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

Abstract

The present application provides novel compounds that inhibit MYLK4 activity and their medical use. A compound of Formula (I) or a pharmaceutically acceptable derivative thereof is provided: (in the formula, R 1 to R 5 each independently is hydrogen or a C 1‑3 linear aliphatic hydrocarbon; R 6 a 5- to 10-membered aromatic hydrocarbon optionally substituted, a 5- to 10-membered heterocycle optionally substituted having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring constituent atoms, or a condensation ring of any of the foregoing with a 4- to 10-membered heterocyclic group optionally substituted having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring constituent atoms), and the like as medicines.

Description

Technical Field

[0001] This invention relates to thiazolyl-pyrazolo[1,5-a]pyridine compounds and their uses. Background Technology

[0002] Myosin is a motor protein that hydrolyzes ATP while moving along actin filaments. 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 the 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 are known: MYLK1, MYLK2, MYLK3, and MYLK4, and it is generally believed that any one of them is involved in the phosphorylation of the regulatory light chain of myosin.

[0004] Besides MYLK, myosin phosphatase (MLCP) is another known protein that regulates the phosphorylation of the myosin light chain. MLCP dephosphorylates the myosin light chain. MLCP activity is regulated by Rho-kinase, which reduces MLCP activity due to MLCP phosphorylation. In other words, Rho-kinase prevents the dephosphorylation of the myosin light chain by phosphorylating MLCP; the inhibition by Rho-kinase induces a reduction in phosphorylated myosin light chains.

[0005] Numerous studies have been conducted on the in vivo roles of MYLK and Rho-kinase, and inhibition of MYLK or Rho-kinase (Rho-kinase inhibitors are also known as ROCK inhibitors) has been reported for the prevention, treatment, or relief of various symptoms or disorders (Non-Patent Literature 1 to 13 and Patent Literature 1, see the tables set forth below in this specification).

[0006] As MYLK inhibitors, compounds with the following structures, referred to as ML-7 or ML-9, have been reported (Non-Patent Literature 2, 3, 7, 10, 11, 12 and 13).

[0007]

[0008] In addition, compounds with the following structures have been reported to have dual inhibitory activity against MYLK4 and Rho-kinase, reducing intraocular pressure in rabbit models of high intraocular pressure (Patent Document 1 and Non-Patent Document 1).

[0009]

[0010] [Existing Technical Documents]

[0011] [Patent Literature]

[0012] Patent document 1: Japanese Patent Application Publication No. 2021-113185.

[0013] [Non-patent literature]

[0014] Non-patent literature 1: Invest. Ophthalmol. Vis. Sci. (2021) 62(13), 12.

[0015] Non-patent literature 2: Exp. Eye Res. (2000) 71(6), 551-566.

[0016] Non-patent literature 3: Exp. Eye Res. (2005) 80(6), 837-845.

[0017] Non-patent literature 4: J. Ophthalmol. (2010) 175163.

[0018] Non-patent literature 5: Invest. Ophthalmol. Vis. Sci. (2015) 56(2), 1335-1348.

[0019] Non-patent literature 6: Invest. Ophthalmol. Vis. Sci. (2017) 58(12), 5584-5593.

[0020] Non-patent literature 7: Invest. Ophthalmol. Vis. Sci. (2013) 54(4), 2705-2710.

[0021] Non-patent literature 8: Curr. Opin. Cell Biol. (2008) 20(2), 242-248.

[0022] Non-patent literature 9: Int. J. Mol. Sci. (2023) 24(13), 11219.

[0023] Non-patent literature 10: Dig. Dis. Sci. (2013) 58(1), 107-114.

[0024] Non-patent literature 11: J. Exp. Clin. Cancer Res. (2021)40(1), 166.

[0025] Non-patent literature 12: Mol. Med. Rep. (2015) 12(3), 4109-4116.

[0026] Non-patent literature 13: J. Proteomics. (2012) 75(17), 5386-5395. Summary of the Invention

[0027] [The problem that the invention aims to solve]

[0028] In view of the above-mentioned technical level, the present invention provides novel compounds that inhibit MYLK4 activity and their pharmaceutical uses. Specifically, as described below.

[0029] [1] A compound of formula (I) or a pharmaceutically permissible derivative thereof:

[0030]

[0031] (in the formula,

[0032] R 1 To R 5 Each is independently hydrogen or C 1-3 Chain-like aliphatic hydrocarbons;

[0033] R 6 (Substituted 5- to 10-membered aromatic hydrocarbons, having a substituted 5- to 10-membered heterocycle having substituted 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring-forming atoms, or any of the above, in a condensation ring with a substituted 4- to 10-membered heterocyclic group having substituted 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring-forming atoms.)

[0034] [2] The compound or its pharmaceutically permissible derivative as described in [1], wherein R 6 The 5- to 10-membered aromatic hydrocarbons, 5- to 10-membered heterocycles, and 4- to 10-membered heterocyclic groups that form condensation rings with them are each independently unsubstituted or may be substituted by substituents selected from the group consisting of:

[0035] (1) Halogen, nitro, cyano, hydroxyl, difluoromethyl, trifluoromethyl,

[0036] (2) -NR 31 2. -N(R) 31 (CH2) 1-5 NR 31 2. -N(R) 31 )S(O)2R 32 -N(R) 31 )C(O)R 31 -N(R) 31 )C(O)(CH2) 0-3 NR 31 2. -N(R) 31 )C(O)(CH2) 0-3 R32 ,

[0037] (3) C 1-6 alkyl, -(CH2) 1-5 OR 31 、-(CH2) 1-5 O(CH2) 1-5 OR 31 、-(CH2) 1-5 R 32 、-(CH2) 1-5 R 33 ,

[0038] (4) -(CH2) 1-5 NR 31 2、-(CH2) 1-5 N(R 31 )R 32 、-(CH2) 1-5 N(R 31 )(CH2) 0-5 R 38 、-(CH2) 1-5 N(R 31 )C(O)R 31 、-(CH2) 1-5 N(R 31 )C(O)(CH2) 1-5 [[ID=​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​OR 31 ,

[0042] (8) -C(O)R 31 -C(O)R 32 ,

[0043] (9) -C(O)OR 31 ,

[0044] (10) -C(O)NR 31 2. -C(O)N(R) 31 (CH2) 0-5 R 32 ,

[0045] (11) -OC(R 31 )2C(O)N(R 31 (CH2) 1-5 OR 31 -OC(R) 31 )2C(O)OR 31 -OC(R) 31 )2C(O)NR 31 2. -OC(R) 31 )2C(O)R 32 ,

[0046] (12) -O(CH2) 1-6 R 31 -(O(CH2) 1-5 ) 1-5 (CH2) 0-3 NR 31 2. -(O(CH2) 1-5 ) 1-5 (CH2) 0-3 NR 31 C(O)R 31 -(O(CH2) 1-5 ) 1-5 NR 31 C(NH)NR 31 2. -O((CH2) 1-5 O) 1-5 R 31 ,

[0047] (13) -OC(O)C(R 31 )2(O(CH2) 1-5 ) 1-5 OR 31 ,as well as

[0048] (14) Depending on the circumstances, via C 1-3 Alkyl-substituted 5- or 6-membered heterocyclic groups containing nitrogen as a ring-forming atom

[0049] R 31 Each is independently hydrogen or C 1-4 Chain aliphatic hydrocarbons,

[0050] R 32 A condensation ring of a 4- to 10-membered heterocyclic group, having 1 to 3 heteroatoms selected from nitrogen, sulfur, and oxygen as ring constituent atoms, and a 5- or 6-membered monocyclic aromatic hydrocarbon, wherein the 4- to 10-membered heterocyclic group forming the aforementioned condensation ring is, depending on the C... 1-5 Substitution of chain aliphatic hydrocarbons,

[0051] R 33 It is a 3- to 10-membered alicyclic hydrocarbon, or a 4- to 10-membered heterocyclic group having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring-forming atoms.

[0052] R 38 It is a cyano group, a hydroxyl group, or S(O)2R. 31 .

[0053] [3] The compound or its pharmaceutically permissible derivative as described in [1], wherein R 6 Choose from the following groups:

[0054] ,

[0055] Among the various types,

[0056] R 7 Each is independently hydrogen, halogen, nitro, cyano, hydroxyl, C 1-6 Alkyl, C 1-6 alkoxy or -NR 31 2,

[0057] R 8 Each person independently chooses from the following groups:

[0058] (1) Hydrogen, halogen, nitro, cyano, hydroxyl

[0059] (2) -NR 31 2. -N(R) 31 )S(O)2R 32-1 (where R is in the formula) 32-1 (4- to 10-membered heterocyclic groups, substituted as appropriate, with 1 to 3 heteroatoms selected from nitrogen and oxygen as ring constituent atoms), -N(R 31 )C(O)R 31 -N(R) 31 )C(O)(CH2) 0- 3NR 31 2. -N(R) 31)C(O)(CH2) 0-3 R 32-2 (where R is in the formula) 32-2 (4- to 10-membered heterocyclic groups, substituted as appropriate, with 1 to 3 heteroatoms selected from nitrogen and oxygen as ring constituent atoms),

[0060] (3) C 1-6 Alkyl group, -(CH2) 1-5 OR 31 -(CH2) 1-5 R 32-3 (where R is in the formula) 32-3 (4- to 10-membered heterocyclic groups, substituted as appropriate, with 1 to 3 heteroatoms selected from nitrogen and oxygen as ring constituent atoms),

[0061] (4) -(CH2) 1-5 NR 31 2. -(CH2) 1-5 N(R 31 )R 32-4 (where R is in the formula) 32-4 (Substituted 3- to 10-membered alicyclic hydrocarbons or, depending on the case, substituted 4- to 10-membered heterocyclic groups having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring constituent atoms), -(CH2). 1-5 N(R 31 )C(O)R 31 -(CH2) 1-5 N(R 31 )C(O)(CH2) 1-5 OR 31 -(CH2) 1-5 N(C(O)R 31 (CH2) 1-5 C(O)OR 31 -(CH2) 1-5 N(R 31 )C(O)(CH2) 0-5 NR 31 2. -(CH2) 1-5 N(R 31 )C(O)R 32-5 (where R is in the formula) 32-5 Substituted 3- to 10-membered alicyclic hydrocarbons or substituted 4- to 10-membered heterocyclic groups having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-forming atoms, as appropriate.

[0062] (5) -(CH2) 1-5 N(R 31 )S(O)2R 33-1 (where R is in the formula) 33-1 (It is a 3- to 10-membered cycloalkyl group),

[0063] (6) -C(R 31 )2C(O)R 32-6 (where R is in the formula) 32-6 (4- to 10-membered heterocyclic groups, substituted as appropriate, with 1 to 3 heteroatoms selected from nitrogen and oxygen as ring constituent atoms),

[0064] (7) -C(R 31 )2C(O)NR 31 2. -C(R) 31 )2C(O)N(R 31 OR 31 ,

[0065] (8) -C(O)R 32-7 (where R is in the formula) 32-7 (A condensed ring of a 4- to 10-membered heterocyclic group, or the like, having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring constituent atoms, substituted as appropriate, and a 5- or 6-membered monocyclic aromatic hydrocarbon, substituted as appropriate).

[0066] (9) -C(O)OR 31 ,

[0067] (10) -C(O)NR 31 2. -C(O)N(R) 31 (CH2) 0-5 R 32-8 (where R is in the formula) 32-8 Substituted 3- to 10-membered alicyclic hydrocarbons or substituted 4- to 10-membered heterocyclic groups having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-forming atoms, as appropriate.

[0068] (11) -OC(R 31 )2C(O)N(R 31 (CH2) 1-5 OR 31 -OC(R) 31 )2C(O)OR 31 -OC(R) 31 )2C(O)NR 31 2. -OC(R) 31 )2C(O)R 32-9 (where R is in the formula) 32-9 (4- to 10-membered heterocyclic groups, substituted as appropriate, with 1 to 3 heteroatoms selected from nitrogen and sulfur as ring-forming atoms),

[0069] (12) -O(CH2) 1-6 R 31 -(O(CH2) 1-5 ) 1-5 (CH2)0-3 NR 31 2. -(O(CH2) 1-5 ) 1-5 (CH2) 0-3 NR 31 C(O)R 31 -(O(CH2) 1-5 ) 1-5 NR 31 C(NH)NR 31 2. -O((CH2) 1-5 O) 1-5 R 31 ,

[0070] (13)-OC(O)C(R 31 )2(O(CH2) 1-5 ) 1-5 OR 31 ,as well as

[0071] (14) Depending on the circumstances, via C 1-3 Alkyl-substituted 5- or 6-membered nitrogen-containing heterocycles,

[0072] R 9 R 10 R 11 and R 12 Each is independently selected from the group consisting of: hydrogen, halogen, cyano, hydroxyl, C 1-5 Alkyl, 3- to 6-membered cycloalkyl, C 1-5 Alkoxy, -N(R) 31 )C(O)R 31 -N(R) 31 )C(O)(CH2) 0-3 NR 31 2. -N(R) 31 (CH2) 1-5 NR 31 2. -(CH2) 1-5 OR 31 -(CH2) 1-5 O(CH2) 1-5 OR 31 -(CH2) 1-5 R 35 -(CH2) 1-5 N(R 31 )C(O)R 31 -(CH2) 1-5 C(O)NR 31 2. -C(R) 31 )2NR 31 2. -(CH2) 1-5 NR 312. -C(O)R 36 -C(O)OR 31 -C(O)NR 31 2. -NR 31 2. -C(H)2R 35 -C(H)R 35 2 and -CR 35 3,

[0073] R 31 Each is independently hydrogen or C 1-4 Chain aliphatic hydrocarbons,

[0074] R 35 Each is independently halogenated, cyano-based, or, depending on the case, C 1-5 Alkyl-substituted 3 to 10-membered alicyclic hydrocarbons or -OR 31 ,

[0075] R 36 Depending on the case, it has 1 to 3 heteroatoms, independently selected from nitrogen, oxygen, and sulfur, as ring-forming atoms, via C... 1-5 Alkyl-substituted 4- to 10-membered heterocyclic groups,

[0076] R 13 Each independently is hydrogen, C 1-5 Alkyl group, -(CH2) 1-5 OR 31 -(CH2) 1-5 NR 31 2. -(CH2) 1-5 N(R 31 )C(O)R 31 -(CH2) 1-5 N(R 31 (CH2) 0-5 R 38 -C(O)R 31 -C(O)R 37 Or -(CH2) 1-5 R 37 ,

[0077] R 37 It is a 3- to 10-membered alicyclic hydrocarbon or a 3- to 10-membered heterocyclic group having 1 to 3 heteroatoms selected from nitrogen and oxygen.

[0078] R 38 It is a cyano group, a hydroxyl group, or S(O)2R. 31 ,

[0079] The heterocycles in the structures shown in formulas (I-2), (I-3), and (I-27) to (I-32), and the benzene ring in the structure shown in (I-33), can each be independently subjected to C as appropriate. 1-5Substitution of chain aliphatic hydrocarbons.

[0080] [4] The compound or its pharmaceutically permissible derivative as described in [1], wherein R 6 Selected from the following:

[0081]

[0082]

[0083]

[0084] .

[0085] [5] A compound selected from the group consisting of:

[0086] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 3),

[0087] 4-Phenyl-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 71),

[0088] 2-Methoxy-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 79),

[0089] 4-(3-Fluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 112),

[0090] 4-(2-Fluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 122),

[0091] 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzene-1,3-diol (compound 120),

[0092] 4-(2,4-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 121),

[0093] 4-(3-methoxyphenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 83),

[0094] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(o-tolyl)thiazole (compound 132),

[0095] 1-Methyl-6-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-3,4-dihydroquinoline-2(1H)-one (compound 131),

[0096] N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 12),

[0097] 4-(4-methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 7),

[0098] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-3-yl)thiazole (compound 15),

[0099] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-4-yl)thiazole (compound 92),

[0100] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-2-yl)thiazole (compound 93),

[0101] 4-(2-chloropyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 94),

[0102] 4-(2-methoxypyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 95),

[0103] 4-(6-methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 96),

[0104] 4-(5-methylpyridin-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 97),

[0105] 6-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-[1,3]dioxacyclopenteno[4,5-b]pyridine (compound 98),

[0106] 4-(2-methylpyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 99),

[0107] 4-(2-Fluoropyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 100),

[0108] 4-(2-bromopyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 101),

[0109] 4-(5-chloropyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 125),

[0110] 4-(4-chloropyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 135),

[0111] 2'-Bromo-2-(pyrazolo[1,5-a]pyridin-3-yl)-4,5'-bithiazole (compound 37),

[0112] 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)aniline hydrochloride (compound 1),

[0113] 4-(3-nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 4),

[0114] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)aniline hydrochloride (compound 10),

[0115] 4-(2-Nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 133),

[0116] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)aniline hydrochloride (compound 134),

[0117] 2-Methoxy-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)aniline (compound 90),

[0118] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 118),

[0119] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzonitrile (compound 115),

[0120] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzonitrile (compound 116),

[0121] 4-(3,5-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 119),

[0122] 4-(2,6-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 123),

[0123] 5-Fluoro-2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)phenol (compound 114),

[0124] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isonicotinamide (compound 126),

[0125] 4-(5-methoxypyridin-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 124),

[0126] 4-(5-methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 127),

[0127] 4-(1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 107),

[0128] 4-(4-chloro-1-methyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 53),

[0129] 4-(1,4-dimethyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrobromide (compound 54),

[0130] 4-(1-Methyl-1H-pyrazol-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrobromide (compound 106),

[0131] 4-(1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 109),

[0132] 5-Methyl-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazolyl hydrobromide (compound 105),

[0133] N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)oxetane-3-sulfonamide (compound 69),

[0134] N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 16),

[0135] N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)morpholine-4-carboxamide (compound 72),

[0136] N-Methyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methylamine hydrochloride (compound 74),

[0137] N-Methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)morpholine-4-carboxamide (compound 76),

[0138] 2-Methoxy-N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 78),

[0139] 1,1-Dimethyl-3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)urea (compound 59),

[0140] 1,1-Dimethyl-3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)urea (compound 75),

[0141] 2-Methoxy-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 77),

[0142] N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)cyclobutanesulfonamide (compound 82),

[0143] N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)oxetane-3-carboxamide (compound 85),

[0144] 2-Amino-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide hydrochloride (compound 64)

[0145] N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)oxetane-3-carboxamide (compound 66)

[0146] 2-Amino-N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide hydrochloride (compound 65)

[0147] 2-Amino-N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide hydrochloride (compound 81)

[0148] 2-Amino-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide hydrochloride (compound 80)

[0149] 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)sodium acetate (compound 5),

[0150] N-acetyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)glycine (compound 73),

[0151] 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)acetamide (compound 26),

[0152] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl-2-(2-(2-methoxyethoxy)ethoxy)acetate (compound 13),

[0153] 4-(3-(2-methoxyethoxy)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 14),

[0154] 4-(3-(2-(2-methoxyethoxy)ethoxy)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 22),

[0155] 4-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 108),

[0156] 4-(1-Ethyl-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 110),

[0157] 4-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (compound 111),

[0158] 2-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethoxy)ethane-1-amine hydrochloride (compound 32),

[0159] 2-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethoxy)ethane-1-amine hydrochloride (compound 20),

[0160] N,N-Dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-amine hydrochloride (compound 47)

[0161] 1-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethyl)guanidine hydrochloride (compound 52),

[0162] 1-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethyl)guanidine hydrochloride (compound 51),

[0163] N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethyl)acetamide (compound 45),

[0164] N-(2-hydroxyethyl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)acetamide (compound 19),

[0165] 2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)methyl acetate (compound 18),

[0166] 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)methyl acetate (compound 25),

[0167] 1-(piperazin-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one (compound 31),

[0168] 1-(1,4-diazacycloheptane-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one hydrochloride (compound 55)

[0169] 1-(4-methyl-1,4-diazacycloheptane-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one hydrochloride (compound 102)

[0170] 1-(2-(hydroxymethyl)pyrrolidin-1-yl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one (compound 21),

[0171] 1-(piperazin-1-yl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one (compound 23),

[0172] 1-(1,1-dioxo-4-thiomorpholinyl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one (compound 24),

[0173] (4-Methylpiperazin-1-yl)(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazolyl-3-yl)methyl ketone hydrochloride (compound 103),

[0174] Piperazin-1-yl(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazolyl-3-yl)methyl ketone hydrochloride (compound 104),

[0175] N-(4'-methyl-2-(pyrazolo[1,5-a]pyridin-3-yl)-[4,5'-bithiazolyl]-2'-yl)acetamide (compound 46),

[0176] N,N-Dimethyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzamide (compound 49),

[0177] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)sodium benzoate (compound 6),

[0178] (3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)(2-oxa-6-azaspiro[3.3]heptane-6-yl)methyl ketone (compound 33),

[0179] N,N-Dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 87),

[0180] N-(cyclopropylmethyl)-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzylyl)azacyclobutane-3-carboxamide (compound 9),

[0181] (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)phenyl)(2-oxa-7-azaspiro[3.5]nonane-7-yl)methyl ketone (compound 40),

[0182] (1,4-oxazacycloheptane-4-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 41),

[0183] (4-(dimethylamino)piperidin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 48),

[0184] (4-Methylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 50),

[0185] (4-Ethylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 56),

[0186] (3-Methylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 58),

[0187] N,N-Dimethyl-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzamide (compound 61),

[0188] 4-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzylyl)piperazin-1-carboxaldehyde (compound 68),

[0189] N-(2-(4-morpholinyl)ethyl)-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzamide (compound 30),

[0190] N-Methyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 88),

[0191] N-Ethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 89),

[0192] N-methoxy-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 91),

[0193] (2,5-diazabicyclo[2.2.1]heptane-2-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 43),

[0194] N-(2-(piperazin-1-yl)ethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzamide hydrochloride (compound 11),

[0195] (3-aminopyrrolidin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 42)

[0196] N-Methyl-N-(piperidin-4-yl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzamide hydrochloride (compound 44),

[0197] Piperazine-1-yl(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 57),

[0198] Piperazine-1-yl(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 63),

[0199] 1-(piperazin-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)ethane-1-one hydrochloride (compound 86)

[0200] N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzylyl)-1,2,3,4-tetrahydroisoquinoline-5-yl)acetamide (compound 60),

[0201] 2-(hydroxymethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 8),

[0202] (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methanol (compound 2),

[0203] 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)ethane-1-ol (compound 84),

[0204] 4-(3-(2,5-dihydro-1H-pyrrolo-3-yl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (compound 17),

[0205] 6-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)-2-oxa-6-azaspiro[3.3]heptane (compound 29),

[0206] N,N-Dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methylamine (compound 27),

[0207] 4-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 28),

[0208] N,N-Dimethyl-4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)morpholine-2-carboxamide (compound 38),

[0209] N,2-Dimethyl-4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)morpholine-2-carboxamide (compound 39),

[0210] 1-(4-morpholino)-2-(4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzyl)piperazin-1-yl)ethane-1,2-dione hydrochloride (compound 36)

[0211] 4-(4-((2,5-diazabicyclo[2.2.1]heptane-2-yl)methyl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (compound 34),

[0212] N-Methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)piperidine-4-amine hydrochloride (compound 35)

[0213] 4-(isoindoline-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (compound 117),

[0214] N-Methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenethyl)acetamide (compound 62),

[0215] 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)ethane-1-amine hydrochloride (compound 113),

[0216] N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 67),

[0217] N-Methyl-N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 70),

[0218] N,N-Dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methylamine (compound 137),

[0219] N,N-Dimethyl-1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methylamine (compound 128),

[0220] N-Methyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methylamine (compound 136),

[0221] N-((5-(2-(pyrazolo[1, 5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methyl)acetamide (compound 129),

[0222] N-Methyl-1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methylamine (compound 130),

[0223] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrolo-3-yl)thiazole (compound 138),

[0224] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrolo-2-yl)thiazole (compound 139),

[0225] 4-(1H-imidazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 140),

[0226] 4-(1H-imidazol-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 141),

[0227] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,3-triazol-4-yl)thiazole (compound 142),

[0228] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,4-triazol-3-yl)thiazole (compound 143),

[0229] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(thiophen-3-yl)thiazole (compound 144),

[0230] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(thiophen-2-yl)thiazole (compound 145),

[0231] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)isothiazolium (compound 146),

[0232] 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)isothiazolyl (compound 147),

[0233] 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)isothiazolium (compound 148),

[0234] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4,4'-bithiazole (compound 149),

[0235] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4,5'-bithiazole (compound 150),

[0236] 2'-(pyrazolo[1,5-a]pyridin-3-yl)-2,4'-bithiazole (compound 151),

[0237] 4-(furan-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 152),

[0238] 4-(furan-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 153),

[0239] 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazole (compound 154),

[0240] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazole (compound 155),

[0241] 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazole (compound 156),

[0242] 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)oxazole (compound 157),

[0243] 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)oxazole (compound 158),

[0244] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)oxazole (compound 159),

[0245] 4-(1-Methyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 160),

[0246] 4-(1-Methyl-1H-pyrrolo-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 161),

[0247] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1,2,4-thiadiazole (compound 162),

[0248] 4-(1-Methyl-1H-pyrrolo-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 163),

[0249] 3-Bromo-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)isoxazole (compound 164),

[0250] 4-(1H-imidazol-1-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 165),

[0251] 4-(1H-pyrazol-1-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 166),

[0252] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrolo-1-yl)thiazole (compound 167),

[0253] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,4-triazol-1-yl)thiazole (compound 168),

[0254] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(2H-1,2,3-triazol-2-yl)thiazole (compound 169),

[0255] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,3-triazol-1-yl)thiazole (compound 170),

[0256] 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)thiophene-3-carboxamide (compound 171),

[0257] 2-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)thiophen-2-yl)acetamide (compound 172),

[0258] N,N-Dimethyl-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)thiophene-3-carboxamide (compound 173),

[0259] N-(2-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)thiophen-2-yl)ethyl)acetamide (compound 174),

[0260] 4-(3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 178),

[0261] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)thiophene-3-ol (compound 175),

[0262] 1-Methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-3-carboxylonitrile (compound 176),

[0263] N-Methyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-1-yl)ethane-1-amine (compound 177),

[0264] 4-(5-Fluoro-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 179),

[0265] 3-Methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-5-amine (compound 181),

[0266] 4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-1-yl)butan-1-ol (compound 180),

[0267] 4-(1-(azacyclobutane-2-ylmethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 182),

[0268] 2-((2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-1-yl)ethyl)amino)acetonitrile (compound 183),

[0269] 3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-1-yl)propane-1-amine (compound 184),

[0270] N-(3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-1-yl)propyl)methanesulfonamide (compound 185),

[0271] 5-Methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-3-ol (compound 186),

[0272] N 1 , N 1 -dimethyl-N 2 -(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazolyl]-2-yl)ethane-1,2-diamine (compound 187)

[0273] 2-(dimethylamino)-N-(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazolyl]-2-yl)acetamide (compound 188),

[0274] 2-amino-N-(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazolyl]-2-yl)acetamide hydrochloride (compound 189)

[0275] 2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazolyl]-2-ol (compound 190),

[0276] 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)furan-2-carboxamide (compound 191),

[0277] 4-(2,5-dihydrofuran-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 192),

[0278] (1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazolyl-4-yl)methanol (compound 193),

[0279] (1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazolyl-4-yl)methylamine hydrochloride (compound 194)

[0280] 3-((1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazol-4-yl)methoxy)propane-1-ol (compound 195),

[0281] 3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazol-1-yl)propane-1-ol (compound 196),

[0282] 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazol-1-yl)ethane-1-amine (compound 197),

[0283] N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazolyl-1-yl)ethyl)acetamide (compound 198),

[0284] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyrimidin-5-yl)thiazole (compound 199),

[0285] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyrimidin-2-yl)thiazole (compound 200),

[0286] 4-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 201),

[0287] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-yl)thiazole (compound 202),

[0288] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazine (compound 203),

[0289] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-4,5,6,7-tetrahydrothiazo[5,4-c]pyridine (compound 204),

[0290] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-4,5,6,7-tetrahydrothiazo[4,5-c]pyridine (compound 205),

[0291] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl)thiazole (compound 206),

[0292] 4-(1H-indazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 207),

[0293] 4-(4-chloro-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 208),

[0294] 2-(6-methylpyrazolo[1,5-a]pyridin-3-yl)-4-phenylthiazole (compound 209),

[0295] 2-(5-methylpyrazolo[1,5-a]pyridin-3-yl)-4-phenylthiazole (compound 210),

[0296] 2-(4-methylpyrazolo[1,5-a]pyridin-3-yl)-4-phenylthiazole (compound 211),

[0297] 4-(4-chloro-1-methyl-1H-pyrazol-3-yl)-2-(5-methylpyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 212) and

[0298] N-((5-(2-(5-methylpyrazolo[1, 5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methyl)acetamide (compound 213).

[0299] [6] A composition comprising a compound described in any one of [1] to [5] or a pharmaceutically permissible derivative thereof, and a pharmaceutically permissible carrier.

[0300] [7] A pharmaceutical composition comprising a compound described in any one of [1] to [5] or a pharmaceutically permissible derivative thereof.

[0301] [8] The pharmaceutical composition described in [7] is used to inhibit the activity of myosin light chain kinase 4 (MYLK4).

[0302] [9] The pharmaceutical composition described in [7] is used to alleviate or treat myosin light chain kinase 4 (MYLK4) related disorders or symptoms.

[0303]

[10] The pharmaceutical composition described in [9] wherein the aforementioned myosin light chain kinase 4 (MYLK4) related disorders, impairments or symptoms are 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.

[0304]

[11] The pharmaceutical composition described in [7] is used to relieve or treat dry eye, uveitis, age-related macular degeneration or diabetic retinopathy.

[0305]

[12] The pharmaceutical composition described in [7] is used to alleviate or treat glaucoma, ocular hypertension or aqueous humor outflow obstruction.

[0306]

[13] The compound or pharmaceutically permissible derivative thereof described in any one of [1] to [5] is used as a medicine.

[0307]

[14] The compounds described in

[13] or their pharmaceutically permissible derivatives, used to inhibit the activity of myosin light chain kinase 4 (MYLK4).

[0308]

[15] The compound described in

[13] or its pharmaceutically permissible derivatives, used to alleviate or treat myosin light chain kinase 4 (MYLK4) related disorders, impairments or symptoms.

