ES2368153T3 - NEW CYCLIC COMPOUND PRESENTING A 4-PIRIDILALQUILTIO GROUP THAT PRESENTS AMINO (NOT) REPLACED INTRODUCED IN THE SAME. - Google Patents

Abstract

Compound represented by the following general formula (1): (wherein ring A represents a benzene ring, or an aromatic five-membered heterocyclic ring or an aromatic six-membered heterocyclic ring that can be fused to a cycloalkane ring; R 1 and R2, which are the same or different, represent a hydrogen atom, a hydroxyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted alkyl group, a substituted cycloalkyl group or unsubstituted, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic ring, an amino group, a substituted or unsubstituted alkylamino group, a substituted or unsubstituted arylamino group or a substituted or unsubstituted acyl group; R 1 and R 2 can be linked together to form a substituted or unsubstituted heterocyclic ring; R 3 and R 4, which are the same or different, represent a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic ring, a hydrocarbonyl group, a substituted or unsubstituted alkylcarbonyl group, a substituted or unsubstituted arylcarbonyl group or ZR 5; R 3 and R 4 can be linked together to form a substituted or unsubstituted heterocyclic ring; Z represents CO, CS, COB 2 O, CSB 2 O, CONB 2 R 6, CSB 2 NR 6, CONB 2 R 6 SO2, CSB 2 NR 6 SO2 or SO2; R 5 represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted aryl group, a ring substituted or unsubstituted heterocyclic, a carboxyl group or an ester thereof or an amide thereof, a hydrocarbonyl group, a substituted or unsubstituted alkylcarbonyl group, a substituted or unsubstituted arylcarbonyl group or a substituted or unsubstituted heterocyclic carbonyl group; R 5 and R 6 can be linked together to form a substituted or unsubstituted heterocyclic ring; R 6 represents a hydrogen atom, a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group; X and Y, which are the same or different, represent one or more groups selected from a hydrogen atom, a halogen atom, a hydroxyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, a group substituted or unsubstituted alkyl, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted alkylamino group, a substituted or unsubstituted arylamino group, a mercapto group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a carboxyl group or an ester thereof or an amide thereof, a cyano group and a nitro group; B 1 represents an alkylene group; B 2 represents a single bond or an alkylene group; p represents 0, 1 or 2; and q represents 0 or 1), or a salt thereof.

Description

New cyclic compound presenting a 4-pyridyl alkylthio group having substituted amino (non) substituted therein.

Technical field

The present invention relates to a new cyclic compound having a 4-pyridyl alkylthio group having a substituted or unsubstituted amino group introduced therein or a salt thereof that is useful as a pharmaceutical product. Such a compound is useful as a therapeutic agent for a disease in which angiogenesis or vascular hyperpermeability is involved, particularly as a therapeutic agent for cancer, rheumatoid arthritis, age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal venous occlusion, polypoid choroidal angiopathy, diabetic macular edema, vulgar psoriasis, atherosclerosis or the like.

Prior art

Angiogenesis is a phenomenon in which a new vascular network is formed from an existing blood vessel and is mainly observed in a microvass. Angiogenesis is originally a physiological phenomenon and is essential for the formation of blood vessels in embryogenesis, but it is usually only observed in a limited place such as the endometrium or follicle or in a limited period such as a wound healing process in Adults. However, pathological angiogenesis is observed in a disease such as cancer, rheumatoid arthritis, age-related macular degeneration, diabetic retinopathy, prematurity retinopathy, retinal venous occlusion, polypoid choroidal angiopathy, diabetic macular degeneration, vulgar psoriasis and atherosclerosis, and It refers closely to the evolution of the patent of these diseases. Angiogenesis or vascular hyperpermeability is considered to be regulated by the balance between its promoter factor and its inhibitory factor, and angiogenesis or vascular hyperpermeability is caused by impaired equilibrium (Molecular Medicine vol. 35, special issue, “Molecular Mechanism of Symptoms and Pathologic conditions ”, Nakayama Shoten, 73-74 (1998), and Protein, Nucleic Acid, Enzyme, extra issue,“ The Most Advanced Development of New Drugs ”, Kyoritsu Shuppan, 1182-1187 (2000)).

A vascular endothelial growth factor (abbreviated hereinafter as "VEGF") is a factor that acts specifically on a receptor (Flt-1, KDR / Flk-1 or the like) present on the surface of vascular endothelial cells , thus on the proliferation and migration of vascular endothelial cells, the construction of a network of capillary vessels due to vasculogenesis. VEGF plays a very important role in the appearance of angiogenesis and vascular hyperpermeability. Therefore, many reports have been submitted on attempts to treat a disease in which angiogenesis or vascular hyperpermeability is involved by inhibiting VEGF to control angiogenesis and vascular hyperpermeability. Examples of drugs to be used for treatment include 2-indolinone derivatives (WO 98/50356), phthalazine derivatives (WO 98/35958), quinazoline derivatives (WO 97/30035), anthranilamide derivatives (WO 00/27819), derivatives of 2-aminonicotinic acid (WO 01/55114) and the like.

However, there is no description of cyclic compounds presenting a 4-pyridyl alkylthio group in these patent documents. Even less, there is no description of compounds having a substituted or unsubstituted amino group introduced into the pyridine ring of a 4-pyridyl alkylthio group.

