, —C(O)C(O)R ３２ , —C(O)NR ３１ ２ , also - (CH ２ ) １－５ 3- to 10-membered alicyclic hydrocarbons, etc.), and m and n are each independently an integer of 1 to 4, preferably an integer of 1 or 2.

[0097] Step A: In this reaction, an aldehyde and an amine or an amine hydrochloride are added to a dry solvent such as dichloromethane, and after stirring, NaBH(OAc) ３ The solvent used varies depending on the starting materials, reagents, etc., and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Preferred examples include toluene, hexane, xylene, dioxane, THF, dichloromethane, dichloroethane, DME, and DMF. Furthermore, NaBH(OAc) is used as a reducing agent. ３ , NaBH ３ CN can be used, and the reaction temperature is usually −20 to 50° C. for 1 to 24 hours, preferably 0° C. for 3 hours.

[0098] (Suzuki-Miyaura Coupling Reaction) When a halide is synthesized in the main reaction or the additional reaction, it can be subjected to an additional reaction represented by the following reaction formula to introduce a desired substituent. (In the formula, Halo is a halogen such as iodine, bromine, chlorine, or fluorine, and is preferably bromine.)

[0099] Step A: This reaction involves the use of a halide, 1-(tert-butoxycarbonyl)-2,5-dihydro-1H-pyrrol-3-yl-boronic acid pinacol ester, and Pd(PPh) as a catalyst. ３ ) ４and sodium carbonate are dissolved in a solvent such as a mixed solvent of DME and water, and heated for a predetermined time to react. Specifically, by reacting an aryl halide with boronic acid or a pinacol boronic acid ester in the presence of a palladium catalyst, the Suzuki-Miyaura coupling reaction proceeds to obtain the corresponding condensation product. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Preferred solvents include toluene, hexane, xylene, methanol, ethanol, dioxane, THF, dichloromethane, dichloroethane, DME, and DMF. Examples of bases that can be used include potassium carbonate, sodium carbonate, sodium bicarbonate, potassium phosphate, potassium acetate, sodium hydride, sodium methoxide, sodium ethoxide, sodium butoxide, sodium hydroxide, potassium hydroxide, DBU, and DBN. Examples of palladium catalysts that can be used include Pd(OAc) ２ , Pd(PPh ３ ) ４ , PdCl ２ (PPh ３ ) ２ , PdCl ２ (dppf), Pd (acac) ２ and the like. Furthermore, XPhos can also be used as a reaction additive. The reaction temperature is usually 40 to 150°C, and the reaction time is 1 to 24 hours, preferably 1 hour at 80°C. Step B: If the introduced substituent has a protecting group, it can be converted to an amino group by a deprotection reaction. This reaction is carried out under the same conditions as in Step C described above (reduction of the nitro group with a metal, protection of the generated amino group, and deprotection reaction).

[0100] (3) Synthesis of Starting Material The compound of formula (III) as a starting material may be a commercially available product, but can also be synthesized, for example, by reacting an acetophenone derivative with a halogenating agent in a solvent to form acetophenone halogenated at the α-position, as shown in the following reaction scheme. (In the formula, R ６is as defined in formula (I) above, and Halo is a halogen such as iodine, bromine, chlorine, or fluorine, preferably bromine.

[0101] Step A: This reaction involves reacting a compound of formula (IX) with CuBr in a solvent such as ethyl acetate. ２ When the substituent on the benzene ring is an alkyl group, the reaction can be carried out by reacting with 2 equivalents of CuBr ２ By heating at 100°C, the bromination of the α-position of the acetyl group proceeds easily in about an hour. In this case, if the reaction continues for a long time, a dibromoacetyl compound will be produced as a by-product. On the other hand, if the substituent is an electron-withdrawing substituent such as an ester, the reaction time must be extended to 2 to 16 hours. Also, if there is a substituent that is sensitive to acid, care must be taken as a small amount of HBr will be generated during the reaction. Furthermore, in the case of a basic substituent, CuBr ２ Since the reaction (I) often does not proceed, phenacyl bromide can be synthesized by using conditions such as bromine-acetic acid. The bromination conditions are not limited to these. This reaction can also be carried out by dissolving the compound of formula (IX) in a solvent such as acetic acid, adding a halogen such as bromine, or a hydrohalic acid such as hydrobromic acid, and reacting the resulting mixture. This reaction can also be carried out by dissolving the compound of formula (IX) in dioxane, adding a bromine-1,4-dioxane complex, and reacting the resulting mixture. It is also possible to synthesize a substituted phenacyl halide by direct haloacetylation using a Friedel-Crafts reaction, for example.

[0102] Furthermore, regarding the synthesis of a compound of formula (IX) or a derivative thereof, a compound of formula (III) or a derivative thereof can be synthesized using the various reactions described in the "Additional Reactions" section, for example, the following reaction. (Protection with Phthalic Anhydride and Synthesis of α-Haloacetylpyridine) The amino group can also be protected with phthalic anhydride before the main reaction, for example, by using Step A exemplified below. Furthermore, a compound having a halogen can be converted to an acetyl group by subjecting it to the reaction of Step B exemplified below. Furthermore, a compound having an acetyl group can be subjected to the reaction of Step C exemplified below to synthesize an α-haloacetylpyridine derivative. (In the formula, Halo is a halogen such as iodine, bromine, chlorine, or fluorine, and is preferably bromine.)

[0103] Step A: In this reaction, an amine derivative is reacted with phthalic anhydride to obtain a phthalimide derivative in which the amino group is protected. The reaction is carried out in a solvent or without a solvent in the presence of an acid. The solvent used varies depending on the starting materials and reagents, etc., and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Examples include ethanol, methanol, DMF, toluene, water, and dichloromethane. The acid used varies depending on the starting materials and solvent used, and is not particularly limited as long as it does not inhibit the reaction. Preferred examples include acetic acid and sulfuric acid. The reaction temperature is 80 to 170°C, and the reaction time is 1 to 24 hours, preferably 1 hour at 120°C. Step B: An acetyl derivative can be obtained by reacting a halogen derivative with tributyl(1-ethoxyvinyl)tin in the presence of a Pd reagent. The solvent to be used varies depending on the starting materials, reagents, etc., and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent, but preferred examples include toluene, benzene, dioxane, DMF, THF, ethyl acetate, acetonitrile, etc. The Pd reagent to be used varies depending on the starting materials, solvent to be used, etc., and is not particularly limited as long as it does not inhibit the reaction, but is preferably PdCl ２ (PPh ３ ) ２ , PdCl２ (dppf), Pd(PPh ３ ) ４ , Pd ２ (dba) ３ In a typical heating reaction, the reaction temperature is 70 to 110°C, and the reaction time is 0.5 to 48 hours, but preferably 5 minutes at 160°C using a microwave synthesizer. Step C: An α-haloacetylpyridine derivative can be obtained by reacting the acetyl derivative with bromine in the presence of an acid. The reaction is carried out in a solvent or without a solvent in the presence of an acid. The solvent used varies depending on the starting materials and reagents, etc., and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Preferred examples include chloroform, dichloromethane, diethyl ether, dioxane, methanol, ethanol, DMF, THF, and acetonitrile. The acid used varies depending on the starting materials and solvent used, and is not particularly limited as long as it does not inhibit the reaction. Preferred examples include acetic acid, hydrobromic acid, p-toluenesulfonic acid, hydrochloric acid, and sulfuric acid. The reaction temperature is 0 to 90°C, and the reaction time is 1 to 12 hours, but preferably 1 hour at 70°C.

[0104] The compound of formula (IV) as a starting material may be a commercially available product, but can also be obtained, for example, by reactions in which a carbonyl compound and a halide are synthesized in this order from a thioamide, as shown in the following reaction scheme. (In the formula, R １ ~R ５ is as defined in formula (I) above, and Halo is a halogen such as iodine, bromine, or chlorine, preferably bromine.

[0105] Step A: In this reaction, a thioamide of formula (II) having a substituent corresponding to the compound of formula (I) is dissolved in a solvent such as DME, acetone, toluene, hexane, xylene, acetonitrile, ethyl acetate, dioxane, THF, ethanol, methanol, dichloromethane, chloroform, dichloroethane, DMF, or water, and a haloacetic acid ester such as methyl bromoacetate, ethyl bromoacetate, or ethyl chloroacetate is added thereto to react, thereby obtaining the corresponding carbonyl compound of formula (X). The reaction temperature is typically 20 to 200°C, and the reaction time is 1 to 24 hours, preferably 80°C for 1 hour. Step B: In this reaction, the compound of formula (X) is dissolved in a solvent such as toluene together with carbon tetrabromide and triphenylphosphine, and the mixture is heated for a predetermined time to react, thereby proceeding with the Appel reaction to obtain the corresponding halide. The solvent used varies depending on the reagents, etc., and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent; however, preferred solvents include DME, acetone, toluene, hexane, xylene, acetonitrile, ethyl acetate, dioxane, THF, ethanol, methanol, dichloromethane, chloroform, dichloroethane, DMF, water, etc. As a reaction reagent, in addition to carbon tetrabromide, carbon tetrachloride, etc. can be used. The reaction temperature is usually 0 to 200°C, and the reaction time is 1 to 24 hours, but preferably 1 hour at 110°C.

[0106] The compound of formula (V) as a starting material may be a commercially available product, but can also be obtained, for example, by the reaction shown below. (In the formula, R １ ~R ５is as defined in formula (I) above, and Tf represents triflate. Step A: In this reaction, the compound represented by formula (X) is dissolved in a solvent such as dichloromethane together with N-phenylbis(trifluoromethanesulfonimide) and a base, and the resulting solution is reacted to obtain the corresponding triflate compound. Examples of the base used include pyridine, 4-dimethylaminopyridine, triethylamine, N,N-diisopropylethylamine, sodium carbonate, potassium carbonate, and tripotassium phosphate. The solvent used varies depending on the reagents and is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. However, preferred solvents include DME, acetone, toluene, hexane, xylene, acetonitrile, ethyl acetate, dioxane, THF, ethanol, methanol, dichloromethane, chloroform, dichloroethane, DMF, and water. The reaction temperature is typically −78° C. to 40° C., and the reaction time is 10 minutes to 24 hours, preferably 15 minutes at 0° C.

[0107] The starting compound of formula (VII) may be a commercially available product, but can also be obtained, for example, as shown in the following reaction scheme. (In the formula, R １ ~R ６ is as defined in formula (I) above, and R ’ and R ’ ’ represents a hydrogen atom, or R ’ and R ’ ’together with the two adjacent oxygen atoms to form an alkylenedioxy group) Step A: In this reaction, the compound represented by formula (V) is dissolved in a solvent such as DME, acetone, toluene, hexane, xylene, acetonitrile, ethyl acetate, dioxane, THF, ethanol, methanol, dichloromethane, chloroform, dichloroethane, DMF, or water, and a diborane compound such as 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) or 4,4,4',4',5,5,5',5'-octaethyl-2,2'-bi(1,3,2-dioxaborolane) is added thereto. is reacted with a palladium catalyst such as palladium acetate, palladium chloride, or tris(dibenzylideneacetone)dipalladium(0), and a bidentate ligand such as 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl, 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, or 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene. The reaction temperature is usually 0°C to 150°C, and the reaction time is 10 minutes to 24 hours, preferably 18 hours at room temperature.

[0108] 3. Thiazolyl-pyrazolo[1,5-a]pyridine Derivatives Thiazolyl-pyrazolo[1,5-a]pyridine derivatives may take the form of a hydrate, solvate, a pharmaceutically acceptable salt (acid addition salt or base addition salt), a prodrug, etc. Thiazolyl-pyrazolo[1,5-a]pyridine or its derivatives include various isomers.

[0109] The term "pharmaceutically acceptable salt" refers to a salt that is pharmaceutically acceptable and capable of exhibiting the desired pharmacological activity of the parent compound. When the compound according to the present invention is obtained as a free form, it can be converted into a salt according to a conventional method. Conversely, when the compound according to the present invention is obtained as a salt, it can be converted into a free form according to a conventional method.

[0110] Pharmaceutically acceptable salts are well known in the art and are described, for example, in S. M. Berge et al., J. Pharmaceutical Sciences, 1977, 66, 1-19, and Remington's Pharmaceutical Sciences, 17 ｔｈ ed., Mack Publishing Company, Easton, PA, 1985, the contents of which are incorporated herein by reference, describe pharmaceutically acceptable salts in detail.

[0111] Examples of pharmaceutically acceptable acid addition salts include those with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid; as well as those with acetic acid, trifluoroacetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, malic acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, 3-(4-hydroxybenzoyl)benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxybenzoylbenzoic acid, and the like. Included are salts formed by the addition of organic acids such as ethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, glucoheptonic acid, 4,4'-methylenebis-(3-hydroxy-2-ene-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, stearic acid, muconic acid, and salicylic acid.

[0112] Examples of pharmaceutically acceptable base addition salts include those in which an acidic proton present in the parent compound is replaced by a metal ion, such as, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, or aluminum salts. Also included are salts derived from organic bases, such as, for example, primary, secondary, and tertiary amines, substituted amines, and cyclic amines. Examples of organic bases include, for example, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, tromethamine, N-methylglucamine, polyamine resins, and the like. Representative organic bases include, for example, isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, caffeine, and the like.

[0113] Examples of solvates include hydrates as well as organic solvent solvates such as dimethyl sulfoxide solvate, dimethylformamide solvate, or alcohol solvates such as ethanol solvate, methanol solvate, or n-propyl alcohol solvate.

[0114] The present compound or its pharmaceutically acceptable salt or solvate (including hydrate) can exist in an amorphous form. It is generally known that many organic compounds and their salts exist in various crystalline polymorphs, and various crystalline forms can be produced by various methods well known in the art. Specifically, various crystalline forms, including amorphous forms, can be produced by, for example, melting methods, extruders, etc. Furthermore, amorphous forms can also be provided in the form of solid dispersions containing excipients, etc. (However, even for the compounds, raw materials, reagents, etc. mentioned so far, the following measures and countermeasures are essential. First, great care must be taken when using compounds that increase the risk of nitrosamine contamination in pharmaceuticals. Furthermore, in accordance with the Elemental Impurities Guidelines, meticulous attention must be paid to avoid the risk of contamination with various heavy metals. Even for elemental impurities other than Class 1, 2A, 2B, and 3, zinc and manganese are known to worsen the symptoms of patients with liver dysfunction, and aluminum is known to worsen the symptoms of patients with renal dysfunction, so sufficient attention must be paid to quality control. Furthermore, in accordance with the Residual Solvents Guidelines, attention must be paid to residual solvents, particularly solvates, such as Class 2 dimethylformamide and methanol, and Class 3 dimethyl sulfoxide and ethanol.)

[0115] The above-mentioned thiazolyl-pyrazolo[1,5-a]pyridine derivatives or pharmaceutically acceptable salts, solvates, hydrates, etc. thereof may be in the form of prodrugs. As used herein, the term "prodrug" refers to a compound that is converted into the present compound (compound of formula (I)) by a reaction such as oxidation, reduction, or hydrolysis mediated by an enzyme or the like under physiological conditions in a living body. Examples of prodrugs include: (1) compounds in which the amino of the present compound is acylated, alkylated, or phosphorylated (for example, compounds in which the amino of compound (I) is eicosanoylated, alanylated, pentylaminocarbonylated, (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxycarbonylated, tetrahydrofuranylated, pyrrolidylmethylated, pivaloyloxymethylated, tert-butylated, ethoxycarbonylated, tert-butoxycarbonylated, acetylated, or cyclopropylcarbonylated); (2) compounds in which the hydroxy of the present compound is acylated, alkylated, phosphorylated, or borated (for example, compounds in which the hydroxy of compound (I) is acetylated, palmitoylated, propanoylated, pivaloylated, succinylated, fumarylated, alanylated, or dimethylaminomethylcarbonylated); (3) Compounds in which the carboxy of the present compound is esterified or amidated (for example, compounds in which the carboxy of compound (I) is ethyl esterified, phenyl esterified, carboxymethyl esterified, dimethylaminomethyl esterified, pivaloyloxymethyl esterified, ethoxycarbonyloxyethyl esterified, phthalidyl esterified, (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl esterified, cyclohexyloxycarbonylethyl esterified, or methylamidized); these compounds can be produced from the present compound by known methods.Prodrugs are described in detail, for example, in T. Higuchi and V. Stella, "Pro-drugs as Novel Delivery Systems", Vol. 14 of the A.C.S. Symposium Series, Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987, and in "Drug Development," Vol. 7, Molecular Design, pp. 163 to 198, Hirokawa Shoten, 1990, the contents of which are incorporated herein by reference.

[0116] Thiazolyl-pyrazolo[1,5-a]pyridine or a derivative thereof can take various isomeric forms, such as geometric isomers, optical isomers, rotational isomers, stereoisomers, tautomers, etc. These isomers can be purified and isolated by conventional separation means, such as recrystallization, the diastereomeric salt method, enzymatic resolution, and various types of chromatography (e.g., thin-layer chromatography, column chromatography, gas chromatography, etc.).

[0117] 4. Pharmaceutical Uses of Thiazolyl-pyrazolo[1,5-a]pyridine and Its Derivatives As demonstrated in the Examples below, the compound of formula (I) can inhibit myosin light chain kinase 4 (MYLK4) activity. Therefore, the compound of formula (I) or a pharmaceutically acceptable derivative thereof, or a pharmaceutical composition containing the same, can be used to inhibit MYLK4 activity in a biological sample or in a living body. Furthermore, the compound of formula (I) or a pharmaceutically acceptable derivative thereof, or a pharmaceutical composition containing the same, can be used to prevent, alleviate, or treat diseases, disorders, or symptoms associated with MYLK4 through its inhibitory effect on MYLK4 activity.

[0118] Diseases, disorders, or symptoms that MYLK4 may be involved in include, for example, arteriosclerosis, inflammatory bowel disease, osteosarcoma, ischemic heart disease, glaucoma, ocular hypertension, aqueous humor outflow disorder, dry eye, uveitis, age-related macular degeneration, or diabetic retinopathy.Therefore, the compound of formula (I) or its pharmaceutically acceptable derivative, or a pharmaceutical composition containing them, can be used to prevent, alleviate, and / or treat these diseases, disorders, or symptoms.Among them, it is effective in preventing, alleviating, and / or treating arteriosclerosis, inflammatory bowel disease, osteosarcoma, ischemic heart disease, glaucoma, ocular hypertension, aqueous humor outflow disorder, dry eye, uveitis, age-related macular degeneration, or diabetic retinopathy, particularly glaucoma, ocular hypertension, or aqueous humor outflow disorder, and is particularly effective when used to reduce intraocular pressure in a subject.

[0119] 5. Pharmaceutical Compositions (Formulations) Pharmaceutical compositions can be prepared by blending an effective amount of the compound of formula (I) or a pharmaceutically acceptable derivative thereof with, as needed, pharmaceutically acceptable carriers and other adjuvants. This does not exclude the use of the compound of formula (I) or a derivative thereof in its original form as a medicine.

[0120] The pharmaceutical composition can be administered orally or parenterally. Oral dosage forms include, for example, tablets, fine granules, coated tablets, powders, granules, pills, capsules (e.g., hard gelatin capsules, soft gelatin capsules), microcapsules, and syrups. Parenteral dosage forms include, for example, injections (including lyophilized injections that are dissolved before use), eye drops, lotions, aerosols, ointments, patches, and suppositories. It can also be prepared as a liposome. Furthermore, the compound of formula (I) or a pharmaceutically acceptable derivative thereof can be pre-dispersed in a pharmaceutically acceptable solvent to form a liquid, such as a syrup for oral administration, an injection for parenteral administration (including lyophilized injections that are dissolved before use), or eye drops.

[0121] The pharmaceutical compositions may also be administered as, for example, a solution, suspension, emulsion, microemulsion, multiple emulsion, foam, salve, paste, plaster, ointment, coated tablet, rinse, rectal capsule, drop, gel, spray, powder, aerosol, inhalant, eye drops, eye ointment, eye rinse, infusion, or implant.

[0122] As such, the pharmaceutical composition can be in various dosage forms, and can be prepared by blending various carriers (excipients) and, if necessary, various adjuvants, depending on the dosage form, administration method, etc. Examples of adjuvants include colorants, sweeteners, flavoring agents, binders, adsorbents, lubricants, disintegrants, softeners, suspending agents, emulsifiers, preservatives, antioxidants, surfactants, stabilizers, pH adjusters, dispersants, isotonic agents, wetting agents, solubilizers, solubilizers, and / or absorption enhancers.

[0123] In the case of a solid dosage form, examples of the carrier (excipient) include crystalline cellulose, sugars (glucose, sucrose, lactose, D-mannitol, D-sorbitol, etc.), starches (corn starch, potato starch, wheat starch, rice starch, etc.), magnesium silicate, sodium hydrogen phosphate, calcium hydrogen phosphate, sodium citrate, talc, etc.

[0124] Examples of disintegrants include sodium carbonate, calcium carbonate, gum arabic, starches (corn starch, potato starch, wheat starch, tapioca starch, rice starch, etc.), agar, alginic acid, silicate complex, tragacanth, crystalline cellulose, low-substituted hydroxypropyl cellulose, croscarmellose sodium, carmellose calcium, carmellose sodium, carboxymethyl starch sodium, etc.

[0125] Binders include, for example, cellulose derivatives, starch, alginates, gelatin, polyvinylpyrrolidone, sucrose, and gum acacia. Wetting agents include, for example, glycerol, cetyl alcohol, glycerol monostearate, magnesium stearate, talc, calcium stearate, solid polyethylene glycol, and sodium lauryl sulfate. Absorption enhancers include, for example, quaternary ammonium compounds. Adsorbents include, for example, kaolin and bentonite. Lubricants include, for example, carnauba wax, hydrogenated oil, magnesium stearate, calcium stearate, sodium hydrogen phosphate, calcium hydrogen phosphate, and white beeswax. Preservatives include, for example, parabens, chlorobutanol, phenol, sorbic acid, and benzalkonium chloride.

[0126] Pharmaceutical compositions in liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs. Pharmaceutical compositions in these dosage forms are generally prepared by dissolving or dispersing the ingredients in a carrier such as a solubilizer or emulsifier, such as distilled water, saline, aqueous dextrose, glycerol, ethanol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, or dimethylformamide; an oil, such as cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil, sesame oil, glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols, or a fatty acid ester oil of sorbitan; or a mixture of these substances, to form a solution or suspension. Liquid pharmaceutical compositions may contain suspending agents, solubilizers, or solubilizers, as needed. Examples of suspending agents include ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, and tragacanth. Examples of solubilizing agents include ethanol, dilute hydrochloric acid, sodium hydroxide, sodium bicarbonate, olive oil, squalene, squalane, physiological saline, water for injection, rapeseed oil, glucose, propylene glycol, polysorbate, and macrogol. Examples of solubilizing agents include L-arginine, α-cyclodextrin, β-cyclodextrin, D-sorbitol, soybean oil, urea, sucrose, hydroxypropyl cellulose, hypromellose, povidone, and D-mannitol.

[0127] Pharmaceutical compositions suitable for injection may be in the form of physiologically acceptable aqueous or nonaqueous sterile solutions, dispersions, suspensions, or emulsions, or sterile powders to be reconstituted into sterile injectable solutions and / or dispersions immediately before use. Representative examples of suitable aqueous or nonaqueous carriers, diluents, solvents, or vehicles include, for example, distilled water, ethanol, polyols (propylene glycol, polyethylene glycol, glycerol, etc.), suitable mixtures thereof, vegetable oils (e.g., olive oil), or injectable organic esters such as ethyl oleate. These aqueous or nonaqueous carriers, diluents, solvents, or vehicles may further contain appropriate salts, pH adjusters, etc., such as physiological saline. Suspending agents, solubilizers, or solubilizers may also be included as needed. Agents for delaying absorption of injectable drugs, such as aluminum monostearate and gelatin, may also be used. When preparing injections or eye drops, pH adjusters, buffers, stabilizers, preservatives, etc., may be added as needed, and the resulting preparations may be administered subcutaneously, intramuscularly, or intravenously by conventional methods. Injections and eye drops may be prepared as a solution by storing the solution in a container and then freeze-drying the solution to form a solid preparation that can be prepared just before use. A single dose may be stored in a container, or multiple doses may be stored in the same container.

[0128] Pharmaceutical compositions suitable for rectal administration are usually prepared as suppositories using non-irritating excipients that are solid at room temperature but melt at body temperature to release the active ingredient in the appropriate body cavity, such as cocoa butter, polyethylene glycol, or certain waxes.

[0129] The pharmaceutical composition of dosage form for topical application includes ointment, powder, spray and inhalant.In such dosage forms, the compounding ingredients are usually mixed with pharmaceutically acceptable carriers and, if necessary, any preservatives, buffers or propellants under sterile conditions to prepare the pharmaceutical composition.Ophthalmic preparations, ointments, powders and solutions are one of the typical examples of topical application, and those skilled in the art will know the suitable carriers (excipients) and adjuvants.

[0130] Methods for preparing pharmaceutical compositions suitable for each dosage form are known in the art and are described, for example, in Remington's Pharmaceutical Sciences, 18 ｔｈ ed., Mack Publishing Company, Easton, PA, 1990, which is incorporated herein by reference.

[0131] When the present compound or its derivative or pharmaceutical composition is administered to a mammal (e.g., mouse, rat, hamster, rabbit, cat, dog, cow, sheep, monkey, or human), particularly to a human, any dosage form suitable for the desired delivery route may be used, and the administration may be, for example, oral, transdermal, intradermal, intrabronchial, intranasal, intraarterial, intravenous, intramuscular, subcutaneous, intraperitoneal, vaginal, rectal, sublingual, intracranial, epidural, intratracheal, intraocular, or other local site.

[0132] The compounds of the present invention can be produced, for example, by the methods described in the following examples, and the effects of the compounds can be confirmed by the methods described in the following examples. However, these are merely illustrative examples, and the present invention is not limited to the following specific examples in any case, and may be modified within the scope of the present invention.