[0309]

[16] The compound described in

[15] or its pharmaceutically permissible derivatives thereof, wherein the aforementioned myosin light chain kinase 4 (MYLK4) related disorders, impairments or symptoms are 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.

[0310]

[17] The compounds described in

[13] or their pharmaceutically permissible derivatives are used to alleviate or treat dry eye, uveitis, age-related macular degeneration or diabetic retinopathy.

[0311]

[18] The compounds described in

[13] or their pharmaceutically permissible derivatives, used to alleviate or treat glaucoma, ocular hypertension or aqueous humor outflow obstruction.

[0312]

[19] The use of any compound or pharmaceutically permissible derivative thereof described in any one of [1] to [5] for the formulation of medicines.

[0313]

[20] As described in

[19] , it is used to formulate medicines for inhibiting the activity of myosin light chain kinase 4 (MYLK4).

[0314]

[21] As described in

[19] , it is used to formulate medicines for the relief or treatment of myosin light chain kinase 4 (MYLK4) related disorders or symptoms.

[0315]

[22] As described in

[21] , the aforementioned myosin light chain kinase 4 (MYLK4) related disorders, impairments or symptoms are 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.

[0316]

[23] As described in

[19] , it is used to prepare medicines for the relief or treatment of dry eye, uveitis, age-related macular degeneration or diabetic retinopathy.

[0317]

[24] As described in

[19] , it is used to prepare medicines for the relief or treatment of glaucoma, ocular hypertension or aqueous humor outflow obstruction.

[0318]

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

[0319]

[26] A method for alleviating or treating myosin light chain kinase 4 (MYLK4)-related disorders, impairments or symptoms, comprising administering to a patient a therapeutically effective amount of a compound or a pharmaceutically permissible derivative thereof described in any one of [1] to [5].

[0320]

[27] The method described in

[26] wherein the aforementioned myosin light chain kinase 4 (MYLK4) related disorders, impairments or symptoms are 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.

[0321]

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

[0322]

[29] A method for alleviating or treating glaucoma, ocular hypertension or aqueous humor outflow obstruction, comprising administering a therapeutically effective amount of any one of the compounds described in [1] to [5] or a pharmaceutically permissible derivative thereof to a patient.

[0323] This specification defines the terms used to refer to structures or substituents. Unless otherwise specified in this specification, the terms used to refer to each substituent have the following meanings.

[0324] The terms "halogen" and "halogen group" refer to fluorine, chlorine, bromine, or iodine, representing a substituent alone, or used as part of a larger substituent or structure. "Halogen compound" and "halogenated compound" refer to compounds formed by the addition of halogens, including fluorides, chlorides, bromides, and iodides.

[0325] The terms “hydroxyl group” and “hydroxyl group” refer to the -OH group, stand alone as a substituent, or are used as part of a larger substituent or structure.

[0326] The terms “cyano” and “cyano group” refer to the -CN group, representing a substituent alone, or used as part of a larger substituent or structure.

[0327] The terms "difluoromethyl" and "difluoromethyl group" refer to the -CHF2 group, representing a substituent alone, or used as a term to indicate a larger substituent or part of a structure. Similarly, the terms "trifluoromethyl" and "trifluoromethyl group" refer to the -CF3 group, representing a substituent alone, or used as a term to indicate a larger substituent or part of a structure.

[0328] The terms “acetyl” and “acetyl group” refer to the CH3-C(O)- group, representing a substituent alone, or used as part of a larger substituent or structure.

[0329] The terms "amine group" and "amine group" refer to the -NR2 group (where R is hydrogen or a substituent, including cases where two Rs and N form a cyclic structure) (the H group attached to the N of ammonia or amine has one functional group removed), representing a substituent alone, or used as part of a larger substituent or structure. Additionally, "amine" refers to a compound containing an "amine group".

[0330] The terms "nitro" and "nitro group" refer to the -NO2 group, representing a substituent alone, or used as part of a larger substituent or structure. Additionally, "nitro compound" refers to a compound containing a "nitro group".

[0331] The terms “aldehyde,” “aldehyde group,” “formyl group,” and “formyl group” refer to the -CHO group, representing a substituent on its own, or used as part of a larger substituent or structure. Additionally, “aldehyde compound” refers to a compound containing the character “aldehyde.”

[0332] The terms “carbonyl” and “carbonyl group” refer to the -C(O)- group of a divalent group, representing a substituent alone, or used as part of a larger substituent or structure.

[0333] The term "thiocarbonyl" refers to the -C(S)- group of a divalent group, representing a substituent alone, or used as part of a larger substituent or structure.

[0334] The terms "alkyl" and "alkyl group" refer to straight-chain or branched saturated hydrocarbon groups (monovalent groups are represented by the general formula: -C). n H 2n＋1 The terms "alkyl" and "alkyl group" are used alone to represent a substituent, or as part of a larger substituent or structure. When used alone to represent a substituent, they represent a monovalent group; when used as part of a larger substituent or structure, they can refer to a divalent or higher group, in which case they have the same meaning as "alkylene". In this specification, "C" is used... x-y The term "alkyl" refers to an alkyl group having x to y carbon atoms.

[0335] Examples of alkyl groups include methyl, ethyl, propyl (e.g., propane-1-yl, propane-2-yl (or isopropyl)), butyl (e.g., 2-methylpropane-2-yl (or tri-butyl), butane-1-yl, butane-2-yl), pentyl (e.g., pentane-1-yl, pentane-2-yl, pentane-3-yl), 2-methylbutane-1-yl, 3-methylbutane-1-yl, hexyl (e.g., hexane-1-yl), etc.

[0336] The terms "alkenyl" and "alkenyl group" refer to a straight-chain or branched unsaturated hydrocarbon group (monovalent groups are expressed in general formula: -C) having at least one double bond. n H 2n-1 The terms "alkenyl" and "alkenyl group" can refer to a substituent alone, or as part of a larger substituent or structure. When used alone to represent a substituent, they represent a monovalent group; when used as part of a larger substituent or structure, they can refer to a divalent or higher group, in which case they have the same meaning as "alkenyl". When used in this specification, "C x-y The term "alkenyl" refers to an alkenyl group having x to y carbon atoms.

[0337] Examples of alkenyl groups include vinyl, 1-propenyl, 2-propenyl, isopropenyl, 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, etc.

[0338] The terms "alkynyl" and "alkynyl group" refer to a straight-chain or branched unsaturated hydrocarbon group (monovalent groups are expressed in general formula: -C) having at least one valence bond. n H2n-3 The terms "alkynyl" and "alkynyl group" are used alone to represent a substituent, or as part of a larger substituent or structure. When used alone to represent a substituent, they represent a monovalent group; when used as part of a larger substituent or structure, they can refer to a divalent or higher group, in which case they have the same meaning as "ethynyl". When used in this specification, "C x-y The term "alkynyl group" refers to an alkynyl group having x to y carbon atoms.

[0339] Examples of alkynyl groups include 2-propynyl, 2-butynyl, and 1,3-hexadien-5-alkynyl.

[0340] The terms "chain aliphatic hydrocarbon" and "chain aliphatic hydrocarbon group" refer to straight-chain or branched non-aromatic hydrocarbon groups. Accordingly, "chain aliphatic hydrocarbon" and "chain aliphatic hydrocarbon group" encompass saturated or unsaturated hydrocarbon groups, and more specifically, straight-chain or branched alkyl, alkenyl, or alkynyl groups. When used in this specification, "C..." x-y The term "chain aliphatic hydrocarbon" refers to a chain aliphatic hydrocarbon with x to y carbon atoms. Examples of alkyl, alkenyl, and alkynyl groups are as described above.

[0341] 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. Additionally, the terms "alicyclic hydrocarbon" and "alicyclic hydrocarbon group" can refer to a substituent alone, or be used as part of a larger substituent or structure. When used alone, it represents a monovalent group; when used as part of a larger substituent or structure, it can refer to a group with a valence of two or more. The term "x to y-membered alicyclic hydrocarbon" refers to a monocyclic or polycyclic non-aromatic cyclic hydrocarbon with a ring consisting of x to y carbon atoms, containing monocyclic or polycyclic cycloalkyl or cycloalkenyl groups consisting of x to y carbon atoms.

[0342] Polycyclic non-aromatic cyclic hydrocarbon groups include 2-cyclic or 3-cyclic non-aromatic cyclic hydrocarbon groups. Additionally, polycyclic non-aromatic cyclic hydrocarbon groups include bridged cyclic hydrocarbons and spirochetes.

[0343] 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, adamantyl, etc.

[0344] The terms "cycloalkyl" and "cycloalkyl group" refer to monocyclic or polycyclic saturated hydrocarbon groups, representing a substituent alone, or used as part of a larger substituent or structure. When "cycloalkyl" and "cycloalkyl group" represent a substituent alone, they represent a monovalent group; when used as part of a larger substituent or structure, they can refer to a group with a valence of two or more, in which case they have the same meaning as "hemisyl" (or "episyl"). The term "x to y-membered cycloalkyl" refers to monocyclic or polycyclic cycloalkyl groups consisting of x to y carbon atoms. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[3.2.1]octyl, etc.

[0345] The terms "cycloalkenyl" and "cycloalkenyl group" refer to a non-aromatic cyclic hydrocarbon group, either monocyclic or polycyclic, containing at least one carbon-carbon double bond. They can stand alone as a substituent or be used as part of a larger substituent or structure. When used alone as a substituent, "cycloalkenyl" represents a monovalent group; when used as part of a larger substituent or structure, it can refer to a group with a valence of two or more, in which case it has the same meaning as "epylene-cycloalkenyl." The term "x to y-membered cycloalkenyl" refers to a monocyclic or polycyclic cycloalkenyl group consisting of x to y carbon atoms.

[0346] Examples of cycloalkenyl groups include cyclopentenyl, cyclohexenyl, and cycloheptenyl.

[0347] The terms "aromatic hydrocarbon" and "aromatic hydrocarbon group" are used interchangeably with "aryl," referring to a hydrocarbon group with a monocyclic or polycyclic cyclic structure composed of carbon atoms with alternating single and double bonds and non-localized electron systems. They can represent a substituent alone or be used as part of a larger substituent or structure. When "aromatic hydrocarbon" and "aromatic hydrocarbon group" represent a substituent alone, they indicate a monovalent group; when used as part of a larger substituent or structure, they can refer to a group with a divalent or higher valence. The term "x to y-membered aromatic hydrocarbon" refers to an aromatic hydrocarbon with a ring consisting of x to y carbon atoms. Examples of aromatic hydrocarbons include phenyl, 1-naphthyl, 2-naphthyl, 1-anthrayl, 2-anthrayl, and 9-anthrayl.

[0348] The terms "heterocyclic" and "heterocyclic group" refer to monocyclic or polycyclic groups with a ring structure containing heteroatoms other than carbon atoms as ring constituent atoms. They can stand alone as a substituent or be used as part of a larger substituent or structure. When used alone as a substituent, "heterocyclic" represents a monovalent group; when used as part of a larger substituent or structure, it can refer to a group with a divalent or higher valence. The term "x to y-membered heterocycle" refers to a heterocycle composed of x to y atoms (including carbon and heteroatoms other than carbon). Heterocycles include aromatic heterocycles, heterocyclic groups, and heterocyclic alkenyl groups.

[0349] The terms "aromatic heterocycle" and "aromatic heterocyclic group" are used interchangeably with "heteroaryl," referring to a monocyclic or polycyclic group with alternating single and double bonds and delocalized electrons, containing heteroatoms other than carbon as ring-forming atoms. They can represent a substituent alone or be used as part of a larger substituent or structure. When "aromatic heterocycle" and "aromatic heterocyclic group" represent a substituent alone, they signify a monovalent group; when used as part of a larger substituent or structure, they can refer to a group with a divalent or higher valence. The term "x to y-membered aromatic heterocycle" refers to an aromatic heterocycle composed of x to y atoms (including carbon and heteroatoms other than carbon).

[0350] As aromatic heterocycles, for example, can be listed as follows:

[0351] 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, tetraazole, triazine, and other 5- to 6-membered monocyclic aromatic heterocycles; and

[0352] Benzothiophene, benzofuran, benzimazole, benzoxazole, benzoisoxazole, benzothiazole, benzoisothiazole, benzotriazole, imidazopyridine, thienopyridine, furan-pyridine, pyrrolopyridine, pyrazolidine, oxazolopyridine, thiazopyridine, imidazopyrazine, imidazopyrimidine, thienopyrimidine, furan-pyrimidine, pyrrolopyrimidine, pyrazolidine, oxazolopyrimidine, thiazopyrimidine, pyrazolidine, pyrazolidine, pyrazolidine, naphtho[2, [3-b] Thiophene, phenothiazine, indole, isoindole, 1H-indazole, purine, isoquinoline, quinoline, terazine, naphthidine, quinoxaline, quinazoline, cyclophosphine, carbazole, β-carboline, phenanthridine, acridine, phenazine, phenanthridine, phenanthridine, phenoxazine, phenoxazine, etc., 8 to 14 member condensed polycyclic aromatic heterocycles (preferably 2 or 3 rings).

[0353] The terms "heterocyclic group" and "heterocyclic group" refer to monocyclic or polycyclic groups with a saturated ring structure consisting of heteroatoms other than carbon atoms as ring constituents. They can stand alone as a substituent or be used as part of a larger substituent or structure. When used alone as a substituent, "heterocyclic group" represents a monovalent group; when used as part of a larger substituent or structure, it can refer to a group with a valence of two or more atoms. The term "x to y-membered heterocyclic group" refers to a heterocyclic group consisting of x to y atoms (including carbon and heteroatoms other than carbon). Polycyclic heterocyclic groups include 2-cyclic or 3-cyclic heterocyclic groups. Additionally, polycyclic heterocyclic groups include bridged rings and spirocyclic rings.

[0354] As heterocyclic groups, examples include saturated heterocycles that typically contain one or more (e.g., one to three) heteroatoms selected from nitrogen, oxygen, and sulfur atoms.

[0355] The terms "heterocyclic alkenyl" and "heterocyclic alkenyl group" refer to non-aromatic heterocyclic groups, either monocyclic or polycyclic, containing at least one carbon-carbon double bond and heteroatoms other than carbon atoms as ring constituents. They can be used alone as a substituent or as part of a larger substituent or structure. When used alone as a substituent, "heterocyclic alkenyl" represents a monovalent group; when used as part of a larger substituent or structure, it can refer to a group with a divalent or higher valence, in which case it has the same meaning as "extrinyl (hemisyl)-heterocyclic alkenyl". The term "x to y-membered heterocyclic alkenyl" refers to cycloalkenyl groups, either monocyclic or polycyclic, consisting of x to y carbon atoms.

[0356] Examples of heterocyclic alkenyl groups include dihydrofuran, pyran, pyrrololine, and pyrazoline.

[0357] The terms "aralkyl" and "aralkyl group" refer to alkyl groups substituted with phenyl groups, indicating a substituent alone or as part of a larger substituent or structure. When used alone to represent a substituent, "aralkyl" and "aralkyl group" represent a monovalent group; when used as part of a larger substituent or structure, they can indicate a divalent or higher group. Additionally, "C..." x-y The term "aralkyl" refers to an aralkyl group having an alkyl moiety of x to y carbon atoms. Examples of aralkyl groups include benzyl, phenethyl, naphthylmethyl, and phenylpropyl.

[0358] The terms "alkoxy" and "alkoxy group" refer to a group represented by the formula: -OR (where R is an alkyl group), indicating a substituent alone or as part of a larger substituent or structure. When "alkoxy" and "alkoxy group" represent a substituent alone, they indicate a monovalent group; when used as part of a larger substituent or structure, they can indicate a divalent or higher group. Additionally, "C..." x-y The term "alkoxy group" refers to an alkoxy group having x to y carbon atoms.

[0359] Examples of alkoxy groups include methoxy, ethoxy, propoxy (e.g., 1-propoxy, 2-propoxy), butoxy (e.g., 1-butoxy, 2-butoxy, 2-methyl-2-propoxy), pentoxy (1-pentoxy, 2-pentoxy), hexoxy (1-hexoxy, 3-hexoxy), etc.

[0360] The terms "cycloalkoxy" and "cycloalkoxy group" refer to a group represented by the formula: -OR (where R is a cycloalkyl group), indicating a substituent alone or as part of a larger substituent or structure. When used alone as a substituent, "cycloalkoxy" represents a monovalent group; when used as part of a larger substituent or structure, it can indicate a divalent or higher group. Additionally, the term "x to y-membered cycloalkoxy" refers to a cycloalkoxy group consisting of a cycloalkyl ring with x to y carbon atoms.

[0361] Examples of cycloalkoxy groups include cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, and cyclooctyloxy.

[0362] The terms "alkylthio" and "alkylthion group" refer to a group represented by the formula: -SR (where R is alkyl), indicating a substituent alone or as part of a larger substituent or structure. When "alkylthio" and "alkylthion group" represent a substituent alone, they indicate a monovalent group; when used as part of a larger substituent or structure, they can indicate a divalent or higher group. Additionally, "C..." x-y The term "alkyl thio" refers to an alkyl thio group having x to y carbon atoms. Examples of alkyl thio groups include methyl thio, difluoromethyl thio, trifluoromethyl thio, ethyl thio, propyl thio, isopropyl thio, butyl thio, 4,4,4-trifluorobutyl thio, pentyl thio, and hexyl thio.

[0363] The terms "cycloalkylthio" and "cycloalkylthio group" refer to a group represented by the formula -SR (where R is cycloalkyl), indicating a substituent alone or as part of a larger substituent or structure. When used alone as a substituent, "cycloalkylthio" represents a monovalent group; when used as part of a larger substituent or structure, it can indicate a divalent or higher group. Additionally, the term "x to y-membered cycloalkylthio" refers to a cycloalkylthio group whose ring consists of x to y carbon atoms.

[0364] The terms "alkylsulfonyl" and "alkylsulfonyl group," "cycloalkylsulfonyl" and "cycloalkylsulfonyl group," and "heterocyclic sulfonyl" and "heterocyclic sulfonyl group" refer to a group represented by the formula -S(O)2-R (where R is alkyl, cycloalkyl, and heterocyclic, respectively), indicating a substituent alone or as part of a larger substituent or structure. When "alkylsulfonyl" and "alkylsulfonyl group," "cycloalkylsulfonyl" and "cycloalkylsulfonyl group," and "heterocyclic sulfonyl" and "heterocyclic sulfonyl group" represent a substituent alone, they represent a monovalent group; when used as part of a larger substituent or structure, they can indicate a divalent or higher group. Additionally, "C..." x-y The term "alkylsulfonyl" refers to an alkylsulfonyl group with x to y carbon atoms. The term "x to y membered cycloalkylsulfonyl" refers to a cycloalkylsulfonyl group whose ring consists of x to y carbon atoms. The term "x to y membered heterocyclic sulfonyl" refers to a heterocyclic sulfonyl group whose heterocycle consists of x to y atoms (including carbon and heteroatoms other than carbon atoms).

[0365] Examples of alkyl sulfonyl groups include methyl sulfonyl, ethyl sulfonyl, propyl sulfonyl, isopropyl sulfonyl, butyl sulfonyl, secondary butyl sulfonyl, tertiary butyl sulfonyl, etc.

[0366] The terms “arylsulfonyl” and “arylsulfonyl group” are used in the same manner as described above. Examples of arylsulfonyl groups include phenylsulfonyl, 1-naphthylsulfonyl, and 2-naphthylsulfonyl.

[0367] The terms "alkylcarbonyl" and "alkylcarbonyl group," "cycloalkylcarbonyl" and "cycloalkylcarbonyl group," and "heterocyclic carbonyl" and "heterocyclic carbonyl group" refer to a group represented by the formula -C(O)-R (where R represents alkyl, cycloalkyl, and heterocyclic groups, respectively), indicating a substituent alone or as part of a larger substituent or structure. When "alkylcarbonyl" and "alkylcarbonyl group," "cycloalkylcarbonyl" and "cycloalkylcarbonyl group," and "heterocyclic carbonyl" and "heterocyclic carbonyl group" represent a substituent alone, they represent a monovalent group; when used as part of a larger substituent or structure, they can indicate a divalent or higher group. Additionally, "C..." x-y The term "alkyl carbonyl" refers to an alkyl carbonyl group having x to y carbon atoms; the term "x to y membered cycloalkyl carbonyl" refers to a cycloalkyl carbonyl group whose ring is composed of x to y carbon atoms; and the term "x to y membered heterocyclic carbonyl" refers to a heterocyclic carbonyl group whose heterocycle is composed of x to y atoms (including carbon and heteroatoms other than carbon atoms).

[0368] Examples of alkyl carbonyl groups include acetyl, propionyl, butyryl, 2-methylpropionyl, valeryl, 3-methylbutyryl, 2-methylbutyryl, 2,2-dimethylpropionyl, hexanoyl, heptanoyl, etc.

[0369] The terms "alkoxycarbonyl" and "alkoxycarbonyl group," as well as "cycloalkoxycarbonyl" and "cycloalkoxycarbonyl group," refer to a group represented by the formula -C(O)-R (where R represents alkoxy and cycloalkoxy, respectively), indicating a substituent alone or as part of a larger substituent or structure. When "alkoxycarbonyl" and "alkoxycarbonyl group," as well as "cycloalkoxycarbonyl" and "cycloalkoxycarbonyl group," represent a monovalent group when used alone, they can refer to a divalent or higher group when used as part of a larger substituent or structure. Additionally, "C..." x-y The term "alkoxycarbonyl" refers to an alkoxycarbonyl group with x to y carbon atoms, while the term "x to y membered cycloalkoxycarbonyl" refers to a cycloalkoxycarbonyl group composed of a cycloalkyl ring with x to y carbon atoms.

[0370] Examples of alkoxycarbonyl groups include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, secondary-butoxycarbonyl, tertiary-butoxycarbonyl, pentyloxycarbonyl, and hexyloxycarbonyl.

[0371] The terms “aryl carbonyl” and “aryl carbonyl group”, “aralkyl carbonyl” and “aralkyl carbonyl group”, “aromatic heterocyclic carbonyl” and “aromatic heterocyclic carbonyl group”, and “heterocyclic carbonyl” and “heterocyclic carbonyl group” are used in the same manner as described above. Examples of aryl carbonyl groups include benzyl, 1-naphthyl, and 2-naphthyl; examples of aralkyl carbonyl groups include phenylacetyl and phenylpropionyl; examples of aromatic heterocyclic carbonyl groups include nicotinyl, isonicotinyl, thiophenecarboxyl, and furanoyl; and examples of heterocyclic carbonyl groups include morpholinyl, piperidinyl, and pyrrolidinyl.

[0372] The terms “amide” and “amide group”, as well as “carboxylic acid amide” and “carboxylic acid amide group”, refer to compounds having a structure represented by the formula: RC(O)-NR'R'' (where R is any substituent or structure, and R, R', and R'' are each independently hydrogen or any substituent or structure, including cases where R' and R'' together with N form a cyclic structure). Additionally, the terms “thioamide” and “thioamide group”, as well as “thioic acid amide” and “thioic acid amide group”, refer to compounds having a structure represented by the formula: RC(S)-NR'R'' (where R is any substituent or structure, and R, R', and R'' are each independently hydrogen or any substituent or structure). The terms “acetamide” and “acetamide group”, and the notation “-NHAc”, refer to a monovalent substituent represented by CH3C(O)NH-.

[0373] The terms "alkylaminoformyl" and "alkylaminoformyl group," "cycloalkylaminoformyl" and "cycloalkylaminoformyl group," and "heterocyclic aminoformyl" and "heterocyclic aminoformyl group" refer to a group represented by the formula: -C(O)-NR'R'' (where R' and R'' are hydrogen atoms or alkyl, cycloalkyl, and heterocyclic groups respectively, and at least one of R' and R'' is alkyl, cycloalkyl, and heterocyclic). These terms alone represent a substituent or represent a larger substituent or part of a structure. When "alkylaminoformyl" and "alkylaminoformyl group," "cycloalkylaminoformyl" and "cycloalkylaminoformyl group," and "heterocyclic aminoformyl" and "heterocyclic aminoformyl group" represent a substituent alone, they represent a monovalent group; when used as part of a larger substituent or structure, they can refer to a divalent or higher group. Additionally, "C..." x-y The term "alkylaminoformyl" refers to an alkylaminoformyl group with x to y carbon atoms. The term "x to y-membered cycloalkylaminoformyl" refers to a cycloalkylaminoformyl group whose ring consists of x to y carbon atoms. The term "x to y-membered heterocyclic aminoformyl" refers to a heterocyclic aminoformyl group whose ring consists of x to y atoms (including carbon and heteroatoms other than carbon atoms).

[0374] Examples of alkylaminoformyl groups include methylaminoformyl, ethylaminoformyl, dimethylaminoformyl, diethylaminoformyl, N-ethyl-N-methylaminoformyl, etc.

[0375] The terms “aralkylaminoformyl” and “aralkylaminoformyl group” are used in the same manner as described above. For example, benzylaminoformyl and phenethylaminoformyl can be listed as “aralkylaminoformyl”.

[0376] The term "ester" refers to an ester defined by the formula: RC(O)O-R' (R is C 1-3The structure represented by alkyl, -OC-, etc. (where R' is a substituent such as alkyl or aromatic hydrocarbon), "ester compound" refers to a compound that has an ester structure.

[0377] The term "ether" refers to a structure represented by the formula RO-R' (where R and R' are substituents such as alkyl and aromatic hydrocarbons, respectively), and "ether compound" refers to a compound that contains ethers. Detailed Implementation

[0378] [Format for implementing the invention]

[0379] The embodiments of the present invention will be described in detail. However, the present invention is not limited to the following embodiments.

[0380] 1. Novel thiazolyl-pyrazolopyridine compounds

[0381] The novel thiazolyl-pyrazolopyridine compound (hereinafter referred to as "this compound") provided by the present invention is a compound of formula (I) or a pharmaceutically permissible derivative thereof:

[0382] .

[0383] In formula (I),

[0384] R 1 To R 5 Each is independently hydrogen or C 1-3 Chain-like aliphatic hydrocarbons;

[0385] R 6 A 5- to 10-membered aromatic hydrocarbon that is substituted, having a 5- to 10-membered heterocycle that is substituted, having 1 to 5 heteroatoms independently selected from nitrogen, oxygen and sulfur as ring-forming atoms, or any of the above, and a condensed ring having a 4- to 10-membered heterocyclic group that is substituted, having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur as ring-forming atoms.

[0386] R in equation (I) 1 To R 5 Each is preferably hydrogen or chain C independently. 1-3 Alkyl groups, preferably hydrogen or straight-chain C4 groups. 1-3 Alkyl, more preferably hydrogen or methyl, particularly preferably hydrogen. Additionally, R 1 R 2 and R 4 Hydrogen is preferred, R 1 R 2 R 4 and R 5 Hydrogen is preferred.

[0387] R as in equation (I) 6The "5- to 10-membered aromatic hydrocarbon" is more preferably a 5- or 6-membered monocyclic aromatic hydrocarbon or an 8- to 10-membered 2- or 3-membered aromatic hydrocarbon, more preferably phenyl, 1-naphthyl or 2-naphthyl, and especially preferably phenyl.

[0388] R in equation (I) 6 The term "5- to 10-membered heterocycle" includes, for example, 5- to 10-membered aromatic heterocycles and 5- or 6-membered heterocyclic alkenyl groups, preferably 5- or 6-membered monocyclic aromatic heterocycles, 8- to 10-membered 2- or 3-membered aromatic heterocycles, or 5-membered heterocyclic alkenyl groups, more preferably 5- or 6-membered monocyclic aromatic heterocycles or 8- to 10-membered 2-membered aromatic heterocycles, and particularly preferably 5- or 6-membered monocyclic aromatic heterocycles. Among these, pyridine, pyrazole, thiazole, isoxazole, pyrrole, imidazole, triazole, thiophene, furan, and isothiazole are more preferred.

[0389] R as in equation (I) 6 The "4- to 10-membered heterocyclic group" that forms a "condensation ring" with a "5- to 10-membered aromatic hydrocarbon" or a "5- to 10-membered heterocycle" (preferably a "5- to 10-membered aromatic heterocycle") can be exemplified by 4- to 10-membered saturated heterocycles containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur atoms. Examples of these "4- to 10-membered heterocyclic groups" include dioxacyclopentanes such as 1,3-dioxacyclopentane, dihydropyridine-2(1H)-ones, oxacyclobutyl, azacyclobutyl, piperazine, piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, tetrahydropiperanyl, tetrahydrofuranyl, oxazolidinyl, thiazodinyl, imidazodinyl, pyrazolidyl, thiohexyl, oxacyclohexyl, thiooxacyclohexyl, azaheptenyl, tropane, etc.

[0390] Preferably, the 5- or 6-membered monocyclic heterocyclic group contains one or two oxygen or nitrogen atoms as ring constituent atoms, and more preferably, the 5- or 6-membered monocyclic heterocyclic group contains one or two nitrogen atoms as ring constituent atoms. Examples of such monocyclic heterocyclic groups include dioxanes such as 1,3-dioxane, dihydropyridine-2(1H)-ones, and pyrrolidinyl groups.

[0391] Therefore, R is used as equation (I) 6The "condensation ring" is preferably a condensation ring of a 5- or 6-membered monocyclic aromatic hydrocarbon and a 5- or 6-membered monocyclic heterocyclic group, wherein the aromatic hydrocarbon is a condensation ring of a thiazole of formula (I), or a condensation ring of a 5- or 6-membered monocyclic nitrogen-containing aromatic heterocycle containing one or two nitrogen atoms as ring constituent atoms and a 5- or 6-membered monocyclic heterocyclic group, wherein the aromatic heterocycle is a condensation ring of a thiazole of formula (I). More preferably, it is a 2-cyclic condensation ring of a phenyl group and a 5- or 6-membered monocyclic nitrogen-containing heterocyclic group, wherein the phenyl group is a condensation ring of a thiazole of formula (I), or a condensation ring of a pyridine group and a 5- or 6-membered monocyclic nitrogen-containing or oxygen-containing heterocyclic group, wherein the pyridine group is a condensation ring of a thiazole of formula (I). Particularly preferred is a 2-cyclic condensation ring of a phenyl group and a 6-membered monocyclic nitrogen-containing heterocyclic group, wherein the phenyl group is a condensation ring of a thiazole of formula (I).

[0392] R in equation (I) 6 The terms "5- to 10-membered aromatic hydrocarbons," "5- to 10-membered heterocycles," and "4- to 10-membered heterocyclic groups" that form condensation rings with these compounds may be substituted, as appropriate. In this document, "substitutable, as appropriate" means unsubstituted or substituted via specified substituents. Substituents are chosen based on their chemically possible positions relative to the ring structures. Substituents for "5- to 10-membered aromatic hydrocarbons" or "5- to 10-membered heterocycles" may be selected from, for example, the group consisting of:

[0393] (1) Halogen, nitro, cyano, hydroxyl, difluoromethyl, trifluoromethyl,

[0394] (2)-NR 31 2. -N(R) 31 (CH2) 1-5 NR 31 2. -N(R) 31 )S(O)2R 32 -N(R) 31 )C(O)R 31 -N(R) 31 )C(O)(CH2) 0-3 NR 31 2. -N(R) 31 )C(O)(CH2) 0-3 R 32 ,

[0395] (3)C 1-6 Alkyl group, -(CH2) 1-5 OR 31 -(CH2) 1-5 O(CH2) 1-5 OR 31 -(CH2) 1-5 R 32 -(CH2) 1-5 R33 、

[0396] (4)-(CH2) 1-5 NR 31 2、-(CH2) 1-5 N(R 31 )R 32 、-(CH2) 1-5 N(R 31 )(CH2) 0-5 R 38 、-(CH2) 1-5 N(R 31 )C(O)R 31 、-(CH2) 1-5 N(R 31 )C(O)(CH2) 1-5 OR 31 、-(CH2) 1-5 N(C(O)R 31 )(CH2) 1-5 C(O)OR 31 、-(CH2) 1-5 N(R 31 )C(O)(CH2) 0-5 NR 31 2、-(CH2) 1-5 N(R 31 )C(O)R 32 、

[0397] (5)-(CH2) 1-5 N(R 31 )S(O)2R 33 、

[0398] (6)-C(R 31 )2C(O)R 32 、

[0399] (7)-C(R 31 )2C(O)NR 31 2、-C(R 31 )2C(O)N(R 31 )OR 31 、

[0400] (8)-C(O)R 31 、-C(O)R 32 、

[0401] (9)-C(O)OR 31 、

[0402] (10)-C(O)NR 31 2、-C(O)N(R 31(CH2) 0-5 R 32 ,

[0403] (11)-OC(R 31 )2C(O)N(R 31 (CH2) 1-5 OR 31 -OC(R) 31 )2C(O)OR 31 -OC(R) 31 )2C(O)NR 31 2. -OC(R) 31 )2C(O)R 32 ,

[0404] (12)-O(CH2) 1-6 R 31 -(O(CH2) 1-5 ) 1-5 (CH2) 0-3 NR 31 2. -(O(CH2) 1-5 ) 1-5 (CH2) 0-3 NR 31 C(O)R 31 -(O(CH2) 1-5 ) 1-5 NR 31 C(NH)NR 31 2. -O((CH2) 1-5 O) 1-5 R 31 ,

[0405] (13)-OC(O)C(R 31 )2(O(CH2) 1-5 ) 1-5 OR 31 ,as well as

[0406] (14) Depending on the circumstances, via C 1-3 Alkyl-substituted 5- or 6-membered heterocyclic groups containing nitrogen as a ring-forming atom.

[0407] R 31 Each is independently hydrogen or C 1-4 Chain aliphatic hydrocarbons, preferably hydrogen or chain C 1-4 Alkyl groups, more preferably hydrogen or straight-chain C4 groups. 1-4 Alkyl, more preferably hydrogen, methyl or ethyl, and especially preferably hydrogen.

[0408] R 32The ring consists of a substituted 4- to 10-membered heterocyclic group having one to three heteroatoms selected from nitrogen, sulfur, and oxygen as ring constituent atoms, or a condensed ring of such a ring with a substituted 5- or 6-membered monocyclic aromatic hydrocarbon, wherein the substituents are preferably selected from C. 1-12 Chain-like aliphatic hydrocarbons, -(CH2) 1-5 OH, halogen, nitro, hydroxyl, cyano, -(CH2) 0-5 NR 31 2. -(CH2) 0-5 N(R 31 )R 33 -(CH2) 0-5 NC(O)R 33 -OR 31 -SR 31 -S(O)2R 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 (CH2) 1-5 R 33 -N(R) 31 SO2R 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)2NR 31 Two components are grouped together, more preferably selected from C. 1-3 Alkyl group, -(CH2) 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 Grouped into 3 to 10-membered alicyclic hydrocarbons and acetyl groups.

[0409] When sulfur is included as a ring-forming atom, the sulfur element forms -S(O)2-.

[0410] R 33 It is a 3- to 10-membered alicyclic hydrocarbon or a 4- to 10-membered heterocyclic group having 1 to 5 heteroatoms independently selected from nitrogen, oxygen and sulfur as ring-forming atoms.

[0411] R 38It is a cyano group, a hydroxyl group, or S(O)2R. 31 .

[0412] Additionally, R 31 R 32 R 33 and R 38 In this application specification, unless otherwise specified, the following descriptions refer to the same base or structure.

[0413] As substituents for "4- to 10-membered heterocyclic groups" that form condensation rings, C can be listed as an example. 1-5 Chain aliphatic hydrocarbons, preferably C 1-3 alkyl.

[0414] The substituents in the "alicyclic hydrocarbon," "aromatic hydrocarbon," "aromatic heterocycle," "heterocyclic alkenyl," "heterocyclic group," or any two of the condensation rings formed therefrom, as described in this application, may be introduced at chemically appropriate positions with a chemically possible number of substituents. In the case of halogens, nitro groups, hydroxyl groups, cyano groups, and amino groups, the number of substituents is generally four or fewer, more preferably three or fewer, and even more preferably two or fewer. Furthermore, regarding substituents other than halogens, nitro groups, hydroxyl groups, cyano groups, and amino groups, the number of substituents is generally two or fewer, more preferably one. In the case of two or more substituents, the substituents may be the same or different.

[0415] In the preferred implementation sample, R 6 Selected from the following groups:

[0416] ,

[0417] More preferably, it is selected from the group consisting of:

[0418] .

[0419] Among the various types,

[0420] R 7 Each is independently hydrogen, halogen, nitro, cyano, hydroxyl, C 1-6 Alkyl, C 1-6 Alkoxy or -NR 31 2,

[0421] R 8 Each is independently selected from the following groups:

[0422] (1) Hydrogen, halogen, nitro, cyano, hydroxyl (2)

[0424] (i)-NR 31 2.

[0425] (ii)-N(R 31 )S(O)2R32-1 (where R is in the formula) 32-1 A 4- to 10-membered heterocyclic group having, where 1 to 3 heteroatoms selected from nitrogen and oxygen are used as ring-forming atoms, preferably substituted with C, wherein the heterocyclic group is preferably substituted with C, where C is used as ring-forming atoms. 1-3 Alkyl group, -(CH2) 1- 3OH, -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 hydrocarbons or acetyl substitution, R 32-1 The preferred heterocyclic group is the one with the following formula:

[0426]

[0427] (where R is in the formula) 20 and R 21 Each is independently selected from hydrogen and C. 1-3 Alkyl group, -(CH2) 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 The group consists of 3 to 10 membered alicyclic hydrocarbons and acetyl groups, preferably hydrogen or methyl, where m and n are each independently integers from 1 to 4, preferably integers from 1 to 2.

[0428] (iii)-N(R 31 )C(O)R 31 ,

[0429] (iv)-N(R 31 )C(O)(CH2) 0-3 NR 31 2,

[0430] (v)-N(R 31 )C(O)(CH2) 0-3 R 32-2 (where R is in the formula) 32-2 A 4- to 10-membered heterocyclic group having, where 1 to 3 heteroatoms selected from nitrogen and oxygen are used as ring-forming atoms, preferably substituted with C, wherein the heterocyclic group is preferably substituted with C, where C is used as ring-forming atoms. 1-3 Alkyl group, -(CH2) 1-3 OH, -NR 31 2. -CHO, -C(O)C(O)R 33 -C(O)NR 312. -C(O)N(R) 31 (CH2) 1-5 3 to 10-membered alicyclic hydrocarbons or acetyl substitution, R 32-2 The preferred heterocyclic group is the one with the following formula:

[0431]

[0432] (where R is in the formula) 20 and R 21 Each is independently selected from hydrogen and C. 1-3 Alkyl group, -(CH2) 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 The group consists of 3 to 10 membered alicyclic hydrocarbons and acetyl groups, preferably hydrogen or methyl, where m and n are each independently integers from 1 to 4, preferably integers from 1 to 2. (3)

[0434] (i)C 1-6 alkyl,

[0435] (ii)-(CH2) 1-5 OR 31 ,

[0436] (iii)-(CH2) 1-5 R 32-3 (where R is in the formula) 32-3 A 4- to 10-membered heterocyclic group having, where 1 to 3 heteroatoms selected from nitrogen and oxygen are used as ring-forming atoms, preferably substituted with C, wherein the heterocyclic group is preferably substituted with C, where C is used as ring-forming atoms. 1-3 Alkyl group, -(CH2) 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 hydrocarbons or acetyl substitution, R 32-3 A preferred heterocyclic group is selected from the following formula:

[0437]

[0438] (where R is in the formula) 20 and R 21 Each is independently selected from hydrogen and C. 1-3 Alkyl group, -(CH2) 1-3 OH, -NR31 2. -CHO, -C(O)C(O)R 33 -C(O)NR 31 2. -C(O)N(R) 31 (CH2) 1-5 Groups consisting of 3 to 10-membered alicyclic hydrocarbons and acetyl groups, with free hydrogen, methyl, and -(CH2) groups being preferred. 1-3 OH、-C(O)C(O)R 33 and -C(O)NR 31 Two institutions were grouped together.

[0439] R 23 and R 24 Each is independently selected from hydrogen and C. 1-12 Grouped with chain-like aliphatic hydrocarbons, preferably hydrogen or methyl,

[0440] R 22 Choose freely from O, SO2, and CR. 31 2 and NR 22-1 Group (R) 22-1 Choose C freely 1-12 Chain-like aliphatic hydrocarbons, -(CH2) 1- 5OH, -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 (CH2) 1-5 R 33 The group formed, more preferably free C 1-3 Alkyl group, -(CH2) 1-3 OH, -CHO, -C(O)C(O)R 33 -C(O)NR 31 2. -C(O)N(R) 31 (CH2) 1-5 (composed of 3 to 10 membered alicyclic hydrocarbons and acetyl groups), preferably O and CR 31 2 or NR 22-2 (R 22-2 Choose C freely 1-3 Alkyl groups and -C(O)C(O)R 33 (Groups formed)

[0441] R 25 Choose freely from O, SO2, and CR. 31 2 and NR 31 The preferred group is NR. 31 ,

[0442] R 31Hydrogen or methyl is preferred, and hydrogen is more preferred.

[0443] m, n, p, and q are each independent integers from 1 to 4. (4)

[0445] (i)-(CH2) 1-5 NR 31 2.

[0446] (ii)-(CH2) 1-5 N(R 31 )R 32-4 (where R is in the formula) 32-4 The substituted 3- to 10-membered alicyclic hydrocarbons or the substituted 4- to 10-membered heterocyclic groups having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-forming atoms, preferably each independently substituted as appropriate. 1-3 Alkyl group, -(CH2) 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 hydrocarbons or acetyl substitution, R 32-4 The preferred form is an alicyclic hydrocarbon or heterocyclic group of the following formula:

[0447] (where R is in the formula) 20 and R 21 Each is independently selected from hydrogen and C. 1-3 Alkyl group, -(CH2) 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 Composed of 3 to 10 membered alicyclic hydrocarbons and acetyl groups, preferably hydrogen or methyl.

[0448] R 22 Choose freely from O, SO2, and CR. 31 2 and NR 31 The preferred group is NR. 31 ,

[0449] R 31 Hydrogen or methyl is preferred.

[0450] m and n are each independent integers from 1 to 4.

[0451] (iii)-(CH2)1-5 N(R 31 )C(O)R 31 ,

[0452] (iv)-(CH2) 1-5 N(R 31 )C(O)(CH2) 1-5 OR 31 ,

[0453] (v)-(CH2) 1-5 N(C(O)R 31 (CH2) 1-5 C(O)OR 31 ,

[0454] (vi)-(CH2) 1-5 N(R 31 )C(O)(CH2) 0-5 NR 31 2.

[0455] (vii)-(CH2) 1-5 N(R 31 )C(O)R 32-5 (where R is in the formula) 32-5 The substituted 3- to 10-membered alicyclic hydrocarbons or the substituted 4- to 10-membered heterocyclic groups having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-forming atoms, preferably each independently substituted as appropriate. 1-3 Alkyl group, -(CH2) 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 hydrocarbons or acetyl substitution, R 32-5 The preferred form is an alicyclic hydrocarbon or heterocyclic group of the following formula:

[0456]

[0457] (where R is in the formula) 20 and R 21 Each is independently selected from hydrogen and C. 1-3 Alkyl group, -(CH2) 1-3 OH, -NR 31 2. -CHO, -C(O)C(O)R 33 -C(O)NR 31 2. -C(O)N(R) 31 (CH2) 1-5Composed of 3 to 10 membered alicyclic hydrocarbons and acetyl groups, preferably hydrogen or methyl.

[0458] R 22 Choose freely from O, SO2, and CR. 31 2 and NR 31 The preferred group is O.

[0459] R 31 Hydrogen or methyl is preferred.

[0460] m and n are each independent integers from 1 to 4.

[0461] (5)-(CH2) 1-5 N(R 31 )S(O)2R 33-1 (where R is in the formula) 33-1 (3 to 10-membered cycloalkyl groups),

[0462] (6)-C(R 31 )2C(O)R 32-6 (where R is in the formula) 32-6 A 4- to 10-membered heterocyclic group having, where 1 to 3 heteroatoms selected from nitrogen and oxygen are used as ring-forming atoms, preferably substituted with C, wherein the heterocyclic group is preferably substituted with C, where C is used as ring-forming atoms. 1-3 Alkyl group, -(CH2) 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 hydrocarbons or acetyl substitution, R 32-6 The preferred heterocyclic group is the one with the following formula:

[0463]

[0464] (where R is in the formula) 20 and R 21 Each is independently selected from hydrogen and C. 1-3 Alkyl group, -(CH2) 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 Composed of 3 to 10 membered alicyclic hydrocarbons and acetyl groups, preferably hydrogen or methyl.

[0465] R 22 Choose freely from O, SO2, and CR. 31 2 and NR31 The preferred group is NR. 31 ,

[0466] R 31 Hydrogen or methyl is preferred.

[0467] m and n are each independent integers from 1 to 4. (7)

[0469] (i)-C(R 31 )2C(O)NR 31 2.

[0470] (ii)-C(R 31 )2C(O)N(R 31 OR 31 ,

[0471] (8)-C(O)R 32-7 (where R is in the formula) 32-7 Depending on the case, it has 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-forming atoms, via C 1-3 Alkyl group, -(CH2) 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 hydrocarbons or 4 to 10-membered heterocyclic groups substituted with acetyl groups, or their equivalents as appropriate via C-transfer. 1-12 A condensation ring of a chain aliphatic hydrocarbon, acetamide (-NHAc), or acetyl-substituted 5- or 6-membered monocyclic aromatic hydrocarbon, R 32-7 The preferred heterocyclic group or condensation ring is the following:

[0472]

[0473] (where R is in the formula) 20 and R 21 Each is independently selected from hydrogen and C. 1-3 Alkyl group, -(CH2) 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 Groups consisting of 3 to 10-membered alicyclic hydrocarbons and acetyl groups, with free hydrogen and C being preferred. 1-3 Alkyl, -NR 31 2. -C(O)N(R) 31 (CH2)1-5 Grouped into 3 to 10-membered alicyclic hydrocarbons and acetyl groups.

[0474] R 23 and R 24 Each is independently selected from hydrogen and C. 1-12 It consists of chain aliphatic hydrocarbons, acetamide groups (-NHAc), and acetyl groups.

[0475] R 22 Choose freely from O, SO2, and CR. 31 2. CR 31 C(O)N(R 31 (CH2) 1-5 3- to 10-membered alicyclic hydrocarbons, NR 31 The combination of NCHO and O and CR is preferred. 31 2. NR 31 Or NCHO, R 31 Hydrogen and C are preferred. 1-3 alkyl,

[0476] R 25 Choose freely from O, SO2, and CR. 31 2 and NR 31 The preferred group is NR. 31 R 31 Hydrogen or methyl is preferred, and hydrogen is more preferred.

[0477] m, n, p, and q are each independent integers from 1 to 4.

[0478] (9)-C(O)OR 31 , (10)

[0480] (i)-C(O)NR 31 2.

[0481] (ii)-C(O)N(R 31 (CH2) 0-5 R 32-8 (where R is in the formula) 32-8 The substituted 3- to 10-membered alicyclic hydrocarbons or the substituted 4- to 10-membered heterocyclic groups having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring constituent atoms, preferably each independently substituted as appropriate. 1-3 Alkyl group, -(CH2) 1-3 OH, -NR 31 2. -CHO, -C(O)C(O)R 33 -C(O)NR 31 2. -C(O)N(R) 31 (CH2) 1-53 to 10 membered alicyclic hydrocarbons or acetyl substitution, preferably R 32-8 For alicyclic hydrocarbons or heterocyclic groups of the following formula:

[0482]

[0483] (where R is in the formula) 20 and R 21 Each is independently selected from hydrogen and C. 1-3 Alkyl group, -(CH2) 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 Composed of 3 to 10 membered alicyclic hydrocarbons and acetyl groups, preferably hydrogen or methyl.

[0484] R 22 Choose freely from O, SO2, and CR. 31 2 and NR 31 The preferred group is O or NR. 31 ,

[0485] R 31 Hydrogen or methyl is preferred.

[0486] m and n are each independent integers from 1 to 4. (11)

[0488] (i)-OC(R 31 )2C(O)N(R 31 (CH2) 1-5 OR 31 ,

[0489] (ii)-OC(R 31 )2C(O)OR 31 ,

[0490] (iii)-OC(R 31 )2C(O)NR 31 2.

[0491] (iv)-OC(R 31 )2C(O)R 32-9 (where R is in the formula) 32-9 A 4- to 10-membered heterocyclic group having, where 1 to 3 heteroatoms selected from nitrogen and sulfur are used as ring-forming atoms, preferably substituted with C, wherein the heterocyclic group is preferably substituted with C, where C is used as ring-forming atoms. 1-3 Alkyl group, -(CH2) 1- 3OH, -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 hydrocarbons or acetyl substitution, R 32-9 The preferred heterocyclic group is the one with the following formula:

[0492]

[0493] (where R is in the formula) 20 and R 21 Each is independently selected from hydrogen and C. 1-3 Alkyl group, -(CH2) 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 Groups consisting of 3 to 10-membered alicyclic hydrocarbons and acetyl groups, with free hydrogen and C being preferred. 1-3 Alkyl groups and -(CH2) 1-3 Groups composed of OH

[0494] R 22 Choose freely from O, SO2, and CR. 31 2 and NR 31 The group formed is preferably composed of free SO2 and CR. 31 2 and NR 31 The group formed

[0495] R 31 Hydrogen or methyl is preferred.

[0496] m and n are each independent integers from 1 to 4. (12)

[0498] (i)-O(CH2) 1-6 R 31 ,

[0499] (ii)-(O(CH2) 1-5 ) 1-5 (CH2) 0-3 NR 31 2.

[0500] (iii)-(O(CH2) 1-5 ) 1-5 (CH2) 0-3 NR 31 C(O)R 31 ,

[0501] (iv)-(O(CH2) 1-5) 1-5 NR 31 C(NH)NR 31 2.

[0502] (v)-O((CH2) 1-5 O) 1-5 R 31 ,

[0503] (13)-OC(O)C(R 31 )2(O(CH2) 1-5 ) 1-5 OR 31 ,as well as

[0504] (14) Depending on the circumstances, via C 1-3 Alkyl-substituted 5- or 6-membered nitrogen-containing heterocycles, preferably nitrogen-containing heterocycles of the following formula:

[0505]

[0506] (where R is in the formula) 20 and R 21 Each is independently selected from hydrogen and C. 1-3 Alkyl groups, preferably hydrogen or methyl,

[0507] R 22 For NR 31 ).

[0508] R 9 R 10 R 11 and R 12 Each is independently selected from hydrogen, halogen, cyano, hydroxyl, and C. 1-5 Alkyl, 3- to 6-membered cycloalkyl, C 1-5 Alkoxy, -N(R) 31 )C(O)R 31 -N(R) 31 )C(O)(CH2) 0-3 NR 31 2. -N(R) 31 (CH2) 1-5 NR 31 2. -(CH2) 1-5 OR 31 -(CH2) 1-5 O(CH2) 1-5 OR 31 -(CH2) 1-5 R 35 -(CH2) 1-5 N(R 31 )C(O)R 31 -(CH2) 1-5C(O)NR 31 2. -C(R) 31 )2NR 31 2. -(CH2) 1-5 NR 31 2. -C(O)R 36 -C(O)OR 31 -C(O)NR 31 2. -NR 31 2. -C(H)2R 35 -C(H)R 35 2 and -CR 35 Three institutions were grouped together.

[0509] R 31 Each is independently hydrogen or C 1-4 Chain aliphatic hydrocarbons,

[0510] R 35 Each is independently halogenated, cyano-based, or, depending on the case, C 1-5 Alkyl-substituted 3- to 10-membered alicyclic hydrocarbons (preferably unsubstituted 3- to 5-membered alicyclic hydrocarbons) or -OR 31 ,

[0511] R 36 Depending on the case, it has 1 to 3 heteroatoms, independently selected from nitrogen, oxygen, and sulfur, as ring-forming atoms, via C... 1-5 Alkyl-substituted 4- to 10-membered heterocyclic groups, preferably heterocyclic groups of the following formula:

[0512]

[0513] (where R is in the formula) 20 and R 21 Each is independently selected from hydrogen and C. 1-3 Alkyl groups, preferably hydrogen,

[0514] R 22 Choose freely from O, SO2, and CR. 31 2 and NR 31 The preferred group is NR. 31 R 31 The preferred choice is free hydrogen and C. 1-3 Alkyl groups, more preferably hydrogen or methyl,

[0515] m and n are each an independent integer from 1 to 4, preferably an integer from 1 to 2.

[0516] R 13 Each independently is hydrogen, C 1-5 Alkyl group, -(CH2) 1-5 OR 31 -(CH2) 1-5NR 31 2. -(CH2) 1-5 N(R 31 )C(O)R 31 -(CH2) 1-5 N(R 31 (CH2) 0-5 R 38 -C(O)R 31 -C(O)R 37 Or -(CH2) 1-5 R 37 ,

[0517] R 37 It is a 3- to 10-membered alicyclic hydrocarbon or a 3- to 10-membered heterocyclic group having 1 to 3 heteroatoms selected from nitrogen and oxygen.

[0518] R 38 It is a cyano group, a hydroxyl group, or S(O)2R. 31 .

[0519] The heterocycles in the structures shown in formulas (I-2), (I-3), and (I-27) to (I-32), and the benzene ring in the structure shown in (I-33), can each be independently, depending on the situation, subjected to C 1-5 Substitution of chain aliphatic hydrocarbons, preferably via C444 as appropriate. 1-3 Alkyl substitution is preferred, with no substitution being particularly desirable.

[0520] In a specific embodiment of the present invention, as R 6 Specific examples can be listed below.

[0521]

[0522]

[0523] .

[0524] As specific examples of this compound, the following compounds can be listed:

[0525] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 3),

[0526] 4-Phenyl-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 71),

[0527] 2-Methoxy-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 79),

[0528] 4-(3-Fluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 112),

[0529] 4-(2-Fluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 122),

[0530] 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzene-1,3-diol (compound 120),

[0531] 4-(2,4-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 121),

[0532] 4-(3-methoxyphenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 83),

[0533] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(o-tolyl)thiazole (compound 132),

[0534] 1-Methyl-6-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-3,4-dihydroquinoline-2(1H)-one (compound 131),

[0535] N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 12),

[0536] 4-(4-methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 7),

[0537] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-3-yl)thiazole (compound 15),

[0538] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-4-yl)thiazole (compound 92),

[0539] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-2-yl)thiazole (compound 93),

[0540] 4-(2-chloropyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 94),

[0541] 4-(2-methoxypyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 95),

[0542] 4-(6-methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 96),

[0543] 4-(5-methylpyridin-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 97),

[0544] 6-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-[1,3]dioxacyclopenteno[4,5-b]pyridine (compound 98),

[0545] 4-(2-methylpyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 99),

[0546] 4-(2-Fluoropyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 100),

[0547] 4-(2-bromopyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 101),

[0548] 4-(5-chloropyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 125),

[0549] 4-(4-chloropyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 135),

[0550] 2'-Bromo-2-(pyrazolo[1,5-a]pyridin-3-yl)-4,5'-bithiazole (compound 37),

[0551] 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)aniline hydrochloride (compound 1),

[0552] 4-(3-nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 4),

[0553] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)aniline hydrochloride (compound 10),

[0554] 4-(2-Nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 133),

[0555] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)aniline hydrochloride (compound 134),

[0556] 2-Methoxy-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)aniline (compound 90),

[0557] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 118),

[0558] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzonitrile (compound 115),

[0559] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzonitrile (compound 116),

[0560] 4-(3,5-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 119),

[0561] 4-(2,6-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 123),

[0562] 5-Fluoro-2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)phenol (compound 114),

[0563] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isonicotinamide (compound 126),

[0564] 4-(5-methoxypyridin-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 124),

[0565] 4-(5-methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 127),

[0566] 4-(1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 107),

[0567] 4-(4-chloro-1-methyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 53),

[0568] 4-(1,4-dimethyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrobromide (compound 54),

[0569] 4-(1-Methyl-1H-pyrazol-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrobromide (compound 106),

[0570] 4-(1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 109),

[0571] 5-Methyl-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazolyl hydrobromide (compound 105),

[0572] N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)oxetane-3-sulfonamide (compound 69),

[0573] N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 16),

[0574] N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)morpholine-4-carboxamide (compound 72),

[0575] N-Methyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methylamine hydrochloride (compound 74),

[0576] N-Methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)morpholine-4-carboxamide (compound 76),

[0577] 2-Methoxy-N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 78),

[0578] 1,1-Dimethyl-3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)urea (compound 59),

[0579] 1,1-Dimethyl-3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)urea (compound 75),

[0580] 2-Methoxy-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 77),

[0581] N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)cyclobutanesulfonamide (compound 82),

[0582] N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)oxetane-3-carboxamide (compound 85),

[0583] 2-Amino-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide hydrochloride (compound 64)

[0584] N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)oxetane-3-carboxamide (compound 66)

[0585] 2-Amino-N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide hydrochloride (compound 65)

[0586] 2-Amino-N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide hydrochloride (compound 81)

[0587] 2-Amino-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide hydrochloride (compound 80)

[0588] 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)sodium acetate (compound 5),

[0589] N-acetyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)glycine (compound 73),

[0590] 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)acetamide (compound 26),

[0591] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl-2-(2-(2-methoxyethoxy)ethoxy)acetate (compound 13),

[0592] 4-(3-(2-methoxyethoxy)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 14),

[0593] 4-(3-(2-(2-methoxyethoxy)ethoxy)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 22),

[0594] 4-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 108),

[0595] 4-(1-Ethyl-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 110),

[0596] 4-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (compound 111),

[0597] 2-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethoxy)ethane-1-amine hydrochloride (compound 32),

[0598] 2-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethoxy)ethane-1-amine hydrochloride (compound 20),

[0599] N,N-Dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-amine hydrochloride (compound 47)

[0600] 1-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethyl)guanidine hydrochloride (compound 52),

[0601] 1-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethyl)guanidine hydrochloride (compound 51),

[0602] N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethyl)acetamide (compound 45),

[0603] N-(2-hydroxyethyl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)acetamide (compound 19),

[0604] 2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)methyl acetate (compound 18),

[0605] 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)methyl acetate (compound 25),

[0606] 1-(piperazin-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one (compound 31),

[0607] 1-(1,4-diazacycloheptane-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one hydrochloride (compound 55)

[0608] 1-(4-methyl-1,4-diazacycloheptane-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one hydrochloride (compound 102)

[0609] 1-(2-(hydroxymethyl)pyrrolidin-1-yl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one (compound 21),

[0610] 1-(piperazin-1-yl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one (compound 23),

[0611] 1-(1,1-dioxo-4-thiomorpholinyl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one (compound 24),

[0612] (4-Methylpiperazin-1-yl)(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazolyl-3-yl)methyl ketone hydrochloride (compound 103),

[0613] Piperazin-1-yl(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazolyl-3-yl)methyl ketone hydrochloride (compound 104),

[0614] N-(4'-methyl-2-(pyrazolo[1,5-a]pyridin-3-yl)-[4,5'-bithiazolyl]-2'-yl)acetamide (compound 46),

[0615] N,N-Dimethyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzamide (compound 49),

[0616] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)sodium benzoate (compound 6),

[0617] (3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)(2-oxa-6-azaspiro[3.3]heptane-6-yl)methyl ketone (compound 33),

[0618] N,N-Dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 87),

[0619] N-(cyclopropylmethyl)-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzylyl)azacyclobutane-3-carboxamide (compound 9),

[0620] (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)phenyl)(2-oxa-7-azaspiro[3.5]nonane-7-yl)methyl ketone (compound 40),

[0621] (1,4-oxazacycloheptane-4-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 41),

[0622] (4-(dimethylamino)piperidin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 48),

[0623] (4-Methylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 50),

[0624] (4-Ethylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 56),

[0625] (3-Methylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 58),

[0626] N,N-Dimethyl-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzamide (compound 61),

[0627] 4-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzylyl)piperazin-1-carboxaldehyde (compound 68),

[0628] N-(2-(4-morpholinyl)ethyl)-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzamide (compound 30),

[0629] N-Methyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 88),

[0630] N-Ethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 89),

[0631] N-methoxy-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 91),

[0632] (2,5-diazabicyclo[2.2.1]heptane-2-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 43),

[0633] N-(2-(piperazin-1-yl)ethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzamide hydrochloride (compound 11),