[0133] Unless otherwise specified, the term "silica gel" in "silica gel column chromatography" described in the examples refers to Wakogel C-200 (particle size 75 to 150 μm) manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., or Cartridge (Universal Column Premium, particle size 30 μm) manufactured by Yamazen Corporation.

[0134] Unless otherwise specified, the term "TLC" in "preparative TLC" used in the present examples refers to TLC glass plate silica gel 60F254 (0.5 mm, 1 mm, 2 mm) manufactured by Merck.

[0135] "Under reduced pressure" refers to a state in which the pressure is reduced to about 1 to 50 mmHg using a vacuum pump or the like.

[0136] "Room temperature" refers to a range of about 10° C. to 30° C. Percentages are by weight unless otherwise specified.

[0137] [1] Synthesis of Compounds [Example 1] Synthesis of 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 3) Compound (3) was synthesized by reacting a thioamide with a substituted α-bromoacetophenone.

[0138] Pyrazolo[1,5-a]pyridine-3-carbothioamide (178 mg, 1.00 mmol) was dissolved in DME (10 mL), and 3-hydroxyphenacyl bromide (228 mg, 1.06 mmol) was added under ice cooling, followed by stirring at room temperature for 16 hours. The reaction mixture was heated and stirred at 50°C for 1 hour, then allowed to cool, and the solvent was evaporated under reduced pressure. Ethanol (10 mL) was added to the residue, followed by excess potassium carbonate (327 mg), and the reaction mixture was heated to reflux at 70°C for 1 hour. After allowing to cool, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography. The title compound (3) (194 mg, 0.661 mmol, yield 66.1%) was obtained from the n-hexane:ethyl acetate (1:4) fraction. 1 H-NMR(CDCl3) δ: 4.93 (1H, brs), 6.83 (1H, d, J=7.8Hz), 6.93 (1H, t, J=6.9Hz), 7.32 (1H, t, J=8.2Hz), 7.36 (1H, s), 7.39 (1H, dd, J=7.1Hz, J=8.5Hz), 7.55 (2H, m), 8.39 (1H, s), 8.46 (1H, d, J=8.7Hz), 8.52 (1H, d, J=6.9Hz).

[0139] [Examples 2 to 26] Synthesis of the following compounds: 4-phenyl-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 71), 2-methoxy-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 79), 4-(3-fluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 112), 4-(2-fluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 122), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzene-1,3-diol (Compound 120), 4-(2,4-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 121), 4-(3-Methoxyphenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 83), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(o-tolyl)thiazole (Compound 132), 1-methyl-6-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-3,4-dihydroquinolin-2(1H)-one (Compound 131), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 12), 4-(4-methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 7), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-3-yl)thiazole (Compound 15), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-4-yl)thiazole (Compound 92), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-2-yl)thiazole (Compound 93), 4-(2-chloropyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 94), 4-(2-methoxypyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 95), 4-(6-methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 96), 4-(5-methylpyridin-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 97), 6-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-[1,3]dioxolo[4,5-b]pyridine (Compound 98), 4-(2-methylpyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 99), 4-(2-fluoropyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 100), 4-(2-bromopyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 101), 4-(5-chloropyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 125), 4-(4-chloropyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 135), and 2'-bromo-2-(pyrazolo[1,5-a]pyridin-3-yl)-4,5'-bithiazole (Compound 37). In accordance with the synthesis method of compound (3), using a substituted α-bromoacetophenone corresponding to the final compound, compound (71), compound (79), compound (112), compound (122), compound (120), compound (121), compound (83), compound (132), compound (131), compound (12), compound (7), compound (15), compound (92), compound (93), compound (94), compound (95), compound (96), compound (97), compound (98), compound (99), compound (100), compound (101), compound (125), compound (135), and compound (37) were synthesized.

[0140] 1 H-NMR(CDCl3) δ: 6.92 (1H, dt, J=1.4Hz, 6.9Hz), 7.37 (3H, m), 7.46 (2H, t, J=7.8Hz), 8.01 (2H, d, J=6.9Hz), 8.40 (1H, s), 8.48 (1H, d, J=8.7Hz), 8.52 (1H, d, J=6.9Hz).

[0141] 1 H-NMR(CDCl3) δ:3.78 (3H, s), 6.97 (1H, t, J=8.7Hz), 7.09 (1H, dt, J=1.4Hz, 6.9Hz), 7.44 (1H, dd, J=2.3Hz, 8.2Hz), 7.50 (1H, d, J=2.3Hz), 7.54 (1H, ddd, J=0.9Hz, 6.9Hz, 8.7Hz), 7.73 (1H, s), 8.38 (1H, d, J=8.7Hz), 8.56 (1H, d), 8.81 (1H, d, J=6.9Hz), 9.09 (1H, brs).

[0142] 1 H-NMR(CDCl3) δ:6.94 (1H, dt, J=0.9Hz, 6.9Hz), 7.05 (1H, dt, J=2.3Hz, 8.2Hz), 7.41 (3H, m), 7.76 (2H, m), 8.39 (1H, s), 8.46 (1H, d, J=8.7Hz), 8.52 (1H, d, J=6.9Hz).

[0143] 1 H-NMR(CDCl3) δ:6.93 (1H, dt, J=1.4Hz, 6.9Hz), 7.17 (1H, m), 7.31 (2H, m), 7.40 (1H, ddd, J=0.9Hz, 6.4Hz, 9.2Hz), 7.67 (1H, d, J=2.3Hz), 8.38 (1H, dt, J=2.8Hz, 7.8Hz), 8.41 (1H, s), 8.45 (1H, d, J=8.7Hz), 8.53 (1H, d, J=6.9Hz).

[0144] 1H-NMR(CDCl3) δ:4.85 (1H, s), 6.44 (1H, dd, J=2.8Hz, 8.2Hz), 6.51 (1H, d, J=2.8Hz), 6.96 (1H, t, J=7.3Hz), 7.12 (1H, s), 7.43 (1H, t, J=6.9Hz), 7.54 (1H, d, J=8.7Hz), 8.13 (1H, d, J=9.2Hz), 8.40 (1H, s), 8.55 (1H, d, J=6.9Hz), 12.18(1H, s).

[0145] 1 H-NMR(CDCl3) δ:6.93 (2H, m), 7.02 (1H, dt, J=1.8Hz, 7.8Hz), 7.41 (1H, ddd, J=1.4Hz, 6.9Hz, 8.7Hz), 7.60 (1H, d, J=2.3Hz), 8.38 (3H, m), 8.53 (1H, d, J=6.9Hz).

[0146] 1 H-NMR(CDCl3) δ:3.90 (3H, s), 6.92 (2H, m), 7.37 (3H, m), 7.58 (2H, m), 8.40 (1H, s), 8.46 (1H, d, J=9.2Hz), 8.52 (1H, d, J=6.9Hz).

[0147] 1 H-NMR(CDCl3) δ:2.55 (3H, s), 6.90 (1H, dt, J=1.4Hz, 6.9Hz), 7.15 (1H, s), 7.29 (3H, m), 7.34 (1H, dd, J=6.0Hz, 6.2Hz), 7.69 (1H, t, J=4.1Hz), 8.39 (2H, m), 8.51 (1H, d, J=7.3Hz).

[0148] 1H-NMR(CDCl3) δ:2.71 (2H, t, J=6.9Hz), 3.01 (2H, t, J=7.8Hz), 3.40 (3H, s), 6.93 (1H, dt, J=1.4Hz, 6.9Hz), 7.06 (1H, d, J=8.3Hz), 7.31 (1H, s), 7.39 (1H, ddd, J=0.9Hz, 6.9Hz, 9.2Hz), 7.82 (1H, m), 7.89 (1H, dd, J=1.8Hz, 8.7Hz), 8.41 (1H, s), 8.43 (1H, d, J=9.2Hz), 8.53 (1H, d, J=7.3Hz).

[0149] 1 H-NMR(CDCl3) δ:2.05 (3H, s), 4.49 (2H, d, J=6.0Hz), 5.74 (1H, brs), 6.93 (1H, dt, J=1.4Hz, 6.9Hz), 7.36-7.41 (4H, m), 7.98 (2H, d, J=8.2Hz), 8.39 (1H, s), 8.45 (1H, d, J=8.7Hz), 8.52 (1H, d, J=7.3Hz).

[0150] 1 H-NMR(CDCl3) δ:3.97 (3H, s), 6.79 (1H, dd, J=2.3Hz, 5.5Hz), 6.93 (1H, dt, J=1.4Hz, 6.9Hz), 7.39 (1H, ddd, J=0.9Hz, 6.9Hz, 8.7Hz), 7.83 (1H, d, J=2.3Hz), 7.98 (1H, s), 8.41 (2H, m), 8.46 (1H, d, J=5.5Hz), 8.53 (1H, d, J=7.3Hz).

[0151] 1H-NMR(CDCl3) δ:6.94 (1H, dt, J=1.4Hz, 6.9Hz), 7.40 (2H, m), 7.45 (1H, s), 8.28 (1H, dt, J=2.3Hz, 8.2Hz), 8.39 (1H, s), 8.46 (1H, d, J=8.7Hz), 8.52 (1H, d, J=6.0Hz), 8.59 (1H, dd, J=1.4Hz, 5.0Hz), 9.25 (1H, d, J=2.3Hz).

[0152] 1 H-NMR(CDCl3) δ:6.96 (1H, ddd, J=1.2Hz, 6.8Hz, 6.8Hz), 7.40-7.47 (1H, m), 7.61 (1H, s), 7.84-7.92 (2H, m), 8.41 (1H, s), 8.46 (1H, d, J=8.8Hz), 8.55 (1H, d, J=6.8Hz), 8.68-8.73 (2H, m).

[0153] 1 H-NMR(CDCl3) δ:6.94 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 7.22-7.30 (1H, m), 7.37-7.44 (1H, m), 7.83 (1H, ddd, J=1.3Hz, 7.8Hz, 7.8Hz), 8.00 (1H, s), 8.26-8.32 (1H, m), 8.43 (1H, s), 8.44-8.49 (1H, m), 8.52-8.57 (1H, m), 8.63-8.67 (1H, m).

[0154] 1 H-NMR(CDCl3) δ:6.98 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 7.43-7.50 (1H, m), 7.64 (1H, s), 7.79 (1H, dd, J=1.4Hz, 5.0Hz), 7.95 (1H, s), 8.40-8.46 (2H, m), 8.47 (1H, d, J=5.2Hz), 8.56 (1H, d, J=7.2Hz).

[0155] 1 H-NMR(CDCl3) δ:4.02 (3H, s), 6.96 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 7.38-7.47 (3H, s), 7.56 (1H, s), 8.25 (1H, d, J=5.6Hz), 8.40 (1H, s), 8.46-8.50 (1H, m), 8.52-8.56 (1H, m).

[0156] 1 H-NMR(CDCl3) δ:4.04 (3H, s), 6.74 (1H, dd, J=0.8Hz, 2.4Hz), 6.91-6.97 (1H, m), 7.36-7.44 (1H, m), 7.68-7.74 (1H, m), 7.87 (1H, dd, J=0.8Hz, 7.2Hz), 7.97 (1H, s), 8.42 (1H, s), 8.45-8.50 (1H, m), 8.51-8.56 (1H, m).

[0157] 1 H-NMR(CDCl3) δ:2.45 (3H, s), 6.96 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 7.39-7.45 (1H, m), 7.46 (1H, s), 8.11 (1H, s), 8.38-8.49 (3H, m), 8.53-8.57 (1H, m), 9.07 (1H, d, J=2.0Hz).

[0158] 1 H-NMR(CDCl3) δ:6.14 (2H, s), 6.94 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 7.28 (1H, s), 7.37-7.44 (1H, m), 7.64 (1H, d, J=2.0Hz), 8.34 (1H, d, J=2.0 Hz), 8.39 (1H, s), 8.42-8.46 (1H, m), 8.51-8.56 (1H, m).

[0159] 1 H-NMR(CDCl3) δ:2.66 (3H, s), 6.96 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 7.40-7.47 (1H, m), 7.58 (1H, s), 7.66-7.71 (1H, m), 7.76 (1H, s), 8.41 (1H, s), 8.43-8.47 (1H, m), 8.52-8.56 (1H, m), 8.58 (1H, d, J=5.6Hz).

[0160] 1 H-NMR(CDCl3) δ:6.94-7.02 (1H, m), 7.41-7.49 (1H, m), 7.57 (1H, s), 7.64 (1H, s), 7.71-7.78 (1H, m), 8.29 (1H, d, J=5.2Hz), 8.41 (1H, s), 8.45 (1H, d, J=9.2Hz), 8.55 (1H, d, J=6.8 Hz).

[0161] 1 H-NMR(CDCl3) δ:6.98 (1H, ddd, J=1.2Hz, 6.8Hz, 6.8Hz), 7.42-7.50 (1H, m), 7.64 (1H, s), 7.79 (1H, dd, J=1.8Hz, 5.4Hz), 7.95 (1H, s), 8.42 (1H, s), 8.42-8.46 (1H, m), 8.47 (1H, d, J=4.8Hz), 8.54-8.58 (1H, m).

[0162] 1 H-NMR(CDCl3) δ:6.92-6.99 (1H, m), 7.38-7.46 (1H, m), 7.79 (1H, dd, J=2.4Hz, 8.4Hz), 7.98 (1H, s), 8.24 (1H, d, J=8.4Hz), 8.30-8.45, (2H, m), 8.53-8.57 (1H, m), 8.59 (1H, d, J=3.2Hz).

[0163] 1 H-NMR(CDCl3) δ: 6.96 (1H, ddd, J=1.1Hz, 6.8Hz, 7.0Hz), 7.23-7.29 (1H, m), 7.41-7.48 (1H, m), 8.02 (1H, s), 8.28 (1H, d, J=2.0Hz), 8.40-8.46 (2H, m), 8.51-8.57 (2H, m).

[0164] 1 H-NMR(CDCl3) δ: 6.95 (1H, t, J=6.9Hz), 7.28 (1H, s), 7.42 (1H, dd, J=0.9Hz, 7.8Hz), 7.93 (1H, s), 8.36 (2H, m), 8.53 (1H, d, J= 6.9Hz).

[0165] Example 27: Synthesis of 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline hydrochloride (Compound 1)

[0166] (1) Synthesis of 4-(4-nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 1-1) Pyrazolo[1,5-a]pyridine-3-carbothioamide (887 mg, 5.00 mmol) was dissolved in DME (50 mL), and 4-nitrophenacyl bromide (1.24 g, 5.53 mmol) was added under ice cooling, followed by stirring at room temperature for 16 hours. The reaction solution was heated and stirred at 50°C for 1 hour, then allowed to cool, and the solvent was distilled off under reduced pressure. Ethanol (40 mL) was added thereto, followed by excess potassium carbonate (1.18 g), and the reaction solution was heated to reflux at 70°C for 1 hour. After allowing the reaction mixture to cool, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (1-1) (1.50 g, 4.64 mmol, yield 92.8%) from the n-hexane:ethyl acetate (1:1) fraction. 1H-NMR(CDCl3) δ: 6.96 (1H, dt, J=1.4Hz, 6.9Hz), 7.44 (1H, ddd, J=0.9Hz, 6.9Hz, 8.7Hz), 7.58 (1H, s) ,8.18 (2H, d, J=9.2Hz), 8.32 (2H, d, J=9.2Hz), 8.41 (1H, s), 8.44 (1H, d, J=9.2Hz), 8.54 (1H, d, J=6.9Hz).

[0167] (2) Synthesis of tert-butyl (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)carbamate (Compound 1-2) 4-(4-nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 1-1) (2.62 g, 8.12 mmol) was dissolved in acetonitrile (600 mL), and zinc powder (19.1 g), calcium chloride (3.28 g), and water (8 mL) were added. The reaction solution was heated to reflux at 90° C. for 1 hour, allowed to cool, and then insoluble matter was filtered through Celite. The filtrate was concentrated under reduced pressure to approximately 50 mL. Excess dibutoxycarbonyl anhydride solution (8 mL) was added under ice-cooling, and the mixture was stirred at room temperature for 16 hours. The solvent was distilled off from the reaction mixture under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (1-2) (1.31 g, 3.37 mmol, yield 41.1%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(CDCl3) δ: 1.53 (9H, s), 6.57 (1H, brs), 6.91 (1H, dd, J=1.4Hz, 6.9Hz), 7.27 (1H, s), 7.37 (1H, dd, J=0.9Hz, 6.9Hz, 8.7Hz), 7.45 (2H, d, J=8.7Hz), 7.93 (2H, d, J=8.7Hz), 8.38 (1H, s), 8.47 (1H, d, J=9.2Hz), 8.51 (1H, d, J=6.9Hz).

[0168] (3) Synthesis of 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline hydrochloride (Compound 1) Under ice-cooling, tert-butyl(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)carbamate (Compound 1-2) (1.12 g, 2.84 mmol) was slowly added to a 4N hydrochloric acid dioxane solution (15 mL), and the mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure. Next, a solvent was added, and the resulting solid was collected by filtration, thoroughly washed with the solvent, and dried to obtain the title compound (1) (1.04 g, 2.84 mmol, yield 99.8%). 1 H-NMR(D2O) δ: 6.91 (1H, t, J=7.0Hz), 7.27 (2H, d, J=8.4Hz), 7.36 (1H, t, J=7.8Hz), 7.47 (1H, brs), 7.62 (2H, d, J=8.4Hz), 7.77 (1H, d, J=8.9Hz), 8.26 (1H, s), 8.30 (1H, d, J=7.0Hz).

[0169] Examples 28-32 Synthesis of the following compounds: 4-(3-nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 4), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline hydrochloride (Compound 10), 4-(2-nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 133), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline hydrochloride (Compound 134), and 2-methoxy-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline (Compound 90). Compounds (4), (10), (133), (134), and (90) were synthesized according to the synthesis method of compound (1), using substituted α-bromoacetophenones corresponding to the target compounds.

[0170] 1H-NMR(CDCl3) δ:6.96 (1H, t, J=6.9Hz), 7.44 (1H, dd, J=7.5Hz, 8.2Hz), 7.53 (1H, s), 7.63 (1H, t, J=7.8Hz), 8.20 (1H, dt, J=0.9Hz, 7.8Hz), 8.34 (1H, dd, J=0.9Hz, 7.8Hz), 8.42 (1H,s), 8.45 (1H, dt, J=0.9Hz, 8.7Hz), 8.54 (1H, dt, J=1.4Hz, 6.9Hz), 8.84 (1H, t, J=1.8Hz).

[0171] 1 H-NMR(D2O) δ:6.32 (1H, t, J=6.0Hz), 6.75 (3H, m), 6.91 (4H, m), 7.53 (1H, s), 7.56 (1H, d, J=6.9Hz).

[0172] 1 H-NMR(CDCl3) δ:6.92 (1H, m), 7.38 (2H, t, m), 7.50 (1H, t, J=6.0Hz), 7.62 (1H, t, J=6.9Hz), 7.79 (2H, m), 8.33 (1H, s), 8.39 (1H, d, J=9.2Hz), 8.50 (1H, d, J=6.4Hz).

[0173] 1 H-NMR(D2O) δ:6.56 (1H, t, J=6.9Hz), 7.02 (2H, m), 7.12 (2H, d, J=6.9Hz), 7.16 (1H, s), 7.20 (2H, t, J=9.2Hz), 7.88 (1H, d, J=6.9Hz), 7.90 (1H, s).

[0174] 1H-NMR(CDCl3) δ: 3.67 (3H, s), 6.80 (1H, d, J=7.8Hz), 6.91 (1H, dd, J=1.4Hz, 6.9Hz), 7.17 (1H, s), 7.36 (1H, dd, J=0.9Hz, 6.9Hz), 7.46 (2H, m) , 8.40 (1H, s), 8.42 (1H, d, J=8.7Hz), 8.51 (1H, d, J=6.9Hz).

[0175] [Example 33] Synthesis of 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 118)

[0176] (1) Synthesis of 2-bromo-1-(2-hydroxyphenyl)ethan-1-one (Compound 118-1) 1-(2-hydroxyphenyl)ethan-1-one (288 mg, 2.11 mmol) was added to ethyl acetate (50 mL), and CuBr ２ (929 mg, 4.32 mmol) was added, and the mixture was heated to reflux for 16 hours. After allowing to cool, insoluble matter was filtered through Celite, the organic solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (118-1) (438 mg, 2.03 mmol, yield 79.8%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(CDCl3) δ: 4.44 (2H, s), 6.93 (1H, dt, J=1.4Hz, 8.2Hz), 7.02 (1H, dt, J=1.4Hz, 8.2Hz), 7.52 (1H, dt, J=2.1Hz, 7.3Hz), 7.74 (1H, dd, J=1.8Hz, 7.8Hz), 11.73 (1H, s).

[0177] (2) Synthesis of 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 118) Pyrazolo[1,5-a]pyridine-3-carbothioamide (186 mg, 1.05 mmol) was dissolved in DME (20 mL), and 2-bromo-1-(2-hydroxyphenyl)ethan-1-one (Compound 118-1) (218 mg, 1.02 mmol) was added under ice-cooling, followed by stirring at room temperature for 16 hours. The reaction solution was heated and stirred at 50°C for 1 hour, then allowed to cool, and the solvent was distilled off under reduced pressure. Ethanol (50 mL) was added to the residue, followed by the addition of excess potassium carbonate (301 mg), and the reaction solution was heated to reflux at 70°C for 1 hour. After allowing the reaction mixture to cool, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (118) (214 mg, 0.729 mmol, yield 69.4%) from the n-hexane:ethyl acetate (1:4) fraction. 1 H-NMR(CDCl3) δ: 6.93 (2H, m), 7.05 (1H, dd, J=0.9Hz, 8.2Hz), 7.28 (1H, m), 7.43 (2H, m), 7.66 (1H, dd, J=1.8Hz, 7.8Hz), 8.16 (1H, d, J=9.2Hz), 8.42 (1H, s), 8.52 (1H, d, J=6.9Hz), 12.01 (1H, s).

[0178] Examples 34-38 Synthesis of the following compounds: 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzonitrile (Compound 115), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzonitrile (Compound 116), 4-(3,5-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 119), 4-(2,6-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 123), and 5-fluoro-2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 114). In accordance with the synthesis method of compound (118), a substituted α-bromoacetophenone was synthesized using a substituted acetophenone corresponding to the final compound, and this was reacted with a thioamide to synthesize compounds (115), (116), (119), (123), and (114).

[0179] 1 H-NMR(CDCl3) δ: 6.96 (1H, t, J=7.3Hz), 7.45 (2H, m), 7.56 (1H, t, J=7.8Hz), 7.63 (1H, d, J=7.8Hz), 8.20 (1H, m), 8.35 (1H, m), 8.40 (1H, s), 8.45 (1H, m), 8.54 (1H, m).

[0180] 1 H-NMR(CDCl3) δ: 6.94 (1H, dt, J=1.4Hz, 6.9Hz), 7.45 (2H, m), 7.69 (1H, dt, J=1.4Hz, 7.8Hz), 7.79 (1H, dd, J=1.4Hz, 7.8Hz), 7.84 (1H, s), 8.16 (1H, d, J= 7.3Hz), 8.40 (1H, s), 8.52 (1H, d, J=6.9Hz), 8.55 (1H, d, J=9.2Hz).

[0181] 11H-NMR (CDCl3) δ: 6.79 (1H, tt, J = 2.3 Hz, 9.2 Hz), 6.95 (1H, dt, J = 1.4 Hz, 6.9 Hz), 7.42 (2H, m), 7.54 (2H, d, J = 6.4 Hz), 8.39 (1H, s), 8.44 (1H, d, J = 9.2 Hz), 8.53 (1H, d, J = 6.9 Hz).

[0182] 1 1H-NMR (CDCl3) δ: 6.91 (1H, dt, J = 1.4 Hz, 6.9 Hz), 7.02 (2H, t, J = 8.2 Hz), 7.34 (2H, m), 7.46 (1H, t, J = 1.4 Hz), 8.39 (1H, s), 8.44 (1H, d, J = 9.2 Hz), 8.51 (1H, d, J = 6.9 Hz).

[0183] 1 1H-NMR (CDCl3) δ: 6.64 (1H, t, J = 2.8 Hz, 8.3 Hz), 6.75 (1H, dd, J = 2.3 Hz, 10.5 Hz), 6.97 (1H, dt, J = 0.9 Hz, 9.2 Hz), 7.33 (1H, s), 7.44 (1H, ddd, J = 0.9 Hz, 6.9 Hz, 9.2 Hz), 7.61 (1H, dd, J = 6.4 Hz, 8.7 Hz), 8.12 (1H, d, J = 8.7 Hz), 8.41 (1H, s), 8.56 (1H, d, J = 8.7 Hz), 12.32 (1H, s).

[0184] [Example 39] Synthesis of 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isonicotinamide (Compound 126)

[0185] (1) Synthesis of 2-(2-bromoacetyl)isonicotinamide hydrobromide (compound 126-1) 2-Acetylisonicotinonitrile (51.6 mg, 0.35 mmol) was dissolved in acetic acid (1 mL), and under ice-cooling, bromine (9 μL, 0.35 mmol) and hydrobromic acid (30% acetic acid solution, approximately 5.1 mol / L) (173 μL, 0.88 mmol) were added, and the reaction solution was heated and stirred at 70°C for 1 hour. After cooling, diethyl ether was added, and the precipitated solid was stirred at room temperature for a while, filtered with suction, washed with diethyl ether, and dried under reduced pressure to obtain the title compound (126-1) (95.6 mg, 0.30 mmol, yield 83.6%). 1 H-NMR(CD3OD) δ: 3.84 (1H, d, J=11.6Hz), 3.96 (1H, d, J=11.2Hz), 8.37-8.50 (1H, m), 8.59 (1H, d, J=1.6Hz), 8.92-8.99 (1H, m).