[0634] (3-aminopyrrolidin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 42)

[0635] N-Methyl-N-(piperidin-4-yl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzamide hydrochloride (compound 44),

[0636] Piperazine-1-yl(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 57),

[0637] Piperazine-1-yl(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 63),

[0638] 1-(piperazin-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)ethane-1-one hydrochloride (compound 86)

[0639] N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzylyl)-1,2,3,4-tetrahydroisoquinoline-5-yl)acetamide (compound 60),

[0640] 2-(hydroxymethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 8),

[0641] (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methanol (compound 2),

[0642] 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)ethane-1-ol (compound 84),

[0643] 4-(3-(2,5-dihydro-1H-pyrrolo-3-yl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (compound 17),

[0644] 6-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)-2-oxa-6-azaspiro[3.3]heptane (compound 29),

[0645] N,N-Dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methylamine (compound 27),

[0646] 4-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 28),

[0647] N,N-Dimethyl-4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)morpholine-2-carboxamide (compound 38),

[0648] N,2-Dimethyl-4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)morpholine-2-carboxamide (compound 39),

[0649] 1-(4-morpholino)-2-(4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzyl)piperazin-1-yl)ethane-1,2-dione hydrochloride (compound 36)

[0650] 4-(4-((2,5-diazabicyclo[2.2.1]heptane-2-yl)methyl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (compound 34),

[0651] N-Methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)piperidine-4-amine hydrochloride (compound 35)

[0652] 4-(isoindoline-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (compound 117),

[0653] N-Methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenethyl)acetamide (compound 62),

[0654] 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)ethane-1-amine hydrochloride (compound 113),

[0655] N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 67),

[0656] N-Methyl-N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 70),

[0657] N,N-Dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methylamine (compound 137),

[0658] N,N-Dimethyl-1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methylamine (compound 128),

[0659] N-Methyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methylamine (compound 136),

[0660] N-((5-(2-(pyrazolo[1, 5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methyl)acetamide (compound 129),

[0661] N-Methyl-1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methylamine (compound 130),

[0662] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrolo-3-yl)thiazole (compound 138),

[0663] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrolo-2-yl)thiazole (compound 139),

[0664] 4-(1H-imidazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 140),

[0665] 4-(1H-imidazol-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 141),

[0666] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,3-triazol-4-yl)thiazole (compound 142),

[0667] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,4-triazol-3-yl)thiazole (compound 143),

[0668] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(thiophen-3-yl)thiazole (compound 144),

[0669] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(thiophen-2-yl)thiazole (compound 145),

[0670] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)isothiazolium (compound 146),

[0671] 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)isothiazolyl (compound 147),

[0672] 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)isothiazolium (compound 148),

[0673] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4,4'-bithiazole (compound 149),

[0674] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4,5'-bithiazole (compound 150),

[0675] 2'-(pyrazolo[1,5-a]pyridin-3-yl)-2,4'-bithiazole (compound 151),

[0676] 4-(furan-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 152),

[0677] 4-(furan-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 153),

[0678] 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazole (compound 154),

[0679] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazole (compound 155),

[0680] 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazole (compound 156),

[0681] 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)oxazole (compound 157),

[0682] 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)oxazole (compound 158),

[0683] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)oxazole (compound 159),

[0684] 4-(1-Methyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 160),

[0685] 4-(1-Methyl-1H-pyrrolo-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 161),

[0686] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1,2,4-thiadiazole (compound 162),

[0687] 4-(1-Methyl-1H-pyrrolo-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 163),

[0688] 3-Bromo-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)isoxazole (compound 164),

[0689] 4-(1H-imidazol-1-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 165),

[0690] 4-(1H-pyrazol-1-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 166),

[0691] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrolo-1-yl)thiazole (compound 167),

[0692] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,4-triazol-1-yl)thiazole (compound 168),

[0693] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(2H-1,2,3-triazol-2-yl)thiazole (compound 169),

[0694] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,3-triazol-1-yl)thiazole (compound 170),

[0695] 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)thiophene-3-carboxamide (compound 171),

[0696] 2-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)thiophen-2-yl)acetamide (compound 172),

[0697] N,N-Dimethyl-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)thiophene-3-carboxamide (compound 173),

[0698] N-(2-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)thiophen-2-yl)ethyl)acetamide (compound 174),

[0699] 4-(3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 178),

[0700] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)thiophene-3-ol (compound 175),

[0701] 1-Methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-3-carboxylonitrile (compound 176),

[0702] N-Methyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-1-yl)ethane-1-amine (compound 177),

[0703] 4-(5-Fluoro-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 179),

[0704] 3-Methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-5-amine (compound 181),

[0705] 4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-1-yl)butan-1-ol (compound 180),

[0706] 4-(1-(azacyclobutane-2-ylmethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 182),

[0707] 2-((2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-1-yl)ethyl)amino)acetonitrile (compound 183),

[0708] 3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-1-yl)propane-1-amine (compound 184),

[0709] N-(3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-1-yl)propyl)methanesulfonamide (compound 185),

[0710] 5-Methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-3-ol (compound 186),

[0711] N 1 , N 1 -dimethyl-N 2 -(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazolyl]-2-yl)ethane-1,2-diamine (compound 187)

[0712] 2-(dimethylamino)-N-(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazolyl]-2-yl)acetamide (compound 188),

[0713] 2-amino-N-(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazolyl]-2-yl)acetamide hydrochloride (compound 189)

[0714] 2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazolyl]-2-ol (compound 190),

[0715] 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)furan-2-carboxamide (compound 191),

[0716] 4-(2,5-dihydrofuran-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 192),

[0717] (1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazolyl-4-yl)methanol (compound 193),

[0718] (1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazolyl-4-yl)methylamine hydrochloride (compound 194)

[0719] 3-((1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazol-4-yl)methoxy)propane-1-ol (compound 195),

[0720] 3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazol-1-yl)propane-1-ol (compound 196),

[0721] 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazol-1-yl)ethane-1-amine (compound 197),

[0722] N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazolyl-1-yl)ethyl)acetamide (compound 198),

[0723] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyrimidin-5-yl)thiazole (compound 199),

[0724] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyrimidin-2-yl)thiazole (compound 200),

[0725] 4-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 201),

[0726] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-yl)thiazole (compound 202),

[0727] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazine (compound 203),

[0728] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-4,5,6,7-tetrahydrothiazo[5,4-c]pyridine (compound 204),

[0729] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-4,5,6,7-tetrahydrothiazo[4,5-c]pyridine (compound 205),

[0730] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl)thiazole (compound 206),

[0731] 4-(1H-indazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 207),

[0732] 4-(4-chloro-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 208),

[0733] 2-(6-methylpyrazolo[1,5-a]pyridin-3-yl)-4-phenylthiazole (compound 209),

[0734] 2-(5-methylpyrazolo[1,5-a]pyridin-3-yl)-4-phenylthiazole (compound 210),

[0735] 2-(4-methylpyrazolo[1,5-a]pyridin-3-yl)-4-phenylthiazole (compound 211),

[0736] 4-(4-chloro-1-methyl-1H-pyrazol-3-yl)-2-(5-methylpyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 212) and

[0737] N-((5-(2-(5-methylpyrazolo[1, 5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methyl)acetamide (compound 213).

[0738] 2. Method for preparing this compound

[0739] This compound can be prepared by combining known reactions. The following discloses illustrative synthetic examples of the compounds of the present invention. Those skilled in the art can also synthesize compounds of formula (I) other than the illustrative compounds and their derivatives based on the following description and the examples.

[0740] (Abbreviated) The meaning of the abbreviations in the following reaction formulas is as follows.

[0741] Δ: Heating

[0742] Halo: Halogen

[0743] DME: Dimethoxyethane

[0744] EtOH: Ethanol

[0745] DMF: Dimethylformamide

[0746] TEA: Triethylamine

[0747] DIPEA: Diisopropylethylamine

[0748] CH3CN: Acetonitrile

[0749] Boc2O: Di-tert-butyl dicarbonate

[0750] Boc-ON: 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile

[0751] aq.: aqueous solution

[0752] N-BocGlycine: N-Butoxycarbonyl-glycine

[0753] BrCH2CO2tBu: Tertiary butyl bromoacetate

[0754] BrCH2COOBn: Benzyl bromoacetate

[0755] Boc: Tertiary-butoxycarbonyl

[0756] DCM: Dichloromethane

[0757] EDC・HCl: N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride

[0758] DCC: N,N'-Dicyclohexylcarbodiimide

[0759] HOBt: 1-Hydroxybenzotriazole (condensation aid)

[0760] HOAt: 1-Hydroxy-7-azabenzotriazole (condensation aid)

[0761] BOP: 1H-benzotriazine-1-yloxys(dimethylamino)phosphonium hexafluorophosphate

[0762] HATU: 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-hexafluorophosphate oxide

[0763] TATU: 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-tetrafluoroborate

[0764] COMU: 1-[bis(cyano-2-ethoxy-2-sideoxyethyleneaminooxy)dimethylamino(4-morpholino)]ureon hexafluorophosphate

[0765] Ac2O: Acetic anhydride

[0766] DBU: 1,8-diazabicyclo[5.4.0]-7-undecene

[0767] DBN: 1,5-diazabicyclo[4.3.0]non-5-ene

[0768] THF: Tetrahydrofuran

[0769] Me: Methyl

[0770] Et: Ethyl

[0771] MeOH: Methanol

[0772] LAH: Lithium Aluminum Hydrogenation

[0773] DIBAL: Diisobutylaluminum Hydrogenation

[0774] LiBH4: Lithium borohydride

[0775] LiBEt3: Lithium triethylborohydride

[0776] AcOEt: Ethyl acetate

[0777] Pd(PPh3)4: Tetra(triphenylphosphine)palladium(0)

[0778] Pd(OAc)2: Palladium acetate

[0779] PdCl2(PPh3)2: Bis(triphenylphosphine)palladium(II) dichloride

[0780] PdCl2(dppf): [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloro

[0781] Pd(acac)2: Palladium(II) acetylacetone

[0782] Pd2(dba)3:Dibenzylacetone)dipalladium(0)

[0783] DMAP: 4-Dimethylaminopyridine

[0784] BocPiperazine: Butoxycarbonylpiperazine

[0785] NaBH(OAc)3: Sodium triacetoxyborohydride

[0786] NaBH3CN: Sodium cyanoborohydride

[0787] AcOH: Acetic acid

[0788] rt: room temperature

[0789] XPhos: 2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl

[0790] Tf: Trifluoromethanesulfonyl group

[0791] DMSO: Dimethyl sulfoxide

[0792] TBS: Tertiary-Butyldimethylsilyl

[0793] TBAF: Tetrabutylammonium fluoride

[0794] TFA: Trifluoroacetic acid

[0795] t-BuOH: Tertiary-butanol

[0796] (1) Main reaction

[0797] Compounds of formula (I) can be synthesized, for example, by the following reaction.

[0798]

[0799] (where R is in the formula) 1 To R 6 As defined in equation (I) above.

[0800] Step A: In this reaction, based on the structure of the synthesized compound of formula (I), select the thioamide of formula (II) and the halide of formula (III) with corresponding substituents or structures. The reaction can be carried out by dissolving the thioamide in solvents such as DME, acetone, toluene, hexane, xylene, ethyl acetate, dioxane, THF, ethanol, methanol, dichloroethane, DMF, and water. After adding the halide to allow the reaction to proceed, the solvent in the reaction solution is distilled off. Ethanol or other solvents and excess bases such as potassium carbonate, sodium hydroxide, potassium hydroxide, sodium carbonate, triethylamine, DBU, DBN, and pyridine are added to the residue. The solvent in the reaction solution is then distilled off again. The crude product can also be purified as needed.

[0801] By R 1 To R 6 By modifying the base with protecting groups or other groups, or by making different bases, derivatives of the compound of formula (I) above can also be obtained. From these derivatives, the compound of formula (I) above can also be synthesized through the additional reaction described later.

[0802] Compound (I) is R 6 A condensation ring consisting of a 5- to 10-membered aromatic heterocycle having at least one nitrogen atom, or a 4- to 10-membered heterocyclic group having one to three heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring-forming atoms, can be synthesized by the following reaction (Goldberg amination).

[0803]

[0804] (where R is in the formula) 1 To R 5 As defined in equation (I) above, R 6’ R is a condensation ring consisting of a substituted 5- to 10-membered heterocycle (preferably a 5- to 10-membered aromatic heterocycle or a 5- or 6-membered heterocyclic alkenyl group) having at least one nitrogen atom, or preferably a 5- to 10-membered aromatic heterocycle, and a substituted 4- to 10-membered heterocyclic group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring-forming atoms. 6’ The nitrogen in the aromatic heterocycle is a carbon atom linked to a thiazole ring. Halo is a halogen such as iodine, bromine, or chlorine, with bromine being the most preferred.

[0805] Step A: For the aryl halide shown in formula (IV), the corresponding condensate can be obtained by heating a nitrogen-containing heterocycle such as imidazole or pyrazole in the presence of a copper catalyst such as copper iodide (I) for a specified time to induce a Goldberg reaction. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction. Preferred solvents include toluene, hexane, xylene, methanol, ethanol, isopropanol, ethylene glycol, acetonitrile, dioxane, THF, dichloromethane, dichloroethane, DME, DMF, and dimethylacetamide. As a base, examples include potassium carbonate, sodium carbonate, sodium bicarbonate, potassium phosphate, potassium acetate, cesium carbonate, potassium phosphate, sodium hydride, sodium methoxide, sodium ethoxide, sodium butyrate, sodium hydroxide, potassium hydroxide, DBU, and DBN. As a copper catalyst, examples include copper chloride (I), copper bromide (I), copper iodide (I), 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. Typically, the reaction temperature is 40 to 200°C, and the reaction time is 1 to 24 hours, with 180°C and 1 hour being preferred.

[0806] In this reaction, the compounds shown in formulas (IV) and (I') are subjected to R... 1 To R 6’ By modifying the base with protecting groups or other similar groups, or by creating different bases, derivatives of the compound of formula (I') can be obtained. These derivatives can then be used to synthesize the compound of formula (I') via the additional reaction described later.

[0807] In addition, compounds of formula (I) can be synthesized, for example, by the following reaction.

[0808]

[0809] (where R is in the formula) 1 To R 6 As defined in formula (I) above, Tf represents trifluoromethanesulfonate, R ’ and R ’’ Represents a hydrogen atom, or R ’ and R ’’ Together with the two adjacent oxygen atoms, it forms an alkyldioxy group.

[0810] Step A: Compound (I) is prepared by reacting the trifluoromethanesulfonate compound of formula (V) with the boric acid compound of formula (VI) in the presence of a palladium catalyst and heating for a specified time to induce a Suzuki-Miyaura coupling reaction. Examples of palladium catalysts include palladium acetate, palladium chloride, bis(triphenylphosphine)palladium(II) dichloride, tetra(triphenylphosphine)palladium(O), tris(benzylacetone)palladium(O), and [1,1'-bis(diphenylphosphine)ferrocene]palladium(II) dichloride, etc., in the presence of a base such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, tripotassium phosphate, sodium methoxide, or potassium tributyloxide, with water added. As a reaction solvent, toluene, hexane, xylene, dioxane, tetrahydrofuran, dimethoxyethane, dichloroethane, N,N-dimethylformamide, etc., can be used. The reaction can be carried out at temperatures from 50 to 200°C for approximately 5 minutes to 20 hours.

[0811] By R 1 To R 6 By modifying the base with protecting groups or other groups, or by making different bases, derivatives of the compound of formula (I) above can also be obtained. From these derivatives, the compound of formula (I) above can also be synthesized through the additional reaction described later.

[0812] Alternatively, compounds of formula (I) can also be synthesized, for example, via the following reaction.

[0813]

[0814] (where R is in the formula) 1 To R 6 As defined in equation (I) above, R ’ and R ’’ Represents a hydrogen atom, or R ’ and R ’’ Together with the two adjacent oxygen atoms, it forms an alkyldioxy group (Halo is a halogen such as iodine, bromine, and chlorine).

[0815] Step A: Compound (I) is prepared by reacting the boric acid compound of formula (VII) with the halogen compound of formula (VIII) in the presence of a palladium catalyst and heating for a specified time to induce a Suzuki-Miyaura coupling reaction. This reaction can be carried out in the same manner as the reactions of formulas (V) and (VI) described above.

[0816] By R 1 To R 6 By modifying the base with protecting groups or other groups, or by making different bases, derivatives of the compound of formula (I) above can also be obtained. From these derivatives, the compound of formula (I) above can also be synthesized through the additional reaction described later.

[0817] (2) Additional reaction

[0818] The substituents of the compound of formula (I) or its derivatives obtained by the above main reactions can also be applied to known reactions to produce compounds of formula (I) or its derivatives with different substituents. Known reactions that can be applied are described, for example, in general experimental books such as Maruzen 4th Edition Lectures on Experimental Chemistry (30 volumes in total), and each reaction can be carried out according to them. These documents are incorporated herein by reference. The following shows exemplary additional reactions. Furthermore, in the following reaction formulas, the structures shown in double circles represent condensed rings of 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 any of the above, and 4- to 10-membered heterocyclic groups having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0819] (Nitro groups are reduced by metals and the resulting amine groups undergo protection and deprotection reactions.)

[0820] In the case of synthesizing compounds with nitro groups in the main reaction or other additional reactions, the additional reaction represented by the following reaction formula is provided, in which the nitro group can be converted into an amino group.

[0821]

[0822] (In the formula, n is an integer greater than or equal to 0 (e.g., an integer from 0 to 3).)

[0823] Step A: In this reaction, the nitro compound is dissolved in a solvent such as acetonitrile, and additives such as zinc powder and calcium chloride are added together with water and heated to obtain the amine group. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction. Preferred solvents include acetone, toluene, hexane, xylene, dioxane, THF, ethanol, methanol, DME, and DMF. Typically, the reaction temperature is 80 to 120°C, and the reaction time is 0.5 to 6 hours, preferably 100°C for 1 hour. Although Step A describes a nitro reduction reaction under neutral conditions, it is not limited to these reaction conditions. As other methods, reduction reactions using metals such as zinc, iron, and tin can also be carried out under acidic conditions.

[0824] Step B: To protect the unstable amine group, a Boc group is used for protection. The obtained amine group is dissolved in a solvent such as acetonitrile, excess Boc-forming agent is added, and the reaction is stirred. If necessary, purification is performed to synthesize a carbamate compound with the amine group protected by the Boc group. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction. Preferred solvents include acetonitrile, acetone, toluene, hexane, xylene, dioxane, THF, ethanol, methanol, DME, and DMF. Boc-forming agents include Boc₂O and Boc-ON. Typically, the reaction temperature is -20 to 80°C, and the reaction time is 1 to 48 hours, preferably at room temperature for 24 hours. While the Boc group is used as a protecting group in Step B, it is not limited to it; other protecting groups such as benzyl groups are also acceptable.

[0825] Step C: Adding a carbamate compound with a Boc group-protected amine group to a dioxane hydrochloride solution to remove the protecting group can synthesize the amine hydrochloride. This reaction involves dissolving the carbamate compound in a solvent, or an acid may be added. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction. Preferred solvents include acetonitrile, acetone, toluene, hexane, xylene, dioxane, dichloromethane, ethanol, methanol, DME, DMF, and water. As acids, nitric acid, sulfuric acid, acetic acid, and trifluoroacetic acid are also acceptable. Typically, the reaction temperature is -20 to 80°C, and the reaction time is 0.5 to 12 hours, preferably 0°C for 1 hour.

[0826] (Reaction of amines with halogens)

[0827] In the case of amine synthesis in the main reaction or other additional reactions, the following reaction equation represents an additional reaction that can synthesize an amine by introducing a desired substituent (R) into the amine group. ’ ) compounds.

[0828]

[0829] (In the formula, n is an integer greater than or equal to 0 (e.g., an integer from 0 to 3), and R is a hydrogen atom or any substituent (e.g., C). 1-3 Alkyl), R ’ For any imported structure or base (e.g., R...) 31 R 32 -C(O)(CH2) 0-3 NR 31 2. -(CH2) 1-3 CN, -(CH2) 1- 3R 32 or -C(O)NR 32 ). )

[0830] Step A: In this reaction, amine hydrochloride is suspended in dichloromethane, a halide is added, and then a base such as triethylamine is added to synthesize an amine group by introducing a desired substituent (R). ’ The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction. Preferred solvents include acetonitrile, acetone, toluene, hexane, xylene, dioxane, THF, dichloromethane, DME, DMF, or mixtures thereof. As an acid complement, bases ranging from equal to excess, such as triethylamine, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium hydride, sodium methoxide, sodium ethoxide, sodium hydroxide, potassium hydroxide, DBU, DBN, or pyridine, can be used. Typically, the reaction temperature is -20 to 80°C, and the reaction time is 1 to 48 hours, preferably 0°C and 1 hour.

[0831] (Condensation reaction of amines and carboxylic acids)

[0832] In the case of amine synthesis via a primary or additional reaction, the following reaction equations represent additional reactions that can synthesize amines by introducing a desired substituent (R) into the amino group. ’ Compounds containing a carbonyl group.

[0833]

[0834] (In the formula, n is an integer greater than or equal to 0 (e.g., an integer from 0 to 3), and R is a hydrogen atom or any substituent (e.g., C). 1-3 Alkyl), R ’ For any imported structure or base (e.g., R...) 31 R 32 -(CH2) 1-5 C(O)OR 31 -(CH2) 1-5 NR 31 2).

[0835] Step A: In this condensation reaction, in an anhydrous solvent such as dichloromethane, amine hydrochloride, having the desired substituent (R) is added. ’Various amides can be synthesized by adding equal to or excess amounts of a base such as triethylamine to a condensing agent such as carboxylic acid and EDC·HCl as an acid complement. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction. Preferred solvents include anhydrous solvents such as dichloromethane, acetonitrile, acetone, toluene, hexane, xylene, dioxane, THF, DME, and DMF. As an acid complement, options include equal to or excess amounts of triethylamine, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium hydride, sodium methoxide, sodium ethoxide, sodium hydroxide, potassium hydroxide, DBU, DBN, or pyridine. Typically, the reaction temperature is -20 to 80°C, and the reaction time is 1 to 48 hours, preferably at room temperature for 24 hours. A reaction catalyst such as DMAP can be used as needed. DEC is used as the condensing agent here; DCC can also be used. Additionally, HOBt or HOAt may be added to prevent isomerization. Furthermore, BOP-based reagents can also be used as condensing agents, as can HATU, TATU, COMU, etc.

[0836] (Introduction reaction via an amino group protected by a Boc group)

[0837] By utilizing the reaction of amines with carboxylic acids, for example, by the reaction represented by the following exemplified reaction formula, an amine group with a protecting group (Boc) that can be converted into an amine group (hydrochloride salt) can be added to the side chain.

[0838]

[0839] (In the formula, R and A are bonds or arbitrary structures (e.g., C) 1-5 Alkyl groups, -C(O)-, -(CH2) 0-5 N(R 31 )C(O)(CH2) 0-5 -、-C(R 31 )2C(O)-、-(CH2) 1-5 O(CH2) 1-5 -、-O(CH2) 1-5 -、-(OCH2) 1-5 -wait).)

[0840] Step A: This reaction is carried out under the same conditions as Step B described above (reduction of the nitro group by metal, protection of the generated amine group, and deprotection reaction).

[0841] (Deprotection reaction of the protecting group (Boc))

[0842] In the case of synthesizing compounds with Boc-protected amine groups in the main reaction or additional reaction, the additional reaction represented by the following exemplified reaction formulas can deprotect the Boc group.

[0843]

[0844] (In the formula, R and A are bonds or arbitrary structures (e.g., C) 1-5 Alkyl groups, -C(O)-, -(CH2) 0-5 N(R 31 )C(O)(CH2) 0-5 -、-C(R 31 )2C(O)-、-(CH2) 1-5 O(CH2) 1-5 -、-O(CH2) 1-5 -、-(OCH2) 1-5 -wait).)

[0845] Step A: This reaction is carried out under the same conditions as step C described above (reduction of the nitro group by metal, protection of the generated amine group, and deprotection reaction).

[0846] (acetylation reaction)

[0847] In the case of synthesizing compounds with amine groups in the main reaction or additional reaction, the following reaction formula is provided as an additional reaction to synthesize an amide with acetyl groups protecting the amine group.

[0848]

[0849] (In the formula, n is an integer greater than or equal to 0 (e.g., an integer from 0 to 3), and R is a hydrogen atom or any substituent (e.g., C). 1-3 alkyl).)

[0850] Step A: In these reactions, an amine is added to a solvent such as acetonitrile, and an acetylation agent and a base such as DMAP or TEA (as a catalyst) are added together to synthesize the acetyl group. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction. Preferred solvents include acetonitrile, acetone, toluene, hexane, xylene, dioxane, THF, dichloromethane, DME, and DMF. Furthermore, as acid supplements, bases such as TEA, DIPEA, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium hydride, sodium methoxide, sodium ethoxide, sodium hydroxide, potassium hydroxide, DBU, DBN, or pyridine can be used. Additionally, as acetylation agents, acetic anhydride and acetyl chloride can be used. Typically, the reaction temperature is -20 to 80°C, and the reaction time is 1 to 48 hours, preferably at room temperature for 24 hours.

[0851] (Deprotection reaction of the protecting group (acetyl group))

[0852] In the case of synthesizing compounds with acetyl groups in the main reaction or additional reaction, the additional reaction represented by the following exemplified reaction formulas can deprotect the acetyl group.

[0853]

[0854] (In the formula, n is an integer greater than or equal to 0 (e.g., an integer from 0 to 3), and R is a hydrogen atom or any substituent (e.g., C). 1-3 alkyl).)

[0855] Step A: In these reactions, a compound with an acetyl group-protected amine group suspended in a solvent is heated for a specified time under acidic or alkaline conditions to deprotect the acetyl group. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction. Preferred solvents include methanol, ethanol, dioxane, DME, DMF, and water. Acids include hydrochloric acid, nitric acid, sulfuric acid, trifluoroacetic acid, and hydrobromic acid. Bases include sodium hydroxide, potassium hydroxide, and lithium hydroxide. Typically, the reaction temperature is 50 to 160°C, and the reaction time is 0.5 to 24 hours, preferably 100°C for 1 hour.

[0856] (Deprotection reaction of the protecting group (phthalimide))

[0857] In the case of the main reaction, which synthesizes a compound whose amino group is protected with phthalic anhydride, deprotection can be carried out in the additional reaction (deprotection) represented by the reaction formulas shown below.

[0858]

[0859] Step A: In this reaction, phthalimide derivatives and hydrazine monohydrate are added to a solvent such as ethanol, and the mixture is heated for a specified time to proceed with the reaction. The amine derivative can be obtained by deprotection. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction. Preferred solvents include ethanol, methanol, water, dichloromethane, THF, DMF, toluene, chloroform, acetonitrile, diethyl ether, 1-butanol, isopropanol, acetic acid, acetone, benzene, tri-butanol, and DMSO.

[0860] (alkylation reaction)

[0861] In the case of synthesizing compounds having amine functional groups such as acetamide groups in the main reaction or additional reaction, the following reaction formula is provided, in which an alkyl group can be introduced into the amine group in the additional reaction.

[0862]

[0863] (where R is in the formula) ’For keys or arbitrary structures (e.g., C 1-3 (Lynylene), R ’’ For any basis (e.g., C), 1-3 Alkyl, C(O)C 1-3 Alkyl), R ’’’ Alkyl (e.g., C10) 1-3 Alkyl groups, etc.

[0864] Step A: In this reaction, a compound with amine functional groups such as acetamide groups is added to a suspension containing sodium hydride in a solvent such as DMF, followed by the dropwise addition of an alkyl halide (Halo-R). ’’’ The reaction proceeds to obtain N-alkylamides. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction; THF, DME, and DMF are preferred examples. Furthermore, strong bases such as sodium hydride, sodium methoxide, sodium ethoxide, sodium butyrate, sodium hydroxide, potassium hydroxide, DBU, and DBN are also acceptable. Typically, the reaction temperature is -20 to 50°C, and the reaction time is 1 to 24 hours, with 0°C and 1 hour being preferred.

[0865] (Reductive amination reaction)

[0866] In the case of synthesizing compounds with an amino group in a major reaction or an additional reaction, the following reaction formula is provided, in which an alkyl group can be introduced into the amino group in the additional reaction.

[0867]

[0868] (In the formula, n is an integer greater than or equal to 0 (e.g., an integer from 0 to 3).)

[0869] Step A: In this reaction, the amine derivative and aldehyde are added to a dry solvent such as methanol, stirred, and then NaBH(OAc)3 is added. After a specified reaction time, an alkylamine derivative can be obtained. The reaction is carried out in a solvent, with or without an acid. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction. Preferred solvents include methanol, ethanol, toluene, benzene, hexane, xylene, dioxane, THF, dichloromethane, dichloroethane, DME, and DMF. The acid used varies depending on the starting materials and solvent used, and is not particularly limited as long as it does not hinder the reaction. Preferred acids include acetic acid and formic acid. Furthermore, NaBH(OAc)3 and NaBH3CN can be used as reducing agents. Typically, the reaction temperature is -20 to 100°C, and the reaction time is 1 to 24 hours, preferably 25°C for 3 hours.

[0870] (N-alkylation of amide groups)

[0871] In the case of synthesizing amine-containing compounds in the main reaction or additional reaction, the following additional reaction provides an amide group that can be further N-alkylated.

[0872]

[0873] (In the formula, n is an integer greater than or equal to 0 (e.g., an integer from 0 to 3).)

[0874] Step A: The solvent used in this reaction varies depending on the starting materials and reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction. THF, DME, and DMF are preferred examples. As a strong base, sodium hydride, sodium methoxide, sodium ethoxide, sodium hydroxide, and potassium hydroxide can be used in equal to excess amounts. Typically, the reaction temperature is -20 to 80°C, and the reaction time is 1 to 48 hours, preferably 0°C and 24 hours. This reaction is similar to Step A of the aforementioned (alkylation reaction).

[0875] Step B: An N-alkylamide group can be synthesized by reacting a compound with a strong base and an alkyl halide in a dry DMF solution.