[0186] (2) Synthesis of 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isonicotinamide (Compound 126) Pyrazolo[1,5-a]pyridine-3-carbothioamide (30.0 mg, 0.17 mmol) was dissolved in DME (2 mL), and 2-(2-bromoacetyl)isonicotinamide hydrobromide (Compound 126-1) (82.4 mg, 0.17 mmol) was added under ice-cooling, followed by stirring at room temperature for 15 hours. The reaction solution was heated and stirred at 50°C for 1 hour, then allowed to cool, and the solvent was evaporated under reduced pressure. Ethanol (10 mL) and potassium carbonate (70.1 mg, 0.51 mmol) were added to the residue, and the mixture was heated to reflux at 80°C for 1 hour. After allowing to cool, the solvent was evaporated under reduced pressure, and dichloromethane and methanol were added to the residue. The suspended solid was filtered off with suction and dried under reduced pressure to obtain the title compound (126) (7.6 mg, 0.024 mmol, yield 14.0%). 1H-NMR(DMSO-d6) δ: 7.16 (1H, ddd, J=0.9Hz, 6.8Hz, 7.0Hz), 7.58-7.67 (1H, m), 7.73-7.78 (1H, m), 7.84 (1H, s), 8.27 (1H, s), 8.42-8.52 (2H, m), 8.56 (1H, s), 8.70 (1H, s), 8.78 (1H, d, J=4.4Hz), 8.88 (1H, d, J=6.8Hz).

[0187] [Examples 40 and 41] Synthesis of 4-(5-methoxypyridin-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 124) and 4-(5-methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 127) Compound (124) and compound (127) were synthesized according to the synthetic method of compound (126).

[0188] 1 H-NMR(CDCl3) δ: 3.98 (3H, s), 6.93-6.99 (1H, m), 7.39-7.45 (1H, m), 7.48 (1H, s), 7.83-7.86 (1H, m), 8.31 (1H, d, J=4.2Hz), 8.42 (1H, s), 8.43-8.48 (1H, m), 8.55 (1H, d, J=6.0Hz), 8.86 (1H, d, J=1.6Hz).

[0189] 1 H-NMR(CDCl3) δ: 3.92 (3H, s), 6.93 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 7.32 (1H, dd, J=3.2Hz, 8.8Hz), 7.36-7.42 (1H, m), 7.82 (1H, s), 8.22 (1H, d, J=8.4Hz), 8.35 (1H, d, J=2.0Hz), 8.40-8.47 (2H, m), 8.51-8.55 (1H, m).

[0190] [Example 42] Synthesis of 4-(1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 107)

[0191] (1) Synthesis of 2-bromo-1-(1H-pyrazol-4-yl)ethan-1-one (compound 107-1) Bromine-dioxane complex (1.25 g, 5.00 mmol) was added to 1-(1H-pyrazol-4-yl)ethan-1-one (0.55 g, 5.00 mmol) in dioxane (10 mL), and the mixture was stirred at room temperature for 56 hours. The precipitate was collected by suction filtration, washed with acetone, and then dried to obtain the title compound (107-1) (1.02 g, 5.00 mmol, yield 100%). 1 H-NMR(DMSO-d6) δ: 2.50 (2H, s), 8.22 (2H, s).

[0192] (2) Synthesis of 4-(1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 107) A solution of pyrazolo[1,5-a]pyridine-3-carbothioamide (5.40 g, 30.5 mmol) and 2-bromo-1-(1H-pyrazol-4-yl)ethan-1-one (Compound 107-1) (5.76 g, 30.5 mmol) in ethanol (200 mL) was stirred at 70°C for 3 hours. After cooling, the mixture was diluted with dichloromethane and water, and a saturated aqueous solution of sodium bicarbonate was added to adjust the pH to 9, followed by extraction with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and filtered, and the solvent was evaporated under reduced pressure. The residue was suspended in ethyl acetate, collected by filtration, and dried to obtain the title compound (107) (5.00 g, 18.7 mmol, yield 61.3%). 1 H-NMR(DMSO-d6) δ: 7.09-7.13 (1H, m), 7.52-7.56 (1H, m), 7.58 (1H, s), 8.14 (2H, s), 8.43-8.46 (1H, m), 8.59 (1H, s), 8.83-8.85 (1H, m).

[0193] [Examples 43 to 74] Synthesis of the following compounds: 4-(4-chloro-1-methyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 53), 4-(1,4-dimethyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrobromide (Compound 54), 4-(1-methyl-1H-pyrazol-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrobromide (Compound 106), 4-(1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 109), 5-methyl-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole hydrobromide (Compound 105), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrol-3-yl)thiazole (Compound 138), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrol-2-yl)thiazole (Compound 139), 4-(1H-imidazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 140), 4-(1H-imidazol-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 141), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,3-triazol-4-yl)thiazole (Compound 142), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,4-triazol-3-yl)thiazole (Compound 143), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(thiophen-3-yl)thiazole (Compound 144), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(thiophen-2-yl)thiazole (Compound 145), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isothiazole (Compound 146), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isothiazole (compound 147), 5-(2-(pyrazolo[1,2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isothiazole (Compound 148), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4,4'-bithiazole (Compound 149), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4,5'-bithiazole (Compound 150), 2'-(pyrazolo[1,5-a]pyridin-3-yl)-2,4'-bithiazole (Compound 151), 4-(furan-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 152), 4-(furan-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 153), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole (Compound 154), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole (Compound 155), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole (Compound 156), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)oxazole (Compound 157), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)oxazole (Compound 158), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)oxazole (Compound 159), 4-(1-methyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 160), 4-(1-methyl-1H-pyrrol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 161), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1,2,4-thiadiazole (Compound 162), 4-(1-methyl-1H-pyrrol-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 163), and 3-bromo-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole (Compound 164).

[0194] Compounds (53), (54), (106), (109), (105), (138), (139), (140), (141), (142), (143), (144), and (145) can be synthesized in accordance with the synthesis method of compound (107), using substituted α-haloketones corresponding to the final compounds instead of 2-bromo-1-(1H-pyrazol-4-yl)ethan-1-one. Compound (145), Compound (146), Compound (147), Compound (148), Compound (149), Compound (150), Compound (151), Compound (152), Compound (153), Compound (154), Compound (155), Compound (156), Compound (157), Compound (158), Compound (159), Compound (160), Compound (161), Compound (162), Compound (163), and Compound (164) were synthesized.

[0195] 1 H-NMR(DMSO-d6) δ: 3.91 (3H, s), 7.09-7.13 (1H, m), 7.55-7.59 (1H, m), 7.83 (1H, s), 8.08 (1H, s), 8.43-8.46 (1H, m), 8.63 (1H, s), 8.83-8.85 (1H, m).

[0196] 1 H-NMR(DMSO-d6) δ: 2.38 (3H, s), 3.84 (3H, s), 7.06-7.14 (1H, m), 7.52-7.60 (2H, m), 7.64 (1H, s), 8.30-8.37 (1H, m), 8.61 (1H, s), 8.81-8.86 (1H, m).

[0197] 1H-NMR(DMSO-d6) δ:4.20 (3H, s), 6.74-6.78 (1H, m), 7.10-7.18 (1H, m), 7.48-7.53 (1H, m), 7.55-7.61 (1H, m), 7.94 (1H, s), 8.33 (1H, d, J=9.2Hz), 8.68 (1H, s), 8.87 (1H, d, J=6.8Hz).

[0198] 1 H-NMR(CDCl3) δ:6.72-6.77 (1H, m), 6.94 (1H, ddd, J=1.3Hz, 6.9Hz, 6.9Hz), 7.39 (1H, ddd, J=1.2Hz, 6.8Hz, 8.9Hz), 7.43 (1H, s), 7.66 (1H, d, J=2.1Hz), 8.38 (1H, ddd, J=1.2Hz, 1.2Hz, 8.9Hz), 8.42 (1H, s), 8.54 (1H, ddd, J=1.0Hz, 1.0Hz, 7.0Hz).

[0199] 1 H-NMR(DMSO-d6) δ:2.51 (3H, s), 6.82 (1H, s), 7.12-7.17 (1H, m), 7.55-7.62 (1H, m), 8.14 (1H, s), 8.38-8.44 (1H, m), 8.67 (1H, s), 8.85-8.90 (1H, m).

[0200] 1 H-NMR(CDCl3) δ:6.63-6.67 (1H, m), 6.83-6.87 (1H, m), 6.90 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 7.03 (1H, s), 7.32-7.37 (1H, m), 7.39-7.42 (1H, m), 8.32 (1H, brs), 8.40 (1H, s), 8.41-8.45 (1H, m), 8.49-8.53 (1H, m).

[0201] 1H-NMR(DMSO-d6) δ:6.14 (1H, dd, J=2.4Hz, 6.0Hz), 6.58-6.64 (1H, m), 6.84-6.89 (1H, m), 7.11 (1H, ddd, J=1.2Hz, 6.8Hz, 6.8Hz), 7.48 (1H, s), 7.51-7.58 (1H, m), 8.54-8.62 (2H, m), 8.83 (1H, d, J=6.8Hz), 11.35 (1H, brs).

[0202] 1 H-NMR(DMSO-d6) δ:7.08-7.14 (1H, m), 7.50-7.58 (2H, m), 7.62 (1H, brs), 7.73 (1H, s), 8.42-8.50 (1H, m), 8.59 (1H, s), 8.82-8.85 (1H, m), 12.26 (1H, brs).

[0203] 1 H-NMR(DMSO-d6) δ:7.18 (1H, ddd, J=1.4Hz, 6.9Hz, 6.9Hz), 7.64 (1H, ddd, J=1.0Hz, 6.9Hz, 8.9Hz), 7.87 (2H, s), 8.43-8.44 (1H, m), 8.73-8.77 (1H, m), 8.75 (1H, s), 8.89 (1H, ddd, J=1.0Hz, 1.0Hz, 6.9Hz).

[0204] 1 H-NMR(DMSO-d6) δ:7.13 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 7.52-7.60 (1H, m), 7.91 (1H, s), 8.30-8.42 (1H, m), 8.45-8.53 (1H, m), 8.64 (1H, s), 8.82-8.88 (1H, m).

[0205] 1H-NMR(CD3OD) δ:7.09 (1H, ddd, J=1.3Hz, 6.6Hz, 7.2Hz), 7.50-7.57 (1H,m), 8.00 (1H, s), 8.30 (1H, s), 8.54 (1H, s), 8.61-8.68 (2H, m).

[0206] 1 H-NMR(DMSO-d6) δ:7.13 (1H, ddd, J=1.4 Hz, 6.9 Hz, 6.9 Hz), 7.56 (1H, ddd, J=0.9 Hz, 6.9 Hz, 8.8 Hz), 7.66 (1H, dd, J=3.0 Hz, 5.0 Hz), 7.71 (1H, dd, J=1.3 Hz, 5.0 Hz), 7.85 (1H, s), 8.08 (1H, dd, J=1.3 Hz, 3.0 Hz), 8.45-8.49 (1H, m), 8.62 (1H, s), 8.83-8.87 (1H, m).

[0207] 1 H-NMR(DMSO-d6) δ:7.11-7.18 (2H, m), 7.57 (1H, dd, J=1.2Hz, 5.0Hz), 7.60 (1H, ddd, J=1.2Hz, 6.9Hz, 8.9Hz), 7.66 (1H, dd, J=1.2Hz, 3.6Hz), 7.86 (1H, s), 8.38 (1H, ddd, J=1.2Hz, 1.2Hz, 8.8Hz), 8.63 (1H, s), 8.85-8.88 (1H, m).

[0208] 1H-NMR(DMSO-d6) δ:7.14 (1H, ddd, J=1.3Hz, 6.9Hz, 6.9Hz), 7.59 (1H, ddd, J=1.1Hz, 6.8Hz, 8.9Hz), 8.03 (1H, d, J=4.6Hz), 8.15 (1H, s), 8.46 (1H, ddd, J=1.2Hz, 1.2Hz, 8.8Hz), 8.67 (1H, s), 8.86 (1H, ddd, J=1.0Hz, 1.0Hz, 7.0Hz), 9.21 (1H, d, J=4.6Hz).

[0209] 1 H-NMR(DMSO-d6) δ:7.13 (1H, ddd, J=1.4Hz, 6.9Hz, 6.9Hz), 7.57 (1H, ddd, J=1.0Hz, 6.8Hz, 8.9Hz), 8.04 (1H, s), 8.49 (1H, ddd, J=1.2Hz, 1.2Hz, 8.8Hz), 8.65 (1H, s), 8.86 (1H, ddd, J=1.0Hz, 1.0Hz, 7.0Hz), 9.20 (1H, s), 9.50 (1H, s).

[0210] 1 H-NMR(DMSO-d6) δ:7.16 (1H, ddd, J=1.3Hz, 6.9Hz, 6.9Hz), 7.63 (1H, ddd, J=0.9Hz, 6.9Hz, 8.8Hz), 7.93 (1H, d, J=1.7Hz), 8.24 (1H, s), 8.32-8.36 (1H, m), 8.61 (1H, d, J=1.7Hz), 8.68 (1H, s), 8.86-8.90 (1H, m).

[0211] 1H-NMR(CDCl3) δ:6.93 (1H, ddd, J=1.4Hz, 6.9Hz, 6.9Hz), 7.39 (1H, ddd, J=1.1Hz, 6.8Hz, 8.9Hz), 7.74 (1H, s), 7.98 (1H, d, J=2.1Hz), 8.42 (1H, ddd, J=1.2Hz, 1.2Hz, 8.9Hz), 8.42 (1H, s), 8.53 (1H, ddd, J=1.0Hz, 1.0Hz, 7.0Hz), 8.87 (1H, d, J=2.1Hz).

[0212] 1 H-NMR(CDCl3) δ:6.95 (1H, ddd, J=1.4Hz, 6.9Hz, 6.9Hz), 7.32 (1H, s), 7.42 (1H, ddd, J=1.0Hz, 6.8Hz, 8.9Hz), 8.32 (1H, d, J=0.5Hz), 8.39 (1H, s), 8.42 (1H, ddd, J=1.2Hz, 1.2Hz, 8.8Hz), 8.54 (1H, ddd, J=1.0Hz, 1.0Hz, 7.0Hz), 8.78 (1H, d, J=0.5Hz).

[0213] 1 H-NMR(DMSO-d6) δ:7.12-7.18 (1H, m), 7.61-7.66 (1H, m), 7.82-7.84 (1H, m), 7.94-9.96 (1H, m), 8.15 (1H, s), 8.35-8.39 (1H, m), 8.69 (1H, s), 8.87-8.90 (1H, m).

[0214] 1H-NMR(DMSO-d6) δ:7.03 (1H, dd, J=0.8Hz, 1.8Hz), 7.12 (1H, ddd, J=1.3Hz, 6.9Hz, 6.9Hz), 7.55 (1H, ddd, J=1.1Hz, 6.8Hz, 8.9Hz), 7.71 (1H, s), 7.77 (1H, dd, J=1.7Hz, 1.7Hz), 8.27-8.29 (1H, m), 8.44 (1H, ddd, J=1.2Hz, 1.2Hz, 8.8Hz), 8.60 (1H, s), 8.84 (1H, ddd, J=1.0Hz, 1.0Hz, 7.0Hz).

[0215] 1 H-NMR(DMSO-d6) δ:6.65 (1H, dd, J=1.8Hz, 3.3Hz), 6.98 (1H, dd, J=0.6Hz, 3.3Hz), 7.13 (1H, ddd, J=1.4Hz, 6.9Hz, 6.9Hz), 7.57 (1H, ddd, J=1.0Hz, 6.8Hz, 8.9Hz), 7.71 (1H, s), 7.79 (1H, dd, J=0.7Hz, 1.8Hz), 8.40 (1H, ddd, J=1.2Hz, 1.2Hz, 8.8Hz), 8.63 (1H, s), 8.85 (1H, ddd, J=1.0Hz, 1.0Hz, 7.0Hz).

[0216] 1 H-NMR(DMSO-d6) δ:7.13 (1H, ddd, J=1.5Hz, 6.8Hz, 7.0Hz), 7.52-7.59 (1H, m), 7.87 (1H, s), 8.46-8.52 (1H, m), 8.63 (1H, s), 8.82-8.87 (1H, m), 9.22 (1H, s), 9.54 (1H, s).

[0217] 1H-NMR(DMSO-d6) δ:7.14 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 7.18 (1H, d, J=1.6Hz), 7.55-7.62 (1H, m), 8.21 (1H, s), 8.39-8.45 (1H, m), 8.68 (1H, s), 8.84-8.89 (1H, m), 9.07 (1H, d, J=1.6Hz).

[0218] 1 H-NMR(DMSO-d6) δ:7.04 (1H, d, J=2.0Hz), 7.15 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 7.56-7.63 (1H, m), 8.23 (1H, s), 8.40-8.46 (1H, m), 8.69 (1H, s), 8.73 (1H, d, J=2.0Hz), 8.87 (1H, d, J=7.2Hz).

[0219] 1 H-NMR(DMSO-d6) δ:7.13 (1H, ddd, J=1.3Hz, 6.9Hz, 6.9Hz), 7.55 (1H, ddd, J=1.1Hz, 6.8Hz, 8.9Hz), 7.78 (1H, d, J=0.4Hz), 8.46 (1H, ddd, J=1.2Hz, 1.2Hz, 8.8Hz), 8.51 (1H, d, J=1.0Hz), 8.63 (1H, s), 8.66 (1H, dd, J=0.4Hz, 1.0Hz), 8.85 (1H, ddd, J=1.0Hz, 1.0Hz, 7.0Hz).

[0220] 1H-NMR(DMSO-d6) δ:7.14 (1H, ddd, J=1.4Hz, 6.9Hz, 6.9Hz), 7.58 (1H, ddd, J=1.0Hz, 6.8Hz, 8.9Hz), 7.70 (1H, s), 7.89 (1H, s), 8.42 (1H, ddd, J=1.2Hz, 1.2Hz, 8.9Hz), 8.50 (1H, s), 8.66 (1H, s), 8.86 (1H, ddd, J=1.0Hz, 1.0Hz, 7.0Hz).

[0221] 1 H-NMR(DMSO-d6) δ:7.15 (1H, ddd, J=1.4Hz, 6.9Hz, 6.9Hz), 7.42-7.43 (1H, m), 7.62 (1H, ddd, J=0.9Hz, 6.9Hz, 8.9Hz), 8.25-8.27 (2H, m), 8.37 (1H, ddd, J=1.2Hz, 1.2Hz, 8.9Hz), 8.69 (1H, s), 8.88 (1H, ddd, J=1.0Hz, 1.0Hz, 7.0Hz).

[0222] 1 H-NMR(DMSO-d6) δ:3.92 (3H, s), 6.76 (1H, d, J=2.2Hz), 7.12 (1H, ddd, J=1.4Hz, 6.9Hz, 6.9Hz), 7.56 (1H, ddd, J=1.0Hz, 6.8Hz, 8.9Hz), 7.70 (1H, s), 7.78 (1H, d, J=2.2Hz), 8.40 (1H, ddd, J=1.2Hz, 1.2Hz, 8.9Hz), 8.61 (1H, s), 8.84 (1H, ddd, J=1.0Hz, 1.0Hz, 6.9Hz).

[0223] 1H-NMR(CDCl3) δ:3.72 (3H, s), 6.52-6.55 (1H, m), 6.62-6.65 (1H, m), 6.90 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 6.97 (1H, s), 7.19-7.22 (1H, m), 7.32-7.38 (1H, m), 8.39 (1H, s), 8.40-8.44 (1H, m), 8.49-8.53 (1H, m).

[0224] 1 H-NMR(DMSO-d6) δ:7.15 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 7.58-7.65 (1H,m), 8.38 (1H, s), 8.40-8.45 (1H, m), 8.69 (1H, s), 8.85-8.90 (1H, m), 10.37 (1H, s).

[0225] 1 H-NMR(CDCl3) δ:3.98 (3H, s), 6.18-6.21 (1H, m), 6.55 (1H, dd, J=1.8Hz, 3.8Hz), 6.71-6.74 (1H, m), 6.91 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 7.10 (1H, s), 7.32-7.38 (1H, m), 8.34-8.38 (1H, m), 8.39 (1H, s), 8.50-8.54 (1H, m).

[0226] 1 H-NMR(CDCl3) δ:6.96 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 7.38-7.44 (1H, m), 7.72 (1H, s), 8.33-8.38 (1H, m), 8.40 (1H, s), 8.52-8.57 (1H, m), 8.96 (1H, s).

[0227] [Example 75] Synthesis of N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)oxetane-3-sulfonamide (Compound 69)

[0228] (1) Synthesis of N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)oxetane-3-sulfonamide (Compound 69-1) 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline hydrochloride (Compound 1) (50.5 mg, 0.120 mmol) was suspended in anhydrous dichloromethane solution (10 mL), and excess oxetane-3-sulfonic acid chloride (0.10 mL) was added under ice-cooling, followed by slow addition of excess triethylamine (0.20 mL). The mixture was gradually returned to room temperature and stirred for 16 hours. Water was added to the reaction solution under ice-cooling, and the dichloromethane layer was washed several times with water. The dichloromethane layer was dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (69-1) (48.5 mg, 0.118 mmol, yield 98.0%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(CDCl3) δ: 4.94 (4H, m), 5.11 (1H, m), 6.95 (1H, t, J=6.9Hz), 7.31 (2H, d, J=8.2Hz), 7.41 (1H, t, J=8.2Hz), 7.46 (1H, s), 8.09 (2H, d, J=8.7Hz), 8.40 (1H, s), 8.43 (1H, d, J=9.2Hz), 8.53 (1H, d, J=6.9Hz).

[0229] (2) Synthesis of N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)oxetane-3-sulfonamide (Compound 69) Sodium hydride (oil dispersion) (21.5 mg) was carefully added to anhydrous DMF (4 mL) to form a suspension, which was then cooled to −15° C., followed by the slow addition of N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)oxetane-3-sulfonamide (Compound 69-1) (25.5 mg, 0.0521 mmol). The mixture was warmed to room temperature, then cooled to −15° C., and excess methyl iodide (0.10 mL) was added dropwise. The mixture was stirred for 16 hours while gradually returning to room temperature. Water (approximately 20 mL) was carefully added to the reaction solution under ice-cooling. The resulting precipitate was stirred at room temperature for a while, collected by filtration, washed thoroughly with a solvent such as n-hexane, and dried to obtain the title compound (69) (6.6 mg, 0.0155 mmol, yield 28.8%). 1 H-NMR(CDCl3) δ: 3.37 (3H, s), 4.54 (1H, m), 4.76 (2H, t, J=8.2Hz), 4.86 (2H, t, J=6.9Hz), 6.94 (1H, t, J=5.5Hz), 7.42 (4H, m), 8.02 (2H, d, J=8.2Hz), 8.40 (1H, s), 8.44 (1H, d, J=8.7Hz), 8.53 (1H, d, J=7.3Hz).

[0230] Example 76 Synthesis of N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 16) Compound (16) was synthesized from compound (12) according to the synthetic method of compound (69) from compound (69-1). 1H-NMR(CDCl3) δ: 2.18+2.19 (3H, s x2), 2.94+2.97 (3H, s x2), 4.57+4.63 (2H, s x2), 6.93 (1H, m), 7.36 (4H, m), 7.96+8.01 (2H, d x2, J= 6.9Hz), 8.39+8.40 (1H, s x2), 8.46 (1H, d, J=8.7Hz), 8.52 (1H, d, J=6.9Hz).

[0231] Example 77 Synthesis of N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-4-carboxamide (Compound 72)

[0232] (1) Synthesis of (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanamine hydrochloride (Compound 72-1) N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 12) (72.1 mg, 0.21 mmol) was suspended in 6N hydrochloric acid (1.0 mL), and the mixture was heated to reflux for 6 hours. After cooling, the solvent was evaporated under reduced pressure, and ethanol was added several times to dry the mixture. The resulting solid was dissolved in water (10 mL), and ethyl acetate (10 mL) was added, followed by partitioning. The aqueous layer was concentrated under reduced pressure, and ethanol was added several times, and the solvent was evaporated under reduced pressure to obtain the title compound (72-1) (66.9 mg, 0.180 mmol, yield 85.5%). 1 H-NMR(D2O) δ: 3.91 (2H, s), 6.71 (1H, t, J=6.9Hz), 7.11 (2H, d, J=7.8Hz), 7.16 (2H, d, J=8.7Hz), 7.27 (2H, d, J=7.8Hz), 7.44 (2H, d, J=8.7Hz), 8.02 (1H, s).

[0233] (2) Synthesis of N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-4-carboxamide (Compound 72) (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanamine hydrochloride (Compound 72-1) (20.5 mg, 0.0544 mmol) was suspended in anhydrous dichloromethane solution (10 mL), and morpholinecarbonyl chloride (0.10 mL) was added under ice-cooling, followed by the slow addition of excess triethylamine (0.20 mL). The mixture was gradually returned to room temperature and stirred for 16 hours. Water was added to the reaction solution under ice-cooling, and the dichloromethane layer was washed with water several times. The dichloromethane layer was dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (72) (14.3 mg, 0.0341 mmol, yield 62.7%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(CDCl3) δ: 3.38 (4H, t, J=5.0Hz), 3.70 (4H, t, J=5.3Hz), 4.49 (2H, d, J=5.5Hz), 4.71+5.73 (1H, brs x2), 6.93 (1H, t, J=7.1Hz), 7.38 (4H, m), 7.98 (2H, d, J=7.3Hz), 8.39 (1H, s), 8.45 (1H, d, J=8.7Hz), 8.52 (1H, d, J=6.9Hz).

[0234] Example 78 Synthesis of N-methyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanamine hydrochloride (Compound 74) Compound (74) was synthesized from compound (16) according to the synthetic method of compound (72-1) from compound (12). 1H-NMR(D2O) δ: 2.61 (3H, s), 4.07 (2H, s), 6.85 (1H, t, J=6.4Hz), 7.28 (3H, m), 7.40 (1H, brs), 7.62 (2H, m), 7.81 (1H, m), 8.17 (1H, s), 8.27 (1H, d, J=6.9Hz).