[0876] (Reaction of hydroxyl groups with halides)

[0877] In the case of synthesizing derivatives having a hydroxyl group in either the main reaction or an additional reaction, the following reaction formula is provided as an example of an additional reaction in which a desired substituent (R) is introduced into the hydroxyl group. ’ It can synthesize ether (phenoxy ether) compounds.

[0878]

[0879] (In the formula, n is an integer greater than or equal to 0 (e.g., an integer from 0 to 3), R) ’ For any substituent (e.g., -C(R) 31 )2C(O)(CH2) 0-3 OH, -C(R) 31 )2C(O)NR 31 2. -C 1-6 Alkyl group, -((CH2) 1-5 O) 1-5 R 31 -C(O)C(R) 31 )2(O(CH2) 1-5 ) 1- 5OR 31 wait).)

[0880] Step A: In this reaction, in DMF, a compound with a hydroxyl group (mainly phenolic derivatives) reacts with a base, followed by a reaction with a halide (Halo-R).’ This reaction can synthesize ether (phenoxy ether) derivatives. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction; preferred solvents include THF, DME, DMF, and dichloromethane. As a base, options include equal to excess amounts of sodium hydride, sodium methoxide, sodium ethoxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, DBU, DBN, and pyridine. Typically, the reaction temperature is -20 to 80°C, and the reaction time is 1 to 48 hours, with 0°C and 24 hours being preferred.

[0881] (Alkaline hydrolysis reaction)

[0882] In the case of ester synthesis in either the main reaction or the additional reaction, alkaline hydrolysis is provided as represented by the following reaction formula.

[0883]

[0884] (where R is in the formula) ’ It is a key, an arbitrary structure (e.g., C). 1-3 (e.g., alkylene, -OC-, R) ’’ (This can be any substituent (e.g., chain alkyl groups, aromatic hydrocarbons, etc.))

[0885] Step A: In this reaction, an ester compound is added to a solvent such as an aqueous solution of sodium hydroxide and a mixture of ethanol, and the mixture is heated and stirred for a specified time. An acid-base treatment is then performed 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 dissolves the starting material to a certain extent without hindering the reaction. Preferably, methanol, ethanol, dioxane, DME, DMF, and water are examples. Furthermore, strong bases such as sodium hydroxide, potassium hydroxide, sodium hydride, sodium methoxide, sodium ethoxide, sodium butyrate, DBU, and DBN are examples. Typically, the reaction temperature is 30 to 140°C, and the reaction time is 1 to 24 hours, preferably 100°C for 1 hour.

[0886] (Reaction of esters (and carboxylic acids) with amines)

[0887] In the case of the synthesis of ester compounds in the main reaction or additional reaction, the following reaction formula is provided to convert the ester to an amino carbonyl group.

[0888]

[0889] (where R is in the formula) ’ For keys, any structure (e.g., C) 1-3 (e.g., alkylene, -OC-, R) ’’ R is hydrogen or any substituent (e.g., chain alkyl, aromatic hydrocarbon, etc.), and R is selected from O, SO2, CR.31 2 and NR 31 The resulting group consists of m and n, each an independent integer from 1 to 4.

[0890] Step A: In these reactions, an equal to to a large excess of a specified amine is added to the ester compound, preferably in a large excess. The solvent is unused or available DME, acetone, toluene, hexane, xylene, dioxane, THF, chloroform, dichloromethane, dichloroethane, etc., preferably solvent-free. The reaction solution is reacted at room temperature or under reflux for 1 hour to 48 hours, preferably under reflux for 12 hours, to obtain the target compound.

[0891] (Transesterification)

[0892] In the case of the synthesis of ester compounds in the main reaction or additional reaction, the following reaction formula is provided to exchange the substituents of the ester.

[0893]

[0894] (where R is in the formula) ’ For keys, any structure (e.g., C) 1-3 (e.g., alkylene, -OC-, R) ’’ Alkyl is an alkyl group (e.g., chain alkyl, aromatic hydrocarbon, etc.) with any substituent (e.g., C12-C ... 1-3 alkyl).)

[0895] Step A: In these reactions, an equal to to a large excess of the specified alkyl alcohol is added to the ester compound, preferably in a large excess. No solvent is used, or DME, acetone, toluene, hexane, xylene, dioxane, THF, chloroform, dichloromethane, dichloroethane, DMF, etc., can be used as the base. Piperazine, sodium hydride, piperidine, pyrrolidine, sodium hydroxide, potassium hydroxide, DBU, DBN, etc., can be used, with piperazine being more preferred. The reaction solution is reacted at room temperature or under reflux for 1 hour to 48 hours, preferably under reflux for 12 hours, to obtain the target compound.

[0896] (Ester reduction reaction)

[0897] In the case of the synthesis of ester compounds in the main reaction or additional reaction, the additional reaction represented by the following reaction formula is provided, which can reduce the ester to an alcohol derivative.

[0898]

[0899] (In the formula, R' is a bond or any structure (e.g., C1-3 alkylene, -OC-, etc.), and R'' is any substituent (e.g., chain alkyl, aromatic hydrocarbon).)

[0900] Step A: In this reaction, a reducing agent such as LAH is added to a solvent such as diethyl ether, and an ester compound is added thereto, and the reaction is carried out for a specified time. The drying solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction; preferred examples include diethyl ether, THF, toluene, and hexane. Furthermore, as a reducing agent, examples include LAH, DIBAL, LiBH4, and LiBEt3. Typically, the reaction temperature is -20 to 50°C, and the reaction time is 1 to 24 hours, preferably 0°C for 2 hours. In addition to hydride reduction, diborane or similar substances can also be used for ester reduction.

[0901] (Condensation reaction of carboxylic acids and amines)

[0902] In the case of the synthesis of carboxylic acid compounds in the main reaction or additional reaction, the following reaction formula is provided as an additional reaction that can convert carboxylic acids into amide compounds.

[0903]

[0904] (where R is in the formula) ’ For keys, any structure (e.g., C) 1-3 (e.g., alkylene, -OC-), R is selected from O, SO2, CR 31 2 and NR 31 The resulting group consists of m and n, each an independent integer from 1 to 4.

[0905] Step A: The details are the same as those described above (condensation reaction of amine and carboxylic acid).

[0906] (Alkyl metal salting of carboxylic acids)

[0907] In the case of the synthesis of carboxylic acids in the main reaction or additional reaction, the following reaction formulas are provided to represent additional reactions that can produce alkyl metal salts of carboxylic acids.

[0908]

[0909] (where R is in the formula) ’ For keys or any structure (e.g., C 1-3 Alkyl groups, -OC-, etc.

[0910] Step A: In this reaction, carboxylic acid and sodium carbonate are added to purified water to react.

[0911] Examples of purified water used here include tap water, ion-exchanged water, and distilled water. Examples of alkyl metal salts include sodium, potassium, calcium, and barium. In particular, in the case of sodium salt preparation, sodium hydroxide and sodium bicarbonate can be used in addition to sodium carbonate. Typically, the reaction temperature is -20 to 50°C, and the reaction time is 1 to 24 hours, preferably at room temperature for 6 hours.

[0912] (Reducive alkylamineation of formyl group)

[0913] In the case of aldehyde synthesis in either the main reaction or the additional reaction, the following reaction formulas are provided to introduce the desired amine group.

[0914]

[0915] (where R is in the formula) ’ For keys, any structure (e.g., C) 1-3 Alkyl is an alkyl group (e.g., C10, C20, C30, C40, C50, C60, C7 ... 1-3 Alkyl), R is selected from O, SO2, C(R) 31 )R 31’ and NR 31’ The group formed, R 31’ Each can be independently hydrogen or any substituent (e.g., C). 1-3 Alkyl, CHO, -C(O)C(O)R 32 -C(O)NR 31 2. Or -(CH2) 1-5 (3 to 10-membered alicyclic hydrocarbons, etc.), where m and n are each an independent integer from 1 to 4, preferably an integer from 1 to 2.

[0916] Step A: In this reaction, an aldehyde and an amine or amine hydrochloride are added to a dry solvent such as dichloromethane. After stirring, NaBH(OAc)3 is added, and the reaction is carried out for a specified time to synthesize alkylamines. The solvent used varies depending on the starting materials and reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction. Preferred solvents include toluene, hexane, xylene, dioxane, THF, dichloromethane, dichloroethane, DME, and DMF. Furthermore, NaBH(OAc)3 and NaBH3CN can be used as reducing agents. Typically, the reaction temperature is -20 to 50°C, and the reaction time is 1 to 24 hours, with 0°C and 3 hours being preferred.

[0917] (Suzuki Miyaura Coupling Reaction)

[0918] In the case of synthesizing halides in the main reaction or additional reaction, the following reaction formulas are provided to introduce the desired substituents in the additional reaction.

[0919]

[0920] (In the formula, Halo is a halogen such as iodine, bromine, chlorine, or fluorine, with bromine being the preferred option.)

[0921] Step A: In this reaction, the halide, 1-(tert-butoxycarbonyl)-2,5-dihydro-1H-pyrrole-3-yl-boronic acid pinacol ester, and Pd(PPh3)4 and sodium carbonate as catalysts are dissolved in a solvent such as a mixture of DME and water, and the reaction is carried out by heating for a specified time. That is, for aryl halides, the reaction is carried out in the presence of boric acid or pinacol borate as a palladium catalyst, thereby performing the Suzuki-Miyaura coupling reaction to obtain the corresponding condensate. The solvent used varies depending on the starting materials and reagents, and there is no particular limitation as long as it dissolves the starting material to a certain extent without hindering the reaction. Preferred solvents include toluene, hexane, xylene, methanol, ethanol, dioxane, THF, dichloromethane, dichloroethane, DME, and DMF. Examples of bases used include potassium carbonate, sodium carbonate, sodium bicarbonate, potassium phosphate, potassium acetate, sodium hydride, sodium methoxide, sodium ethoxide, sodium butyrate, sodium hydroxide, potassium hydroxide, DBU, and DBN. Examples of palladium catalysts used include Pd(OAc)₂, Pd(PPh₃)₄, PdCl₂(PPh₃)₂, PdCl₂(dppf), and Pd(acac)₂. XPhos can also be used as a reaction additive. Typically, the reaction temperature is 40 to 150°C, and the reaction time is 1 to 24 hours, preferably 80°C for 1 hour.

[0922] Step B: If the introduced substituent has a protecting group, it can be converted to an amino group via a deprotection reaction. This reaction is carried out under the same conditions as step C described above (reduction of the nitro group by a metal, protection of the generated amino group, and deprotection reaction).

[0923] (3) Synthesis of starting materials

[0924] Although commercially available products can be used as starting materials, acetophenone derivatives can be reacted with a halogenating agent in a solvent, as shown in the following reaction formula, to produce α-halogenated acetophenone.

[0925]

[0926] (where R is in the formula) 6 As defined in formula (I) above, Halo is a halogen such as iodine, bromine, chlorine, or fluorine, with bromine being the most preferred.

[0927] Step A: This reaction can be carried out in a solvent such as ethyl acetate by reacting the compound of formula (IX) with a metal halide such as CuBr2. When the substituent on the benzene ring is an alkyl group, the α-bromination of the acetyl group is readily achieved by heating in ethyl acetate with 2 equal parts CuBr2 for about 1 hour. In this case, a dibromoacetyl group is generated as a byproduct during prolonged reaction. On the other hand, when the substituent is an electron-withdrawing substituent such as an ester, the reaction time must be extended to 2 to 16 hours. Furthermore, when the substituent is weakly acidic, trace amounts of HBr are generated during the reaction, which must be carefully considered. Moreover, in the case of basic substituents, the reaction with CuBr2 is mostly not carried out; therefore, benzoylbromomethane can be synthesized using conditions such as bromo-acetic acid. The bromination conditions are not limited to these.

[0928] Alternatively, this reaction can be carried out by dissolving the (IX) compound in solvents such as acetic acid, and by adding halogens such as bromine or hydrohalic acids such as hydrobromic acid.

[0929] Alternatively, this reaction can be carried out by adding a bromo-1,4-dioxane complex to a dioxane-soluble (IX) compound.

[0930] Alternatively, substituted benzoyl methyl halides can also be synthesized directly by haloacetylation, such as through the Frid-Kualfz reaction.

[0931] In addition, regarding the synthesis of compounds of formula (IX) or their derivatives, various reactions described in “Additional Reactions” can be used to synthesize compounds of formula (III) or their derivatives, for example, the following reactions can be listed.

[0932] (Through the protection of phthalic anhydride and the synthesis of α-haloacetylpyridine)

[0933] The amine group can be protected by phthalic anhydride prior to the main reaction, for example, using step A as illustrated below. Alternatively, by providing a halogenated compound in step B as illustrated below, it can be converted to an acetyl group. Furthermore, by providing an acetyl group in step C as illustrated below, an α-haloacetylpyridine derivative can be synthesized.

[0934]

[0935] (In the formula, Halo is a halogen such as iodine, bromine, chlorine, or fluorine, with bromine being the preferred option.)

[0936] Step A: In this reaction, an amine derivative is reacted with phthalic anhydride to obtain an amino-protected phthalimide derivative. The reaction is carried out in a solvent or without a solvent, and in the presence of an acid. The solvent used varies depending on the starting material, reagents, etc., and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction; examples include ethanol, methanol, DMF, toluene, water, dichloromethane, etc. The acid used varies depending on the starting material, solvent, etc., and is not particularly limited as long as it does not hinder the reaction; acetic acid, sulfuric acid, etc. are preferred. The reaction temperature is 80 to 170°C, and the reaction time is 1 to 24 hours, preferably 120°C for 1 hour.

[0937] Step B: The halogen derivative is reacted with tributyl(1-ethoxyvinyl)tin in the presence of a Pd reagent to obtain an acetyl derivative. The solvent used varies depending on the starting material and reagent, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction. Preferred solvents include toluene, benzene, dioxane, DMF, THF, ethyl acetate, and acetonitrile. The Pd reagent used varies depending on the starting material and solvent, and is not particularly limited as long as it does not hinder the reaction. Preferred reagents include PdCl2(PPh3)2, PdCl2(dppf), Pd(PPh3)4, and Pd2(dba)3. Typical heating reactions are carried out at 70 to 110°C for 0.5 to 48 hours; a microwave synthesis apparatus at 160°C for 5 minutes is preferred.

[0938] Step C: The acetyl derivative is reacted with bromine in the presence of an acid to obtain an α-haloacetylpyridine derivative. The reaction is carried out in a solvent or without a solvent, and in the presence of an acid. The solvent used varies depending on the starting material and reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction. Preferred solvents include chloroform, dichloromethane, diethyl ether, dioxane, methanol, ethanol, DMF, THF, and acetonitrile. The acid used varies depending on the starting material and solvent used, and is not particularly limited as long as it does not hinder the reaction. Preferred acids 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, preferably 70°C for 1 hour.

[0939] The starting material of formula (IV) can be commercially available; however, it can be obtained, for example, by the sequential synthesis of a carbonyl compound and a halide from a thioamide, as shown in the following reaction formula.

[0940]

[0941] (where R is in the formula) 1 To R 5As defined in formula (I) above, Halo is a halogen such as iodine, bromine, or chlorine, with bromine being the most preferred.

[0942] Step A: In this reaction, the thioamide of formula (II) corresponding to compound (I) with substituents is dissolved in solvents such as DME, acetone, toluene, hexane, xylene, acetonitrile, ethyl acetate, dioxane, THF, ethanol, methanol, dichloromethane, chloroform, dichloroethane, DMF, and water. A haloacetate such as methyl bromoacetate, ethyl bromoacetate, or ethyl chloroacetate is added to the solvent to react and obtain the corresponding carbonyl compound shown in formula (X). Typically, the reaction temperature is 20 to 200°C, and the reaction time is 1 to 24 hours, preferably 80°C for 1 hour.

[0943] Step B: In this reaction, the compound shown in formula (X) is dissolved together with carbon tetrabromide and triphenylphosphine in a solvent such as toluene, and the reaction is carried out by heating for a specified time to perform the Appel reaction, yielding the corresponding halide. The solvent used varies depending on the reagents, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction. Preferred solvents include DME, acetone, toluene, hexane, xylene, acetonitrile, ethyl acetate, dioxane, THF, ethanol, methanol, dichloromethane, chloroform, dichloroethane, DMF, and water. Carbon tetrachloride, in addition to carbon tetrabromide, can be used as a reaction reagent. Typically, the reaction temperature is 0 to 200°C, and the reaction time is 1 to 24 hours, preferably 110°C for 1 hour.

[0944] The starting material of formula (V) compound can be obtained from commercially available products, however, for example, by the reaction shown below.

[0945]

[0946] (where R is in the formula) 1 To R 5 As defined in equation (I) above, Tf represents trifluoromethanesulfonate.

[0947] Step A: In this reaction, the compound shown in (X), together with N-phenylbis(trifluoromethanesulfonylimide) and a base, is dissolved in a solvent such as dichloromethane, and the corresponding trifluoromethanesulfonate compound is obtained by reaction. Examples of bases used include pyridine, 4-dimethylaminopyridine, triethylamine, N,N-diisopropylethylamine, sodium carbonate, potassium carbonate, and tripotassium phosphate. The solvent used varies depending on the reagent, and is not particularly limited as long as it dissolves the starting material to a certain extent without hindering the reaction; preferred solvents include DME, acetone, toluene, hexane, xylene, acetonitrile, ethyl acetate, dioxane, THF, ethanol, methanol, dichloromethane, chloroform, dichloroethane, DMF, and water. Typically, the reaction temperature is from -78°C to 40°C, and the reaction time is from 10 minutes to 24 hours, preferably 0°C and 15 minutes.

[0948] The starting material of the compound of formula (VII) can be obtained from commercially available products, however, for example, as shown in the following reaction formula.

[0949]

[0950] (where R is in the formula) 1 To R 6 As defined in equation (I) above, R ’ and R ’ ’ Represents a hydrogen atom, or R ’ and R ’ ’ Together with the two adjacent oxygen atoms, it forms an alkyldioxy group.

[0951] Step A: In this reaction, the compound shown in formula (V) is dissolved in solvents such as DME, acetone, toluene, hexane, xylene, acetonitrile, ethyl acetate, dioxane, THF, ethanol, methanol, dichloromethane, chloroform, dichloroethane, DMF, and water. It reacts with diborane compounds such as 4,4,4', 4', 5, 5, 5', 5'-octamethyl-2,2'-bis(1,3,2-dioxaborhexacyclopentane) or 4,4, 4',4', 5, 5, 5', 5'-octaethyl-2,2'-bis(1,3,2-dioxaborhexacyclopentane), and palladium catalysts such as palladium acetate, palladium chloride, and triphenylacetone (dibenzylacetone)dipalladium(O), and 2-dicyclohexylphosphino-2', 4', The reaction is carried out together with bidentate ligands such as 6'-triisopropylbiphenyl, 2-di-tri-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl, 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthine. Typically, the reaction temperature is from 0°C to 150°C, and the reaction time is from 10 minutes to 24 hours, preferably at room temperature for 18 hours.

[0952] 3. Thiazolyl-pyrazolo[1,5-a]pyridine derivatives

[0953] Thiazolyl-pyrazolo[1,5-a]pyridine derivatives can be in the form of hydrates, solvates, or pharmaceutically permissible salts (acid addition salts or base addition salts), prodrugs, etc. Thiazolyl-pyrazolo[1,5-a]pyridine or its derivatives include various isomers.

[0954] "Pharmaceutical-permissible salt" means a pharmaceutically permissible salt that can exhibit the desired pharmacological activity of the parent compound. When the compounds of the present invention are obtained in their free form, they can be converted into salts using conventional methods; conversely, when the compounds of the present invention are obtained in their salt form, they can be converted into their free form using conventional methods.

[0955] Pharmaceutically permissible salts are well-known within the relevant technical field, for example, SMBerge et al., J. Pharmaceutical Sciences, 1977, 66, 1-19, and Remington's Pharmaceutical Sciences, 17. th The pharmaceutically permissible salts are detailed in publications such as ed., Mack Publishing Company, Easton, PA, 1985, etc., and this information is incorporated into this specification by reference.

[0956] Examples of pharmaceutically permissible acid addition salts include those derived from inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid; as well as 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-hydroxybenzyl)benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, and 1... Salts formed by the addition of organic acids such as 2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, glucoheptanoic acid, 4,4'-methylenebis-(3-hydroxy-2-ene-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tri-butylacetic acid, lauryl sulfate, gluconic acid, glutamic acid, hydroxynaphthoic acid, stearic acid, mucoconic acid, and salicylic acid.

[0957] Pharmaceutically permissible examples of base addition salts include salts in which acidic protons present in parent compounds such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, and aluminum salts are replaced by metal ions. Furthermore, salts derived from organic bases, such as primary, secondary, and tertiary amines, substituted amines, and cyclic amines, are also included. Examples of organic bases include isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucosamine, theobromine, purine, piperazine, piperidine, N-ethylpiperidine, glycerol, N-methylglucosamine, and polyamine resins. Representative organic bases include isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine.

[0958] In addition to hydrates, organic solvates such as dimethyl sulfoxide solvates, dimethylformamide solvates, ethanol solvates, methanol solvates, or n-propyl alcohol solvates can be listed as examples.

[0959] This compound or its pharmaceutically permissible salts or solvates (including hydrates) may exist in an amorphous form. Generally, various crystalline polymorphs are known for most organic compounds and their salts, and various crystalline forms can be produced using various methods well-known in the art. Specifically, for example, various crystalline forms containing amorphous components can be produced via melt processing, extrusion, etc. Furthermore, the amorphous body may also be provided in the form of a solid dispersion containing excipients, etc. (However, even for compounds, raw materials, reagents, etc., as recorded to date, corresponding countermeasures and measures for the following points are indispensable. First, when using compounds that increase the "risk of contamination with nitrosamines in pharmaceuticals," full attention must be paid to their use. In addition, based on the "Elemental Impurity Guidelines," care must be taken to avoid the risk of contamination with various heavy metals, etc. For elemental impurities other than Groups 1, 2A, 2B, and 3, since 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 kidney dysfunction, full attention to quality management is indispensable. Furthermore, based on the "Residual Solvent Guidelines," attention must be paid to residual solvents such as dimethylformamide and methanol of Group 2, or dimethyl sulfoxide or ethanol of Group 3, especially solvent compounds.)

[0960] The aforementioned thiazolyl-pyrazolo[1,5-a]pyridine derivatives, or their pharmaceutically permissible salts, solvates, or hydrates, may also be in the form of prodrugs.

[0961] In the context of this specification, the term "prodrug" refers to a compound that is converted into this compound (compound of formula (I)) under physiological conditions in vivo through reactions such as oxidation, reduction, and hydrolysis initiated by enzymes.

[0962] As a prodrug, for example, can be listed as follows:

[0963] (1) Compounds in which the amino group of this compound is acylated, alkylated, or phosphorylated (e.g., compounds in which the amino group of compound (I) is icosanolylated, furanylated, pentylaminocarbonylated, (5-methyl-2-sideoxy-1,3-dioxacyclopenten-4-yl)methoxycarbonylated, tetrahydrofuranylated, pyrrolidinylmethylated, trimethylacetyloxymethylated, tertiary-butylated, ethoxycarbonylated, tertiary-butoxycarbonylated, acetylated, or cyclopropylcarbonylated);

[0964] (2) Compounds in which the hydroxyl group of the present compound is acylated, alkylated, phosphorylated, or borated (e.g., compounds in which the hydroxyl group of compound (I) is acetylated, palmitoylated, propionylated, trimethylacetylated, succinylated, fumarylated, alanine-acylated, or dimethylaminomethylcarbonylated).

[0965] (3) Compounds in which the carboxyl group of this compound has been esterified or amidated (e.g., compounds in which the carboxyl group of compound (I) has been esterified by ethyl esterification, phenyl esterification, carboxyl methyl esterification, dimethylamino methyl esterification, trimethylacetyloxymethyl esterification, ethoxycarbonyloxyethyl esterification, phthaloyl esterification, (5-methyl-2-sideoxy-1,3-dioxacyclopenten-4-yl) methyl esterification, cyclohexyloxycarbonyl ethyl esterification, or methylamidation). These compounds can be manufactured from this compound by methods known to the public.

[0966] Detailed information about the prodrug is described in T. Higuchi and V. Stella, “Pro-drugs as Novel Delivery Systems”, Vol. 14 of the ACS Symposium Series, Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987, and Hirokawa Shoten, 1990, “Pharmaceutical Development”, Vol. 7, Molecular Design, pp. 163-198. The contents of these documents are incorporated herein by reference.

[0967] Thiazolyl-pyrazolo[1,5-a]pyridine or its derivatives can exist in various isomeric forms, such as geometric isomers, optical isomers, rotational isomers, stereoisomers, tautomers, etc. These isomers can be purified and isolated using common separation methods, such as recrystallization, non-mirror image salting, enzyme fractionation, and various chromatographic methods (e.g., thin-layer chromatography, column chromatography, gas chromatography, etc.).

[0968] 4. Pharmaceutical uses of thiazolyl-pyrazolo[1,5-a]pyridine and its derivatives

[0969] Compound (I) has been shown in the examples described below to inhibit myosin light chain kinase 4 (MYLK4) activity. Accordingly, compound (I) or its pharmaceutically permissible derivatives, or pharmaceutical compositions comprising these compounds, may be used in biological samples or in vivo to inhibit MYLK4 activity. Furthermore, compound (I) or its pharmaceutically permissible derivatives, or pharmaceutical compositions comprising these compounds, through their MYLK4 activity inhibition, may be used to prevent, alleviate, or treat MYLK4-related disorders, impairments, or symptoms.

[0970] As for diseases, disorders, or symptoms that may be associated with MYLK4, examples include 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. Accordingly, the compound of formula (I) or its pharmaceutically permissible derivatives, or pharmaceutical compositions comprising these, may be used for the prevention, mitigation, and / or treatment of these diseases, disorders, or symptoms. It is particularly effective for the prevention, mitigation, and / or treatment of 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, especially for the prevention, mitigation, and / or treatment of glaucoma, ocular hypertension, or aqueous humor outflow obstruction, and is especially effective for use in lowering intraocular pressure in a subject.

[0971] 5. Pharmaceutical Compositions (Formulation)

[0972] Pharmaceutical compositions may be formulated by incorporating an effective amount of a compound of formula (I) or a pharmaceutically permissible derivative thereof, along with a pharmaceutically permissible carrier and other excipients as required. Furthermore, the use of a compound of formula (I) or its derivatives as is not excluded as a pharmaceutical product.

[0973] The above-mentioned pharmaceutical compositions can be administered orally or indirectly. For oral administration, dosage forms include, for example, lozenges, granules, coated lozenges, powders, pellets, pills, capsules (e.g., hard gelatin capsules, soft gelatin capsules), microcapsules, syrups, etc. For non-oral administration, dosage forms include, for example, injections (including freeze-dried injectable formulations dissolved before use), eye drops, lotions, aerosols, ointments, patches, suppositories, etc. They can also be formulated as liposomes. Furthermore, compounds of formula (I) or their pharmaceutically permissible derivatives can be prepared as liquids pre-dispersed in pharmaceutically permissible solvents. In this case, they can be formulated as, for example, syrups for oral administration or injections (including freeze-dried injectable formulations dissolved before use), eye drops, etc., for non-oral administration.

[0974] In addition, the above-mentioned pharmaceutical compositions can also be formulated as solutions, suspensions, emulsifiers, microemulsions, multiphase emulsifiers, foams, plasters, pastes, muds, ointments, coated tablets, rinsing solutions, rectal capsules, drops, gels, sprays, powders, aerosols, inhalers, eye drops, eye ointments, eye rinsing solutions, infusions, or transplant tablets for administration.

[0975] In this way, the above-mentioned pharmaceutical composition can be made into various dosage forms, and its preparation can be carried out by adding various carriers (excipients) and various adjuvants as needed, depending on the dosage form, administration method, etc.

[0976] Examples of adjuvants include colorants, sweeteners, flavoring agents, binders, adsorbents, lubricants, disintegrants, softeners, suspending agents, emulsifiers, preservatives, antioxidants, surfactants, stabilizers, pH adjusters, dispersants, isotonic adjusters, wetting agents, solvents, dissolution aids, and / or absorption promoters.

[0977] In addition, regarding solid drug delivery methods...

[0978] Examples of carriers (excipients) include crystalline cellulose, sugars (glucose, white sugar, 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.

[0979] Examples of disintegrants include sodium carbonate, calcium carbonate, gum arabic, starches (corn starch, potato starch, wheat starch, cassava starch, rice starch, etc.), agar, alginic acid, silicate compounds, tragacanth gum, crystalline cellulose, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, and sodium carboxymethyl starch.

[0980] Examples of adhesives include cellulose derivatives, starch, alginates, gelatin, methyl pyrrolidone, sucrose, and gum arabic.

[0981] Examples of humectants include glycerin, cetyl alcohol and glycerin monostearate, magnesium stearate, talc, calcium stearate, solid polyethylene glycol, sodium lauryl sulfate, etc.

[0982] Examples of absorption enhancers include, for example, quaternary ammonium compounds.

[0983] Examples of adsorbents include kaolin and bentonite.

[0984] Examples of lubricants include palm wax, hardened oil, magnesium stearate, calcium stearate, sodium hydrogen phosphate, calcium hydrogen phosphate, and beeswax.

[0985] Examples of preservatives include parabens, chlorobutanol, phenols, sorbic acid, and benzalkonium chloride.

[0986] Pharmaceutical compositions in liquid form for oral administration include pharmaceutically permissible emulsifiers, solutions, suspensions, syrups, and elixirs. These dosage forms are generally prepared by dissolving or dispersing the admixtures in carriers such as distilled water, physiological saline, aqueous dextran, glycerin, ethanol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butanediol, and dimethylformamide to form a solution or suspension; oils such as cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil, sesame oil, glycerin, tetrahydrofurfuryl alcohol, polyethylene glycol, and fatty acid esters of sorbitan; or mixtures of these substances, thereby forming a solution or suspension.

[0987] Pharmaceutical compositions in liquid form may include suspending agents, solubilizers, or dissolving aids as needed. Examples of suspending agents include ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum hydroxide, bentonite, agar, and tragali gum. Examples of solubilizers 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 polyethylene glycol. Examples of dissolving aids include L-arginine, α-cyclodextrin, β-cyclodextrin, D-sorbitol, soybean oil, urea, white sugar, hydroxypropyl cellulose, hydroxypropyl methylcellulose, povidone, and D-mannitol.

[0988] Suitable injectable formulations of pharmaceutical compositions include physiologically permissible aqueous or non-aqueous sterile solutions, dispersions, suspensions, or emulsifiers, or sterile powders that are reconstituted upon use from sterilized injectable solutions and / or dispersions. Examples of suitable aqueous or non-aqueous carriers, diluents, solvents, or mediators include distilled water, ethanol, polyols (propylene glycol, polyethylene glycol, glycerin, etc.), suitable mixtures of these, vegetable oils (e.g., olive oil), or injectable organic esters such as ethyl oleate. These aqueous or non-aqueous carriers, diluents, solvents, or mediators, such as physiological saline, may further contain suitable salts, pH adjusters, etc. Additionally, suspending agents, solubilizers, or dissolving aids may be included as needed. Furthermore, aluminum monostearate and gelatin may be used as agents to delay the absorption of injectable drugs.

[0989] When preparing injectable and eye drops, pH adjusters, buffers, stabilizers, and preservatives may be added as needed to prepare subcutaneous, intramuscular, or intravenous injections using standard methods. Injectable and eye drops can also be stored in containers and then freeze-dried to form solid preparations for immediate use. Furthermore, a single dosage can be stored in a single container, or multiple dosages can be stored in the same container.

[0990] Pharmaceutical compositions suitable for rectal administration typically use non-irritating excipients that are solid at room temperature but dissolve at body temperature and release the active ingredient into a suitable body cavity, such as suppositories. Examples of such excipients include cocoa butter, polyethylene glycol, or specified waxes.

[0991] Pharmaceutical compositions in dosage forms intended for topical application include ointments, powders, sprays, and inhalers. In these dosage forms, the compounding ingredients are typically prepared by mixing under sterile conditions with a pharmaceutically acceptable carrier and, if necessary, any preservatives, buffers, or sprays. Ophthalmic formulations, ointments, powders, and solutions are typical examples of topical application; those skilled in the art will readily understand the appropriate carriers (excipients) and adjuvants.

[0992] Methods for preparing pharmaceutical compositions suitable for various delivery forms are well known in the relevant technical field, for example, as described in Remington's Pharmaceutical Sciences, 18. th Ed., Mack Publishing Company, Easton, PA, 1990, etc., are incorporated herein by reference.

[0993] When administering the above-described compound or its derivatives or pharmaceutical compositions to mammals (e.g., mice, rats, hamsters, rabbits, cats, dogs, cattle, sheep, monkeys, humans), especially to humans, any dosage form suitable for the desired route of delivery may be used, such as oral, dermal, intradermal, intrabronchial, intranasal, intraarterial, intravenous, intramuscular, subcutaneous, intraperitoneal, vaginal, rectal, sublingual, intracranial, epidural, intratracheal, intraocular, or other local sites.

[0994] [Example]

[0995] The compounds of the present invention can be manufactured, 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 examples, and the present invention is not limited to the following specific examples in any case, and variations can be made without departing from the scope of the present invention.

[0996] In this embodiment, "silicone" in "silicone column chromatography" refers to Wakogel C-200 (particle size 75 to 150 μm) manufactured by Fujifilm and Koichi Pure Chemical Industries, Ltd., and Cartridge (Universal Column Premium, particle size 30 μm) manufactured by YAMAZEN, unless otherwise specified.

[0997] In this embodiment, "TLC" in "preparative TLC" refers to Merck's TLC glass slide silicone 60F254 (0.5mm, 1mm, 2mm) unless otherwise specified.

[0998] "Under decompression" refers to a state of decompression of approximately 1 to 50 mmHg using a vacuum pump or similar device.

[0999] "Room temperature" refers to a range of approximately 10°C to 30°C. % indicates weight unless otherwise specified.

[1000] [1] Synthesis of compounds

[1001] [Example 1] Synthesis of 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)phenol (compound 3)

[1002] Thioamides were reacted with substituted α-bromoacetophenones to synthesize compound (3).

[1003]

[1004] Pyrazolo[1,5-a]pyridine-3-thiocarboxamide (178 mg, 1.00 mmol) was dissolved in DME (10 mL). 3-hydroxybenzoyl bromide (228 mg, 1.06 mmol) was added under ice-cold conditions, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was heated and stirred at 50 °C for 1 hour, then cooled. The solvent was removed by distillation under reduced pressure. Ethanol (10 mL) was added to the residue, followed by excess potassium carbonate (327 mg). The reaction mixture was refluxed at 70 °C for 1 hour. After cooling, the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography, followed by separation in a hexane:ethyl acetate (1:4) mixture to obtain the title compound (3) (194 mg, 0.661 mmol, yield 66.1%).

[1005]

[1006] 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).

[1007] [Examples 2 to 26] Synthesis of the following compounds:

[1008] 4-Phenyl-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 71),

[1009] 2-Methoxy-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 79),

[1010] 4-(3-Fluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 112),

[1011] 4-(2-Fluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 122),

[1012] 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzene-1,3-diol (compound 120),

[1013] 4-(2,4-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 121),

[1014] 4-(3-methoxyphenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 83),

[1015] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(o-tolyl)thiazole (compound 132),

[1016] 1-Methyl-6-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-3,4-dihydroquinoline-2(1H)-one (compound 131),

[1017] N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 12),

[1018] 4-(4-methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 7),

[1019] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-3-yl)thiazole (compound 15),

[1020] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-4-yl)thiazole (compound 92),

[1021] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(pyridin-2-yl)thiazole (compound 93),

[1022] 4-(2-chloropyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 94),

[1023] 4-(2-methoxypyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 95),

[1024] 4-(6-methoxypyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 96),

[1025] 4-(5-methylpyridin-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 97),

[1026] 6-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-[1,3]dioxacyclopenteno[4,5-b]pyridine (compound 98),

[1027] 4-(2-methylpyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 99),

[1028] 4-(2-Fluoropyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 100),

[1029] 4-(2-bromopyridin-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 101),

[1030] 4-(5-chloropyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 125),

[1031] 4-(4-chloropyridin-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 135) and

[1032] 2'-Bromo-2-(pyrazolo[1,5-a]pyridin-3-yl)-4,5'-bithiazole (compound 37)

[1033] According to the synthesis method of compound (3), compounds (71), (79), (112), (122), (120), (121), (83), (132), (131), (12), (7), (15), (92), (93), (94), (95), (96), (97), (98), (99), (100), (101), (125), (135) and (37) were synthesized using substituted α-bromoacetophenones corresponding to the final compounds.

[1034]

[1035] 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).

[1036]

[1037] 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).

[1038]

[1039] 1H-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).

[1040]

[1041] 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).

[1042]

[1043] 1 H-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).

[1044]

[1045] 1H-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).

[1046]

[1047] 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).

[1048]

[1049] 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).

[1050]

[1051] 1 H-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).

[1052]

[1053] 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).

[1054]

[1055] 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).

[1056]

[1057] 1 H-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).

[1058]

[1059] 1H-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).

[1060]

[1061] 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).

[1062]

[1063] 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).

[1064]

[1065] 1H-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).

[1066]

[1067] 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).

[1068]

[1069] 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).

[1070]

[1071] 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=2.0Hz), 8.39 (1H, s), 8.42-8.46 (1H, m), 8.51-8.56 (1H, m).

[1072]

[1073] 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).

[1074]

[1075] 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).

[1076]

[1077] 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).

[1078]

[1079] 1H-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).

[1080]

[1081] 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).

[1082]

[1083] 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).

[1084] [Example 27] Synthesis of 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)aniline hydrochloride (compound 1)

[1085]

[1086] (1) Synthesis of 4-(4-nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 1-1)

[1087] Pyrazolo[1,5-a]pyridine-3-thiocarboxamide (887 mg, 5.00 mmol) was dissolved in DME (50 mL). Under ice-cold conditions, 4-nitrobenzyl bromide (1.24 g, 5.53 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was heated and stirred at 50 °C for 1 hour, then cooled. The solvent was removed by distillation under reduced pressure. Ethanol (40 mL) was added, followed by excess potassium carbonate (1.18 g). The mixture was then refluxed at 70 °C for 1 hour. After cooling, the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography, followed by separation in a hexane:ethyl acetate (1:1) mixture to give the title compound (1-1) (1.50 g, 4.64 mmol, 92.8% yield).

[1088] 1 H-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).

[1089] (2) Synthesis of tributyl 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)carbamate (compounds 1-2)

[1090] 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 under reflux at 90 °C for 1 hour. After cooling, the insoluble matter was filtered through diatomaceous earth. The filtrate was concentrated to about 50 mL under reduced pressure. Under ice-cold conditions, excess anhydrous dibutoxycarbonyl solution (8 mL) was added, and the mixture was stirred at room temperature for 16 hours. The solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography. The final product was obtained by separation of hexane:ethyl acetate (1:1) to give the title compound (1-2) (1.31 g, 3.37 mmol, yield 41.1%).

[1091] 1H-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).

[1092] (3) Synthesis of 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)aniline hydrochloride (compound 1)

[1093] (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)carbamate tributyl ester (compounds 1-2) (1.12 g, 2.84 mmol)) was slowly added to a 4N dioxane hydrochloride solution (15 mL) under ice-cold conditions and stirred at room temperature for 2 hours. The solvent was removed by distillation under reduced pressure. Next, the solvent was added, the resulting solid was filtered off, thoroughly washed with the solvent, and dried to give the title compound (1) (1.04 g, 2.84 mmol, yield 99.8%).

[1094]

[1095] 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).

[1096] [Examples 28 to 32] Synthesis of the following compounds:

[1097] 4-(3-nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 4),

[1098] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)aniline hydrochloride (compound 10),

[1099] 4-(2-Nitrophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 133),

[1100] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)aniline hydrochloride (compound 134) and

[1101] 2-Methoxy-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)aniline (Compound 90)

[1102] According to the synthesis method of compound (1), compounds (4), (10), (133), (134) and (90) were synthesized using substituted α-bromoacetophenones corresponding to the target compound.

[1103]

[1104] 1 H-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).

[1105]

[1106] 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).

[1107]

[1108] 1H-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).

[1109]

[1110] 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).

[1111]

[1112] 1 H-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).

[1113] [Example 33] Synthesis of 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)phenol (compound 118)

[1114]

[1115] (1) Synthesis of 2-bromo-1-(2-hydroxyphenyl)ethane-1-one (compound 118-1)

[1116] Add 1-(2-hydroxyphenyl)ethane-1-one (288 mg, 2.11 mmol) to ethyl acetate (50 mL), then add CuBr2 (929 mg, 4.32 mmol) and heat under reflux for 16 hours. After cooling, filter the insoluble matter through diatomaceous earth, distill off the organic solvent under reduced pressure, and purify the residue by silica gel column chromatography. The final product, obtained by separation of hexane and ethyl acetate (1:1), yielded the title compound (118-1) (438 mg, 2.03 mmol, 79.8% yield).

[1117] 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).

[1118] (2) Synthesis of 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 118)

[1119] Pyrazolo[1,5-a]pyridine-3-thiocarboxamide (186 mg, 1.05 mmol) was dissolved in DME (20 mL). Under ice-cold conditions, 2-bromo-1-(2-hydroxyphenyl)ethane-1-one (compound 118-1) (218 mg, 1.02 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was heated and stirred at 50 °C for 1 hour, then cooled, and the solvent was removed by distillation under reduced pressure. Ethanol (50 mL) was added to the residue, followed by excess potassium carbonate (301 mg). The reaction mixture was heated under reflux at 70 °C for 1 hour. After cooling, the solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography. The final product, compound (118) (214 mg, 0.729 mmol, 69.4% yield), was obtained by separation in a hexane:ethyl acetate (1:4) solution.

[1120]

[1121] 1H-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).

[1122] [Examples 34 to 38] Synthesis of the following compounds:

[1123] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzonitrile (compound 115),

[1124] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzonitrile (compound 116),

[1125] 4-(3,5-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 119),

[1126] 4-(2,6-difluorophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 123) and

[1127] 5-Fluoro-2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 114)

[1128] According to the synthesis method of compound (118), substituted α-bromoacetophenone was synthesized by using substituted acetophenones corresponding to the final compound, which was reacted with thioamide to synthesize compounds (115), (116), (119), (123) and (114).

[1129]

[1130] 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).

[1131]

[1132] 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).

[1133]

[1134] 1 H-NMR(CDCl3) δ:6.79 (1H, tt, J=2.3Hz, 9.2Hz), 6.95 (1H, dt, J=1.4Hz,6.9Hz), 7.42 (2H, m), 7.54 (2H, d, J=6.4Hz), 8.39 (1H, s), 8.44 (1H, d, J=9.2Hz), 8.53 (1H, d, J=6.9Hz).

[1135]

[1136] 1 H-NMR(CDCl3) δ:6.91 (1H, dt, J=1.4Hz, 6.9Hz), 7.02 (2H, t, J=8.2Hz),7.34 (2H, m), 7.46 (1H, t, J=1.4Hz), 8.39 (1H, s), 8.44 (1H, d, J=9.2Hz),8.51 (1H, d, J=6.9Hz).

[1137]

[1138] 1H-NMR(CDCl3) δ: 6.64 (1H, t, J=2.8Hz, 8.3Hz), 6.75 (1H, dd, J=2.3Hz, 10.5Hz), 6.97 (1H, dt, J=0.9Hz, 9.2Hz), 7.33 (1H, s), 7.44 (1H, ddd, J=0.9Hz, 6.9Hz, 9.2Hz), 7.61 (1H, dd, J=6.4Hz, 8.7Hz), 8.12 (1H, d, J=8.7Hz), 8.41 (1H,s), 8.56 (1H, d, J=8.7Hz), 12.32 (1H, s).

[1139] [Example 39] Synthesis of 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isonicotinamide (compound 126)

[1140]

[1141] (1) Synthesis of 2-(2-bromoacetyl)isonicotinamide hydrobromide (compound 126-1)

[1142] 2-Acetylisocyanate formonitrile (51.6 mg, 0.35 mmol) was dissolved in acetic acid (1 mL). Under ice-cold conditions, 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. The reaction mixture was heated and stirred at 70 °C for 1 hour. After cooling, diethyl ether was added. The precipitated solid was stirred briefly at room temperature, filtered by suction, washed with diethyl ether, and dried under reduced pressure to give the title compound (126-1) (95.6 mg, 0.30 mmol, yield 83.6%).

[1143] 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).

[1144] (2) Synthesis of 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isonicotinamide (compound 126)

[1145] Pyrazolo[1,5-a]pyridine-3-thiocarboxamide (30.0 mg, 0.17 mmol) was dissolved in DME (2 mL). 2-(2-bromoacetyl)isonicotinamide hydrobromide (compound 126-1) (82.4 mg, 0.17 mmol) was added under ice-cold conditions, and the mixture was stirred at room temperature for 15 hours. The reaction mixture was heated and stirred at 50 °C for 1 hour, then cooled, and the solvent was removed by distillation 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 under reflux at 80 °C for 1 hour. After cooling, the solvent was removed by distillation under reduced pressure, and dichloromethane and methanol were added to the residue. After filtration through suction of the suspended solids, the mixture was dried under reduced pressure to give the title compound (126) (7.6 mg, 0.024 mmol, yield 14.0%).

[1146]

[1147] 1 H-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).

[1148] [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)

[1149] Based on the synthesis method of compound (126), compounds (124) and (127) were synthesized.

[1150]

[1151] 1H-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).

[1152]

[1153] 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).

[1154] [Example 42] Synthesis of 4-(1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 107)

[1155]

[1156] (1) Synthesis of 2-bromo-1-(1H-pyrazol-4-yl)ethane-1-one (compound 107-1)

[1157] A bromo-dioxane complex (1.25 g, 5.00 mmol) was added to 10 mL of dioxane containing 0.55 g (5.00 mmol) of 1-(1H-pyrazol-4-yl)ethane-1-one, and the mixture was stirred at room temperature for 56 hours. The precipitate was collected by suction filtration, washed with acetone, and dried to give the title compound (107-1) (1.02 g, 5.00 mmol, 100% yield).

[1158] 1 H-NMR(DMSO-d6) δ: 2.50 (2H, s), 8.22 (2H, s).

[1159] (2) Synthesis of 4-(1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 107)

[1160] A solution of pyrazolo[1,5-a]pyridine-3-thiocarboxamide (5.40 g, 30.5 mmol) and 2-bromo-1-(1H-pyrazol-4-yl)ethane-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. The mixture was then extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was removed by distillation under reduced pressure. The residue was suspended in ethyl acetate, filtered, and dried to give the title compound (107) (5.00 g, 18.7 mmol, yield 61.3%).

[1161]

[1162] 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).

[1163] [Examples 43 to 74] Synthesis of the following compounds:

[1164] 4-(4-chloro-1-methyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 53),

[1165] 4-(1,4-dimethyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrobromide (compound 54),

[1166] 4-(1-Methyl-1H-pyrazol-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrobromide (compound 106),

[1167] 4-(1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 109),

[1168] 5-Methyl-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazolyl hydrobromide (compound 105),

[1169] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrolo-3-yl)thiazole (compound 138),

[1170] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrolo-2-yl)thiazole (compound 139),

[1171] 4-(1H-imidazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 140),

[1172] 4-(1H-imidazol-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 141),

[1173] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,3-triazol-4-yl)thiazole (compound 142),

[1174] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-1,2,4-triazol-3-yl)thiazole (compound 143),

[1175] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(thiophen-3-yl)thiazole (compound 144),

[1176] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(thiophen-2-yl)thiazole (compound 145),

[1177] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)isothiazolium (compound 146),

[1178] 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)isothiazolyl (compound 147),

[1179] 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)isothiazolium (compound 148),

[1180] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4,4'-bithiazole (compound 149),

[1181] 2-(pyrazolo[1,5-a]pyridin-3-yl)-4,5'-bithiazole (compound 150),

[1182] 2'-(pyrazolo[1,5-a]pyridin-3-yl)-2,4'-bithiazole (compound 151),

[1183] 4-(furan-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 152),

[1184] 4-(furan-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 153),

[1185] 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazole (compound 154),

[1186] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazole (compound 155),

[1187] 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazole (compound 156),

[1188] 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)oxazole (compound 157),

[1189] 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)oxazole (compound 158),

[1190] 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)oxazole (compound 159),

[1191] 4-(1-Methyl-1H-pyrazol-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 160),

[1192] 4-(1-Methyl-1H-pyrrolo-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 161),

[1193] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1,2,4-thiadiazole (compound 162),

[1194] 4-(1-Methyl-1H-pyrrolo-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 163) and

[1195] 3-Bromo-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)isoxazole (compound 164)

[1196] By substituting 2-bromo-1-(1H-pyrazol-4-yl)ethane-1-one with substituted α-haloketones corresponding to the final compounds, compounds (53), (54), (106), (109), (105), (138), (139), (140), (141), (142), (143), (144), (145), (146), (147), (148), (149), (150), (151), (152), (153), (154), (155), (156), (157), (158), (159), (160), (161), (162), (163), and (164) were synthesized according to the synthetic method of compound (107).

[1197]

[1198] 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).

[1199]

[1200] 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).

[1201]

[1202] 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).

[1203]

[1204] 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).

[1205]

[1206] 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).

[1207]

[1208] 1H-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).

[1209]

[1210] 1 H-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).

[1211]

[1212] 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).

[1213]

[1214] 1H-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).

[1215]

[1216] 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).

[1217]

[1218] 1 H-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).

[1219]

[1220] 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).

[1221]

[1222] 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).

[1223]

[1224] 1 H-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).

[1225]

[1226] 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).

[1227]

[1228] 1H-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).

[1229]

[1230] 1 H-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).

[1231]

[1232] 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).

[1233]

[1234] 1H-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).

[1235]

[1236] 1 H-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).

[1237]

[1238] 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).

[1239]

[1240] 1H-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).

[1241]

[1242] 1 H-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).

[1243]

[1244] 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).

[1245]

[1246] 1H-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).

[1247]

[1248] 1 H-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).

[1249]

[1250] 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).

[1251]

[1252] 1H-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).

[1253]

[1254] 1 H-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).

[1255]

[1256] 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).

[1257]

[1258] 1H-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).

[1259]

[1260] 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).

[1261] [Example 75] Synthesis of N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)oxetane-3-sulfonamide (compound 69)

[1262]

[1263] (1) Synthesis of N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)oxetane-3-sulfonamide (compound 69-1)

[1264] 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)aniline hydrochloride (compound 1) (50.5 mg, 0.120 mmol) was suspended in anhydrous dichloromethane solution (10 mL). Under ice-cold conditions, excess oxetane-3-sulfonic acid chloride (0.10 mL) was added, followed by the slow addition of excess triethylamine (0.20 mL). The mixture was slowly warmed to room temperature and stirred for 16 hours. Under ice-cold conditions, water was added to the reaction mixture, and the dichloromethane layer was washed several times with water. The dichloromethane layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (69-1) (48.5 mg, 0.118 mmol, 98.0% yield) was obtained by separation of hexane:ethyl acetate (1:1).

[1265] 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).

[1266] (2) Synthesis of N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)oxetane-3-sulfonamide (compound 69)

[1267] Sodium hydride (oil dispersion) (21.5 mg) was carefully added to anhydrous DMF (4 mL) to form a suspension. After cooling to -15 °C, N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)oxetane-3-sulfonamide (compound 69-1) (25.5 mg, 0.0521 mmol) was slowly added. Once heated to room temperature, the mixture was cooled to -15 °C, and excess methyl iodine (0.10 mL) was added dropwise. The mixture was slowly brought back to room temperature while stirring for 16 hours. Water (approximately 20 mL) was carefully added slowly while the reaction mixture was ice-cold. The resulting precipitate was stirred briefly at room temperature, filtered, thoroughly washed with solvents such as n-hexane, and dried to obtain the title compound (69) (6.6 mg, 0.0155 mmol, yield 28.8%).

[1268]

[1269] 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).

[1270] [Example 76] Synthesis of N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 16)

[1271] According to the synthesis method of compound (69) of compound (69-1), compound (16) is synthesized from compound (12).

[1272]

[1273] 1 H-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).

[1274] [Example 77] Synthesis of N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)morpholine-4-carboxamide (compound 72)

[1275]

[1276] Synthesis of (1) (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methylamine hydrochloride (compound 72-1)

[1277] N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 12) (72.1 mg, 0.21 mmol) was suspended in 1.0 mL of 6 N hydrochloric acid and heated under reflux for 6 hours. After cooling, the solvent was removed by distillation under reduced pressure, and ethanol was added several times for drying and solidification. The resulting solid was dissolved in water (10 mL), and ethyl acetate (10 mL) was added for partitioning. The aqueous layer was concentrated under reduced pressure, and ethanol was added several times for distillation under reduced pressure to obtain the title compound (72-1) (66.9 mg, 0.180 mmol, yield 85.5%).

[1278] 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).

[1279] (2) Synthesis of N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)morpholine-4-carboxamide (compound 72)

[1280] (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methylamine hydrochloride (compound 72-1) (20.5 mg, 0.0544 mmol)) was suspended in anhydrous dichloromethane solution (10 mL). Morpholine carbonyl chloride (0.10 mL) was added under ice-cold conditions, followed by the slow addition of excess triethylamine (0.20 mL). The mixture was slowly warmed to room temperature and stirred for 16 hours. Water was added to the reaction mixture under ice-cold conditions, and the dichloromethane layer was washed several times with water. The dichloromethane layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (72) (14.3 mg, 0.0341 mmol, yield 62.7%) was obtained by separation of hexane:ethyl acetate (1:1).

[1281]

[1282] 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).

[1283] [Example 78] Synthesis of N-methyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methylamine hydrochloride (compound 74)

[1284] Compound (74) is synthesized from compound (16) according to the synthesis method of compound (72-1) of compound (12).

[1285]

[1286] 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).

[1287] [Example 79] Synthesis of N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)morpholine-4-carboxamide (compound 76)

[1288] According to the synthesis method of compound (72) from compound (72-1), compound (76) is synthesized from compound (74).

[1289]

[1290] 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).

[1291] [Example 80] Synthesis of 2-methoxy-N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 78)

[1292] According to the synthesis method of compound (72) from compound (72-1), compound (78) is synthesized from compound (74).

[1293]

[1294] 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, sx2), 8.45 (1H, d, J=8.7Hz), 8.52 (1H, d, J=6.9Hz).

[1295] [Example 81] Synthesis of 1,1-dimethyl-3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)urea (compound 59)

[1296] According to the synthesis method of compound (72) of compound (72-1), compound (59) is synthesized from compound (1).

[1297]

[1298] 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).

[1299] [Examples 82 to 85] Synthesis of the following compounds:

[1300] 1,1-Dimethyl-3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)urea (compound 75),

[1301] 2-Methoxy-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 77),

[1302] N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)cyclobutanesulfonamide (compound 82) and

[1303] N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)oxetane-3-carboxamide (compound 85)

[1304] According to the synthesis method of compound (72) from compound (72-1), compounds (75), (77), (82) and (85) are synthesized from compound (72-1).

[1305]

[1306] 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).

[1307]

[1308] 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).

[1309]

[1310] 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).

[1311]

[1312] 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).

[1313] [Example 86] Synthesis of 2-amino-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide hydrochloride (compound 64)

[1314]

[1315] (1) Synthesis of tributyl 2-((4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)amino)ethyl)carbamate (compound 64-1)

[1316] In anhydrous dichloromethane solution (50 mL), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-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. Under ice-cold conditions, excess triethylamine (1.00 mL) was slowly added. The mixture was slowly warmed to room temperature and stirred for 16 hours. Under ice-cold conditions, water was added to the reaction solution, and the dichloromethane layer was washed several times with water. The dichloromethane layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography and separated by hexane:ethyl acetate (1:1) to give the title compound (64-1) (170 mg, 0.379 mmol, yield 18.3%).

[1317] 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).

[1318] (2) Synthesis of 2-amino-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide hydrochloride (compound 64)

[1319] (2-S-oxy-2-((4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)amino)ethyl)carbamate tributyl ester (compound 64-1) (170 mg, 0.378 mmol)) was slowly added to a 4N dioxane hydrochloride solution (3.0 mL) under ice-cold conditions and stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the mixture was dried and solidified. Next, the solvent was added, the resulting solid was filtered, thoroughly washed with the solvent, and dried to obtain the title compound (64) (159 mg, 0.378 mmol, yield 99.8%).

[1320]

[1321] 1H-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).

[1322] [Example 87] Synthesis of N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)oxetane-3-carboxamide (compound 66)

[1323] According to the synthesis method of compound (64-1) of compound (1), compound (66) is synthesized from compound (1).

[1324]

[1325] 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).

[1326] [Examples 88 to 90] Synthesis of the following compounds:

[1327] 2-Amino-N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide hydrochloride (compound 65)

[1328] 2-amino-N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide hydrochloride (compound 81) and

[1329] 2-Amino-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide hydrochloride (compound 80)

[1330] According to the synthesis method of compound (64) from compound (1), compound (65) is synthesized from compound (10), compound (81) is synthesized from compound (74), and compound (80) is synthesized from compound (72-1).

[1331]

[1332] 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).

[1333]

[1334] 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).

[1335]

[1336] 1 H-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).

[1337] [Example 91] Synthesis of sodium 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)acetate (compound 5)

[1338]

[1339] (1) Synthesis of 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 5-1)

[1340] Pyrazolo[1,5-a]pyridine-3-thiocarboxamide (718 mg, 4.05 mmol) was dissolved in DME (40 mL). Under ice-cold conditions, 4-hydroxybenzoyl bromide (871 mg, 4.05 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was heated and stirred at 50 °C for 1 hour, then cooled. The solvent was removed by distillation under reduced pressure. Ethanol (40 mL) was added, followed by excess potassium carbonate (996 mg). The mixture was then refluxed at 70 °C for 1 hour. After cooling, the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography, followed by separation in a hexane:ethyl acetate (1:1) mixture to give the title compound (5-1) (1.03 g, 3.53 mmol, 88.2% yield).

[1341] 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).

[1342] (2) Synthesis of 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)benzyl acetate (compound 5-2)

[1343] Sodium hydride (oil dispersion) (154 mg) was carefully added to anhydrous DMF (10 mL) to form a suspension. After cooling to -15 °C, 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)phenol (compound 5-1) (153 mg, 0.522 mmol) was slowly added. Once heated to room temperature, the mixture was cooled to -15 °C, and excess benzyl bromoacetate (0.30 mL) was added dropwise. The mixture was slowly warmed to room temperature while stirring for 16 hours. Water (approximately 100 mL) was carefully and slowly added to the reaction mixture while it was ice-cold. The resulting solid was stirred briefly at room temperature, filtered, thoroughly washed with solvents such as n-hexane, and dried to obtain the title compound (5-2) (148 mg, 0.334 mmol, yield 64.2%).

[1344] 1H-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).

[1345] (3) Synthesis of 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)acetic acid (compound 5-3)

[1346] 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)benzyl acetate (compound 5-2) (139 mg, 0.315 mmol) was added to a mixed solvent of 4N sodium hydroxide aqueous solution (3 mL) and ethanol (3 mL). The reaction solution was heated and stirred at 100 °C for 1.5 hours. After cooling, the reaction solution was injected into ice water (100 mL) to dissolve. After filtering the insoluble matter, the title compound (5) (76.3 mg, 0.20 mmol, yield 64.9%) was obtained. Furthermore, 2N hydrochloric acid was added to the aqueous layer to make it weakly acidic. The precipitated solid was stirred for a short time and then filtered off. After thorough washing with water, it was dried to obtain the title compound (5-3) (19.0 mg, 0.0256 mmol, yield 8.1%).

[1347] 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).

[1348] (4) Synthesis of sodium 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)acetate (compound 5)

[1349] 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)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 until completely dissolved. The solution was filtered to remove trace amounts of insoluble matter, and the resulting pale yellow aqueous solution was freeze-dried to give the title compound (5) (592 mg, 1.50 mmol, 99.3% yield).

[1350]

[1351] 1 H-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).