[0235] Example 79 Synthesis of N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-4-carboxamide (Compound 76) Compound (76) was synthesized from compound (74) according to the synthetic method of compound (72) from compound (72-1). 1 H-NMR(CDCl3) δ: 2.79 (3H, s), 3.28 (4H, t, J=5.1Hz), 3.70 (4H, t, J=4.6Hz), 4.44 (2H, s), 6.91 (1H, dt, J=1.4Hz, 6.9Hz), 7.37 (4H, m), 7.98 (2H, d, J=8.2Hz), 8.39 (1H, s), 8.45 (1H, d, J=8.7Hz), 8.51 (1H, d, J=6.9Hz).

[0236] Example 80 Synthesis of 2-methoxy-N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 78) Compound (78) was synthesized from compound (74) according to the synthetic method of compound (72) from compound (72-1). 1H-NMR(CDCl3) δ: 2.92+2.93 (3H, s x2), 3.45+3.48 (3H, s x2), 4.17+4.19 (2H, s x2), 4.58+4.65 (2H, d x2, J=3.7Hz), 6.93 (1H, t, J=6.9Hz), 7.28 (1H, d, J=8.2Hz), 7.38 (3H, m), 7.96+8.01 (2H, d x2, J=7.8Hz), 8.39+8.40 (1H, s x2), 8.45 (1H, d, J=8.7Hz), 8.52 (1H, d, J=6.9Hz).

[0237] Example 81 Synthesis of 1,1-dimethyl-3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)urea (Compound 59) Compound (59) was synthesized from compound (1) according to the synthetic method of compound (72) from compound (72-1). 1 H-NMR(CDCl3) δ: 3.06 (6H, s), 6.39 (1H, brs), 6.91 (1H, dt, J=1.4Hz, 6.9Hz), 7.28 (1H, s), 7.38 (1H, ddd, J=0.9Hz, 6.9Hz, 8.7Hz), 7.48 (2H, d, J=8.7Hz), 7.93 (2H, d, J=8.7Hz), 8.39 (1H, s), 8.45 (1H, d, J=8.7Hz), 8.51 (1H, d, J=6.9Hz).

[0238] Examples 82-85 Synthesis of the following compounds: 1,1-dimethyl-3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)urea (Compound 75), 2-methoxy-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 77), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)cyclobutanesulfonamide (Compound 82), and N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)oxetane-3-carboxamide (Compound 85).

[0239] Compounds (75), (77), (82), and (85) were synthesized from compound (72-1) in accordance with the method for synthesizing compound (72) from compound (72-1).

[0240] 1 H-NMR(CDCl3) δ: 2.94 (6H, s), 4.48 (2H, d, J=5.5Hz), 4.66 (1H, brs), 6.92 (1H, dt, J=1.4Hz, 7.3Hz), 7.38 (4H, m), 7.98 (2H, m), 8.39 (1H, s), 8.46 (1H, d, J=7.8Hz), 8.52 (1H, d, J=6.9Hz).

[0241] 1 H-NMR(CDCl3) δ: 3.41 (3H, s), 3.97 (2H, s), 4.54 (2H, d, J=6.0Hz), 6.85 (1H, brs), 6.93 (1H, t, J=6.9Hz), 7.38 (4H, m), 7.98 (2H, d, J=8.2Hz), 8.39 (1H, s), 8.45 (1H, d, J=8.7Hz), 8.52 (1H, d, J=7.3Hz).

[0242] 1H-NMR(CDCl3) δ: 1.99 (2H, m), 2.24 (2H, m), 2.49 (2H, m), 3.72 (1H, m), 4.37 (3H, m), 6.93 (1H, dt, J=1.4Hz, 6.9Hz), 7.39 (4H, m), 8.01 (2H, d, J=8.2Hz), 8.40 (1H, s), 8.46 (1H, d, J=8.7Hz), 8.53 (1H, d, J=6.9Hz).

[0243] 1 H-NMR(CDCl3) δ: 3.73 (1H, m), 4.53 (2H, d, J=5.5Hz), 4.82 (2H, dd, J=6.0Hz, 8.7Hz), 4.91 (2H, t, J=6.4Hz), 5.76 (1H, brs), 6.93 (1H, t, J=6.9Hz), 7.36 (4H, m), 7.98 (2H, d, J=8.2Hz), 8.39 (1H, s), 8.45 (1H, d, J=8.7Hz), 8.52 (1H, d, J=6.9Hz).

[0244] [Example 86] Synthesis of 2-amino-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide hydrochloride (Compound 64)

[0245] (1) Synthesis of tert-butyl (2-oxo-2-((4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)amino)ethyl)carbamate (Compound 64-1) 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline hydrochloride (Compound 1) (605 mg, 2.07 mmol), N-Boc-glycine (387 mg, 2.21 mmol), and EDC hydrochloride (586 mg, 3.54 mmol) were added to anhydrous dichloromethane solution (50 mL), and excess triethylamine (1.00 mL) was slowly added under ice-cooling. The mixture was gradually returned to room temperature and stirred for 16 hours. Water was added to the reaction solution under ice-cooling, and the dichloromethane layer was washed with water several times. The dichloromethane layer was dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (64-1) (170 mg, 0.379 mmol, yield 18.3%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(DMSO-d6) δ: 1.51 (9H, s), 3.71 (2H, d, J=8.2Hz), 7.04 (1H, t, J=6.0Hz), 7.15 (1H, dd, J=1.4Hz, 6.9Hz), 7.55 (1H, t, J=6.0Hz), 7.67 (2H, d, J=8.7Hz), 7.87 (1H, s), 8.00 (2H, d, J=8.7Hz), 8.42 (1H, d, J=9.2Hz), 8.59 (1H, s), 8.81 (1H, d, J=7.3Hz), 10.04 (1H, s).

[0246] (2) Synthesis of 2-amino-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide hydrochloride (Compound 64) Under ice-cooling, tert-butyl (2-oxo-2-((4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)amino)ethyl)carbamate (Compound 64-1) (170 mg, 0.378 mmol) was slowly added to a 4N hydrochloric acid dioxane solution (3.0 mL), and the mixture was stirred at room temperature for 2 hours. The solvent was evaporated to dryness under reduced pressure. Next, a solvent was added, and the resulting solid was collected by filtration, thoroughly washed with the solvent, and dried to obtain the title compound (64) (159 mg, 0.378 mmol, yield 99.8%). 1 H-NMR(D2O) δ: 3.85 (2H, s), 6.85 (1H, t, J=6.2Hz), 7.15 (2H, d, J=7.8Hz), 7.23 (2H, m), 7.34 (2H, d, J=7.3Hz), 7.62 (1H, d, J=8.7Hz), 8.15 (1H, s), 8.23 ​​(1H, d, J=6.9Hz).

[0247] Example 87 Synthesis of N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)oxetane-3-carboxamide (Compound 66) Compound (66) was synthesized from compound (1) according to the synthetic method for compound (64-1) from compound (1). 1 H-NMR(CDCl3) δ: 3.88 (1H, m), 4.89 (2H, dd, J=6.4Hz, 8.2Hz), 4.99 (2H, d, J=6.4Hz), 6.92 (1H, t, J=5.5Hz), 7.21 (1H, brs), 7.33 (1H, s), 7.40 (1H, d, J=8.5Hz), 7.65 (2H, d, J=8.7Hz), 8.00 (2H, d, J=8.2Hz), 8.40 (1H, s), 8.45 (1H, d, J=9.2Hz), 8.52 (1H, d, J=6.9Hz).

[0248] Examples 88-90 Synthesis of the following compounds: 2-amino-N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide hydrochloride (Compound 65), 2-amino-N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide hydrochloride (Compound 81), and 2-amino-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide hydrochloride (Compound 80).

[0249] Compound (65), compound (81), and compound (80) were synthesized from compound (10), compound (74), and compound (72-1), respectively, in accordance with the method for synthesizing compound (64) from compound (1).

[0250] 1 H-NMR(D2O) δ: 3.82 (2H, s), 6.70 (1H, t, J=6.9Hz), 7.03 (5H, m), 7.20 (1H, s), 7.37 (1H, d, J=8.2Hz), 7.94 (1H, s), 8.05 (1H, d, J=6.9Hz).

[0251] 1 H-NMR(D2O) δ: 2.85+2.86 (3H, s x2), 3.95+3.99 (2H, s x2), 4.04+4.45 (2H, s x2), 6.88 (1H, t, J=6.9Hz), 7.06 (2H, d, J=8.2Hz), 7.30 (2H, m), 7.36+7.42 (2H, d x2, J=8.2Hz), 7.61+7.64 (1H, d x2, J=8.2Hz), 8.19 (1H, s), 8.24 (1H, d, J=6.9Hz).

[0252] 1H-NMR(D2O) δ: 3.77 (2H, s), 4.25 (2H, s), 6.78 (1H, t, J=8.7Hz), 7.04 (2H, d, J=8.2Hz), 7.14 (1H, brs), 7.17 (1H, t, J=7.8Hz), 7.30 (2H, d, J=7.8Hz), 7.52 (1H, d, J=8.7Hz), 8.06 (1H, s), 8.15 (1H, d, J=6.9Hz).

[0253] [Example 91] Synthesis of sodium 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetic acid (Compound 5)

[0254] (1) Synthesis of 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 5-1) Pyrazolo[1,5-a]pyridine-3-carbothioamide (718 mg, 4.05 mmol) was dissolved in DME (40 mL), and 4-hydroxyphenacyl bromide (871 mg, 4.05 mmol) was added under ice-cooling, followed by stirring at room temperature for 16 hours. The reaction solution was heated and stirred at 50°C for 1 hour, then allowed to cool, and the solvent was distilled off under reduced pressure. Ethanol (40 mL) was added thereto, followed by excess potassium carbonate (996 mg), and the reaction solution was heated to reflux at 70°C for 1 hour. After allowing the reaction mixture to cool, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (5-1) (1.03 g, 3.53 mmol, yield 88.2%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(CDCl3) δ: 6.92 (3H, m), 7.23 (1H, s),7.38 (1H, ddd, J=0.9Hz, 6.4Hz, 8.7Hz), 7.91 (2H, d, J=8.7Hz), 8.39 (1H, s), 8.45 (1H, d, J=7.8Hz), 8.51 (1H, d, J=6.9Hz).

[0255] (2) Synthesis of benzyl 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetic acid (Compound 5-2) Sodium hydride (oil dispersion) (154 mg) was carefully added to anhydrous DMF (10 mL) to form a suspension, which was then cooled to −15° C., and 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 5-1) (153 mg, 0.522 mmol) was slowly added. The mixture was warmed to room temperature, cooled to −15° C., and then excess benzyl bromoacetate (0.30 mL) was added dropwise. The mixture was stirred for 16 hours while gradually returning to room temperature. Water (approximately 100 mL) was carefully and slowly added to the reaction solution under ice-cooling. The resulting solid was stirred at room temperature for a while, filtered, washed thoroughly with a solvent such as n-hexane, and then dried to obtain the title compound (5-2) (148 mg, 0.334 mmol, yield 64.2%). 1 H-NMR(CDCl3) δ: 4.72 (2H, s), 5.25 (2H, s), 6.92 (1H, t, J=6.9Hz), 6.98 (2H, d, J=9.2Hz), 7.34 (7H, m), 7.93 (2H, d, J=8.7Hz), 8.38 (1H, s), 8.45 (1H, d, J=9.2Hz), 8.51 (1H, d, J=6.9Hz).

[0256] (3) Synthesis of 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetic acid (compound 5-3) Benzyl 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetic acid (compound 5-2) (139 mg, 0.315 mmol) was added to a mixed solvent of 4N aqueous sodium hydroxide (3 mL) and ethanol (3 mL), and the reaction solution was heated and stirred at 100° C. for 1.5 hours. After cooling, the reaction solution was poured into ice water (100 mL) and dissolved. The insoluble matter was filtered off to obtain the title compound (5) (76.3 mg, 0.20 mmol, yield 64.9%). Furthermore, the aqueous layer was made weakly acidic by adding 2N hydrochloric acid, and the precipitated solid was stirred for a while and then collected by filtration. After washing thoroughly with water, the precipitate was dried to obtain the title compound (5-3) (19.0 mg, 0.0256 mmol, yield 8.1%). 1 H-NMR(CDCl3) δ: 4.70 (2H, s), 6.98 (2H, d, J=8.7Hz), 7.08 (1H, t, J=6.9Hz), 7.53 (1H, d, J=7.8Hz), 7.83 (1H, s), 7.97 (2H, d, J=8.7Hz), 8.39 (1H, d, J=8.7Hz), 8.58 (1H, s), 8.81 (1H, d, J=6.9Hz).

[0257] (4) Synthesis of sodium 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetic acid (compound 5) 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetic acid (compound 5-3) (531 mg, 1.51 mmol) and anhydrous sodium carbonate (80.5 mg, 0.76 mmol) were added to purified water (100 mL) and stirred at room temperature to completely dissolve. Traces of insoluble matter were removed by filtration, and the resulting pale yellow aqueous solution was lyophilized to obtain the title compound (5) (592 mg, 1.50 mmol, yield 99.3%). 1H-NMR(D2O) δ: 4.24 (2H, s), 6.61 (2H, d, J=8.7Hz), 6.70 (1H, t, J=6.9Hz), 6.92 (1H, s), 7.30 (2H, d, J=8.7Hz), 7.52 (2H, d, J=8.7Hz), 7.98 (1H, s,), 8.12 (1H, d, J=6.9Hz).

[0258] Example 92 Synthesis of N-acetyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)glycine (Compound 73) (1) Synthesis of tert-butyl N-acetyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)glycine (Compound 73-1) Sodium hydride (oil dispersion) (48.3 mg) was carefully added to anhydrous DMF (4 mL) to form a suspension, which was then cooled to −15° C., and N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 12) (106 mg, 0.305 mmol) was slowly added. The mixture was warmed to room temperature, cooled to −15° C., and then tert-butyl bromoacetate (0.10 mL) was added dropwise. The mixture was stirred for 16 hours while gradually returning to room temperature. The reaction solution was ice-cooled, and water was carefully and slowly added. Ethyl acetate was added to the reaction solution, which was washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and then insoluble matter was filtered off. The organic layer was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (73-1) (62.8 mg, 0.136 mmol, yield 64.2%) from the n-hexane:ethyl acetate (1:1) fraction. From another fraction, the starting compound (12) (58.0 mg, 0.125 mmol, yield 55.0%) was recovered. 1H-NMR(CDCl3) δ: 1.56 (9H, s), 2.05 (3H, s), 4.48 (2H, d, J=6.0Hz), 6.60 (2H, s), 6.93 (1H, dt, J=1.4Hz, 6.9Hz), 7.34 (4H, m), 7.98 (2H, d, J=8.2Hz), 8.39 (1H, s), 8.46 (1H, d, J=9.2Hz), 8.52 (1H, d, J=7.3Hz).

[0259] (2) Synthesis of N-acetyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)glycine (Compound 73) tert-Butyl N-acetyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)glycine (compound 73-1) (63.1 mg, 0.136 mmol) was added to a mixed solvent of 4N aqueous sodium hydroxide (1 mL) and ethanol (1 mL), and the reaction solution was heated and stirred at 100°C for 3 hours. After cooling, the reaction solution was poured into ice water (100 mL) and dissolved. The insoluble matter was filtered off to obtain the sodium salt of the title compound (73) (27.4 mg, 0.20 mmol, yield 64.9%). Furthermore, the aqueous layer was made weakly acidic with the addition of 2N hydrochloric acid, and the precipitated solid was stirred for a while, then filtered, washed thoroughly with water, and dried to obtain the title compound (73) (27.4 mg, 0.067 mmol, yield 49.6%). 1 H-NMR(DMSO-d6) δ: 1.99+2.05 (3H, s x2), 3.91+4.04 (2H, s x2), 4.50+4.64 (2H, s x2), 7.09 (1H, t, J=6.9Hz), 7.34+7.55 (3H, m x2), 7.98+8.06 (3H, m x2), 8.40 (1H, d, J=8.7Hz), 8.60 (1H, d, J=5.5Hz), 8.82 (1H, d, J=6.9Hz).

[0260] [Example 93] Synthesis of 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetamide (Compound 26) To a solution of 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (compound 5-1) (0.10 g, 0.34 mmol) in N,N-dimethylformamide (2 mL) were added 2-iodoacetamide (0.10 g, 0.54 mmol) and potassium carbonate (0.60 g, 4.34 mmol), and the mixture was stirred at room temperature for 2 hours. Water (10 mL) was added, and the resulting precipitate was collected by suction filtration and dried to obtain the title compound (26) (24.0 mg, 0.07 mmol, 20.1%). 1 H-NMR(DMSO-d6) δ: 4.88 (2H, s), 7.02-7.08 (2H, m), 7.10-7.16 (1H, m), 7.55-7.62 (1H, m), 7.89 (1H, s), 7.99-8.06 (2H, m), 8.44 (1H, d, J=8.4Hz), 8.63 (1H, s), 8.86 (1H, d, J=6.8Hz).

[0261] [Examples 94 to 99] Synthesis of the following compounds: 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl-2-(2-(2-methoxyethoxy)ethoxy)acetate (Compound 13), 4-(3-(2-methoxyethoxy)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 14), 4-(3-(2-(2-methoxyethoxy)ethoxy)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 22), 4-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 108), 4-(1-ethyl-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 110), and 4-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (compound 111).

[0262] The synthesis method of compound (26), compound (3), compound (13), compound (14), and compound (22) Compound (107), Compound (108), Compound (110), Compound (111), Compound (111).

[0263] 1 H-NMR(DMSO-d6) δ: 3.25 (3H, s), 3.43-3.48 (2H, m), 3.53-3.58 (2H, m), 3.59-3.63 (2H, m), 3.71-3.76 (2H, m), 4.50 (2H, s), 7.11-7.22 (2H, m), 7.52-7.63 (2H, m), 7.85-7.89 (1H, m), 7.99-8.04 (1H, m), 8.11 (1H, s), 8.42 (1H, d, J=9.2Hz), 8.66 (1H, s), 8.86 (1H, d, J=6.8Hz).

[0264] 1 H-NMR(CDCl3) δ: 3.49 (3H, s), 3.81 (2H, t, J=4.6Hz), 4.23 (2H, t, J=4.6Hz), 6.88-6.98 (2H, m), 7,30-7.43 (3H, m), 7.56-7.66 (2H, m), 8.40 (1H, s), 8.44-8.56 (2H, m).

[0265] 1 H-NMR(DMSO-d6) δ: 3.26 (3H, s), 3.47-3.50 (2H, m), 3.61-3.63 (2H, m), 3.78-3.83 (2H, m), 4.19-4.21 (2H, m), 6.96-6.98 (1H, m), 7.13-7.15 (1H, m), 7.40 (1H, t, J=7.9Hz), 7.60-7.63 (2H, m), 7.69 (1H, t, J=7.8Hz), 8.08 (1H, s), 8.41 (1H, d, J=8.8Hz), 8.64 (1H, s), 8.86 (1H, d, J=7.0Hz).

[0266] 1 H-NMR(DMSO-d6) δ: 0.38-0.45 (2H, m), 0.52-0.60 (2H, m), 1.25-1.38 (1H, m), 4.04 (2H, d, J=6.8Hz), 7.10-7.16 (1H, m), 7.52-7.60 (1H, m), 7.59 (1H, s), 7.97 (1H, s), 8.30 (1H, s), 8.41-8.46 (1H, m), 8.60 (1H, s), 8.82-8.88 (1H, m).

[0267] 1 H-NMR(DMSO-d6) δ: 1.43 (3H, t, J=7.4Hz), 4.20 (2H, q, J=7.3Hz), 7.08-7.15 (1H, m), 7.52-7.58 (1H, m), 7.56 (1H, s), 7.95 (1H, s), 8.28 (1H, s), 8.42-8.47 (1H, m), 8.59 (1H, s), 8.82-8.87 (1H, m).

[0268] 1 H-NMR(DMSO-d6) δ: 3.26 (3H, s), 3.74 (2H, t, J=5.4Hz), 4.33 (2H, t, J=5.2Hz), 7.10-7.16 (1H, m), 7.52-7.60 (1H, m), 7.59 (1H, s), 7.98 (1H, s), 8.25 (1H, s), 8.41-8.47 (1H, m), 8.60 (1H, s), 8.82-8.88 (1H, m).

[0269] Example 100: Synthesis of 2-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethoxy)ethan-1-amine hydrochloride (Compound 32)

[0270] To a solution of 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (compound 5-1) (0.10 g, 0.27 mmol) in DMF (1 mL) were added potassium carbonate (0.5 g) and tert-butyl N-[2-(2-bromoethoxy)ethyl]carbamate (0.2 mL, 0.78 mmol), and the mixture was stirred at room temperature for 2 hours. Saturated brine (5 mL) was added, and the resulting oil was separated by decantation. A 4N solution of hydrochloric acid in dioxane (5 mL) was added to this, and the mixture was stirred at room temperature for 3 hours. Acetone (20 mL) was added, and the resulting precipitate was filtered by suction, washed with diethyl ether, and dried to obtain the title compound (32) (94.0 mg, 0.225 mmol, yield 87.2%). 1 H-NMR(DMSO-d6) δ: 2.97-3.06 (2H, m), 3.67-3.73 (2H, m), 3.80-3.87 (2H, m), 4.18-4.24 (2H, m), 7.04-7.16 (3H, m), 7.54-7.62 (1H, m), 7.88 (1H, s), 7.98-8.08 (2H, m), 8.43 (1H, d, J=8.8Hz), 8.63 (1H, s), 8.86 (1H, d, J=6.8Hz).

[0271] Examples 101 and 102 Synthesis of 2-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethoxy)ethan-1-amine hydrochloride (Compound 20), and N,N-dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-amine hydrochloride (Compound 47) Compound (20) was synthesized from compound (3), and compound (47) was synthesized from compound (5-1), respectively, according to the synthetic method of compound (32).

[0272] 1H-NMR(DMSO-d6) δ: 2.97-3.07 (2H, m), 3.68-3.75 (2H, m), 3.82-3.88 (2H, m), 4.21-4.28 (2H, m), 6.95-7.01 (1H, m), 7.11-7.17 (1H, m), 7.41 (1H, t, J=8.0Hz), 7.56-7.65 (2H, m), 7,70 (1H, d, J=8.0Hz), 8.10 (1H, s), 8.37-8.44 (1H, m), 8.65 (1H, s), 8.84-8.89 (1H, m).

[0273] 1 H-NMR(DMSO-d6) δ: 2.87 (3H, s), 2.88 (3H, s), 3.51-3.58(2H, m), 4.39-4.45 (2H, m), 7.10-7.16 (3H, m), 7.54-7.62 (1H, m), 7.91 (1H, s), 7.96-8.10 (2H, m), 8.39-8.46 (1H, m), 8.64 (1H, s), 8.84-8.90 (1H, m).

[0274] Example 103: Synthesis of 1-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethyl)guanidine hydrochloride (Compound 52)

[0275] (1) Synthesis of tert-butyl (2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethyl)carbamate (Compound 52-1) Potassium carbonate (0.5 g, 3.60 mmol) was added to a solution of 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 3) (0.38 g, 1.00 mmol) in DMF (2 mL), and then 2-(tert-butoxycarbonylamino)ethyl bromide (0.30 g, 1.30 mmol) was added and the mixture was stirred at 70° C. for 10 hours. Insoluble matter was filtered off, and water (50 mL) was added to the filtrate. The resulting precipitate was collected by filtration and purified by preparative thin-layer chromatography (TLC), and the title compound (52-1) (0.33 g, 0.76 mmol, yield 76.0%) was obtained from the chloroform:methanol (98:2) fraction. 1 H-NMR(DMSO-d6) δ: 1.46 (9H, s), 3.34-3.37 (2H, m), 4.05-4.08 (2H, m), 6.95-6.97 (1H, m), 7.13-7.15 (1H, m), 7.40 (1H, t, J=8.0Hz), 7.57-7.62 (2H, m), 7.67-7.70 (1H, m), 8.08 (1H, s), 8.38-8.44(1H, m), 8.65 (1H, s), 8.84-8.89 (1H, m).

[0276] (2) Synthesis of 2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethanamine hydrochloride (Compound 52-2) A 4N solution of hydrochloric acid in dioxane (5 mL) was added to tert-butyl (2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethyl)carbamate (Compound 52-1) (0.33 g, 0.76 mmol), and the mixture was stirred at room temperature for 1 hour. Acetone (20 mL) was added, and the resulting precipitate was collected by filtration and dried to obtain the title compound (52-2) (308 mg, 0.76 mmol, quantitative). 1H-NMR(DMSO-d6) δ: 3.26-3.28 (2H, m), 4.29-4.31 (2H, m), 7.02-7.04 (1H, m), 7.14-7.17 (1H, m), 7.45 (1H, t, J=8.0Hz), 7.58-7.70 (1H, m), 7.70-7.76 (2H, m), 8.10 (1H, s), 8.40-8.46 (1H, m), 8.66 (1H, s), 8.85-8.90(1H, m).

[0277] (3) Synthesis of 1,3-bis(tert-butoxycarbonyl)-2-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethaneguanidine (Compound 52-3) To a solution of 2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethanamine hydrochloride (compound 52-2) (0.1 g, 0.27 mmol) in dichloromethane (2 mL), triethylamine (0.5 mL, 3.60 mmol) and 1,3-bis(tert-butoxycarbonyl)-2-(trifluoromethanesulfonyl)guanidine (0.2 g, 0.51 mmol) were added, and the mixture was stirred at room temperature for 4 hours, and the solvent was distilled off under reduced pressure. Diethyl ether was added to the residue, and insoluble matter was filtered off. The filtrate was concentrated under reduced pressure to obtain the title compound (52-3) (0.15 g, 0.26 mmol, yield 96.3%). 1 H-NMR(DMSO-d6) δ: 1.39-1.47 (18H, m), 3.73-3.76 (2H, m), 4.10-4.21 (2H, m), 7.03-7.06 (1H, m), 7.10-7.15 (1H, m), 7.41 (1H, t, 8.84-8.88 (1H, m), 11.51 (1H, s).