[1352] [Example 92] Synthesis of N-acetyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)glycine (compound 73)

[1353]

[1354] (1) Synthesis of N-acetyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)glycine tributyl ester (compound 73-1)

[1355] In anhydrous DMF (4 mL), sodium hydride (oil dispersion) (48.3 mg) was carefully added to form a suspension. After cooling to -15 °C, N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 12) (106 mg, 0.305 mmol) was slowly added. Once the solution was heated to room temperature, it was cooled to -15 °C, and 0.10 mL of tributyl bromoacetate was added dropwise. The solution was slowly warmed to room temperature while stirring for 16 hours. The reaction mixture was kept ice-cold, and water was added carefully and slowly. Ethyl acetate was added to the reaction mixture, and the mixture was washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the insoluble matter was filtered off. The organic layer was then distilled off under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography. The title compound (73-1) (62.8 mg, 0.136 mmol, yield 64.2%) was obtained by separation of hexane and ethyl acetate (1:1). Additionally, the starting compound (12) (58.0 mg, 0.125 mmol, yield 55.0%) was recovered by further separation.

[1356] 1 H-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).

[1357] (2) Synthesis of N-acetyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)glycine (compound 73)

[1358]

[1359] N-acetyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)glycine tributyl ester (compound 73-1) (63.1 mg, 0.136 mmol) was added to a mixed solvent of 4N sodium hydroxide aqueous solution (1 mL) and ethanol (1 mL). The reaction solution was heated and stirred at 100 °C for 3 hours. After cooling, the reaction solution was injected into ice water (100 mL) for dissolution. The insoluble matter was filtered to obtain the sodium salt of the title compound (73) (27.4 mg, 0.20 mmol, yield 64.9%). Furthermore, 2N hydrochloric acid was added to the aqueous layer to make it weakly acidic. The precipitated solid was stirred for a short time, filtered, thoroughly washed with water, and dried to obtain the title compound (73) (27.4 mg, 0.067 mmol, yield 49.6%).

[1360] 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).

[1361] [Example 93] Synthesis of 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)acetamide (compound 26)

[1362]

[1363] In a solution of 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)phenol (compound 5-1) (0.10 g, 0.34 mmol) in N,N-dimethylformamide (2 mL), 2-iodoacetamide (0.10 g, 0.54 mmol) and potassium carbonate (0.60 g, 4.34 mmol) were added, and the mixture was stirred at room temperature for 2 hours. Water (10 mL) was added, and the precipitate was collected by suction filtration and dried to give the title compound (26) (24.0 mg, 0.07 mmol, 20.1%).

[1364]

[1365] 1H-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).

[1366] [Examples 94 to 99] Synthesis of the following compounds:

[1367] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl-2-(2-(2-methoxyethoxy)ethoxy)acetate (compound 13),

[1368] 4-(3-(2-methoxyethoxy)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 14),

[1369] 4-(3-(2-(2-methoxyethoxy)ethoxy)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 22),

[1370] 4-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 108),

[1371] 4-(1-Ethyl-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 110) and

[1372] 4-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (compound 111)

[1373] According to the synthesis method of compound (26), compounds (13), (14) and (22) are synthesized from compound (3), and compounds (108), (110) and (111) are synthesized from compound (107).

[1374]

[1375] 1H-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).

[1376]

[1377] 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).

[1378]

[1379] 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).

[1380]

[1381] 1H-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).

[1382]

[1383] 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).

[1384]

[1385] 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).

[1386] Synthesis of [Exercise 100] 2-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethoxy)ethane-1-amine hydrochloride (compound 32)

[1387]

[1388] Potassium carbonate (0.5 g) and N-[2-(2-bromoethoxy)ethyl]carbamate tributyl ester (0.2 mL, 0.78 mmol) were added to a DMF (1 mL) solution of 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)phenol (compound 5-1) (0.10 g, 0.27 mmol), and the mixture was stirred at room temperature for 2 hours. Saturated brine (5 mL) was added, and the resulting oily substance was separated by decantation. A solution of 4N dioxane hydrochloride (5 mL) was added, and the mixture was stirred at room temperature for 3 hours. Acetone (20 mL) was added, and the precipitate was filtered by suction. The precipitate was washed with diethyl ether and dried to give the title compound (32) (94.0 mg, 0.225 mmol, yield 87.2%).

[1389]

[1390] 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).

[1391] [Examples 101 and 102] Synthesis of 2-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)phenoxy)ethoxy)ethane-1-amine hydrochloride (compound 20) and N,N-dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)phenoxy)ethane-1-amine hydrochloride (compound 47)

[1392] According to the synthesis method of compound (32), compound (20) is synthesized from compound (3) and compound (47) is synthesized from compound (5-1).

[1393]

[1394] 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).

[1395]

[1396] 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).

[1397] [Example 103] Synthesis of 1-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethyl)guanidine hydrochloride (compound 52)

[1398]

[1399] (1) Synthesis of tributyl 2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethyl)carbamate (compound 52-1)

[1400] Potassium carbonate (0.5 g, 3.60 mmol) was added to a DMF (2 mL) solution of 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)phenol (compound 3) (0.38 g, 1.00 mmol), followed by the addition of 2-(tri-butoxycarbonylamino)ethyl bromide (0.30 g, 1.30 mmol). The mixture was stirred at 70 °C for 10 hours. The insoluble matter was filtered off, and water (50 mL) was added to the filtrate. The precipitate was collected and purified by preparative TLC (separative thin-layer chromatography) followed by separation in chloroform:methanol (98:2) to give the title compound (52-1) (0.33 g, 0.76 mmol, 76.0% yield).

[1401] 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).

[1402] (2) Synthesis of 2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethaneamine hydrochloride (compound 52-2)

[1403] (2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethyl)carbamate tributyl ester (compound 52-1) (0.33 g, 0.76 mmol)) was added to a solution of 4N dioxane hydrochloride (5 mL), and stirred at room temperature for 1 hour. Acetone (20 mL) was added, the precipitate was filtered off, dried, and the title compound (52-2) (308 mg, 0.76 mmol, quantitative) was obtained.

[1404] 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).

[1405] (3) Synthesis of 1,3-bis(tert-butoxycarbonyl)-2-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethylguanidine (compound 52-3)

[1406] In a solution of 2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethaneamine 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. The mixture was stirred at room temperature for 4 hours, and the solvent was removed by distillation under reduced pressure. Diethyl ether was added to the residue, and the insoluble matter was filtered off. The filtrate was concentrated under reduced pressure to give the title compound (52-3) (0.15 g, 0.26 mmol, 96.3% yield).

[1407] 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, J=8.0Hz), 7.56-7.64 (2H, m), 7.68-7.74 (1H, m), 8.09 (1H, s), 8.38-8.44 (1H, m), 8.57 (1H,t, J=5.6Hz), 8.64 (1H, s), 8.84-8.88 (1H, m), 11.51 (1H, s).

[1408] (4) Synthesis of 1-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethyl)guanidine hydrochloride (compound 52)

[1409] 1,3-bis(tert-butoxycarbonyl)-2-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethaneguanidine (compound 52-3) (0.15 g, 0.26 mmol) was added to a solution of 4N dioxane hydrochloride (5 mL) and stirred at room temperature for 12 hours. Acetone (10 mL) was added, the precipitate was filtered off, washed with diethyl ether, and dried to give the title compound (52) (85.0 mg, 0.20 mmol, yield 76.9%).

[1410]

[1411] 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).

[1412] [Example 104] Synthesis of 1-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethyl)guanidine hydrochloride (compound 51)

[1413] According to the synthesis method of compound (52), compound (51) is synthesized from compound (5-1).

[1414]

[1415] 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).

[1416] [Example 105] Synthesis of N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethyl)acetamide (compound 45)

[1417] According to the synthesis method of compound (52-2), compound (45) is synthesized from compound (5-1).

[1418]

[1419] 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).

[1420] [Example 106] Synthesis of N-(2-hydroxyethyl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)acetamide (compound 19)

[1421]

[1422] (1) Synthesis of 2-(3-(2-pyrazolo[1,5-a]pyridin-3-yl)-4-(thiazolyl-4-yl)phenoxyacetic acid benzyl ester (19-1)

[1423] 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-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, followed by benzyl bromoacetate (0.23 g, 1.0 mmol). The mixture was stirred at room temperature for 6 hours. Ice water (100 mL) was added, and the precipitate was filtered off. The precipitate was washed with methanol to give the title compound (19-1) (1.31 g, 2.96 g, 88% yield).

[1424] 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).

[1425] (2) Synthesis of N-(2-hydroxyethyl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)acetamide (compound 19)

[1426] 2-(3-(2-pyrazolo[1,5-a]pyridin-3-yl)-4-(thiazo-4-yl)phenoxyacetic acid benzyl ester (compound 19-1) (28 mg, 0.063 mmol) was added to ethanolamine (1 mL) and stirred at room temperature for 12 hours. Water (10 mL) was added, and the precipitate was filtered by suction. The precipitate was washed in the order of water, methanol, and diethyl ether, and dried to give the title compound (19) (28 mg, 0.053 mmol, yield 84.1%).

[1427]

[1428] 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).

[1429] [Example 107] Synthesis of methyl 2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)acetate (compound 18)

[1430] According to the synthesis method of compound (19), compound (3) is synthesized into compound (18).

[1431]

[1432] 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).

[1433] [Example 108] Synthesis of methyl 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)acetate (compound 25)

[1434]

[1435] At room temperature, 20 mL of methanol and 1.0 g of piperazine (11.6 mmol) were added to 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)benzyl acetate (compound 5-2) (0.3 g, 0.68 mmol), and the mixture was stirred for 12 hours. The precipitate was filtered by suction, washed with methanol, and dried to give the title compound (25) (226.0 mg, 0.62 mmol, yield 91.1%).

[1436]

[1437] 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).

[1438] [Example 109] Synthesis of 1-(piperazin-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one (compound 31)

[1439]

[1440] Anhydrous piperazine (3.0 g, 34.8 mmol) was added to 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)benzyl acetate (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) was added, followed by saturated brine (5 mL). The mixture was extracted with chloroform and dried over anhydrous magnesium sulfate. After filtration, the solvent was removed by distillation under reduced pressure, and the mixture was dried to give the title compound (31) (0.23 g, 0.55 mmol, yield 80.9%).

[1441]

[1442] 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).

[1443] [Examples 110 and 111] Synthesis of 1-(1,4-diazacycloheptane-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)phenoxy)ethane-1-one hydrochloride (compound 55) and 1-(4-methyl-1,4-diazacycloheptane-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)phenoxy)ethane-1-one hydrochloride (compound 102)

[1444] According to the synthesis method of compound (31), compound (55) and compound (102) were synthesized from compound (5-2), respectively.

[1445]

[1446] 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).

[1447]

[1448] 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).

[1449] [Examples 112 to 114] Synthesis of the following compounds:

[1450] 1-(2-(hydroxymethyl)pyrrolidin-1-yl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one (compound 21),

[1451] 1-(piperazin-1-yl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one (compound 23) and

[1452] Synthesis of 1-(1,1-dioxo-4-thiomorpholinyl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one (compound 24)

[1453] According to the synthesis method of compound (31), compounds (21), (23) and (24) are synthesized from compound (19-1).

[1454]

[1455] 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).

[1456]

[1457] 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).

[1458]

[1459] 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).

[1460] [Example 115] Synthesis of (4-methylpiperazin-1-yl)(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazolyl)methyl ketone hydrochloride (compound 103)

[1461]

[1462] (1) Synthesis of ethyl 5-(2-pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazole-3-carboxylate (compound 103-1)

[1463] A solution of pyrazolo[1,5-a]pyridine-3-thiocarboxamide (0.50 g, 2.82 mmol) in acetone (15 mL) and ethyl 5-(2-bromoacetyl)isoxazole-3-carboxylate (0.74 g, 2.82 mmol) was stirred at room temperature for 4 hours. Water (40 mL) was added, the precipitate was filtered by suction, washed with methanol, and dried to give the title compound (103-1) (0.8 g, 1.87 mmol, yield 66%).

[1464] 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).

[1465] (2) Synthesis of (4-methylpiperazin-1-yl)(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazolyl-3-yl)methyl ketone hydrochloride (compound 103)

[1466] Ethyl 5-(2-pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazole-3-carboxylate (compound 103-1) (50 mg, 0.15 mmol) was reacted with a dichloromethane (1 mL) solution of 1-methylpiperazine (1 mL, 11.0 mmol) and stirred at room temperature for 16 hours. Water (10 mL) was added to the reaction solution, and some solvent was removed by distillation under reduced pressure. The precipitate was filtered and dried to obtain the crude compound. Four drops of 4N dioxane hydrochloride solution were added to a dioxane (2 mL) solution of the crude compound, and the precipitate was filtered to obtain the title compound (103) (14 mg, 0.032 mmol, yield 21.7%).

[1467]

[1468] 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).

[1469] [Example 116] Synthesis of piperazine-1-yl (5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazolyl-3-yl)methyl ketone hydrochloride (compound 104)

[1470] According to the synthesis method of compound (103), compound (104) is synthesized from compound (103-1).

[1471]

[1472] 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).

[1473] [Example 117] Synthesis of N-(4'-methyl-2-(pyrazolo[1,5-a]pyridin-3-yl)-[4,5'-bithiazolyl]-2'-yl)acetamide (compound 46)

[1474]

[1475] Potassium carbonate (0.1 g, 0.72 mmol) was added to a solution of pyrazolo[1,5-a]pyridine-3-thiocarboxamide (75 mg, 0.4 mmol) and 1-(2-amino-4-methylthiazo-5-yl)-2-bromoethane-1-one (100 mg, 0.4 mmol) in acetone (3 mL), and the mixture was stirred at room temperature for 12 hours. Water (20 mL) was added, and the precipitate was filtered by suction. The precipitate was washed with methanol and diethyl ether in that order and dried to obtain the crude compound. Anhydrous DMF (2 mL) was added to the crude compound, followed by acetic anhydride (1 mL, 10.6 mmol), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and water (20 mL) was added. The precipitate was filtered by suction and dried to obtain the title compound (46) (30.0 mg, 0.08 mmol, yield 53%).

[1476]

[1477] 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).

[1478] [Example 118] Synthesis of N,N-dimethyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzamide (compound 49)

[1479]

[1480] (1) Synthesis of ethyl 4-(bromoacetyl)benzoate (compound 49-1)

[1481] Ethyl 4-acetylbenzoate (5.10 g, 26.5 mmol) was added to 100 mL of ethyl acetate, followed by CuBr2 (12.5 g, 55.9 mmol), and the mixture was heated under reflux for 16 hours. After cooling, the insoluble matter was filtered through diatomaceous earth, and the organic solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography, followed by separation in a hexane:ethyl acetate (4:1) mixture to give the title compound (49-1) (7.11 g, 26.2 mmol, 98.9% yield).

[1482] 1H-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).

[1483] (2) Synthesis of ethyl 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzoate (compound 49-2)

[1484] Pyrazolo[1,5-a]pyridine-3-thiocarboxamide (711 mg, 4.01 mmol) was dissolved in DME (40 mL). Under ice-cold conditions, ethyl 4-(bromoacetyl)benzoate compound (49-1) (1.08 g, 3.99 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was heated and stirred at 50 °C for 1 hour, then cooled. The solvent was removed by distillation under reduced pressure. Ethanol (40 mL) was added to the residue, followed by excess potassium carbonate (1.06 g). The reaction mixture was refluxed at 70 °C for 1 hour. After cooling, the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography, followed by separation in a hexane:ethyl acetate (1:1) mixture to give the title compound (49-2) (1.22 g, 3.50 mmol, 87.4% yield).

[1485] 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).

[1486] (3) Synthesis of 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzoic acid (compound 49-3)

[1487] Ethyl 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzoate (compound 49-2) (2.63 g, 7.51 mmol) was added to a mixed solvent of 4N sodium hydroxide aqueous solution (8 mL) and ethanol (4 mL). The reaction mixture was heated and stirred at 100 °C for 1 hour. After cooling, the reaction mixture was injected into ice water (100 mL), and 2N hydrochloric acid was added to make it weakly acidic. The precipitated solid was stirred for a short time and then filtered. After thorough washing with water, it was dried to obtain the title compound (49-3) (2.28 g, 7.08 mmol, yield 94.3%).

[1488] 1 H-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).

[1489] (4) Synthesis of N,N-dimethyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzamide (compound 49)

[1490] In anhydrous dichloromethane solution (10 mL), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-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. Under ice-cold conditions, excess TEA (0.20 mL) was slowly added. The mixture was slowly warmed to room temperature and stirred for 16 hours. Under ice-cold conditions, water was added to the reaction solution, and the dichloromethane layer was washed several times with water. The dichloromethane layer was dried with anhydrous magnesium sulfate, filtered, and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography and separated by hexane:ethyl acetate (1:1) to obtain the title compound (49) (44.8 mg, 0.129 mmol, yield 75.6%).

[1491]

[1492] 1H-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).

[1493] [Examples 119 and 120] Synthesis of sodium 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzoate (compound 6) and (3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)(2-oxa-6-azaspiro[3.3]heptane-6-yl)methyl ketone (compound 33)

[1494] Based on the synthesis method of compound (49), compounds (6) and (33) were synthesized.

[1495]

[1496] 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).

[1497]

[1498] 1H-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).

[1499] [Example 121] Synthesis of N,N-dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 87)

[1500]

[1501] (1) Synthesis of ethyl 4-(bromoacetyl)phenyl acetate (compound 87-1)

[1502] To ethyl acetate (100 mL), 4-acetylphenyl ethyl acetate (425 mg, 2.06 mmol) was added, followed by CuBr2 (967 mg, 4.33 mmol), and the mixture was heated under reflux for 11 hours. After cooling, the insoluble matter was filtered through diatomaceous earth, and the organic solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography, followed by separation of hexane:ethyl acetate (1:1) to obtain the title compound (87-1) (581 mg, 0.458 mmol, 99.0% yield).

[1503] 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).

[1504] (2) Synthesis of ethyl acetate 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetate (compound 87-2)

[1505] Pyrazolo[1,5-a]pyridine-3-thiocarboxamide (379 mg, 2.14 mmol) was dissolved in DME (20 mL). Under ice-cold conditions, ethyl 4-(bromoacetyl)phenyl acetate (compound 87-1) (621 mg, 2.18 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was heated and stirred at 50 °C for 1 hour, then cooled. The solvent was removed by distillation under reduced pressure. Ethanol (20 mL) was added, followed by excess potassium carbonate (503 mg). The mixture was then refluxed at 70 °C for 1 hour. After cooling, the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography, followed by separation in a hexane:ethyl acetate (1:1) mixture to give the title compound (87-2) (645 mg, 2.00 mmol, 92.5% yield).

[1506] 1 H-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).

[1507] (3) Synthesis of 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetic acid (compound 87-3)

[1508] Ethyl 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetate (compound 87-2) (566 mg, 1.56 mmol) was added to a mixed solvent of 4N sodium hydroxide aqueous solution (3 mL) and ethanol (6 mL). The reaction mixture was heated and stirred at 100 °C for 1 hour. After cooling, ice water (50 mL) was added to the reaction mixture, and 2N hydrochloric acid was added to make it weakly acidic. The precipitated solid was stirred for a short time, filtered, thoroughly washed with water, and dried to obtain the title compound (87-3) (489 mg, 1.46 mmol, yield 91.0%).

[1509] 1H-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).

[1510] (4) Synthesis of N,N-dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 87)

[1511] In anhydrous dichloromethane solution (10 mL), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-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. Under ice-cold conditions, excess triethylamine (0.20 mL) was slowly added. The mixture was slowly warmed to room temperature and stirred for 16 hours. Under ice-cold conditions, water was added to the reaction solution, and the dichloromethane layer was washed several times with water. The dichloromethane layer was dried with anhydrous magnesium sulfate, filtered, and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography and separated by hexane:ethyl acetate (1:1) to obtain the title compound (87) (27.8 mg, 0.0767 mmol, yield 55.6%).

[1512]

[1513] 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).

[1514] [Examples 122 to 128] Synthesis of the following compounds:

[1515] N-(cyclopropylmethyl)-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzylyl)azacyclobutane-3-carboxamide (compound 9),

[1516] (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)phenyl)(2-oxa-7-azaspiro[3.5]nonane-7-yl)methyl ketone (compound 40),

[1517] (1,4-oxazacycloheptane-4-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 41),

[1518] (4-(dimethylamino)piperidin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 48),

[1519] (4-Methylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 50),

[1520] (4-Ethylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 56) and

[1521] (3-Methylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 58)

[1522] According to the synthesis method of compound (49), compounds (9), (40), (41), (48), (50), (56) and (58) were synthesized from compound (49-3).

[1523]

[1524] 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).

[1525]

[1526] 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).

[1527]

[1528] 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).

[1529]

[1530] 1 H-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).

[1531]

[1532] 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).

[1533]

[1534] 1H-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).

[1535]

[1536] 1 H-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).

[1537] [Examples 129 to 131] Synthesis of the following compounds:

[1538] N,N-Dimethyl-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzamide (compound 61),

[1539] 4-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzylyl)piperazin-1-carboxaldehyde (compound 68) and

[1540] N-(2-(4-morpholinyl)ethyl)-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzamide (compound 30)

[1541] According to the synthesis method of compound (49) from compound (49-3), compounds (61), (68) and (30) are synthesized from compound (6).

[1542]

[1543] 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).

[1544]

[1545] 1 H-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).

[1546]

[1547] 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).

[1548] [Examples 132 to 134] Synthesis of the following compounds:

[1549] N-Methyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 88),

[1550] N-ethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 89) and

[1551] N-methoxy-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 91)

[1552] Based on the synthesis method of compound (87), compounds (88), (89) and (91) were synthesized from compound (87-3).

[1553]

[1554] 1 H-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).

[1555]

[1556] 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).

[1557]

[1558] 1H-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).

[1559] [Example 135] Synthesis of (2,5-diazabicyclo[2.2.1]heptane-2-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 43)

[1560]

[1561] (1) Synthesis of 5-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzylyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylic acid tributyl ester (compound 43-1)

[1562] In anhydrous dichloromethane solution (10 mL), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-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. Under ice-cold conditions, excess TEA (0.50 mL) was slowly added. The mixture was slowly warmed to room temperature and stirred for 16 hours. Water was added to the reaction solution under ice-cold conditions, and the dichloromethane layer was washed several times with water. The dichloromethane layer was dried with anhydrous magnesium sulfate, filtered, and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography and obtained by separation of hexane:ethyl acetate (1:1) to give the title compound (43-1) (37.2 mg, 0.0742 mmol, yield 43.6%).

[1563] 1H-NMR(CDCl3) δ:1.43+1.49 (9H, s 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).

[1564] (2) Synthesis of (2,5-diazabicyclo[2.2.1]heptane-2-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 43)

[1565] Under ice-cold conditions, 5-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzylyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylic acid tributyl ester (compound 43-1) (32.5 mg, 0.0648 mmol) was slowly added to a 4N dioxane hydrochloride solution (1.0 mL), and the mixture was stirred at room temperature for 2 hours. The solvent was removed by distillation under reduced pressure, and the solid was dried and cured. Next, the solvent was added, the solid was filtered off, thoroughly washed with the solvent, and dried to obtain the title compound (43) (28.1 mg, 0.281 mmol, yield 91.3%).

[1566]

[1567] 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).

[1568] [Examples 136 to 139] Synthesis of the following compounds:

[1569] N-(2-(piperazin-1-yl)ethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzamide hydrochloride (compound 11),

[1570] (3-aminopyrrolidin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 42)

[1571] N-methyl-N-(piperidin-4-yl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzamide hydrochloride (compound 44) ​​and

[1572] Piperazin-1-yl(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 57)

[1573] According to the synthesis method of compound (43), compounds (11), (42), (44) and (57) were synthesized from compounds (49-3).

[1574]

[1575] 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).

[1576]

[1577] 1H-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).

[1578]

[1579] 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).

[1580]

[1581] 1 H-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).

[1582] [Example 140] Synthesis of piperazine-1-yl (3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 63)

[1583] According to the synthesis method of compound (43), compound (63) is synthesized from compound (6).

[1584]

[1585] 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).

[1586] [Example 141] Synthesis of 1-(piperazin-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)ethane-1-one hydrochloride (compound 86)

[1587] According to the synthesis method of compound (43), compound (86) is synthesized from compound (87-3).

[1588]

[1589] 1 H-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).

[1590] [Example 142] Synthesis of N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzylyl)-1,2,3,4-tetrahydroisoquinoline-5-yl)acetamide (compound 60)

[1591]

[1592] Synthesis of (1) (5-amino-3,4-dihydroisoquinoline-2(1H)-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 60-1)

[1593] In anhydrous dichloromethane solution (10 mL), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)benzoic acid (compound 49-3) (53.5 mg, 0.166 mmol), 1,2,3,4-tetrahydroisoquinoline-5-amine (56.5 mg, 0.381 mmol), and EDC hydrochloride (153 mg, 0.800 mmol) were added. Under ice-cold conditions, excess triethylamine (0.20 mL) was slowly added. The mixture was slowly warmed to room temperature and stirred for 16 hours. Water was added to the reaction solution under ice-cold conditions, and the dichloromethane layer was washed several times with water. The dichloromethane layer was dried with anhydrous magnesium sulfate, filtered, and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography and obtained by separation of hexane:ethyl acetate (1:1) to give the title compound (60-1) (29.6 mg, 0.0924 mmol, yield 39.5%).

[1594] 1 H-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).

[1595] (2) Synthesis of N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzylyl)-1,2,3,4-tetrahydroisoquinoline-5-yl)acetamide (compound 60)

[1596] In an acetonitrile solution (10 mL), under water cooling, (5-amino-3,4-dihydroisoquinoline-2(1H)-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl) methyl ketone (compound 60-1) (35.2 mg, 0.0780 mmol), acetic anhydride (0.10 mL), excess TEA (0.20 mL), and a catalyst amount of DMAP (5.1 mg) were added, and the mixture was stirred at room temperature for 16 hours. The reaction solution was distilled off the solvent under reduced pressure, and the residue was purified by silica gel column chromatography. The final product was obtained by separation of hexane:ethyl acetate (1:1) to give the title compound (60) (26.5 mg, 0.537 mmol, yield 74.6%).

[1597]

[1598] 1 H-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).

[1599] [Example 143] Synthesis of 2-(hydroxymethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 8)

[1600]

[1601] (1) Synthesis of methyl 5-(2-bromoacetyl)-2-hydroxybenzoate (compound 8-1)

[1602] 50 mL of ethyl acetate was mixed with methyl 5-acetylsalicylate (1.01 g, 5.19 mmol) and CuBr2 (2.35 g, 10.5 mmol), and the mixture was heated under reflux for 3 hours. After cooling, the insoluble matter was filtered through diatomaceous earth, and the organic solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography, followed by separation in a hexane:ethyl acetate (1:4) mixture to give the title compound (8-1) (1.37 g, 4.98 mmol, 95.8% yield).

[1603] 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).

[1604] (2) Synthesis of methyl 2-hydroxy-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzoate (compound 8-2)

[1605] Pyrazolo[1,5-a]pyridine-3-thiocarboxamide (96.1 mg, 0.542 mmol) was dissolved in DME (20 mL). Methyl 5-(2-bromoacetyl)-2-hydroxybenzoate (compound 8-1) (146 mg, 0.534 mmol) was added under ice-cold conditions, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was heated and stirred at 50 °C for 1 hour, then cooled. The solvent was removed by distillation under reduced pressure. Ethanol (20 mL) was added, followed by excess potassium carbonate (246 mg). The reaction mixture was heated under reflux at 70 °C for 1 hour. After cooling, the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography, followed by separation in a hexane:ethyl acetate (1:1) mixture to give the title compound (8-2) (76.5 mg, 0.218 mmol, yield 40.2%).

[1606] 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).

[1607] (3) Synthesis of 2-(hydroxymethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 8)

[1608] In a dry diethyl ether (10 mL), excess LAH (138 mg) was carefully added to a solution, and the mixture was brought to -20 °C. Then, methyl 2-hydroxy-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzoate (compound 8-2) (98.4 mg, 0.28 mmol) was slowly added. The mixture was slowly warmed to room temperature and stirred for 16 hours. The reaction mixture was chilled, and a saturated aqueous solution of Na₂SO₄ was added. The insoluble residue was filtered off and washed with ethyl acetate. The organic layers were combined, dried over anhydrous magnesium sulfate, filtered, and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography, followed by separation in a hexane:ethyl acetate (1:4) to give the title compound (8) (6.5 mg, 0.0201 mmol, yield 7.2%).

[1609]

[1610] 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).

[1611] [Examples 144 and 145] Synthesis of (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methanol (compound 2) and 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)ethane-1-ol (compound 84)

[1612] According to the synthesis method of compound (8) from compound (8-2), compound (2) is synthesized from compound (49-2), and compound (84) is synthesized from compound (87-2).

[1613]

[1614] 1H-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).

[1615]

[1616] 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).

[1617] [Example 146] Synthesis of 4-(3-(2,5-dihydro-1H-pyrrolo-3-yl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (compound 17)

[1618]

[1619] (1) Synthesis of 3-iodobenzoyl bromide (compound 17-1)

[1620] Add 3-iodoacetophenone (5.17 g, 21.0 mmol) and CuBr2 (12.1 g, 58.4 mmol) to ethyl acetate (200 mL), and heat under reflux for 3 hours. After cooling, filter the insoluble matter through diatomaceous earth, distill off the organic solvent under reduced pressure, and purify the residue by silica gel column chromatography. The final product (3.69 g, 11.7 mmol, 54.1% yield) was obtained by separation of hexane and ethyl acetate (1:1).

[1621] 1H-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).

[1622] (2) Synthesis of 4-(3-iodophenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 17-2)

[1623] Pyrazolo[1,5-a]pyridine-3-thiocarboxamide (273 mg, 1.54 mmol) was dissolved in DME (15 mL). Under ice-cold conditions, 3-iodobenzoyl bromide (compound 17-1) (494 mg, 1.52 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was heated and stirred at 50 °C for 1 hour, then cooled. The solvent was removed by distillation under reduced pressure. Ethanol (15 mL) was added to the residue, followed by potassium carbonate (503 mg). The reaction mixture was heated under reflux at 70 °C for 1 hour. After cooling, the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography, followed by separation in a hexane:ethyl acetate (1:1) mixture to give the title compound (17-2) (355 mg, 0.880 mmol, yield 57.9%).

[1624] 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).