[0278] (4) Synthesis of 1-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethyl)guanidine hydrochloride (Compound 52) A 4N solution of hydrochloric acid in dioxane (5 mL) was added to 1,3-bis(tert-butoxycarbonyl)-2-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethaneguanidine (Compound 52-3) (0.15 g, 0.26 mmol), and the mixture was stirred at room temperature for 12 hours. Acetone (10 mL) was added, and the resulting precipitate was collected by filtration, washed with diethyl ether, and then dried to obtain the title compound (52) (85.0 mg, 0.20 mmol, yield 76.9%). 1 H-NMR(DMSO-d6) δ: 3.59-3.61 (2H, m), 4.19 (2H, t, J=5.2Hz), 6.98-7.01(1H, m), 7.12-7.16 (1H, m), 7.43(1H, t, J=8.0Hz), 7.60 (1H, t, J=8.2Hz), 7.65 (1H, s), 7.72 (1H, d, J=7.8Hz), 7.84 (1H, brs), 8.09 (1H, s), 8.39-8.44 (1H, m), 8.65 (1H, s), 8.87 (1H, d, J=6.8Hz).

[0279] Example 104 Synthesis of 1-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethyl)guanidine hydrochloride (Compound 51) Compound (51) was synthesized from compound (5-1) according to the synthetic method of compound (52). 1 H-NMR(DMSO-d6) δ: 3.53-3.61 (2H, m), 4.14 (2H, t, J=5.4Hz), 7.04-7.17 (3H, m), 7.55-7.62 (1H, m), 7.77 (1H, brs), 7.89 (1H, s), 8.02-8.08 (2H, m), 8.40-8.46 (1H, m), 8.63 (1H, s), 8.84-8.88 (1H, m).

[0280] Example 105 Synthesis of N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethyl)acetamide (Compound 45) Compound (45) was synthesized from compound (5-1) according to the synthetic method of compound (52-2). 1 H-NMR(DMSO-d6) δ: 2.03 (3H, s), 3.64-3.74 (2H, m), 4.06-4.12 (2H, m), 6.88-7.04 (3H, m), 7.23 (1H, s), 7.27 (1H, s), 7.33-7.42 (1H, m), 7.90-7.98 (2H, m), 8.39 (1H, s), 8.40-8.47 (1H, m), 8,48-8.54 (1H, m).

[0281] [Example 106] Synthesis of N-(2-hydroxyethyl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetamide (Compound 19)

[0282] (1) Synthesis of benzyl 2-(3-(2-pyrazolo[1,5-a]pyridin-3-yl)-4-(thiazol-4-yl)phenoxyacetate (19-1) 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (compound 3) (0.30 g, 1.0 mmol) was dissolved in anhydrous DMF (10 mL), and 60% sodium hydride (150 mg, 3.75 mmol) was added. Then, benzyl bromoacetate (0.23 g, 1.0 mmol) was added and the mixture was stirred at room temperature for 6 hours. Ice water (100 mL) was added, and the precipitate was collected by filtration. The precipitate was washed with methanol to obtain the title compound (19-1) (1.31 g, 2.96 g, yield 88%). 1H-NMR(DMSO-d6) δ: 5.00 (2H, s), 5.23 (2H, s), 6.95-6.98 (1H, m), 7.10-7.15 (1H, m), 7.31-7.42 (6H, m), 7.55-7.76 (1H, m), 7.64-7.65 (1H, m), 7.72 (1H, d, J=7.8Hz), 8.06 (1H, s), 8.42 (1H, d, J=7.8Hz), 8.65 (1H, s), 8.87 (1H, d, J=7.3Hz).

[0283] (2) Synthesis of N-(2-hydroxyethyl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetamide (Compound 19) Ethanolamine (1 mL) was added to benzyl 2-(3-(2-pyrazolo[1,5-a]pyridin-3-yl)-4-(thiazol-4-yl)phenoxyacetate (Compound 19-1) (28 mg, 0.063 mmol), and the mixture was stirred at room temperature for 12 hours. Water (10 mL) was added, and the resulting precipitate was filtered with suction, washed with water, methanol, and diethyl ether, in that order, and dried to obtain the title compound (19) (28 mg, 0.053 mmol, yield 84.1%). 1 H-NMR(DMSO-d6) δ: 3.20-3.29 (2H, m), 3.42-3.49 (2H, m), 4.59 (2H, s), 4.76 (1H, t, J=5.6Hz), 6.98 (dd, 1H, J=8.2, 1.8Hz), 7.11-7.18 (1H, m), 7.42 (1H, t, J=7.8Hz), 7.59-7.64 (1H, m), 7.67-7.75 (2H, m), 8.06 (1H, s), 8.10-8.17 (1H, m), 8.44 (1H, d, J=8.4Hz), 8.65 (1H, s), 8.87 (1H, d, J=7.6Hz).

[0284] Example 107 Synthesis of methyl 2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetate (Compound 18) Compound (18) was synthesized from compound (3) according to the synthetic method of compound (19). 1 H-NMR(DMSO-d6) δ: 3.74 (3H, s), 4.92(2H, s), 6.95 (dd, 1H, J=8.0, 2.4Hz), 7.11-7.18 (1H, m), 7.41 (1H, t, J=8.0Hz), 7.57-7.67 (2H, m), 7.71 (d, 1H, J=7.2Hz), 8.09 (1H, s), 8.43 (1H, d, J=8.8Hz), 8.65 (1H, s), 8.87 (1H, d, J=6.8Hz).

[0285] [Example 108] Synthesis of methyl 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetate (Compound 25) Methanol (20 mL) and piperazine (1.0 g, 11.6 mmol) were added to benzyl 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetic acid (compound 5-2) (0.3 g, 0.68 mmol) at room temperature, and the mixture was stirred for 12 hours. The resulting precipitate was filtered with suction, washed with methanol, and dried to obtain the title compound (25) (226.0 mg, 0.62 mmol, yield 91.1%). 1 H-NMR(DMSO-d6) δ: 3.72 (3H, s), 4.87 (2H, s), 7.01-7.07 (2H, m), 7.09-7.15 (1H, m), 7.54-7.61 (1H, m), 7.88 (1H, s), 7.98-8.04 (2H, m), 8.40-8.46 (1H, m), 8.62 (1H, s), 8.83-8.87 (1H, m).

[0286] [Example 109] Synthesis of 1-(piperazin-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one (Compound 31) Anhydrous piperazine (3.0 g, 34.8 mmol) was added to benzyl 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetic acid (compound 5-2) (0.3 g, 0.68 mmol), and the mixture was heated and stirred at 120° C. for 1 hour. Water (50 mL) and then saturated brine (5 mL) were added, and the mixture was extracted with chloroform and then dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure, and after drying, the title compound (31) (0.23 g, 0.55 mmol, yield 80.9%) was obtained. 1 H-NMR(DMSO-d6)δ: 3.10-3.20 (4H, m), 3.70-3.80 (4H, m), 5.00 (2H, s), 7.07 (2H, d, J=8.7Hz), 7.11-7.16 (1H, m), 7.57-7.61 (1H, m), 7.89 (1H, s), 8.02 (2H, d, J=9.1Hz), 8.44 (1H, d, J=8.7Hz), 8.64 (1H, s), 8.87 (1H, d, J=6.9Hz).

[0287] [Examples 110 and 111] Synthesis of 1-(1,4-diazepan-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one hydrochloride (Compound 55) and 1-(4-methyl-1,4-diazepan-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one hydrochloride (Compound 102)

[0288] Compounds (55) and (102) were synthesized from compound (5-2) according to the synthesis method of compound (31).

[0289] 1H-NMR(DMSO-d6) δ: 3.12-3.82 (10H, m), 4.92 (2H, s), 7.02-7.18 (3H, m), 7.54-7.62 (1H, m), 7.86(1H, s), 8.00 (2H, d, J=8.8Hz), 8.42 (1H, d, J=9.2Hz), 8.62 (1H, s), 8.84 (1H, d, J=7.2Hz).

[0290] 1 H-NMR(DMSO-d6) δ: 2.78-2.80 (2H, m), 3.57 (3H, s), 3.42-3.63 (8H, m), 4.88-4.92 (2H, m), 7.03-7.17 (3H, m), 7.54-7.62 (1H, m), 7.86-7.90 (1H, m), 7.98-8.05 (2H, m), 8.40-8.46 (1H, m), 8.62 (1H, s), 8.84-8.88(1H, m).

[0291] Examples 112 to 114 Synthesis of the following compounds: 1-(2-(hydroxymethyl)pyrrolidin-1-yl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one (Compound 21), 1-(piperazin-1-yl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one (Compound 23), and 1-(1,1-dioxidethiomorpholino)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one (Compound 24)

[0292] Compounds (21), (23), and (24) were synthesized from compound (19-1) according to the synthesis method of compound (31).

[0293] 1H-NMR(CDCl3) δ: 1.52-1.68 (1H, m), 1.82-2.12 (3H, m), 3.51-3.66 (2H, m), 3.70-3.79 (2H, m), 4.23-4.32 (1H, m), 4.51-4.59 (1H, m), 4.77 (2H, s), 6.90-6.98 (2H, m), 7.35-7.46 (3H, m), 7.61-7.66 (1H, m), 7.68-7.72 (1H, m), 8.41 (1H, s), 8.46-8.56 (2H, m).

[0294] 1 H-NMR(DMSO-d6) δ: 2.65-2.76 (4H, m), 3.40-3.44 (4H, m), 4.91 (2H, s), 6.93-6.86 (1H, m), 7.14-7.16 (1H, m), 7.40 (1H, t, J=7.9Hz), 7.60-7.69 (3H, m), 8.05 (1H, s), 8.45-8.47 (1H, d, J=8.9Hz), 8.65 (1H, s), 8.87 (1H, d, J=7.0Hz).

[0295] 1 H-NMR(DMSO-d6) δ: 3.10-3.20 (2H, m), 3.30-3.46 (2H, m), 3.88-3.94 (4H, m), 5.02 (2H, s), 6.96-7.01 (1H, m), 7.11-7.16 (1H, m), 7.37-7.43 (1H, m), 7.56-7.72 (3H, m), 8.05 (1H, s), 8.41-8.46 (1H, m), 8.64 (1H, s), 8.86 (1H, d, J=6.8Hz).

[0296] [Example 115] Synthesis of (4-methylpiperazin-1-yl)(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazol-3-yl)methanone hydrochloride (Compound 103)

[0297] (1) Synthesis of ethyl 5-(2-pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole-3-carboxylate (Compound 103-1) A solution of pyrazolo[1,5-a]pyridine-3-carbothioamide (0.50 g, 2.82 mmol) and ethyl 5-(2-bromoacetyl)isoxazole-3-carboxylate (0.74 g, 2.82 mmol) in acetone (15 mL) was stirred at room temperature for 4 hours. Water (40 mL) was added, and the precipitate was filtered with suction, washed with methanol, and dried to obtain the title compound (103-1) (0.8 g, 1.87 mmol, yield 66%). 1 H-NMR(DMSO-d6) δ: 1.37 (3H, t, J=7.1Hz), 4.45 (2H, q, J=7.1Hz), 7.14-7.18 (1H, m), 7.43 (1H, s), 7.58-7.63 (1H, m), 8.38 (1H, s), 8.48 (1H, t, J=8.8Hz), 8.71 (1H, s), 8.88 (1H, d, J=7.0Hz).

[0298] (2) Synthesis of (4-methylpiperazin-1-yl)(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazol-3-yl)methanone hydrochloride (Compound 103) A solution of ethyl 5-(2-pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole-3-carboxylate (Compound 103-1) (50 mg, 0.15 mmol) and 1-methylpiperazine (1 mL, 11.0 mmol) in dichloromethane (1 mL) was stirred at room temperature for 16 hours. Water (10 mL) was added to the reaction solution, and the solvent was partially evaporated under reduced pressure. The resulting precipitate was suction filtered and dried to obtain a crude compound. To a solution of the crude compound in dioxane (2 mL) were added four drops of 4N hydrochloric acid in dioxane, and the precipitate was collected by filtration to obtain the title compound (103) (14 mg, 0.032 mmol, yield 21.7%). 1H-NMR(DMSO-d6) δ: 2.23 (3H, s), 2.32-2.46 (4H, m), 3.58-3.73 (4H, m), 7.12-7.20 (1H, m), 7.28 (1H, s), 7.56-7.62 (1H, m), 8.32 (1H, s), 8.44-8.52 (1H, m), 8.71 (1H, s), 8.84-8.91 (1H, m).

[0299] Example 116 Synthesis of piperazin-1-yl(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazol-3-yl)methanone hydrochloride (compound 104) Compound (104) was synthesized from compound (103-1) according to the synthetic method of compound (103). 1 H-NMR(DMSO-d6) δ: 3.19-3.30 (4H, m), 3.88-3.96 (4H, m), 7.14-7.21 (1H, m), 7.27-7.32 (1H, m), 7.58-7.66 (1H, m), 8.31-8.36 (1H, m), 8.44 (1H, d, J=8.8Hz), 8.70 (1H, s), 8.86 (1H, d, J=6.8Hz).

[0300] [Example 117] Synthesis of N-(4'-methyl-2-(pyrazolo[1,5-a]pyridin-3-yl)-[4,5'-bithiazol]-2'-yl)acetamide (Compound 46)

[0301] To a solution of pyrazolo[1,5-a]pyridine-3-carbothioamide (75 mg, 0.4 mmol) and 1-(2-amino-4-methylthiazol-5-yl)-2-bromoethan-1-one (100 mg, 0.4 mmol) in acetone (3 mL), potassium carbonate (0.1 g, 0.72 mmol) was added and the mixture was stirred at room temperature for 12 hours. Water (20 mL) was added, and the resulting precipitate was filtered under suction, washed with methanol and diethyl ether, and then dried to obtain the crude compound. Anhydrous DMF (2 mL) and then acetic anhydride (1 mL, 10.6 mmol) were added to the mixture, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, water (20 mL) was added, and the resulting precipitate was collected by suction filtration and dried to obtain the title compound (46) (30.0 mg, 0.08 mmol, yield 53%). 1 H-NMR(DMSO-d6) δ: 2.16 (3H, s), 2.55 (3H, s), 7.10-7.16 (1H, m), 7.57-7.64 (2H, m), 8.27-8.33 (1H, m), 8.63 (1H, s), 8.82-8.88 (1H, m), 12.13 (1H, s).

[0302] [Example 118] Synthesis of N,N-dimethyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide (Compound 49) (1) Synthesis of ethyl 4-(bromoacetyl)benzoate (compound 49-1) Ethyl 4-acetylbenzoate (5.10 g, 26.5 mmol) was added to ethyl acetate (100 mL), and CuBr ２ (12.5 g, 55.9 mmol) was added, and the mixture was heated to reflux for 16 hours. After allowing to cool, insoluble matter was filtered through Celite, the organic solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (49-1) (7.11 g, 26.2 mmol, yield 98.9%) from the n-hexane:ethyl acetate (4:1) fraction. 1 H-NMR(CDCl3) δ: 1.41 (3H, t, J=6.9Hz), 4.40 (2H, d, J=6.9Hz), 4.46 (2H, s), 8.03 (2H, d, J=8.7Hz), 8.14 (2H, d, J=8.7Hz).

[0303] (2) Synthesis of ethyl 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoate (Compound 49-2) Pyrazolo[1,5-a]pyridine-3-carbothioamide (711 mg, 4.01 mmol) was dissolved in DME (40 mL), and ethyl 4-(bromoacetyl)benzoate (Compound (49-1)) (1.08 g, 3.99 mmol) was added under ice-cooling, followed by stirring at room temperature for 16 hours. The reaction solution was heated and stirred at 50°C for 1 hour, then allowed to cool, and the solvent was distilled off under reduced pressure. Ethanol (40 mL) was added to the residue, followed by the addition of excess potassium carbonate (1.06 g), and the reaction solution was heated to reflux at 70°C for 1 hour. After allowing the reaction mixture to cool, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (49-2) (1.22 g, 3.50 mmol, yield 87.4%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(CDCl3) δ: 1.42 (3H, t, J=7.3Hz), 4.40 (2H, q, J=7.3Hz), 6.94 (1H, dt, J=1.4Hz, 6.9Hz), 7.42 (1H, t, J=8.5Hz), 7.50 (1H, s), 8.08 (2H, d, J=8.7Hz), 8.14 (2H, d, J=8.7Hz), 8.40 (1H, s), 8.47 (1H, d, J=9.2Hz), 8.53 (1H, d, J=6.9Hz).

[0304] (3) Synthesis of 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoic acid (compound 49-3) Ethyl 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoate (compound 49-2) (2.63 g, 7.51 mmol) was added to a mixed solvent of 4N aqueous sodium hydroxide (8 mL) and ethanol (4 mL), and the reaction solution was heated and stirred at 100° C. for 1 hour. After cooling, the reaction solution was poured into ice water (100 mL), and 2N hydrochloric acid was added to make the mixture weakly acidic. The precipitated solid was stirred for a while and then collected by filtration. The solid was thoroughly washed with water and then dried to obtain the title compound (49-3) (2.28 g, 7.08 mmol, yield 94.3%). 1H-NMR(DMSO-d6) δ: 7.10 (1H, dt, J=1.4Hz, 6.9Hz), 7.57 (1H, ddd, J=0.9Hz, 5.5Hz, 8.7Hz), 8.01 (2H, d, J=8.7Hz), 8.19 (3H, m), 8.42 (1H, d, J=9.2Hz), 8.63 (1H, s), 8.83 (1H, d, J=6.9Hz).

[0305] (4) Synthesis of N,N-dimethyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide (Compound 49) 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoic acid (Compound 49-3) (53.8 mg, 0.167 mmol), dimethylamine hydrochloride (56.2 mg, 0.690 mmol), and EDC hydrochloride (174 mg, 0.908 mmol) were added to anhydrous dichloromethane solution (10 mL), and excess TEA (0.20 mL) was slowly added under ice-cooling. The mixture was gradually returned to room temperature and stirred for 16 hours. Water was added to the reaction solution under ice-cooling, and the dichloromethane layer was washed several times with water. The dichloromethane layer was dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (49) (44.8 mg, 0.129 mmol, yield 75.6%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(CDCl3) δ: 3.03 (3H, s), 3.13 (3H, s), 6.92 (1H, dt, J=1.4Hz, 6.9Hz), 7.39 (1H, ddd, J=1.4Hz, 6.9Hz, 9.2Hz), 7.42 (1H, s), 7.51 (2H, d, J=8.7Hz), 8.04 (2H, d, J=8.7Hz), 8.39 (1H, s), 8.45 (1H, d, J=8.7Hz), 8.51 (1H, d, J=6.9Hz).

[0306] [Examples 119 and 120] Synthesis of sodium 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoate (Compound 6) and (3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)(2-oxa-6-azaspiro[3.3]heptan-6-yl)methanone (Compound 33)

[0307] Compound (6) and compound (33) were synthesized according to the synthesis method of compound (49).

[0308] 1 H-NMR(D2O) δ: 6.38 (1H, t, J=6.8Hz), 6.65 (1H, s), 6.68-6.74 (1H, m), 6.92 (1H, t, J=7.8Hz), 7.02-7.09 (2H, m), 7.41 (1H, d, J=8.0Hz), 7.57-7.62 (2H, m), 7.74 (1H, d, J=7.2Hz).

[0309] 1 H-NMR(CDCl3) δ: 4.39 (2H, s), 4.51 (2H, s), 4.78 (2H, s), 4.83 (2H, s), 6.94 (1H, t, J=6.0Hz), 7.40 (1H, m), 7.42 (1H, s), 7.50 (1H, t, J=7.8Hz), 7.57 (1H, d, J=7.8Hz), 8.12 (1H, d, J=7.8Hz), 8.27 (1H, m), 8.40 (1H, s), 8.45 (1H, d, J=8.7Hz), 8.53 (1H, d, J=6.9Hz).

[0310] [Example 121] Synthesis of N,N-dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 87)

[0311] (1) Synthesis of ethyl 4-(bromoacetyl)phenylacetate (Compound 87-1) Ethyl 4-acetylphenylacetate (425 mg, 2.06 mmol) was added to ethyl acetate (100 mL), and CuBr ２ (967 mg, 4.33 mmol) was added, and the mixture was heated to reflux for 11 hours. After allowing to cool, insoluble matter was filtered through Celite, the organic solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (87-1) (581 mg, 0.458 mmol, yield 99.0%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(CDCl3) δ: 1.25 (3H, t, J=7.1Hz), 3.68 (2H, s), 4.15 (2H, d, J=7.1Hz), 4.28 (2H, s), 7.42 (2H, d, J=8.1Hz), 7.94 (2H, d, J=8.5Hz).

[0312] (2) Synthesis of ethyl 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetate (Compound 87-2) Pyrazolo[1,5-a]pyridine-3-carbothioamide (379 mg, 2.14 mmol) was dissolved in DME (20 mL), and ethyl 4-(bromoacetyl)phenylacetate (Compound 87-1) (621 mg, 2.18 mmol) was added under ice-cooling, followed by stirring at room temperature for 16 hours. The reaction solution was heated and stirred at 50°C for 1 hour, then allowed to cool, and the solvent was distilled off under reduced pressure. Ethanol (20 mL) was added thereto, followed by excess potassium carbonate (503 mg), and the reaction solution was heated to reflux at 70°C for 1 hour. After allowing the reaction mixture to cool, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (87-2) (645 mg, 2.00 mmol, yield 92.5%) from the n-hexane:ethyl acetate (1:1) fraction. 1H-NMR(CDCl3) δ: 1.26 (3H, t, J=7.1Hz), 3.66 (2H, s), 4.16 (2H, q, J=7.1Hz), 6.92 (1H, dt, J=1.4Hz, 6.8Hz), 7.38 (4H, m), 7.97 (2H, d, J=8.4Hz), 8.39 (1H, s), 8.46 (1H, d, J=8.8Hz), 8.51 (1H, d, J=7.0Hz).

[0313] (3) Synthesis of 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetic acid (Compound 87-3) Ethyl 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetate (Compound 87-2) (566 mg, 1.56 mmol) was added to a mixed solvent of 4N aqueous sodium hydroxide (3 mL) and ethanol (6 mL), and the reaction solution was heated and stirred at 100° C. for 1 hour. After cooling, ice water (50 mL) was poured into the reaction solution, and 2N hydrochloric acid was added to make it weakly acidic. The precipitated solid was stirred for a while, then filtered, washed thoroughly with water, and dried to obtain the title compound (87-3) (489 mg, 1.46 mmol, yield 91.0%). 1 H-NMR(CDCl3) δ: 3.72 (2H, s), 6.92 (1H, dt, J=1.3Hz, 6.8Hz), 7.38 (4H, m), 7.99 (2H, d, J=8.4Hz), 8.40 (1H, s), 8.47 (1H, d, J=8.9Hz), 8.54 (1H, d, J=7.0Hz).

[0314] (4) Synthesis of N,N-dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 87) 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetic acid (Compound 87-3) (46.3 mg, 0.138 mmol), dimethylamine hydrochloride (58.5 mg, 1.30 mmol), and EDC hydrochloride (129 mg, 0.67 mmol) were added to anhydrous dichloromethane solution (10 mL), and excess triethylamine (0.20 mL) was slowly added under ice-cooling. The mixture was gradually returned to room temperature and stirred for 16 hours. Water was added to the reaction solution under ice-cooling, and the dichloromethane layer was washed several times with water. The dichloromethane layer was dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (87) (27.8 mg, 0.0767 mmol, yield: 55.6%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(CDCl3) δ: 2.98 (3H, s), 3.01 (3H, s), 3.77 (2H, s), 6.92 (1H, t, J=1.4Hz, 6.9Hz), 7.38 (4H, m), 7.96 (2H, d, J=8.2Hz), 8.39 (1H, s), 8.46 (1H, d, J=9.2Hz), 8.52 (1H, d, J=7.3Hz).

[0315] [Examples 122 to 128] Synthesis of the following compounds: N-(cyclopropylmethyl)-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoyl)azetidine-3-carboxamide (Compound 9), (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)(2-oxa-7-azaspiro[3.5]nonan-7-yl)methanone (Compound 40), (1,4-oxazepan-4-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 41), (4-(dimethylamino)piperidin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 48), (4-methylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 50), (4-ethylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 56), and (3-methylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 58).

[0316] Compound (9), compound (40), compound (41), compound (48), compound (50), compound (56), and compound (58) were synthesized from compound (49-3) according to the synthetic method for compound (49).

[0317] 1H-NMR(CDCl3) δ:0.21 (2H, m), 0.53 (2H, m), 0.95 (1H, m), 3.15 (2H, dd, J=5.5Hz, 7.3Hz), 3.33 (1H, m), 4.38 (3H, m), 4.66 (1H, t, J=6.9Hz), 5.70 (1H, brs), 6.93 (1H, dt, J=1.4Hz, 7.3Hz), 7.40 (1H, ddd, J=1.4Hz, 7.3Hz), 7.45 (1H, s), 7.73 (2H, d, J=8.2Hz), 8.04 (2H, d, J=8.7Hz), 8.39 (1H, s), 8.44 (1H, d, J=8.7Hz), 8.53 (1H, d, J=6.9Hz).

[0318] 1 H-NMR(CDCl3) δ:1.91 (4H, m), 3.40 (2H, m), 3.68 (2H, m), 4.48 (4H, s), 6.93 (1H, dt, J=1.4Hz, 6.9Hz), 7.39 (1H, dd, J=7.8Hz, 8.8Hz), 7.42 (1H, s), 7.48 (2H, d, J=8.2Hz), 8.04 (2H, d, J=8.2Hz), 8.40 (1H, s), 8.44 (1H, d, J=9.2Hz), 8.52 (1H, d, J=6.9Hz).

[0319] 1 H-NMR(CDCl3) δ:1.84 (1H, m), 2.07 (1H, m), 3.57 (2H, m), 3.67 (1H, m), 3.84 (5H, m), 6.93 (1H, dt, J=0.9Hz, 6.9Hz), 7.39 (1H, m), 7.42 (1H, s), 7.49 (2H, m), 8.05 (2H, d, J=7.8Hz), 8.40 (1H, s), 8.46 (1H, d, J=9.2Hz), 8.53 (1H, d, J=6.9Hz).

[0320] 1H-NMR(CDCl3) δ:1.45 (2H, m), 1.85 (2H, m), 2.29 (6H, s), 2.38 (2H, m), 2.84 (1H, m), 3.05 (1H, m), 3.20 (1H, m), 6.93 (1H, dt J=1.4Hz, 6.9Hz), 7.40 (1H, ddd, J=1.4Hz, 6.9Hz, 9.2Hz), 7.42 (1H, s), 7.49 (2H, d, J=8.7Hz), 8.04 (2H, d, J=8.2Hz), 8.39 (1H, s), 8.45 (1H, d, J=8.7Hz), 8.53 (1H, d, J=6.9Hz).

[0321] 1 H-NMR(CDCl3) δ:2.33 (3H, s), 2.45 (4H, m), 3.67 (4H, m), 6.93 (1H, dt, J=1.4Hz, 6.9Hz), 7.40 (1H, ddd, J=1.4Hz, 6.9Hz, 9.2Hz), 7.42 (1H, s), 7.50 (2H, d, J=8.2Hz), 8.05 (2H, d, J=8.2Hz), 8.39 (1H, s), 8.45 (1H, d, J=9.2Hz), 8.52 (1H, d, J=7.8Hz).

[0322] 1 H-NMR(CDCl3) δ:1.09 (3H, t, J=7.3Hz), 2.52(4H, m), 2.46 (2H, q, J=7.3Hz), 3.68 (4H, m), 6.93 (1H, dt, J=1.4Hz, 6.9Hz), 7.39 (1H, ddd, J=0.9Hz, 6.9Hz, 8.70Hz), 7.42 (1H, s), 7.50 (2H, d, J=8.2Hz), 8.04 (2H, d, J=8.2Hz), 8.39 (1H, s), 8.44 (1H, d, J=9.2Hz), 8.53 (1H, d, J=7.3Hz).

[0323] 1H-NMR(CDCl3) δ: 1.24 (3H, m), 2.99 (5H, m), 3.79 (1H, m), 4.67 (1H, m), 6.94 (1H, dt, J=1.4Hz, 6.9Hz), 7.40 (1H, ddd, J=0.9Hz, 6.9Hz, 8.7Hz ), 7.43 (1H, s), 7.50 (2H, d, J=8.2Hz), 8.06 (2H, d, J=8.2Hz), 8.40 (1H, s), 8.46 (1H, d, J=8.9Hz), 8.53 (1H, d, J=6.9Hz).

[0324] Examples 129-131 Synthesis of the following compounds: N,N-dimethyl-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide (Compound 61), 4-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoyl)piperazine-1-carbaldehyde (Compound 68), and N-(2-morpholinoethyl)-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide (Compound 30).

[0325] Compounds (61), (68), and (30) were synthesized from compound (6) in accordance with the synthesis method of compound (49) from compound (49-3).

[0326] 1 H-NMR(CDCl3) δ: 3.02 (3H, s), 3.15 (3H, s), 6.92 (1H, dt, J=1.4Hz, 6.9H), 7.35(1H, s), 7.38 (3H, m), 7.48 (1H, t, J=8.2Hz), 8.05 (1H, m), 8.40 (1H, s), 8.44 (1H, d, J=8.7Hz), 8.51 (1H, d, J=6.9Hz).

[0327] 1H-NMR(CDCl3) δ: 3.65 (8H, m), 6.92 (1H, t, J=6.9Hz), 7.39 (3H, m), 7.49 (1H, d, J=6.9Hz), 8.07 (2H, m), 8.39 (1H, s), 8.43 (1H, t, J=8.7Hz), 8.52 (2H, d, J=6.9Hz).

[0328] 1 H-NMR(D2O) δ: 3.17 (2H, m), 3.31 (2H, t, J=5.7Hz), 3.56 (2H, m), 3.65 (2H, t, J=6.0Hz), 3.75 (2H, m), 4.03 (2H, m), 6.72(1H, t, J=6.6Hz), 7.14 (3H, m), 7.35 (1H, d, J=8.2Hz), 7.48 (1H, d, J=7.8Hz), 7.52 (1H, d, J=8.7Hz), 7.59 (1H, brs), 7.95 (1H, s) ,8.08 (1H, d, J=6.9Hz).

[0329] Examples 132-134 Synthesis of the following compounds: N-methyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 88), N-ethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 89), and N-methoxy-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 91).

[0330] Compounds (88), (89), and (91) were synthesized from compound (87-3) according to the synthesis method of compound (87).

[0331] 1H-NMR(CDCl3) δ: 2.77 (3H, d, J=5.0Hz), 3.64 (2H, s), 5.37 (1H, brs), 6.92 (1H, t, J=6.9Hz), 7.37 (4H, m), 8.00 (2H, d, J=8.2Hz), 8.40 (1H, s), 8.45 (1H, d, J=9.2Hz), 8.53 (1H, d, J=6.9Hz).

[0332] 1 H-NMR(CDCl3) δ: 1.06 (3H, t, J=7.3Hz), 3.26 (2H, q, J=7.3Hz), 3.62 (2H, s), 5.36 (1H, brs), 6.93 (1H, dt, J=1.4Hz, 6.9Hz), 7.38 (4H, m), 8.00 (2H, d, J=8.5Hz), 8.40 (1H, s), 8.45 (1H, d, J=8.2Hz), 8.52 (1H, d, J=7.3Hz).

[0333] 1 H-NMR(CDCl3) δ: 3.60 (3H, s), 3.73 (2H, s), 6.93 (1H, t, J=6.9Hz), 7.38 (4H, m), 7.98 (2H, d, J=8.2Hz), 8.06 (1H, brs), 8.39 (1H, s), 8.45 (1H, d, J=8.7Hz), 8.54 (1H, d, J=6.9Hz).

[0334] [Example 135] Synthesis of (2,5-diazabicyclo[2.2.1]heptan-2-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 43)

[0335] (1) Synthesis of tert-butyl 5-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (Compound 43-1) 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoic acid (Compound 49-3) (53.9 mg, 0.166 mmol), N-(tert-butoxycarbonyl)-2,5-azabicyclo[2.2.1]heptane (53.2 mg, 0.268 mmol), and EDC hydrochloride (141 mg, 0.733 mmol) were added to anhydrous dichloromethane (10 mL), and excess TEA (0.50 mL) was slowly added under ice-cooling. The mixture was gradually returned to room temperature and stirred for 16 hours. Water was added to the reaction mixture under ice cooling, and the dichloromethane layer was washed several times with water. The dichloromethane layer was dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (43-1) (37.2 mg, 0.0742 mmol, yield 43.6%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(CDCl3) δ: 1.43+1.49 (9H, s x2), 1.87 (2H, m), 3.59 (4H, m), 4.55 (2H, m), 6.93 (1H, t, J=6.9Hz), 7.40 (1H, t, J=8.2Hz), 7.44 (1H, s), 7.61 (2H, t, J=8.2Hz), 8.03+8.07 (2H, d x2, J=8.2Hz), 8.39 (1H, s), 8.45 (1H, d, J=9.2Hz), 8.52 (1H, d, J=7.3Hz).

[0336] (2) Synthesis of (2,5-diazabicyclo[2.2.1]heptan-2-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 43) Under ice-cooling, tert-butyl 5-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (Compound 43-1) (32.5 mg, 0.0648 mmol) was slowly added to a 4N hydrochloric acid solution in dioxane (1.0 mL), and the mixture was stirred at room temperature for 2 hours. The solvent was evaporated under reduced pressure and the mixture was dried. Next, a solvent was added, and the solid was collected by filtration, washed thoroughly with the solvent, and dried to obtain the title compound (43) (28.1 mg, 0.281 mmol, yield 91.3%). 1 H-NMR(D2O) δ: 2.05 (2H, m), 3.35 (1H, m), 3.51 (2H, m), 3.70 (1H, m), 4.54 (2H, m), 6.70 (1H, t, J=6.6Hz), 7.09 (1H, m), 7.25 (3H, m), 7.46 (2H, m), 7.52 (1H, m), 7.93 (1H, d, J=6.0Hz), 8.08 (1H, d, J=6.9Hz).

[0337] Examples 136-139 Synthesis of the following compounds: N-(2-(piperazin-1-yl)ethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide hydrochloride (Compound 11), (3-aminopyrrolidin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 42), N-methyl-N-(piperidin-4-yl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide hydrochloride (Compound 44), and piperazin-1-yl(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 57).

[0338] The synthesis method of compound (43) is accurate, the synthesis method of compound (49-3) is compound (11), compound (42), compound (44), and compound (57) is synthesized.

[0339] 1 H-NMR(D2O) δ: 3.35 (4H, t, J=8.2Hz), 3.45 (4H, t, J=8.6Hz), 3.52 (2H, m), 3.61 (2H, m), 6.59 (1H, t, J=6.9Hz), 7.00 (1H, t, J=8.2Hz), 7.07 (1H, s), 7.12 (2H, d, J=8.2Hz), 7.26 (3H, m), 7.83 (1H, s), 8.90 (1H, d, J=7.3Hz).

[0340] 1 H-NMR(D2O) δ: 2.04 (1H, m), 2.31 (1H, m), 3.55 (2H, m), 3.71 (1H, m), 3.89 (2H, m), 6.66 (1H, t, J=6.9Hz), 7.03 (1H, t, J=7.8Hz), 7.09 (1H, d, J=6.5Hz), 7.24 (2H, t, J=8.2Hz), 7.35 (1H, d, J=8.2Hz), 7.43 (2H, m), 7.89 (1H, d, J=10.1Hz), 8.05 (1H, t, J=6.9Hz).

[0341] 1 H-NMR(D2O) δ: 1.89 (4H, m), 2.65+2.85 (3H, s x2), 3.07 (1H, t, J=11.5Hz), 3.27 (1H, d, J=11.0Hz), 3.48 (1H, d, J=11.9Hz), 3.58 (2H, m), 6.62 (1H, d, J=6.4Hz), 7.10 (6H, m), 7.45 (1H, t, J=9.6Hz), 7.79 (1H, s), 8.02 (1H, d, J=6.4Hz).

[0342] 1H-NMR(D2O) δ: 3.17 (2H, m), 3.30 (2H, m), 3.60 (2H, m), 3.88 (2H, m), 6.69 (1H, t, J=6.9Hz), 7.08 (1H, t, J=6.9Hz), 7.15 (1H, brs), 7.21 (2H, d, J=8.2Hz), 7.41 (2H, d, J=8.2Hz), 7.45 (1H, d, J=9.2Hz), 7.92 (1H, s), 8.06 (1H, d, J=6.9Hz).

[0343] Example 140 Synthesis of piperazin-1-yl(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 63) Compound (63) was synthesized from compound (6) according to the synthetic method of compound (43). 1 H-NMR(D2O) δ: 3.13 (2H, m), 3.30 (2H, m), 3.61 (2H, m), 3.89 (2H, m), 6.66 (1H, dt, J=1.4Hz, 6.9Hz), 7.03 (1H, dd, J=0.9Hz, 6.9H), 7.09 (1H, s), 7.22 (2H, m), 7.41 (3H, m), 7.87 (1H, s), 8.03 (1H, d, J=6.9Hz).

[0344] Example 141 Synthesis of 1-(piperazin-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)ethan-1-one hydrochloride (Compound 86) Compound (86) was synthesized from compound (87-3) according to the synthetic method of compound (43). 1H-NMR(D2O) δ: 3.12 (4H, m), 3.63 (2H, s), 3.72 (4H, m), 6.71 (1H, t, J=6.9Hz), 6.94 (2H, d, J=8.2Hz), 7.01 (1H, s), 7.08 (1H, t, J=8.2Hz), 7.24 (2H, d, J=8.2Hz), 7.38 (1H, d, J=9.2Hz), 7.97 (1H, s), 8.08 (1H, d, J=6.9Hz).

[0345] [Example 142] Synthesis of N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)acetamide (Compound 60)

[0346] (1) Synthesis of (5-amino-3,4-dihydroisoquinolin-2(1H)-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 60-1) 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoic acid (Compound 49-3) (53.5 mg, 0.166 mmol), 1,2,3,4-tetrahydroisoquinolin-5-amine (56.5 mg, 0.381 mmol), and EDC hydrochloride (153 mg, 0.800 mmol) were added to anhydrous dichloromethane (10 mL), and excess triethylamine (0.20 mL) was slowly added under ice cooling. The mixture was gradually returned to room temperature and stirred for 16 hours. Water was added to the reaction solution under ice-cooling, and the dichloromethane layer was washed with water several times. The dichloromethane layer was dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (60-1) (29.6 mg, 0.0924 mmol, yield 39.5%) from the n-hexane:ethyl acetate (1:1) fraction. 1H-NMR(CDCl3) δ: 2.66 (2H, m), 3.64 (2H, m), 3.74 (1H, m), 4.10 (1H, m), 4.61 (1H, m), 4.68 (1H, m), 6.38 (0.5H, m), 6.59 (1H, d, J=7.8Hz), 6.68 (0.5H, m), 6.94 (1H, dt, J=1.4Hz, 5.5Hz), 7.02 (1H, m), 7.41 (1H, t, J=6.9Hz), 7.44 (1H, s), 7.56 (2H, m), 8.07 (2H, d, J=7.8Hz), 8.41 (1H, s), 8.48 (1H, d, J=9.2Hz), 8.53 (1H, d, J=6.9Hz).

[0347] (2) Synthesis of N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)acetamide (Compound 60) To an acetonitrile solution (10 mL) were added (5-amino-3,4-dihydroisoquinolin-2(1H)-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 60-1) (35.2 mg, 0.0780 mmol), acetic anhydride (0.10 mL), excess TEA (0.20 mL), and a catalytic amount of DMAP (5.1 mg) under water cooling, followed by stirring at room temperature for 16 hours. The solvent was evaporated under reduced pressure from the reaction mixture, and the residue was purified by silica gel column chromatography to obtain the title compound (60) (26.5 mg, 0.537 mmol, yield 74.6%) from the n-hexane:ethyl acetate (1:1) fraction. 1H-NMR(CDCl3) δ: 2.20 (3H, s), 2.80 (2H, m), 3.69 (1H, m), 4.02 (1H, m), 4.66 (1H, m), 4.90 (1H, m), 6.94 (1H, t, J=8.2Hz), 7.16 (2H, m), 7.41 (1H, t, J=7.8Hz), 7.43 (1H, s), 7.53 (2H, m), 7.60 (1H, m), 8.06 (2H, d, J=8.7Hz), 8.40 (1H, s), 8.46 (1H, d, J=8.7Hz), 8.53 (1H, d, J=6.9Hz).

[0348] [Example 143] Synthesis of 2-(hydroxymethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 8)

[0349] (1) Synthesis of methyl 5-(2-bromoacetyl)-2-hydroxybenzoate (compound 8-1) Methyl 5-acetylsalicylate (1.01 g, 5.19 mmol) was added to ethyl acetate (50 mL), and the mixture was cooled to 100°C. ２ (2.35 g, 10.5 mmol) was added and the mixture was heated to reflux for 3 hours. After cooling, insoluble matter was filtered through Celite, the organic solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (8-1) (1.37 g, 4.98 mmol, yield 95.8%) from the n-hexane:ethyl acetate (1:4) fraction. 1 H-NMR(CDCl3) δ: 4.00 (3H, s), 4.39 (2H, s), 7.06 (1H, t, J=8.7Hz), 8.10 (1H, dd, J=2.3Hz, 9.1Hz), 8.51 (1H, d, J=2.3Hz), 11.35 (1H, s).

[0350] (2) Synthesis of methyl 2-hydroxy-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoate (Compound 8-2) Pyrazolo[1,5-a]pyridine-3-carbothioamide (96.1 mg, 0.542 mmol) was dissolved in DME (20 mL), and methyl 5-(2-bromoacetyl)-2-hydroxybenzoate (Compound 8-1) (146 mg, 0.534 mmol) was added under ice-cooling, followed by stirring at room temperature for 16 hours. The reaction solution was heated and stirred at 50°C for 1 hour, then allowed to cool, and the solvent was distilled off under reduced pressure. Ethanol (20 mL) was added thereto, followed by excess potassium carbonate (246 mg), and the reaction solution was heated to reflux at 70°C for 1 hour. After cooling, the reaction solution was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (8-2) (76.5 mg, 0.218 mmol, yield 40.2%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(CDCl3) δ: 4.01 (3H, s), 6.93 (1H, t, J=6.9Hz), 7.08 (1H, d, J=8.7Hz), 7.28 (1H, s), 7.39 (1H, t, J=7.8Hz), 8.14 (1H, dd, J=2.3Hz, 8.7Hz), 8.43 (3H, m), 8.52 (1H, d, J=6.9Hz).

[0351] (3) Synthesis of 2-(hydroxymethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 8) Excess LAH (138 mg) was carefully added to dry diethyl ether (10 mL), and 2-hydroxy-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)methyl benzoate (Compound 8-2) (98.4 mg, 0.28 mmol) was slowly added at −20° C. The temperature was gradually returned to room temperature and stirred for 16 hours. The reaction solution was ice-cooled, and saturated Na ２ SO ４An aqueous solution was added. The precipitated insoluble matter was filtered and washed with ethyl acetate. The organic layers were combined, dried over anhydrous magnesium sulfate, and filtered. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (8) (6.5 mg, 0.0201 mmol, yield 7.2%) from the n-hexane:ethyl acetate (1:4) fraction. 1 H-NMR(CDCl3) δ: 4.97 (2H, d, J=5.5Hz), 6.91 (1H, t, J=5.5Hz), 6.97 (1H, d, J=8.7Hz), 7.20 (1H, s), 7.37 (1H, t, J=7.3Hz), 7.50 (1H, brs), 7.70 (1H, d, J=2.3Hz), 7.83 (1H, dd, J=2.3Hz, 8.7Hz), 8.38 (1H, s), 8.41 (1H, d, J=8.7Hz), 8.50 (1H, d, J=6.9Hz).

[0352] [Examples 144 and 145] Synthesis of (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanol (Compound 2) and 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)ethan-1-ol (Compound 84) Compound (2) was synthesized from compound (49-2) and compound (84) was synthesized from compound (87-2) in accordance with the synthetic method of compound (8) from compound (8-2).

[0353] 1 H-NMR(CDCl3) δ: 1.68 (1H, t, J=6.0Hz), 4.75 (2H, d, J=5.5Hz), 6.92 (1H, t, J=6.9Hz), 7.36 (1H, s), 7.38 (1H, dd, J=2.3Hz, 6.9Hz), 7.45 (2H, d, J=8.2Hz), 8.00 (2H, d, J=7.8Hz), 8.39 (1H, s), 8.46 (1H, d, J=9.2Hz), 8.52 (1H, d, J=7.3Hz).

[0354] 1 H-NMR(CDCl3) δ: 2.92 (2H, t, J=6.4Hz), 3.90 (2H, t, J=5.5Hz), 6.92 (1H, dt, J=1.4Hz, 6.9Hz), 7.33 (3H, m), 7.38 (1H, ddd, J=0.9Hz, 6.9Hz, 7.8Hz), 7.96 (2H, d, J= 8.2Hz), 8.39 (1H, s), 8.46 (1H, d, J=8.7Hz), 8.52 (1H, d, J=7.3Hz).

[0355] [Example 146] Synthesis of 4-(3-(2,5-dihydro-1H-pyrrol-3-yl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (Compound 17)

[0356] (1) Synthesis of 3-iodophenacyl bromide (Compound 17-1) 3-iodoacetophenone (5.17 g, 21.0 mmol) was added to ethyl acetate (200 mL), and CuBr ２ (12.1 g, 58.4 mmol) was added, and the mixture was heated to reflux for 3 hours. After allowing to cool, insoluble matter was filtered through Celite, the organic solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (17-1) (3.69 g, 11.7 mmol, yield 54.1%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(CDCl3) δ: 4.40 (2H, s), 7.25 (2H, m), 7.94 (1H, dd, J=0.9Hz, 8.2Hz), 8.30 (1H, d, J=1.4Hz).

[0357] (2) Synthesis of 4-(3-iodophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 17-2) Pyrazolo[1,5-a]pyridine-3-carbothioamide (273 mg, 1.54 mmol) was dissolved in DME (15 mL), and 3-iodophenacyl bromide (Compound 17-1) (494 mg, 1.52 mmol) was added under ice cooling, followed by stirring at room temperature for 16 hours. The reaction solution was heated and stirred at 50°C for 1 hour, then allowed to cool, and the solvent was distilled off under reduced pressure. Ethanol (15 mL) was added to the residue, followed by potassium carbonate (503 mg), and the reaction solution was heated to reflux at 70°C for 1 hour. After allowing the reaction mixture to cool, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (17-2) (355 mg, 0.880 mmol, yield 57.9%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(CDCl3) δ: 6.94 (1H, dt, J=1.4Hz, 6.7Hz), 7.18 (1H, t, J=8.7Hz), 7.37 (1H, s), 7.41 (1H, ddd, J=1.4Hz, 6.9Hz, 9.2Hz), 7.67 (1H, dt, J=1.8Hz, 7.8Hz), 7.96 (1H, dt, J=1.8Hz, 8.7Hz), 8.35 (1H, t, J=1.8Hz), 8.40 (1H, s), 8.43 (1H, d, J=7.3Hz), 8.52 (1H, d, J=6.9Hz).

[0358] (3) Synthesis of tert-butyl 3-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate (Compound 17-3) 4-(3-iodophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 17-2) (50.6 mg, 0.125 mmol), 1-(tert-butoxycarbonyl)-2,5-dihydro-1H-pyrrol-3-yl-boronic acid pinacol ester (55.3 mg, 0.187 mmol), a catalytic amount of Pd(PPh ３ ) ４(16.6 mg) and excess sodium carbonate (162 mg) were dissolved in a mixed solvent of DME (4 mL) and water (1 mL), and the mixture was heated to reflux for 1 hour. After cooling, the reaction mixture was distilled under reduced pressure to remove the solvent, and the residue was purified by silica gel column chromatography to obtain the title compound (17-3) (21.2 mg, 0.0467 mmol, yield 25.5%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(CDCl3) δ: 1.53 (9H, s), 4.35 (2H, m), 4.58 (2H, m), 6.25 (1H, m), 6.93 (1H, t, J=6.9Hz), 7.41 (4H, m), 7.94 (1H, t, J=8.2Hz), 8.00 (1H, d, J=5.0Hz), 8.41 (1H, s), 8.43 (1H, d, J=9.2Hz), 8.53(1H, d, J=6.9Hz).

[0359] (4) Synthesis of 4-(3-(2,5-dihydro-1H-pyrrol-3-yl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (Compound 17) Under ice-cooling, tert-butyl 3-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate (Compound 17-3) (16.7 mg, 0.0378 mmol) was slowly added to a 4N hydrochloric acid dioxane solution (1.0 mL), and the mixture was stirred at room temperature for 2 hours. The solvent was evaporated to dryness under reduced pressure. The solvent was added, and the resulting solid was collected by filtration, washed with the solvent, and then dried to obtain the title compound (17) (12.8 mg, 0.308 mmol, yield 81.5%). 1 H-NMR(D2O) δ: 4.02 (4H, m), 5.81 (1H, s), 6.58 (1H, t, J=6.7Hz), 6.74 (3H, m), 6.91 (3H, m), 7.08 (1H, d, J=8.7Hz), 7.72 (1H, s), 7.89 (1H, d, J=6.9Hz).

[0360] [Example 147] Synthesis of 6-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)-2-oxa-6-azaspiro[3.3]heptane (Compound 29)

[0361] (1) Synthesis of 4-bromoacetylbenzaldehyde (Compound 29-1) 4-acetylbenzaldehyde (2.24 g, 15.1 mmol) was added to ethyl acetate (75 mL), and CuBr ２ (6.89 g, 30.8 mmol) was added and the mixture was heated to reflux for 3 hours. After cooling, insoluble matter was filtered through Celite, the organic solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (Compound 29-1) (3.19 g, 14.1 mmol, yield 93.4%) from the n-hexane:ethyl acetate (4:1) fraction. 1 H-NMR(CDCl3) δ: 4.42 (2H, s), 8.00 (2H, d, J=8.2Hz), 8.14 (2H, d, J=8.2Hz), 10.10 (1H, s).

[0362] (2) Synthesis of 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzaldehyde (Compound 29-2) Pyrazolo[1,5-a]pyridine-3-carbothioamide (1.23 g, 6.96 mmol) was dissolved in DME (40 mL), and 4-bromoacetylbenzaldehyde (Compound 29-1) (1.55 g, 6.83 mmol) was added under ice-cooling, followed by stirring at room temperature for 16 hours. The reaction solution was heated and stirred at 50°C for 1 hour, then allowed to cool, and the solvent was distilled off under reduced pressure. Ethanol (80 mL) was added to the residue, followed by the addition of excess potassium carbonate (1.25 g), and the reaction solution was heated to reflux at 70°C for 1 hour. After allowing the reaction mixture to cool, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (29-2) (638 mg, 2.09 mmol, yield 30.6%) from the n-hexane:ethyl acetate (1:1) fraction. 1H-NMR(CDCl3) δ: 6.95 (1H, dt, J=1.4Hz, 6.9Hz), 7.45 (1H, t, J=0.9Hz, 6.9Hz, 8.7Hz), 7.55 (1H, s), 7.97 (2H, d, J=8.2Hz), 8.18 (2H, d, J=8.7Hz), 8.41 (1H, s), 8.46 (1H, d, J=8.7Hz), 8.53 (1H, d, J=7.3Hz), 10.05 (1H, s).