[1625] (3) Synthesis of 3-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)-2,5-dihydro-1H-pyrrole-1-carboxylic acid tributyl ester (compound 17-3)

[1626] 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-pyrrolo-3-yl-boronic acid pinacol ester (55.3 mg, 0.187 mmol), a catalyst amount of Pd(PPh3)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 heated to reflux for 1 hour. After cooling, the reaction solution was distilled off the solvent under reduced pressure, and the residue was purified by silica gel column chromatography. The solution was separated by hexane:ethyl acetate (1:1) to give the title compound (17-3) (21.2 mg, 0.0467 mmol, yield 25.5%).

[1627] 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).

[1628] (4) Synthesis of 4-(3-(2,5-dihydro-1H-pyrrolo-3-yl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (compound 17)

[1629] Under ice-cold conditions, 3-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)-2,5-dihydro-1H-pyrrole-1-carboxylic acid tributyl ester (compound 17-3) (16.7 mg, 0.0378 mmol) was slowly added to a 4N dioxane hydrochloride solution (1.0 mL), and the mixture was stirred at room temperature for 2 hours. The solvent was removed by distillation under reduced pressure, and the solid was dried and cured. The solvent was added back, the resulting solid was filtered off, washed with the solvent, and dried to give the title compound (17) (12.8 mg, 0.308 mmol, yield 81.5%).

[1630]

[1631] 1H-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).

[1632] [Example 147] Synthesis of 6-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)-2-oxa-6-azaspiro[3.3]heptane (compound 29)

[1633]

[1634] (1) Synthesis of 4-bromoacetylbenzaldehyde (compound 29-1)

[1635] Add 4-acetylbenzaldehyde (2.24 g, 15.1 mmol) and CuBr2 (6.89 g, 30.8 mmol) to 75 mL of ethyl acetate, and heat under reflux for 3 hours. After cooling, filter the insoluble matter through diatomaceous earth, distill off the organic solvent under reduced pressure, and purify the residue by silica gel column chromatography. The extract was then separated by hexane:ethyl acetate (4:1) to give the title compound (compound 29-1) (3.19 g, 14.1 mmol, yield 93.4%).

[1636] 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).

[1637] (2) Synthesis of 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzaldehyde (compound 29-2)

[1638] Pyrazolo[1,5-a]pyridine-3-thiocarboxamide (1.23 g, 6.96 mmol) was dissolved in DME (40 mL). Under ice-cold conditions, 4-bromoacetylbenzaldehyde (compound 29-1) (1.55 g, 6.83 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was heated and stirred at 50 °C for 1 hour, then cooled. The solvent was removed by distillation under reduced pressure. Ethanol (80 mL) was added to the residue, followed by excess potassium carbonate (1.25 g). The reaction mixture was heated under reflux at 70 °C for 1 hour. After cooling, the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography, followed by separation in a hexane:ethyl acetate (1:1) mixture to give the title compound (29-2) (638 mg, 2.09 mmol, yield 30.6%).

[1639] 1 H-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).

[1640] (3) Synthesis of 6-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)-2-oxa-6-azaspiro[3.3]heptane (compound 29)

[1641] 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-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 stirred at room temperature for 1 hour. Then, NaBH(OAc)3 (72.9 mg, 0.433 mmol) was added under ice-cold conditions, and the mixture was stirred for 16 hours after returning to room temperature. Water was added to the reaction mixture under ice-cold conditions, and the dichloromethane layer was washed several times with water. The mixture was dried with anhydrous magnesium sulfate, filtered, and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography and separated by hexane:ethyl acetate (1:1) to obtain the title compound (29) (25.2 mg, 0.0649 mmol, yield 36.0%).

[1642]

[1643] 1H-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).

[1644] [Examples 148 to 151] Synthesis of the following compounds:

[1645] N,N-Dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methylamine (compound 27),

[1646] 4-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 28),

[1647] N,N-Dimethyl-4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)morpholine-2-carboxamide (compound 38) and

[1648] N,2-Dimethyl-4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)morpholine-2-carboxamide (Compound 39)

[1649] Using compound (29-2), compounds (27), (28), (38) and (39) were synthesized according to the synthesis method of compound (29).

[1650]

[1651] 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).

[1652]

[1653] 1H-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).

[1654]

[1655] 1 H-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).

[1656]

[1657] 1H-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).

[1658] [Example 152] Synthesis of 1-(4-morpholinyl)-2-(4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)piperazin-1-yl)ethane-1,2-dione hydrochloride (compound 36)

[1659]

[1660] Add 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)benzaldehyde (compound 29-2) (58.1 mg, 0.190 mmol) and 1-(4-morpholino)-2-(piperazin-1-yl)ethane-1,2-dione (50.5 mg, 0.222 mmol) to dichloromethane (10 mL). Stir at room temperature for 1 hour, then add NaBH(OAc)3 (113 mg, 0.533 mmol) under ice-cold conditions. Return to room temperature and stir for 16 hours. Water was added to the reaction solution under ice-cold conditions, and the dichloromethane layer was washed several times with water. After drying with anhydrous magnesium sulfate, the solution was filtered and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography and obtained by separation of hexane:ethyl acetate (1:4) to give the title compound (36-1) (35.5 mg, 0.0687 mmol, yield 36.2%).

[1661] 1H-NMR(CDCl3) δ: 2.50 (4H, m), 3.43 (4H, m), 3.58 (2H, s), 3.70 (8H,m), 6.92 (1H, dt, J=1.4Hz, 8.5Hz), 7.36 (4H, m), 7.97 (2H, d, J=7.8Hz), 8.40(1H, s), 8.46 (1H, d, J=8.7Hz), 8.52 (1H, d, J=6.9Hz).

[1662] Next, the amine (compound 36-1) is prepared into the hydrochloride salt of the title compound (36) by conventional methods.

[1663]

[1664] 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).

[1665] [Examples 153 and 154] Synthesis of 4-(4-((2,5-diazabicyclo[2.2.1]heptane-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)thiazole-4-yl)benzyl)piperidine-4-amine hydrochloride (compound 35)

[1666] Based on the synthesis methods of compounds (29) and (1), compounds (34) and (35) were synthesized.

[1667]

[1668] 1H-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).

[1669]

[1670] 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).

[1671] [Example 155] Synthesis of 4-(isoindoline-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (compound 117)

[1672]

[1673] (1) Synthesis of 1,1'-(isoindoline-2,5-diyl)bis(ethane-1-one) (compound 117-1)

[1674] 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-cold conditions. The mixture was stirred at room temperature for 16 hours. The solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography. The solution was separated by hexane:ethyl acetate (1:4) to give the title compound (117-1) (366 mg, 1.80 mmol, yield 72.3%).

[1675] 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).

[1676] (2) Synthesis of 1-(2-acetylisoindololin-5-yl)-2-bromoethane-1-one (compound 117-2)

[1677] 1,1'-(isoindoline-2,5-diyl)bis(ethane-1-one) (compound 117-1) (194 mg, 0.952 mmol) was added to ethyl acetate (50 mL), followed by CuBr2 (522 mg, 2.34 mmol), and the mixture was heated under reflux for 6.5 hours. After cooling, the insoluble matter was filtered through diatomaceous earth, and the organic solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography, and the title compound (117-2) (106 mg, 0.375 mmol, 39.4% yield) was obtained by separation of hexane:ethyl acetate (1:4).

[1678] 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).

[1679] (3) Synthesis of 1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoindolin-2-yl)ethane-1-one (compound 117-3)

[1680] Pyrazolo[1,5-a]pyridine-3-thiocarboxamide (73.5 mg, 0.415 mmol) was dissolved in DME (10 mL). Under ice-cold conditions, 1-(2-acetylisoindolin-5-yl)-2-bromoethane-1-one (compound 117-2) (106 mg, 0.375 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was heated and stirred at 50 °C for 1 hour, then cooled, and the solvent was removed by distillation under reduced pressure. Ethanol (10 mL) was added to the residue, followed by excess potassium carbonate (141 mg). The reaction mixture was heated under reflux at 70 °C for 1 hour. After cooling, the solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography. Separation of n-hexane:ethyl acetate (1:4) yielded the title compound (117-3) (66.8 mg, 0.185 mmol, yield 44.7%).

[1681] 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).

[1682] (4) Synthesis of 4-(isoindoline-5-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole hydrochloride (compound 117)

[1683] 1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoindolin-2-yl)ethane-1-one (compound 117-3) (44.5 mg, 0.123 mmol) was suspended in 1.0 mL of 6 N hydrochloric acid and heated under reflux for 6 hours. After cooling, the solvent was removed by distillation under reduced pressure, and ethanol was added several times for drying and solidification. The resulting solid was dissolved in water (30 mL), and ethyl acetate (30 mL) was added. The mixture was separated. The aqueous layer was concentrated under reduced pressure, and ethanol was added several times for distillation under reduced pressure. After drying, the title compound (117) (30.1 mg, 0.0773 mmol, yield 62.8%) was obtained.

[1684]

[1685] 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).

[1686] [Example 156] Synthesis of N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenethyl)acetamide (compound 62)

[1687] Compound (62) was synthesized according to the synthesis methods of compounds (117-1), (69), and (118).

[1688]

[1689] 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).

[1690] [Example 157] Synthesis of 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)ethane-1-amine hydrochloride (compound 113)

[1691] Compound (113) was synthesized according to the synthesis method of compound (118).

[1692]

[1693] 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).

[1694] [Examples 158 and 159] Synthesis of N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)benzyl)acetamide (compound 67) and N-methyl-N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)benzyl)acetamide (compound 70)

[1695] According to the synthesis methods of compounds (117-1) and (118), compound (67) is synthesized, and according to the synthesis method of compound (69), compound (70) is synthesized from compound (67).

[1696]

[1697] 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).

[1698]

[1699] 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).

[1700] [Example 160] Synthesis of N,N-dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methylamine (compound 137)

[1701]

[1702] (1) Synthesis of 2-((4-bromopyridin-2-yl)methyl)isoindoline-1,3-dione (compound 137-1)

[1703] (4-Bromopyridin-2-yl)methylamine (2.0 g, 11 mmol) was dissolved in acetic acid (25 mL), and phthalic anhydride (2.3 g, 16 mmol) was added. The mixture was heated under reflux at 130 °C for 3 hours. After cooling, the acetic acid was removed by distillation under reduced pressure. The residue was then extracted with an aqueous potassium carbonate solution and dried over anhydrous magnesium sulfate. After filtration, the solvent was removed by distilla...

Claims

1. A compound of formula (I) or a pharmaceutically permissible derivative thereof, In the formula, R 1 To R 5 Each is independently hydrogen or C 1-3 Chain-like aliphatic hydrocarbons; R 6 A 5- to 10-membered aromatic hydrocarbon that is substituted, having a 5- to 10-membered heterocycle that is substituted, having 1 to 5 heteroatoms independently selected from nitrogen, oxygen and sulfur as ring-forming atoms, or any of the above, and a condensed ring having a 4- to 10-membered heterocyclic group that is substituted, having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur as ring-forming atoms.

2. The compound according to claim 1 or a pharmaceutically permissible derivative thereof, wherein, R 6 The 5- to 10-membered aromatic hydrocarbons, 5- to 10-membered heterocycles, and 4- to 10-membered heterocyclic groups that form condensation rings with them are each independently unsubstituted or may be substituted by substituents selected from the group consisting of: (1) Halogen, nitro, cyano, hydroxyl, difluoromethyl, trifluoromethyl, (2)-NR 31 2、-N(R 31 )(CH2) 1-5 NR 31 2、-N(R 31 )S(O)2R 32 、-N(R 31 )C(O)R 31 、-N(R 31 )C(O)(CH2) 0- 3NR 31 2、-N(R 31 )C(O)(CH2) 0-3 R 32 , (3)C 1-6 Alkyl group, -(CH2) 1-5 OR 31 -(CH2) 1-5 O(CH2) 1-5 OR 31 -(CH2) 1-5 R 32 -(CH2) 1-5 R 33 , (4)-(CH2) 1-5 NR 31 2、-(CH2) 1-5 N(R 31 )R 32 、-(CH2) 1-5 N(R 31 )(CH2) 0-5 R 38 、-(CH2) 1-5 N(R 31 )C(O)R 31 、-(CH2) 1-5 N(R 31 )C(O)(CH2) 1-5 OR 31 、-(CH2) 1-5 N(C(O)R 31 )(CH2) 1-5 C(O)OR 31 、-(CH2) 1-5 N(R 31 )C(O)(CH2) 0-5 NR 31 2、-(CH2) 1-5 N(R 31 )C(O)R 32 , (5)-(CH2) 1-5 N(R 31 )S(O)2R 33 , (6)-C(R 31 )2C(O)R 32 , (7)-C(R 31 )2C(O)NR 31 2、-C(R 31 )2C(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 )(CH2) 0-5 R 32 , (11)-OC(R 31 )2C(O)N(R 31 )(CH2) 1-5 OR 31 、-OC(R 31 )2C(O)OR 31 、-OC(R 31 )2C(O)NR 31 2、-OC(R 31 )2C(O)R 32 , (12)-O(CH2) 1-6 R 31 、-(O(CH2) 1-5 ) 1-5 (CH2) 0-3 NR 31 2、-(O(CH2) 1-5 ) 1-5 (CH2) 0-3 NR 31 C(O)R 31 、-(O(CH2) 1-5 ) 1-5 NR 31 C(NH)NR 31 2、-O((CH2) 1-5 O) 1-5 R 31 , (13)-OC(O)C(R 31 )2(O(CH2) 1-5 ) 1-5 OR 31 ,as well as (14) Depending on the circumstances, via C 1-3 Alkyl-substituted 5- or 6-membered heterocyclic groups containing nitrogen as a ring-forming atom R 31 Each is independently hydrogen or C 1-4 Chain aliphatic hydrocarbons, R 32 A condensation ring of a 4- to 10-membered heterocyclic group, having 1 to 3 heteroatoms selected from nitrogen, sulfur, and oxygen as ring constituent atoms, and a 5- or 6-membered monocyclic aromatic hydrocarbon, wherein the 4- to 10-membered heterocyclic group forming the aforementioned condensation ring is, depending on the C... 1-5 Substitution of chain aliphatic hydrocarbons, R 33 It is a 3- to 10-membered alicyclic hydrocarbon, or a 4- to 10-membered heterocyclic group having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur as ring-forming atoms. R 38 It is a cyano group, a hydroxyl group, or S(O)2R. 31 .

3. The compound according to claim 1 or a pharmaceutically permissible derivative thereof, wherein, R 6 Choose from the following groups: ， Among the various types, R 7 Each is independently hydrogen, halogen, nitro, cyano, hydroxyl, C 1-6 Alkyl, C 1-6 alkoxy or -NR 31 2, R 8 Each person independently chooses from the following groups: (1) Hydrogen, halogen, nitro, cyano, hydroxyl, (2)-NR 31 2; -N(R) 31 )S(O)2R 32-1 In the formula, R 32-1 Having a 4- to 10-membered heterocyclic group, with 1 to 3 heteroatoms selected from nitrogen and oxygen as ring constituent atoms, substituted as appropriate; -N(R 31 )C(O)R 31 ;-N(R 31 )C(O)(CH2) 0-3 NR 31 2; -N(R) 31 )C(O)(CH2) 0-3 R 32-2 In the formula, R 32-2 A 4- to 10-membered heterocyclic group having, as appropriate, substituted 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-forming atoms. (3)C 1-6 Alkyl group, -(CH2) 1-5 OR 31 -(CH2) 1-5 R 32-3 In the formula, R 32-3 A 4- to 10-membered heterocyclic group having, as appropriate, substituted 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-forming atoms. (4)-(CH2) 1-5 NR 31 2;-(CH2) 1-5 N(R 31 )R 32-4 In the formula, R 32-4 Substituted 3- to 10-membered alicyclic hydrocarbons or, as appropriate, substituted 4- to 10-membered heterocyclic groups having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-forming atoms; -(CH2) 1-5 N(R 31 )C(O)R 31 ;-(CH2) 1-5 N(R 31 )C(O)(CH2) 1-5 OR 31 ;-(CH2) 1-5 N(C(O)R 31 (CH2) 1-5 C(O)OR 31 ;-(CH2) 1-5 N(R 31 )C(O)(CH2) 0-5 NR 31 2;-(CH2) 1-5 N(R 31 )C(O)R 32-5 In the formula, R 32-5 Substituted 3- to 10-membered alicyclic hydrocarbons or substituted 4- to 10-membered heterocyclic groups having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-forming atoms, as appropriate. (5)-(CH2) 1-5 N(R 31 )S(O)2R 33-1 In the formula, R 33-1 It is a 3- to 10-membered cycloalkyl group. (6)-C(R 31 )2C(O)R 32-6 In the formula, R 32-6 A 4- to 10-membered heterocyclic group having, as appropriate, substituted 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-forming atoms. (7)-C(R 31 )2C(O)NR 31 2、-C(R 31 )2C(O)N(R 31 )OR 31 , (8)-C(O)R 32-7 In the formula, R 32-7 A condensation ring of a 4- to 10-membered heterocyclic group or the like, optionally substituted with 1 to 3 heteroatoms selected from nitrogen and oxygen as ring constituent atoms, and optionally substituted with a 5- or 6-membered monocyclic aromatic hydrocarbon. (9)-C(O)OR 31 , (10)-C(O)NR 31 2;-C(O)N(R) 31 (CH2) 0-5 R 32-8 In the formula, R 32-8 Substituted 3- to 10-membered alicyclic hydrocarbons or substituted 4- to 10-membered heterocyclic groups having 1 to 3 heteroatoms selected from nitrogen and oxygen as ring-forming atoms, as appropriate. (11)-OC(R 31 )2C(O)N(R 31 (CH2) 1-5 OR 31 ;-OC(R 31 )2C(O)OR 31 ;-OC(R 31 )2C(O)NR 31 2; -OC(R) 31 )2C(O)R 32-9 In the formula, R 32-9 A 4- to 10-membered heterocyclic group having, as appropriate, substituted 1 to 3 heteroatoms selected from nitrogen and sulfur as ring-forming atoms. (12)-O(CH2) 1-6 R 31 、-(O(CH2) 1-5 ) 1-5 (CH2) 0-3 NR 31 2、-(O(CH2) 1-5 ) 1-5 (CH2) 0-3 NR 31 C(O)R 31 、-(O(CH2) 1-5 ) 1-5 NR 31 C(NH)NR 31 2、-O((CH2) 1-5 O) 1-5 R 31 , (13)-OC(O)C(R 31 )2(O(CH2) 1-5 ) 1-5 OR 31 ,as well as (14) Depending on the circumstances, via C 1-3 Alkyl-substituted 5- or 6-membered nitrogen-containing heterocycles, R 9 R 10 R 11 and R 12 Each of the following groups is selected independently: hydrogen, halogen, cyano, hydroxyl, C 1-5 Alkyl, 3- to 6-membered cycloalkyl, C 1-5 Alkoxy, -N(R) 31 )C(O)R 31 -N(R) 31 )C(O)(CH2) 0-3 NR 31 2. -N(R) 31 (CH2) 1-5 NR 31 2. -(CH2) 1-5 OR 31 -(CH2) 1-5 O(CH2) 1-5 OR 31 -(CH2) 1-5 R 35 -(CH2) 1-5 N(R 31 )C(O)R 31 -(CH2) 1-5 C(O)NR 31 2. -C(R) 31 )2NR 31 2. -(CH2) 1-5 NR 31 2. -C(O)R 36 -C(O)OR 31 -C(O)NR 31 2. -NR 31 2. -C(H)2R 35 -C(H)R 35 2 and -CR 35 3, R 31 Each is independently hydrogen or C 1-4 Chain aliphatic hydrocarbons, R 35 Each is independently halogenated, cyano-based, or, depending on the case, C 1-5 Alkyl-substituted 3 to 10-membered alicyclic hydrocarbons or -OR 31 , R 36 Depending on the case, it has 1 to 3 heteroatoms, independently selected from nitrogen, oxygen, and sulfur, as ring-forming atoms, via C... 1-5 Alkyl-substituted 4- to 10-membered heterocyclic groups, R 13 Each independently is hydrogen, C 1-5 Alkyl group, -(CH2) 1-5 OR 31 -(CH2) 1-5 NR 31 2. -(CH2) 1-5 N(R 31 )C(O)R 31 -(CH2) 1-5 N(R 31 (CH2) 0-5 R 38 -C(O)R 31 -C(O)R 37 Or -(CH2) 1-5 R 37 , R 37 It is a 3- to 10-membered alicyclic hydrocarbon or a 3- to 10-membered heterocyclic group having 1 to 3 heteroatoms selected from nitrogen and oxygen. R 38 It is a cyano group, a hydroxyl group, or S(O)2R. 31 , The heterocycles in the structures shown in formulas (I-2), (I-3), and (I-27) to (I-32), and the benzene ring in the structure shown in (I-33), can each be independently subjected to C as appropriate. 1-5 Substitution of chain aliphatic hydrocarbons.

4. The compound according to claim 1 or a pharmaceutically permissible derivative thereof, wherein, R 6 Selected from the following: 。 5. A compound selected from the group consisting of: 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 3), 4-Phenyl-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 71), 2-Methoxy-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)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)thiazolyl)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)thiazolyl)-3,4-dihydroquinoline-2(1H)-one (compound 131), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)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)thiazolyl)-[1,3]dioxacyclopenteno[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)thiazolyl)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)thiazolyl)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)thiazolyl)aniline hydrochloride (compound 134), 2-Methoxy-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)aniline (compound 90), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 118), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzonitrile (compound 115), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)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)thiazo-4-yl)phenol (compound 114), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)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)thiazolyl)isoxazolyl hydrobromide (compound 105), N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)oxetane-3-sulfonamide (compound 69), N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 16), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)morpholine-4-carboxamide (compound 72), N-Methyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methylamine hydrochloride (compound 74), N-Methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)morpholine-4-carboxamide (compound 76), 2-Methoxy-N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 78), 1,1-Dimethyl-3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)urea (compound 59), 1,1-Dimethyl-3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)urea (compound 75), 2-Methoxy-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 77), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)cyclobutanesulfonamide (compound 82), N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)oxetane-3-carboxamide (compound 85), 2-Amino-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide hydrochloride (compound 64) N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)oxetane-3-carboxamide (compound 66), 2-Amino-N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide hydrochloride (compound 65) 2-Amino-N-methyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide hydrochloride (compound 81) 2-Amino-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide hydrochloride (compound 80) 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)sodium acetate (compound 5), N-acetyl-N-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)glycine (compound 73), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)acetamide (compound 26), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)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)thiazolyl)phenoxy)ethoxy)ethane-1-amine hydrochloride (compound 32), 2-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethoxy)ethane-1-amine hydrochloride (compound 20), N,N-Dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-amine hydrochloride (compound 47) 1-(2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethyl)guanidine hydrochloride (compound 52), 1-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethyl)guanidine hydrochloride (compound 51), N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethyl)acetamide (compound 45), N-(2-hydroxyethyl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)acetamide (compound 19), 2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)methyl acetate (compound 18), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)methyl acetate (compound 25), 1-(piperazin-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one (compound 31), 1-(1,4-diazacycloheptane-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one hydrochloride (compound 55) 1-(4-methyl-1,4-diazacycloheptane-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one hydrochloride (compound 102) 1-(2-(hydroxymethyl)pyrrolidin-1-yl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one (compound 21), 1-(piperazin-1-yl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one (compound 23), 1-(1,1-dioxo-4-thiomorpholinyl)-2-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenoxy)ethane-1-one (compound 24), (4-Methylpiperazin-1-yl)(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazolyl-3-yl)methyl ketone hydrochloride (compound 103), Piperazin-1-yl(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazolyl-3-yl)methyl ketone hydrochloride (compound 104), N-(4'-methyl-2-(pyrazolo[1,5-a]pyridin-3-yl)-[4,5'-bithiazolyl]-2'-yl)acetamide (compound 46), N,N-Dimethyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzamide (compound 49), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)sodium benzoate (compound 6), (3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)(2-oxa-6-azaspiro[3.3]heptane-6-yl)methyl ketone (compound 33), N,N-Dimethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 87), N-(cyclopropylmethyl)-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzylyl)azacyclobutane-3-carboxamide (compound 9), (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)phenyl)(2-oxa-7-azaspiro[3.5]nonane-7-yl)methyl ketone (compound 40), (1,4-oxazacycloheptane-4-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 41), (4-(dimethylamino)piperidin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 48), (4-Methylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 50), (4-Ethylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 56), (3-Methylpiperazin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone (compound 58), N,N-Dimethyl-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzamide (compound 61), 4-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzylyl)piperazin-1-carboxaldehyde (compound 68), N-(2-(4-morpholinyl)ethyl)-3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzamide (compound 30), N-Methyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 88), N-Ethyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 89), N-methoxy-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)acetamide (compound 91), (2,5-diazabicyclo[2.2.1]heptane-2-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 43), N-(2-(piperazin-1-yl)ethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzamide hydrochloride (compound 11), (3-aminopyrrolidin-1-yl)(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 42) N-Methyl-N-(piperidin-4-yl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzamide hydrochloride (compound 44), Piperazine-1-yl(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 57), Piperazine-1-yl(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methyl ketone hydrochloride (compound 63), 1-(piperazin-1-yl)-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)ethane-1-one hydrochloride (compound 86) N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzylyl)-1,2,3,4-tetrahydroisoquinoline-5-yl)acetamide (compound 60), 2-(hydroxymethyl)-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenol (compound 8), (4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methanol (compound 2), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)ethane-1-ol (compound 84), 4-(3-(2,5-dihydro-1H-pyrrolo-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)thiazolyl)benzyl)-2-oxa-6-azaspiro[3.3]heptane (compound 29), N,N-Dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)methylamine (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)thiazolyl)benzyl)morpholine-2-carboxamide (compound 38), N,2-Dimethyl-4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)morpholine-2-carboxamide (compound 39), 1-(4-morpholino)-2-(4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl-4-yl)benzyl)piperazin-1-yl)ethane-1,2-dione hydrochloride (compound 36) 4-(4-((2,5-diazabicyclo[2.2.1]heptane-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)thiazolyl)benzyl)piperidine-4-amine hydrochloride (compound 35) 4-(isoindoline-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)thiazolyl)phenethyl)acetamide (compound 62), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)phenyl)ethane-1-amine hydrochloride (compound 113), N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 67), N-Methyl-N-(3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)benzyl)acetamide (compound 70), N,N-Dimethyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methylamine (compound 137), N,N-Dimethyl-1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methylamine (compound 128), N-Methyl-1-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methylamine (compound 136), N-((5-(2-(pyrazolo[1, 5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methyl)acetamide (compound 129), N-Methyl-1-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)pyridin-2-yl)methylamine (compound 130), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrolo-3-yl)thiazole (compound 138), 2-(pyrazolo[1,5-a]pyridin-3-yl)-4-(1H-pyrrolo-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)thiazo-4-yl)isothiazolium (compound 146), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)isothiazolyl (compound 147), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-4-yl)isothiazolium (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)thiazolyl)isoxazole (compound 154), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazole (compound 155), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)isoxazole (compound 156), 4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)oxazole (compound 157), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)oxazole (compound 158), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)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-pyrrolo-3-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 161), 3-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1,2,4-thiadiazole (compound 162), 4-(1-Methyl-1H-pyrrolo-2-yl)-2-(pyrazolo[1,5-a]pyridin-3-yl)thiazole (compound 163), 3-Bromo-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazo-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-pyrrolo-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)thiazolyl)thiophene-3-carboxamide (compound 171), 2-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)thiophen-2-yl)acetamide (compound 172), N,N-Dimethyl-5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)thiophene-3-carboxamide (compound 173), N-(2-(5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)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)thiazolyl)thiophene-3-ol (compound 175), 1-Methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-3-carboxylonitrile (compound 176), N-Methyl-2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-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)thiazolyl)-1H-pyrazol-5-amine (compound 181), 4-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-1-yl)butan-1-ol (compound 180), 4-(1-(azacyclobutane-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)thiazolyl)-1H-pyrazol-1-yl)ethyl)amino)acetonitrile (compound 183), 3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-1-yl)propane-1-amine (compound 184), N-(3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-1-yl)propyl)methanesulfonamide (compound 185), 5-Methyl-4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-pyrazol-3-ol (compound 186), N 1 , N 1 -dimethyl-N 2 -(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bisthiazolyl]-2-yl)ethane-1,2-diamine (compound 187) 2-(dimethylamino)-N-(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazolyl]-2-yl)acetamide (compound 188), 2-amino-N-(2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bithiazolyl]-2-yl)acetamide hydrochloride (compound 189) 2'-(pyrazolo[1,5-a]pyridin-3-yl)-[4,4'-bisthiazolyl]-2-ol (compound 190), 5-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)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)thiazolyl)-1H-imidazolyl-4-yl)methanol (compound 193), (1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazolyl-4-yl)methylamine hydrochloride (compound 194) 3-((1-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazol-4-yl)methoxy)propane-1-ol (compound 195), 3-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazol-1-yl)propane-1-ol (compound 196), 2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazol-1-yl)ethane-1-amine (compound 197), N-(2-(4-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-1H-imidazolyl-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)thiazolyl)-5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazine (compound 203), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-4,5,6,7-tetrahydrothiazo[5,4-c]pyridine (compound 204), 2-(2-(pyrazolo[1,5-a]pyridin-3-yl)thiazolyl)-4,5,6,7-tetrahydrothiazo[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)thiazolyl)pyridin-2-yl)methyl)acetamide (compound 213).

6. A composition comprising the compound or a pharmaceutically permissible derivative thereof according to any one of claims 1 to 5, and a pharmaceutically permissible carrier.

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

8. The pharmaceutical composition according to claim 7, which is used to inhibit the activity of myosin light chain kinase 4 (MYLK4).

9. The pharmaceutical composition of claim 7, for alleviating or treating myosin light chain kinase 4 (MYLK4) related disorders, impairments, or symptoms.

10. The pharmaceutical composition according to claim 9, wherein, The aforementioned myosin light chain kinase 4 (MYLK4) related disorders, impairments, or symptoms include 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.

11. The pharmaceutical composition according to claim 7, used to alleviate or treat dry eye, uveitis, age-related macular degeneration, or diabetic retinopathy.

12. The pharmaceutical composition according to claim 7, used to alleviate or treat glaucoma, ocular hypertension, or aqueous humor outflow obstruction.

Images