[0363] (3) Synthesis of 6-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)-2-oxa-6-azaspiro[3.3]heptane (Compound 29) 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzaldehyde (Compound 29-2) (53.5 mg, 0.175 mmol) and 2-oxa-6-azaspiro[3.3]heptane (62.1 mg, 0.626 mmol) were added to dichloromethane (10 mL), and the mixture was stirred at room temperature for 1 hour. After stirring, the mixture was cooled with NaBH(OAc) under ice-cooling. ３ (72.9 mg, 0.433 mmol) was added, and the mixture was stirred for 16 hours while returning to room temperature. Water was added to the reaction mixture under ice-cooling, and the dichloromethane layer was washed several times with water, dried over anhydrous magnesium sulfate, and filtered. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (29) (25.2 mg, 0.0649 mmol, yield 36.0%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(CDCl3) δ: 3.39 (4H, s), 3.58 (2H, s), 4.75 (4H, s), 6.92 (1H, dt, J=1.6Hz, 6.9Hz), 7.33 (3H, m), 7.38 (1H, m), 7.95 (2H, d, J=8.2Hz), 8.39 (1H, s), 8.46 (1H, d, J=8.7Hz), 8.51 (1H, d, J=7.3Hz).

[0364] [Examples 148 to 151] Synthesis of the following compounds: N,N-dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanamine (Compound 27), 4-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 28), N,N-dimethyl-4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-2-carboxamide (Compound 38), and N,2-dimethyl-4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-2-carboxamide (Compound 39).

[0365] Compounds (27), (28), (38), and (39) were synthesized using compound (29-2) according to the synthesis method for compound (29).

[0366] 1 H-NMR(CDCl3) δ: 2.27 (6H, s), 3.48 (2H, s), 6.92 (1H, dt, J=1.4Hz, 6.9Hz), 7.38 (4H, m), 7.96 (2H, d, J=8.2Hz), 8.39 (1H, s), 8.47 (1H, d, J=8.7Hz), 8.51 (1H, d, J=7.3Hz).

[0367] 1 H-NMR(CDCl3) δ: 2.28 (3H, s), 2.48 (8H, m), 3.54 (2H, s), 6.91 (1H, dt, J=0.9Hz, 6.9Hz), 7.33 (1H, s), 7.37 (1H, m), 7.40 (2H, d, J=8.2Hz), 7.94 (2H, d, J=8.7Hz), 8.38 (1H, s), 8.46 (1H, d, J=8.7Hz), 8.51 (1H, d, J=7.3Hz).

[0368] 1H-NMR(CDCl3) δ: 2.29 (1H, t, J=11.5Hz), 2.42 (1H, t, J=11.5Hz), 2.71 (1H, d, J=11.5Hz), 2.92 (1H, d, J=8.2Hz), 2.93 (3H, s), 3.05 (3H, s), 3.60 (2H, d, J=3.1Hz), 3.72 (1H, t, J=11.5Hz), 3.94 (1H, d, J=13.3Hz), 4.29 (1H, d, J=7.8Hz), 6.92 (1H, dt, J=1.8Hz, 6.9Hz), 7.35 (1H, s), 7.39 (1H, t, J=7.8Hz), 7.41 (2H, d, J=7.3Hz), 7.96 (2H, d, J=7.8Hz), 8.40 (1H, s), 8.47 (1H, d, J=8.7Hz), 8.52 (1H, d, J=6.9Hz).

[0369] 1 H-NMR(CDCl3) δ: 1.44 (3H, s), 2.34 (1H, m), 2.44 (1H, m), 2.50 (1H, d, J=11.5Hz), 2.70 (1H, d, J=10.4Hz), 2.83 (3H, d, J=5.0Hz), 3.54 (2H, s), 3.75 (1H, m), 3.83 (1H, m), 6.71 (1H, m), 6.91 (1H, dt, J=1.4Hz, 6.9Hz), 7.34 (1H, s), 7.38 (3H, m), 7.95 (2H, d, J=8.2Hz), 8.39 (1H, s), 8.47 (1H, d, J=8.7Hz), 8.51 (1H, d, J=6.9Hz).

[0370] [Example 152] Synthesis of 1-morpholino-2-(4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)piperazin-1-yl)ethane-1,2-dione hydrochloride (Compound 36) 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzaldehyde (Compound 29-2) (58.1 mg, 0.190 mmol) and 1-morpholino-2-(piperazin-1-yl)ethane-1,2-dione (50.5 mg, 0.222 mmol) were added to dichloromethane (10 mL), and the mixture was stirred at room temperature for 1 hour. After that, the mixture was cooled with NaBH(OAc) ３ (113 mg, 0.533 mmol) was added, and the mixture was stirred for 16 hours while returning to room temperature. Water was added to the reaction mixture under ice-cooling, and the dichloromethane layer was washed several times with water, dried over anhydrous magnesium sulfate, and filtered. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (36-1) (35.5 mg, 0.0687 mmol, yield 36.2%) from the n-hexane:ethyl acetate (1:4) fraction. 1 H-NMR (CDCl) δ: 2.50 (4H, m), 3.43 (4H, m), 3.58 (2H, s), 3.70 (8H, m), 6.92 (1H, dt, J = 1.4 Hz, 8.5 Hz), 7.36 (4H, m), 7.97 (2H, d, J = 7.8 Hz), 8.40 (1H, s), 8.46 (1H, d, J = 8.7 Hz), 8.52 (1H, d, J = 6.9 Hz). The amine (compound 36-1) was then converted to the hydrochloride salt of the title compound (36) by a standard method. 1 H-NMR(D2O) δ: 3.21 (4H, m), 3.34 (2H, m), 3.50 (2H, m), 3.62 (8H, m), 4.17 (2H, s), 6.62 (1H, t, J=6.9Hz), 6.98 (2H, m), 7.14 (2H, d, J=8.2Hz), 7.33 (3H, m), 7.75 (1H, s), 7.99 (1H, d, J=6.9Hz).

[0371] [Examples 153 and 154] Synthesis of 4-(4-((2,5-diazabicyclo[2.2.1]heptan-2-yl)methyl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (Compound 34), and N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)piperidin-4-amine hydrochloride (Compound 35) Compounds (34) and (35) were synthesized according to the synthetic methods of compound (29) and compound (1).

[0372] 1 H-NMR(D2O) δ: 2.24 (1H, d, J=13.3Hz), 2.56 (1H, d, J=13.3Hz), 3.56 (2H, m), 3.70 (2H, m), 4.30 (1H, d, J=13.3Hz), 4.43 (1H, d, J=13.3Hz), 4.53 (1H, s), 4.59 (1H, s), 6.83 (1H, t, J=6.6Hz), 7.26 (1H, t, J=8.2Hz), 7.35 (2H, d, J=8.2Hz), 7.40 (1H, s), 7.60 (2H, d, J=8.2Hz), 7.76 (1H, d, J=9.2Hz), 8.12 (1H, s), 8.23 ​​(1H, d, J=6.9Hz).

[0373] 1 H-NMR(D2O) δ: 1.15 (2H, m), 2.00 (2H, m), 2.31 (2H, m), 2.65 (3H, s), 3.03 (2H, t, J=11.5Hz), 3.60 (1H, m), 4.10 (1H, m), 4.39(1H, m), 6.79 (1H, t, J=6.9Hz), 7.22 (1H, t, J=8.2Hz), 7.28 (1H, s), 7.31 (2H, d, J=9.6Hz), 7.54 (2H, d, J=7.8Hz), 7.68 (1H, d, J=8.7Hz), 8.07 (1H, s), 8.17 (1H, d, J=6.9Hz).

[0374] [Example 155] Synthesis of 4-(isoindolin-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (Compound 117)

[0375] (1) Synthesis of 1,1'-(isoindoline-2,5-diyl)bis(ethan-1-one) (Compound 117-1) 5-Acetylisoindoline (402 mg, 2.49 mmol) was added to acetonitrile (20 mL), and acetic anhydride (0.35 mL) and excess TEA (0.70 mL) were added under ice cooling, followed by stirring at room temperature for 16 hours. The solvent was distilled off from the reaction mixture under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (117-1) (366 mg, 1.80 mmol, yield 72.3%) from the n-hexane:ethyl acetate (1:4) fraction. 1 H-NMR(CDCl3) δ: 2.18 (3H, s), 2.61 (3H, s), 4.83 (2H, s), 4.85 (2H, s), 7.35 (1H, dd, J=8.2Hz, 10.0Hz), 7.87 (1H, d, J= 10.0Hz,), 7.90 (1H, d, J=8.2Hz).

[0376] (2) Synthesis of 1-(2-acetylisoindolin-5-yl)-2-bromoethan-1-one (Compound 117-2) 1,1'-(isoindoline-2,5-diyl)bis(ethan-1-one) (Compound 117-1) (194 mg, 0.952 mmol) was added to ethyl acetate (50 mL), and CuBr ２ (522 mg, 2.34 mmol) was added, and the mixture was heated to reflux for 6.5 hours. After allowing to cool, insoluble matter was filtered through Celite, the organic solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (117-2) (106 mg, 0.375 mmol, yield 39.4%) from the n-hexane:ethyl acetate (1:4) fraction. 1 H-NMR(CDCl3) δ: 2.15 (3H, brs), 4.43 (2H, s), 4.88 (4H, brs), 7.43 (1H, m), 7.91 (2H, m).

[0377] (3) Synthesis of 1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoindolin-2-yl)ethan-1-one (Compound 117-3) Pyrazolo[1,5-a]pyridine-3-carbothioamide (73.5 mg, 0.415 mmol) was dissolved in DME (10 mL), and 1-(2-acetylisoindolin-5-yl)-2-bromoethan-1-one (Compound 117-2) (106 mg, 0.375 mmol) was added under ice-cooling, followed by stirring at room temperature for 16 hours. The reaction solution was heated and stirred at 50°C for 1 hour, then allowed to cool, and the solvent was distilled off under reduced pressure. Ethanol (10 mL) was added to the residue, followed by the addition of excess potassium carbonate (141 mg), and the reaction solution was heated to reflux at 70°C for 1 hour. After allowing the reaction mixture to cool, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (117-3) (66.8 mg, 0.185 mmol, yield 44.7%) from the n-hexane:ethyl acetate (1:4) fraction. 1 H-NMR(CDCl3) δ: 2.19 (3H, s), 4.85 (4H, dd, J=10.5Hz, 16.3Hz), 6.93 (1H, dt, J=1.4Hz, 6.9Hz), 7.38 (3H, m), 7.93 (2H, m), 8.42 (2H, m), 8.52 (1H, d, J=6.9Hz).

[0378] (4) Synthesis of 4-(isoindolin-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (Compound 117) 1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoindolin-2-yl)ethan-1-one (Compound 117-3) (44.5 mg, 0.123 mmol) was suspended in 6N hydrochloric acid (1.0 mL), and the mixture was heated to reflux for 6 hours. After cooling, the solvent was evaporated under reduced pressure, and ethanol was added several times to dry the mixture. The resulting solid was dissolved in water (30 mL), and ethyl acetate (30 mL) was added, followed by partitioning. The aqueous layer was concentrated under reduced pressure, and ethanol was added several times. The solvent was evaporated under reduced pressure, and the mixture was dried to obtain the title compound (117) (30.1 mg, 0.0773 mmol, yield 62.8%). 1H-NMR(D2O) δ: 4.36 (4H, d, J=5.5Hz), 6.66 (1H, t, J=7.1Hz), 6.93 (1H, d, J=8.2Hz), 7.04 (3H, m), 7.15 (1H, brs), 7.38 (1H, d, J=8.7Hz), 7.86 (1H, s), 7.98 (1H, d, J=6.9Hz).

[0379] Example 156 Synthesis of N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenethyl)acetamide (Compound 62) Compound (62) was synthesized according to the synthetic methods of compound (117-1), compound (69), and compound (118). 1 H-NMR(CDCl3) δ: 1.95 (3H, s), 2.86 (2H, t, J=6.9Hz), 2.98 (3H, s), 3.55 (2H, q, J=6.9Hz), 6.92 (1H, dt, J=1.4Hz, 6.9Hz), 7.28 (2H, d, J=8.2Hz), 7.34 (1H, s), 7.38 (1H, ddd, J=0.9Hz, 6.9Hz, 8.7Hz), 7.95 (2H, d, J=8.2Hz), 8.39 (1H, s), 8.45 (1H, d, J=9.2Hz), 8.51 (1H, d, J=7.3Hz).

[0380] Example 157 Synthesis of 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)ethan-1-amine hydrochloride (Compound 113) Compound (113) was synthesized according to the synthetic method of compound (118). 1H -NMR(D2O) δ: 2.87 (2H, t, J=8.2Hz), 3.07 (2H, m), 7.09 (1H, t, J= 6.9Hz), 7.35 (2H, d, J=8.2Hz), 7.55 (1H, d, J=7.8Hz), 7.75 (2H, brs), 7.98 (1H, s), 8.02 (2H, d, J=8.2Hz), 8.39 (1H, d, J=8.7Hz), 8.61 (1H, s), 8.83 (1H, d, J=9.2Hz).

[0381] Examples 158 and 159 Synthesis of N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 67), and N-methyl-N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 70) Compound (67) was synthesized according to the synthetic methods of compound (117-1) and compound (118), and compound (70) was synthesized from compound (67) according to the synthetic method of compound (69).

[0382] 1 H-NMR(CDCl3) δ: 2.06 (3H, s), 4.53 (2H, d, J=5.5Hz), 5.76 (1H, brs), 6.93 (1H, dt, J=1.1Hz, 6.9Hz), 7.29 (1H, d, J=7.3Hz), 7.43 (3H, m), 7.93 (2H, m), 8.40 (1H, s), 8.45 (1H, d, J=9.2Hz), 8.52 (1H, d, J=6.9Hz).

[0383] 1H-NMR(CDCl3) δ: 2.19+2.21 (3H, s x2), 2.96+3.00 (3H, s x2), 4.62+6.42 (2H, s x2), 6.93 (1H, m), 7.18 (1H, d, J=7.8Hz), 7.42 (3H, m), 7.86 (1H, d, J=10.4Hz), 7.92 (1H, m), 8.40 (1H, s), 8.44 (1H, d, J=9.2Hz), 8.52 (1H, d, J=6.9Hz).

[0384] [Example 160] Synthesis of N,N-dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 137)

[0385] (1) Synthesis of 2-((4-bromopyridin-2-yl)methyl)isoindoline-1,3-dione (Compound 137-1) (4-Bromopyridin-2-yl)methanamine (2.0 g, 11 mmol) was dissolved in acetic acid (25 mL), phthalic anhydride (2.3 g, 16 mmol) was added, and the mixture was heated to reflux at 130° C. for 3 hours. After cooling, the acetic acid was distilled off under reduced pressure, an aqueous potassium carbonate solution was added to the residue, extracted with dichloromethane, and then dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure, and dichloromethane and methanol were added to the residue. The suspended solid was filtered with suction and dried under reduced pressure to obtain the title compound (137-1) (1.9 g, 6.0 mmol, yield 57.3%). 1 H-NMR(CDCl3) δ: 4.99 (2H, s), 7.34 (1H, dd, J=1.8Hz, 5.4Hz), 7.46 (1H, d, J=2.0Hz), 7.73-7.79 (2H, m), 7.87-7.94 (2H, s), 8.34 (1H, d, J=5.6Hz).

[0386] (2) Synthesis of 2-((4-acetylpyridin-2-yl)methyl)isoindoline-1,3-dione (Compound 137-2) 2-((4-bromopyridin-2-yl)methyl)isoindoline-1,3-dione (Compound 137-1) (1.9 g, 6.0 mmol) was dissolved in toluene (12 mL), and tributyl(1-ethoxyvinyl)tin (2.4 mL, 7.2 mmol), PdCl ２ (PPh ３ ) ２ (43.7 mg, 0.062 mmol) was added, and the mixture was heated at 160°C for 5 minutes using a microwave synthesis apparatus. After cooling, 2N hydrochloric acid (12 mL) was added to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. Aqueous sodium hydroxide solution was added to the resulting reaction mixture, and the mixture was extracted with ethyl acetate and then dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (137-2) (0.9 g, 3.3 mmol, yield 54.5%) from the n-hexane:ethyl acetate (1:1) fraction. 1 H-NMR(CDCl3) δ: 2.62 (3H, s), 5.10 (2H, s), 7.59-7.63 (1H, m), 7.72-7.74 (1H, m), 7.75-7.78 (2H, m), 7.87-7.94 (2H, m), 8.71 (1H, d, J=5.2Hz).

[0387] (3) Synthesis of 2-((4-(2-bromoacetyl)pyridin-2-yl)methyl)isoindoline-1,3-dione hydrobromide (Compound 137-3) 2-((4-acetylpyridin-2-yl)methyl)isoindoline-1,3-dione (Compound 137-2) (919.1 mg, 3.3 mmol) was dissolved in acetic acid (10 mL), and bromine (169 μL, 3.3 mmol) and hydrobromic acid (30% acetic acid solution, approximately 5.1 mol / L) (1.6 mL, 8.2 mmol) were added under ice cooling, followed by heating and stirring at 70° C. for 1 hour. After cooling, diethyl ether was added, and the precipitated solid was stirred at room temperature for a while, filtered with suction, washed with diethyl ether, and dried under reduced pressure to obtain the title compound (137-3) (1.3 g, 3.0 mmol, yield 92.9%). 1H-NMR(CD3OD) δ: 3.68 (1H, d, J=10.8Hz), 3.77 (1H, d, J=10.8Hz), 5.28 (2H, s), 7.85-7.90 (2H, m), 7.94-7.97 (2H, m), 8.14 (1H, d, J=5.6Hz), 8.18-8.21 (1H, m), 8.78 (1H, d, J=6.0Hz).

[0388] (4) Synthesis of 2-((4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methyl)isoindoline-1,3-dione (Compound 137-4) Pyrazolo[1,5-a]pyridine-3-carbothioamide (479.0 mg, 2.7 mmol) was dissolved in DME (20 mL), and 2-((4-(2-bromoacetyl)pyridin-2-yl)methyl)isoindoline-1,3-dione hydrobromide (Compound 137-3) (1.3 g, 2.7 mmol) was added under ice cooling, followed by stirring at room temperature for 15 hours. The reaction solution was heated and stirred at 50°C for 1 hour, then allowed to cool, and the solvent was distilled off under reduced pressure. Ethanol (20 mL) and potassium carbonate (1.1 g, 8.1 mmol) were added to the residue, and the mixture was heated to reflux at 80°C for 1 hour. After cooling, dichloromethane and methanol were added to the reaction mixture, which was then filtered with suction. The filtrate was dried under reduced pressure to obtain the title compound (137-4) (917.4 mg, 2.1 mmol, yield 77.7%). 1 H-NMR(CDCl3) δ: 5.12 (2H, s), 6.96 (1H, ddd, J=1.1Hz, 6.8Hz, 6.8Hz), 7.36-7.43 (1H, m), 7.60 (1H, s), 7.72-7.81 (3H, m), 7.91-7.95 (3H, m), 8.39 (1H, s), 8.43 (1H, d, J=9.2Hz), 8.54 (1H, d, J=6.8Hz), 8.61 (1H, d, J=5.2Hz).

[0389] (5) Synthesis of (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 137-5) 2-((4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methyl)isoindoline-1,3-dione (Compound 137-4) (721.9 mg, 1.7 mmol) was dissolved in ethanol (15 mL), and hydrazine monohydrate (0.3 mL, 6.6 mmol) was added, followed by heating at 160° C. for 10 minutes using a microwave synthesis apparatus. After allowing to cool, dichloromethane and methanol were added to the resulting reaction solution. The suspended solid was filtered with suction and dried under reduced pressure to obtain the title compound (137-5) (373.3 mg, 1.2 mmol, yield 73.6%). 1 H-NMR(CD3OD) δ: 4.19 (2H, s), 7.10 (1H, ddd, J=1.0Hz, 7.0Hz, 7.0Hz), 7.53-7.59 (1H, m), 7.81-7.87 (2H, m), 7.99 (1H, dd, J=1.6Hz, 5.2Hz), 8.12 (1H, s), 8.16-8.22 (2H, m), 8.50 (1H, d, J=8.8Hz), 8.63 (1H, d, J=5.2Hz), 8.67 (1H, d, J=7.2Hz).

[0390] (6) Synthesis of N,N-dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 137) (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 137-5) (131.9 mg, 0.43 mmol) was dissolved in methanol (4 mL), and the solution was added with formaldehyde (342 μL, 3.4 mmol), acetic acid (59 μL, 1.0 mmol), NaBH(OAc) ３(727.0 mg, 3.4 mmol) was added and stirred at room temperature for 4 hours. Aqueous sodium bicarbonate solution was added to the resulting reaction mixture, which was extracted with dichloromethane and then dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (137) (30.0 mg, 0.089 mmol, yield 20.8%) from the dichloromethane:methanol (40:1) fraction. 1 H-NMR(CDCl3) δ: 2.36 (6H, s), 3.68 (2H, s), 6.96 (1H, ddd, J=1.1Hz, 6.8Hz, 7.0Hz), 7.40-7.47 (1H, m), 7.64 (1H, s), 7.81-7.87 (1H, m), 7.91 (1H, s), 8.42 (1H, s), 8.45 (1H, d, J=9.2Hz), 8.55 (1H, d, J=7.6Hz), 8.66 (1H, d, J=4.8Hz).

[0391] Example 161 Synthesis of N,N-dimethyl-1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 128) Compound (128) was synthesized according to the synthetic method of compound (137). 1 H-NMR(CDCl3) δ: 2.37 (6H, s), 3.65 (2H, s), 6.94 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 7.36-7.42 (1H, m), 7.43 (1H, s), 7.49 (1H, d, J=8.4Hz), 8.26 (1H, dd, J=2.2Hz, 8.4Hz), 8.40 (1H, s), 8.45 (1H, d, J=8.8Hz), 8.53 (1H, d, J=6.8Hz), 9.17-9.23 (1H, m).

[0392] [Example 162] Synthesis of N-methyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 136)

[0393] (1) Synthesis of N-((4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methyl)acetamide (Compound 136-1) (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 137-5) (101.9 mg, 0.33 mmol) was dissolved in dichloromethane (3 mL), acetic anhydride (63 μL, 0.66 mmol) and TEA (93 μL, 0.66 mmol) were added, and the mixture was stirred at room temperature for 2 hours. Aqueous sodium hydrogen carbonate solution was added to the resulting reaction mixture, which was extracted with dichloromethane and then dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (136-1) (74.1 mg, 0.21 mmol, yield 63.9%) from the dichloromethane:methanol (40:1) fraction. 1 H-NMR(CD3OD) δ: 2.11 (3H, s), 4.57 (2H, s), 7.10 (1H, ddd, J=1.6Hz, 6.8Hz, 6.8Hz), 7.52-7.59 (1H, m), 7.94 (1H, dd, J=1.4Hz, 5.4Hz), 8.05 (1H, s), 8.10 (1H, s), 8.46-8.53 (2H, m), 8.54 (1H, d, J=5.6Hz), 8.66 (1H, d, J=7.2Hz).

[0394] (2) Synthesis of N-methyl-N-((4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methyl)acetamide (Compound 136-2) Sodium hydride (oil dispersion) (87.8 mg, 1.8 mmol) was carefully added to anhydrous DMF (4 mL) to form a suspension, and then cooled to 0° C., followed by slow addition of N-((4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methyl)acetamide (Compound 136-1) (159.8 mg, 0.46 mmol). The mixture was warmed to room temperature, cooled to 0° C., and then methyl iodide (31 μL, 0.50 mmol) was added dropwise. The mixture was stirred for 1 hour while gradually returning to room temperature. Water was carefully and gradually added to the reaction solution under ice-cooling. Aqueous sodium hydrogen carbonate solution was added to the resulting reaction mixture, which was then extracted with dichloromethane and dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure, and the residue was subjected to preparative thin-layer chromatography (TLC). The title compound (136-2) (120.4 mg, 0.33 mmol, yield 72.5%) was obtained from the dichloromethane:methanol (20:1) fraction. 1 H-NMR(CDCl3) δ: 2.22+2.23 (3H, s x2), 3.09+3.11 (3H, s x2), 4.71+4.80 (2H, s x2), 6.93-7.00 (1H, m), 7.40-7.51 (1H, m), 7.61+7.62 (1H, s x2), 7.73-7.85 (2H, m x2), 8.38-8.48 (2H, m), 8.52-8.58 (1H, m), 8.61-8.69 (1H, m x2).

[0395] (3) Synthesis of N-methyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 136) N-methyl-N-((4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methyl)acetamide (Compound 136-2) (51.6 mg, 0.14 mmol) was dissolved in methanol (3 mL), and 6N aqueous sodium hydroxide solution (3 mL) was added. The mixture was heated at 120° C. for 30 minutes and at 140° C. for 10 minutes using a microwave synthesizer. Water was added to the resulting reaction mixture, and the mixture was extracted with dichloromethane and then dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure, and the residue was subjected to preparative thin layer chromatography (TLC). From the dichloromethane:methanol (40:1) fraction, the title compound (136) (37.7 mg, 0.12 mmol, yield 82.7%) was obtained. 1 H-NMR(CDCl3) δ: 2.55 (3H, s), 3.97 (2H, s), 6.95 (1H, ddd, J=1.2Hz, 6.8Hz, 6.8Hz), 7.38-7.48 (1H, m), 7.61 (1H, s), 7.79 (1H, dd, J=1.8Hz, 5.0Hz), 7.87 (1H, s), 8.41 (1H, s), 8.44 (1H, d, J=9.2Hz), 8.54 (1H, d, J=7.2Hz), 8.61 (1H, d, J=4.8Hz).

[0396] Examples 163 and 164: Synthesis of N-((5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methyl)acetamide (Compound 129), and N-methyl-1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 130) Compound (129) and compound (130) were synthesized according to the synthetic method of compound (136).

[0397] 1H-NMR(CDCl3) δ: 2.12 (3H, s), 4.63 (2H, d, J=5.2Hz), 6.76 (1H, brs), 6.96 (1H, ddd, J=1.3Hz, 6.8Hz, 7.0Hz), 7.37 (1H, d, J=8.0Hz), 7.39-7.44 (1H, m), 7.46 (1H, s), 8.27 (1H, dd, J=2.2Hz, 8.2Hz), 8.41 (1H, s), 8.47 (1H, d, J=8.4Hz), 8.55 (1H, d, J=6.8Hz), 9.20 (1H, d, J=2.0Hz).

[0398] 1 H-NMR(CDCl3) δ: 2.53 (3H, s), 3.94 (2H, s), 6.95 (1H, ddd, J=1.3Hz, 6.8Hz, 7.2Hz), 7.38-7.44 (2H, m), 7.44 (1H, s), 8.26 (1H, dd, J=2.2Hz, 8.2Hz), 8.41 (1H, s), 8.47 (1H, d, J=8.8Hz), 8.54 (1H, d, J=7.2Hz), 9.20 (1H, d, J=1.2Hz).

[0399] [Example 165] Synthesis of 4-(1H-imidazol-1-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 165)

[0400] (1) Synthesis of 4-bromo-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 165-1) Triphenylphosphine (30.9 g, 118 mmol) and carbon tetrabromide (19.6 g, 59.1 mmol) were added to a toluene (500 mL) solution of 2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4(5H)-one (Compound 199-1) (12.8 g, 58.9 mmol), and the mixture was stirred under reflux for 1 hour. After cooling, water was added to the reaction mixture, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (165-1) (6.92 g, 24.7 mmol, yield 41.9%) was obtained from the n-hexane:ethyl acetate (1:1) fr...

Claims

1. A compound of formula (I) or a pharma- ceutically acceptable derivative thereof: (In the formula, R １ ~R ５ are each independently hydrogen or C １－３ A chain aliphatic hydrocarbon; R ６ is an optionally substituted 5- to 10-membered aromatic hydrocarbon, an optionally substituted 5- to 10-membered heterocycle having 1 to 5 heteroatoms independently selected from nitrogen, oxygen and sulfur as ring-constituting atoms, or a fused ring of any of these with an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur as ring-constituting atoms.

2. R ６ The 5- to 10-membered aromatic hydrocarbons, 5- to 10-membered heterocycles, and 4- to 10-membered heterocyclyls that form condensed rings in R are each independently unsubstituted or (1) halogen, nitro, cyano, hydroxy, difluoromethyl, trifluoromethyl, (2) -NR ３１ ２ , -N(R ３１ )(CH ２ ), １－５ NR ３１ ２ , -N(R ３１ )(S(O)) ２ R ３２ , -N(R ３１ )(C(O))R ３１ , -N(R ３１ )(C(O))(CH ２ ), ０－３ NR ３１ ２ , -N(R ３１ )(C(O))(CH ２ ), ０－３ R ３２ , (3) C １－６ alkyl, -(CH ２ ), １－５ OR ３１ , -(CH ２ ), １－５ O(CH ２ ), １－５ OR ３１ , -(CH ２ ), １－５ R ３２ , -(CH ２ ), １－５ R ３３ , (4) -(CH ２ ), １－５ NR ３１ ２ , -(CH ２ ), １－５ N(R ３１ )R ３２ , -(CH ２ ), １－５ N(R ３１ )(CH ２ ), ０－５ R ３８ , -(CH ２ ), １－５ N(R ３１ )(C(O))R ３１ , -(CH ２ ) １－５ N(R ３１ )(CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ N(C(O)R ３１ )(CH ２ ) １－５ C(O)OR ３１ , -(CH ２ ) １－５ N(R ３１ )(CH ２ ) ０－５ NR ３１ ２ , -(CH ２ ) １－５ N(R ３１ )(CH ３２ ), (5)-(CH ２ ) １－５ N(R ３１ )(SO ２ R ３３ ), (6)-C(R ３１ )(CH ２ C(O)R ３２ ), (7)-C(R ３１ )(CH ２ C(O)NR ３１ ２ , -C(R ３１ )(CH ２ C(O)N(R ３１ )OR ３１ , (8)-C(O)R ３１ , -C(O)R ３２ , (9)-C(O)OR ３１ , (10)-C(O)NR ３１ ２ , -C(O)N(R ３１ )(CH ２ ) ０－５ R ３２ , (11)-OC(R ３１ )(CH ２ C(O)N(R ３１ )(CH ２ ) １－５ OR ３１ , -OC(R ３１ )(CH ２ C(O)OR ３１ , -OC(R ３１ ) ２ C(O)NR ３１ ２ , -OC(R ３１ ) ２ C(O)R ３２ , (12)-O(CH ２ ) １－６ R ３１ , -(O(CH ２ ) １－５ ) １－５ (CH ２ ) ０－３ NR ３１ ２ , -(O(CH ２ ) １－５ ) １－５ (CH ２ ) ０－３ NR ３１ C(O)R ３１ , -(O(CH ２ ) １－５ ) １－５ NR ３１ C(NH)NR ３１ ２ , -O((CH ２ ) １－５ O) １－５ R ３１ , (13)-OC(O)C(R ３１ ) ２ (O(CH ２ ) １－５ ) １－５ OR ３１ , and (14) optionally substituted with a substituent selected from the group consisting of a 5- or 6-membered heterocyclyl containing nitrogen as a ring-constituting atom and substituted with C alkyl, R １－３ is, each independently, hydrogen, or C ３１ is a chain aliphatic hydrocarbon, R １－４ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen, sulfur, and oxygen as ring-constituting atoms, or a condensed ring thereof with an optionally substituted 5- or 6-membered monocyclic aromatic hydrocarbon, and the 4- to 10-membered heterocyclyl forming the condensed ring is optionally substituted with C ３２ is a chain aliphatic hydrocarbon, R １－５ is substituted with a chain aliphatic hydrocarbon, R ３３ is a 3- to 10-membered alicyclic hydrocarbon or a 4- to 10-membered heterocyclyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring-constituting atoms, and R ３８ is cyano, hydroxy, or S(O) ２ R ３１ The compound according to claim 1 or a pharmaceutically acceptable derivative thereof, wherein it is 3. R ６ is selected from the group consisting of , and in each formula, R ７ is, independently of one another, hydrogen, halogen, nitro, cyano, hydroxy, C １－６ alkyl, C １－６ alkoxyl, or -NR ３１ ２ , and R ８ is, independently of one another, (1) hydrogen, halogen, nitro, cyano, hydroxy, (2) -NR ３１ ２ , -N(R ３１ )S(O) ２ R ３２－１ (wherein R ３２－１ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-constituting atoms), -N(R ３１ )C(O)R ３１ , -N(R ３１ )C(O)(CH ２ ) ０－３ NR ３１ ２ , -N(R ３１ )C(O)(CH ２ ) ０－３ R ３２－２ (wherein R ３２－２ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-constituting atoms), (3) C １－６ alkyl, -(CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ R ３２－３ (wherein R ３２－３ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-constituting atoms), (4) -(CH ２ ) １－５ NR ３１ ２ , -(CH ２ ) １－５ N(R ３１ )R ３２－４ (wherein, R ３２－４ is an optionally substituted 3- to 10-membered alicyclic hydrocarbon, or an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-constituting atoms.), -(CH ２ ) １－５ N(R ３１ )C(O)R ３１ , -(CH ２ ) １－５ N(R ３１ )C(O)(CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ N(C(O)R ３１ )(CH ２ ) １－５ C(O)OR ３１ , -(CH ２ ) １－５ N(R ３１ )C(O)(CH ２ ) ０－５ NR ３１ ２ , -(CH ２ ) １－５ N(R ３１ )C(O)R ３２－５ (wherein, R ３２－５ is an optionally substituted 3- to 10-membered alicyclic hydrocarbon, or an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-constituting atoms.), (5)-(CH ２ ) １－５ N(R ３１ )S(O) ２ R ３３－１ (wherein, R ３３－１ is a 3- to 10-membered cycloalkyl.), (6)-C(R ３１ ) ２ C(O)R ３２－６ (wherein, R ３２－６ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-constituting atoms.), (7)-C(R ３１ ) ２ C(O)NR ３１ ２ , -C(R ３１ ), ２ C(O)N(R ３１ )OR ３１ , (8)-C(O)R ３２－７ (wherein, R ３２－７ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-constituting atoms, or a condensed ring thereof with an optionally substituted 5- or 6-membered monocyclic aromatic hydrocarbon.), (9)-C(O)OR ３１ , (10)-C(O)NR ３１ ２ , -C(O)N(R ３１ )(CH ２ ) ０－５ R ３２－８ (wherein, R ３２－８ is an optionally substituted 3- to 10-membered alicyclic hydrocarbon, or an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-constituting atoms.), (11)-OC(R ３１ ) ２ C(O)N(R ３１ )(CH ２ ) １－５ OR ３１ , -OC(R ３１ ) ２ C(O)OR ３１ , -OC(R ３１ ) ２ C(O)NR ３１ ２ , -OC(R ３１ ) ２ C(O)R ３２－９ (wherein, R ３２－９ is an optionally substituted 4- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and sulfur as ring-constituting atoms.), (12)-O(CH ２ ) １－６ R ３１ , -(O(CH ２ )) １－５ ) １－５ (CH ２ ) ０－３ NR ３１ ２ , -(O(CH ２ )) １－５ ) １－５ (CH ２ ) ０－３ N.R. ３１ C(O)R ３１ , -(O(CH ２ ) １－５ ) １－５ N.R. ３１ C(NH)NR ３１ ２ , -O((CH ２ ) １－５ O) １－５ R ３１ , (13)-OC(O)C(R ３１ ) ２ (O(CH ２ ) １－５ ) １－５ OR ３１ (14) optionally C １－３ R is selected from the group consisting of 5- or 6-membered nitrogen-containing heterocycles substituted with alkyl; ９ , R １０ , R １１ and R １２ are each independently hydrogen, halogen, cyano, hydroxy, C １－５ Alkyl, 3-6 membered cycloalkyl, C １－５ Alkoxyl, -N(R ３１ ) C(O)R ３１ , -N(R ３１ )C(O)(CH ２ ) ０－３ N.R. ３１ ２　 , -N(R ３１ ) (CH ２ ) １－５ N.R. ３１ ２ , -(CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ O (CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ R ３５ , -(CH ２ ) １－５ N (R ３１ ) C(O)R ３１ , -(CH ２ ) １－５ C(O)NR ３１ ２ , -C(R ３１ ) ２ NR ３１ ２ , -(CH ２ ) １－５ NR ３１ ２ , -C(O)R ３６ , -C(O)OR ３１ , -C(O)NR ３１ ２ , -NR ３１ ２ , -C(H) ２ R ３５ , -C(H)R ３５ ２ , and -CR ３５ ３ selected from the group consisting of, where R ３１ is, independently of each other, hydrogen, or a C １－４ chain aliphatic hydrocarbon, and R ３５ is, independently of each other, halogen, cyano, a 3- to 10-membered alicyclic hydrocarbon optionally substituted with C １－５ alkyl, or -OR ３１ , and R ３６ is a 4- to 10-membered heterocyclyl optionally substituted with C １－５ alkyl and having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur as ring-constituting atoms, and R １３ is, independently of each other, hydrogen, C １－５ alkyl, -(CH ２ ) １－５ OR ３１ , -(CH ２ ) １－５ NR ３１ ２ , -(CH ２ ) １－５ N(R ３１ )C(O)R ３１ , -(CH ２ ) １－５ N(R ３１ )(CH ２ ) ０－５ R ３８ , -C(O)R ３１ , -C(O)R ３７ or -(CH ２ ) １－５ R ３７ wherein R ３７ is a 3- to 10-membered alicyclic hydrocarbon or a 3- to 10-membered heterocyclyl having 1 to 3 heteroatoms selected from nitrogen and oxygen, and R ３８ is cyano, hydroxy, or S(O) ２ R ３１ wherein the heterocyclic rings in the structures represented by formulae (I-2), (I-3), and (I-27) to (I-32) and the benzene ring in the structure represented by (I-33) are each independently optionally substituted with a C １－５ chain aliphatic hydrocarbon, the compound according to claim 1 or a pharmaceutically acceptable derivative thereof.

4. R ６ is selected from and is the compound according to claim 1 or a pharmaceutically acceptable derivative thereof.

5. 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (compound 3), 4-phenyl-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol (compound 71), 2-methoxy-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (compound 79), 4-(3-fluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol (compound 112), 4-(2-fluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol (compound 122), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzene-1,3-diol (compound 120), 4-(2,4-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 121), 4-(3-methoxyphenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 83), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(o-tolyl)thiazole (compound 132), 1-methyl-6-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-3,4-dihydroquinolin-2(1H)-one (compound 131), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (compound 12), 4-(4-methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 7), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-3-yl)thiazole (compound 15), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-4-yl)thiazole (compound 92), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-2-yl)thiazole (compound 93), 4-(2-chloropyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 94), 4-(2-methoxypyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 95), 4-(6-Methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 96), 4-(5-methylpyridin-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 97), 6-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-[1,3]dioxolo[4,5-b]pyridine (Compound 98), 4-(2-methylpyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 99), 4-(2-fluoropyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 100), 4-(2-bromopyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 101), 4-(5-chloropyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 125), 4-(4-chloropyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 135), 2'-bromo-2-(pyrazolo[1,5-a]pyridin-3-yl)-4,5'-bithiazole (Compound 37), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline hydrochloride (Compound 1), 4-(3-nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 4), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline hydrochloride (Compound 10), 4-(2-nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 133), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline hydrochloride (Compound 134), 2-methoxy-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)aniline (Compound 90), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 118), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzonitrile (Compound 115), 2-(2-(pyrazolo[1,5-a](5-a) Pyridin-3-yl)thiazol-4-yl)benzonitrile (Compound 116), 4-(3,5-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 119), 4-(2,6-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 123), 5-fluoro-2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 114), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isonicotinamide (Compound 126), 4-(5-methoxypyridin-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 124), 4-(5-methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 127), 4-(1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 107), 4-(4-chloro-1-methyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 53), 4-(1,4-dimethyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrobromide (Compound 54), 4-(1-methyl-1H-pyrazol-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrobromide (Compound 106), 4-(1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 109), 5-methyl-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole hydrobromide (Compound 105), N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)oxetane-3-sulfonamide (Compound 69), N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 16), N-(4-(2-(pyrazolo[1,5-a]5-a] Pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-4-carboxamide (Compound 72), N-methyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanamine hydrochloride (Compound 74), N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-4-carboxamide (Compound 76), 2-methoxy-N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 78), 1,1-dimethyl-3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)urea (Compound 59), 1,1-dimethyl-3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)urea (Compound 75), 2-methoxy-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 77), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)cyclobutanesulfonamide (Compound 82), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)oxetane-3-carboxamide (Compound 85), 2-amino-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide hydrochloride (Compound 64), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)oxetane-3-carboxamide (Compound 66), 2-amino-N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide hydrochloride (Compound 65), 2-amino-N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide hydrochloride (Compound 81), 2-amino-N-(4-(2-(pyrazolo[1,5-a]5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide hydrochloride (Compound 80), sodium 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetic acid (Compound 5), N-acetyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)glycine (Compound 73), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetamide (Compound 26), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl-2-(2-(2-methoxyethoxy)ethoxy)acetate (Compound 13), 4-(3-(2-methoxyethoxy)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 14), 4-(3-(2-(2-methoxyethoxy)ethoxy)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 22), 4-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 108), 4-(1-ethyl-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 110), 4-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (compound 111), 2-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethoxy)ethan-1-amine hydrochloride (compound 32), 2-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethoxy)ethan-1-amine hydrochloride (compound 20), N,N-dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-amine hydrochloride (compound 47), 1-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethyl)guanidine hydrochloride (compound 52), 1-(2-(4-(2-(pyrazolo[1,(5-a) Pyridin-3-yl)thiazol-4-yl)phenoxy)ethyl)guanidine hydrochloride (Compound 51), N-(2-(4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethyl)acetamide (Compound 45), N-(2-Hydroxyethyl)-2-(3-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetamide (Compound 19), Methyl 2-(3-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetate (Compound 18), Methyl 2-(4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)acetate (Compound 25), 1-(Piperazin-1-yl)-2-(4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one (Compound 31), 1-(1,4-Diazepan-1-yl)-2-(4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one hydrochloride (Compound 55), 1-(4-Methyl-1,4-diazepan-1-yl)-2-(4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one hydrochloride (Compound 102), 1-(2-(Hydroxymethyl)pyrrolidin-1-yl)-2-(3-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one (Compound 21), 1-(Piperazin-1-yl)-2-(3-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one (Compound 23), 1-(1,1-Dioxidothiomorpholino)-2-(3-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenoxy)ethan-1-one (Compound 24), (4-Methylpiperazin-1-yl)(5-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazol-3-yl)methanone hydrochloride (Compound 103), Piperazin-1-yl(5-(2-(Pyrazolo[1,5-a]5-a] Pyridin-3-yl)thiazol-4-yl)isoxazol-3-yl)methanone hydrochloride (Compound 104), N-(4'-methyl-2-(pyrazolo[1,5-a]pyridin-3-yl)-[4,5'-bithiazol]-2'-yl)acetamide (Compound 46), N,N-dimethyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide (Compound 49), Sodium 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoate (Compound 6), (3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)(2-oxa-6-azaspiro[3.3]heptan-6-yl)methanone (Compound 33), N,N-dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 87), N-(cyclopropylmethyl)-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoyl)azetidine-3-carboxamide (Compound 9), (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)(2-oxa-7-azaspiro[3.5]nonan-7-yl)methanone (Compound 40), (1,4-oxazepan-4-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 41), (4-(dimethylamino)piperidin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 48), (4-methylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 50), (4-ethylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 56), (3-methylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone (Compound 58), N,N-dimethyl-3-(2-(pyrazolo[1,5-a]5-a] Pyridin-3-yl)thiazol-4-yl)benzamide (Compound 61), 4-(3-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoyl)piperazine-1-carbaldehyde (Compound 68), N-(2-Morpholinoethyl)-3-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide (Compound 30), N-Methyl-2-(4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 88), N-Ethyl-2-(4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 89), N-Methoxy-2-(4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)acetamide (Compound 91), (2,5-Diazabicyclo[2.2.1]heptan-2-yl)(4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 43), N-(2-(Piperazin-1-yl)ethyl)-4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide hydrochloride (Compound 11), (3-Aminopyrrolidin-1-yl)(4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 42), N-Methyl-N-(piperidin-4-yl)-4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzamide hydrochloride (Compound 44), Piperazin-1-yl(4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 57), Piperazin-1-yl(3-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanone hydrochloride (Compound 63), 1-(Piperazin-1-yl)-2-(4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)ethan-1-one hydrochloride (Compound 86), N-(2-(4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzoyl)-1,2,3,4-Tetrahydroisoquinolin-5-yl)acetamide (Compound 60), 2-(Hydroxymethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenol (Compound 8), (4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanol (Compound 2), 2-(4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)ethan-1-ol (Compound 84), 4-(3-(2,5-Dihydro-1H-pyrrol-3-yl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (Compound 17), 6-(4-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)-2-oxa-6-azaspiro[3.3]heptane (Compound 29), N,N-Dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)methanamine (Compound 27), 4-(4-((4-Methylpiperazin-1-yl)methyl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 28), N,N-Dimethyl-4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-2-carboxamide (Compound 38), N,2-Dimethyl-4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)morpholine-2-carboxamide (Compound 39), 1-Morpholino-2-(4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)piperazin-1-yl)ethane-1,2-dione hydrochloride (Compound 36), 4-(4-(((2,5-Diazabicyclo[2.2.1]heptan-2-yl)methyl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (Compound 34), N-Methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)piperidin-4-amine hydrochloride (Compound 35), 4-(Isoindolin-5-yl)-2-(pyrazolo[1,5-a] Pyridin-3-yl)thiazole hydrochloride (Compound 117), N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenethyl)acetamide (Compound 62), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)phenyl)ethan-1-amine hydrochloride (Compound 113), N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 67), N-methyl-N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)benzyl)acetamide (Compound 70), N,N-dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 137), N,N-dimethyl-1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 128), N-methyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 136), N-((5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methyl)acetamide (Compound 129), N-methyl-1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methanamine (Compound 130), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrol-3-yl)thiazole (Compound 138), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrol-2-yl)thiazole (Compound 139), 4-(1H-imidazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 140), 4-(1H-imidazol-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 141), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,3-triazol-4-yl)thiazole (Compound 142), 2-(pyrazolo[1,5-a]5-a] Pyridin-3-yl)-4-(1H-1,2,4-triazol-3-yl)thiazole (Compound 143), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(thiophen-3-yl)thiazole (Compound 144), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(thiophen-2-yl)thiazole (Compound 145), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isothiazole (Compound 146), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isothiazole (Compound 147), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isothiazole (Compound 148), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4,4'-bithiazole (Compound 149), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4,5'-bithiazole (Compound 150), 2'-(pyrazolo[1,5-a]pyridin-3-yl)-2,4'-bithiazole (Compound 151), 4-(furan-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 152), 4-(furan-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 153), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole (Compound 154), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole (Compound 155), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole (Compound 156), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)oxazole (Compound 157), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)oxazole (Compound 158), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)oxazole (Compound 159), 4-(1-methyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a] Pyridin-3-yl)thiazole (Compound 160), 4-(1-Methyl-1H-pyrrol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 161), 3-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1,2,4-thiadiazole (Compound 162), 4-(1-Methyl-1H-pyrrol-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 163), 3-Bromo-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)isoxazole (Compound 164), 4-(1H-Imidazol-1-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 165), 4-(1H-Pyrazol-1-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 166), 2-(Pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrol-1-yl)thiazole (Compound 167), 2-(Pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,4-triazol-1-yl)thiazole (Compound 168), 2-(Pyrazolo[1,5-a]pyridin-3-yl)-4-(2H-1,2,3-triazol-2-yl)thiazole (Compound 169), 2-(Pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,3-triazol-1-yl)thiazole (Compound 170), 5-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiophene-3-carboxamide (Compound 171), 2-(5-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiophen-2-yl)acetamide (Compound 172), N,N-Dimethyl-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiophene-3-carboxamide (Compound 173), N-(2-(5-(2-(Pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiophen-2-yl)ethyl)acetamide (Compound 174), 4-(3-(Difluoromethyl)-1-methyl-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 178), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)thiophen-3-ol (Compound 175), 1-methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazole-3-carbonitrile (Compound 176), N-methyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-1-yl)ethane-1-amine (Compound 177), 4-(5-fluoro-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 179), 3-methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazole-5-amine (Compound 181), 4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-1-yl)butan-1-ol (Compound 180), 4-(1-(azetidin-2-ylmethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 182), 2-((2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-1-yl)ethyl)amino)acetonitrile (Compound 183), 3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-1-yl)propane-1-amine (Compound 184), N-(3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazol-1-yl)propyl)methanesulfonamide (Compound 185), 5-methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-pyrazole-3-ol (Compound 186), N, １ , N １ -dimethyl-N ２ -(2'-(Pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazole]-2-yl)ethane-1,2-diamine (Compound 187), 2-(dimethylamino)-N-(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazole]-2-yl)acetamide (Compound 188), 2-amino-N-(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazole]-2-yl)acetamide hydrochloride (Compound 189), 2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazole]-2-ol (Compound 190), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)furan-2-carboxamide (Compound 191), 4-(2,5-dihydrofuran-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 192), (1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-4-yl)methanol (Compound 193), (1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-4-yl)methanamine hydrochloride (Compound 194), 3-((1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-4-yl)methoxy)propan-1-ol (Compound 195), 3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-1-yl)propan-1-ol (Compound 196), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-1-yl)ethane-1-amine (Compound 197), N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-1H-imidazol-1-yl)ethyl)acetamide (Compound 198), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyrimidin-5-yl)thiazole (Compound 199), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyrimidin-2-yl)thiazole (Compound 200), 4-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 201), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-yl)thiazole (Compound 202), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazine (Compound 203), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (Compound 204), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)-4,5,6,7-tetrahydrothiazolo[4,5-c]pyridine (Compound 205), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl)thiazole (Compound 206), 4-(1H-indazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 207), 4-(4-chloro-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 208), 2-(6-methylpyrazolo[1,5-a]pyridin-3-yl)-4-phenylthiazole (Compound 209), 2-(5-methylpyrazolo[1,5-a]pyridin-3-yl)-4-phenylthiazole (Compound 210), 2-(4-methylpyrazolo[1,5-a]pyridin-3-yl)-4-phenylthiazole (Compound 211), 4-(4-chloro-1-methyl-1H-pyrazol-3-yl)-2-(5-methylpyrazolo[1,5-a]pyridin-3-yl)thiazole (Compound 212), and N-((5-(2-(5-methylpyrazolo[1,5-a]pyridin-3-yl)thiazol-4-yl)pyridin-2-yl)methyl)acetamide (Compound 213), a compound selected from the group consisting of., 6. A composition comprising the compound according to any one of claims 1 to 5 or a pharmaceutically acceptable derivative thereof and a pharmaceutically acceptable carrier.

7. A pharmaceutical composition comprising the compound according to any one of claims 1 to 5 or a pharmaceutically acceptable derivative thereof.

8. The pharmaceutical composition according to claim 7 for inhibiting myosin light chain kinase 4 (MYLK4) activity.

9. The pharmaceutical composition according to claim 7 for alleviating or treating a disease, disorder or symptom involving myosin light chain kinase 4 (MYLK4).

10. The pharmaceutical composition according to claim 9, wherein the disease, disorder or symptom involving myosin light chain kinase 4 (MYLK4) is atherosclerosis, inflammatory bowel disease, osteosarcoma, ischemic heart disease, glaucoma, ocular hypertension, aqueous humor outflow disorder, dry eye, uveitis, age-related macular degeneration, or diabetic retinopathy.

11. The pharmaceutical composition according to claim 7 for alleviating or treating dry eye, uveitis, age-related macular degeneration, or diabetic retinopathy.

12. The pharmaceutical composition according to claim 7 for alleviating or treating glaucoma, ocular hypertension, or aqueous humor outflow disorder.

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