On the other hand, II Farmaco-Ed. Sc., 18, 288 (1963) and WO 02/066470 reported compounds having chemical structures relatively close to those of cyclic compounds having a 4-pyridylalkylthio group having a substituted or unsubstituted amino group introduced therein. The compound disclosed in II Farmaco-Ed. Sc., 18, 288 (1963) is a benzoic acid amide derivative that has a 3-pyridyl alkylthio group, and an antibacterial action is cited as its use. WO 02/066470 refers to substituted alkylamine derivatives and their pharmaceutical use, and discloses compounds that have enormous combinations of chemical structures. WO 02/066470 just discloses a derivative that presents an 4-pyridyl alkylamino group as an example among those compounds, and does not describe at all a cyclic compound having a 4-pyridyl alkylthio group having an introduced substituted or unsubstituted amino group. in the same.

Description of the invention

It is a very interesting subject to study the synthesis of new cyclic compounds that have a 4-pyridyl-alkylthio group that has a substituted or unsubstituted amino group introduced therein and find a pharmacological action of the compounds.

The synthesis of new cyclic compounds that have a 4-pyridyl alkylthio group that has a substituted or unsubstituted amino group introduced therein and have been successful in the production of several new compounds has been studied.

In addition, the pharmacological actions of these compounds were extensively studied, and it was found that the compounds have an inhibitory effect of cell proliferation, an inhibitory effect of tumor growth, an inhibitory effect of leg edema and / or an inhibitory effect of choroidal neovascularization, and are useful as a therapeutic agent for a disease in which angiogenesis and / or vascular hyperpermeability is (n) involved, particularly as a therapeutic agent for cancer, rheumatoid arthritis, macular degeneration

10 related to age, diabetic retinopathy, retinopathy of prematurity, retinal venous occlusion, polypoid choroidal angiopathy, diabetic macular edema, vulgar psoriasis, atherosclerosis or the like, thus completing the present invention.

The present invention provides a new cyclic compound having a 4-pyridyl alkylthio group having

A substituted or unsubstituted amino group introduced therein or a salt thereof that is useful as a pharmaceutical product. The new cyclic compound according to the present invention has an excellent inhibitory effect on cell proliferation, an inhibitory effect on tumor growth, an inhibitory effect on leg edema and / or an inhibitory effect on choroidal neovascularization, and is useful as a therapeutic agent. for a disease in which angiogenesis and / or vascular hyperpermeability (s) are involved, for example, cancer, rheumatoid arthritis,

20 age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal venous occlusion, polypoid choroidal angiopathy, diabetic macular edema, vulgar psoriasis, atherosclerosis or the like.

The present invention relates to a compound represented by the general formula (1) or a salt thereof (hereinafter referred to as "the compound of the present invention" unless it is

25 specify otherwise) and a pharmaceutical composition containing the compound of the present invention. The compound of the present invention has a chemical structural characteristic in which a substituted or unsubstituted amino group has been introduced into the pyridine ring moiety of the 4-pyridyl alkylthio group.

To describe a pharmaceutical application of the compound of the present invention in greater detail, it is made

Reference to a therapeutic agent that contains the compound of the present invention as an active ingredient for a disease in which angiogenesis and / or vascular hyperpermeability is (s) involved, for example, refers to a therapeutic agent for cancer, rheumatoid arthritis, age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal venous occlusion, polypoid choroidal angiopathy, diabetic macular edema, vulgar psoriasis, atherosclerosis or the like.

(In the formula, ring A represents a benzene ring, or an aromatic five-membered heterocyclic ring or an aromatic six-membered heterocyclic ring that can be fused to a cycloalkane ring;

R1 and R2, which are the same or different, represent a hydrogen atom, a hydroxyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted alkyl group, a substituted cycloalkyl group or unsubstituted, a substituted or unsubstituted aryl group, a substituted heterocyclic ring

or unsubstituted, an amino group, a substituted or unsubstituted alkylamino group, a substituted or unsubstituted arylamino group, or a substituted or unsubstituted acyl group;

R1 and R2 can be linked together to form a substituted or unsubstituted heterocyclic ring;

R3 and R4, which are the same or different, represent a hydrogen atom, a substituted or unsubstituted alkyl group,

A substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic ring, a hydrocarbonyl group, a substituted or unsubstituted alkylcarbonyl group, a substituted or unsubstituted arylcarbonyl group, or Z-R5;

R3 and R4 can be linked together to form a substituted or unsubstituted heterocyclic ring; Z represents CO, CS, COB2O, CSB2O, CONB2R6, CSB2NR6, CONB2R6SO2, CSB2NR6SO2 or SO2;

R5 represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted aryl group, a heterocyclic ring substituted or unsubstituted, a carboxyl group or an ester thereof or an amide thereof, a hydrocarbonyl group, a substituted or unsubstituted alkylcarbonyl group, a substituted or unsubstituted arylcarbonyl group, or a substituted or unsubstituted heterocyclic carbonyl group;

R5 and R6 can be linked together to form a substituted or unsubstituted heterocyclic ring;

R6 represents a hydrogen atom, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted aryl group;

X and Y, which are the same or different, represent one or more groups selected from a hydrogen atom, a halogen atom, a hydroxyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, an alkyl group substituted or unsubstituted, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted alkylamino group, a substituted or unsubstituted arylamino group, a mercapto group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted arylthio group, a carboxyl group or an ester thereof or an amide thereof, a cyano group and a nitro group;

B1 represents an alkylene group;

B2 represents a single bond or an alkylene group;

p represents 0, 1 or 2; Y

q represents 0 or 1. The same definitions apply hereinafter.)

The respective atoms, rings or groups defined above are defined to present the following meanings throughout this specification.

The "cycloalkane ring" refers to a cycloalkane ring having 3 to 8 carbon atoms. Specific examples thereof include a cyclopropane ring, a cyclobutane ring, a cyclopentane ring, a cyclohexane ring, a cycloheptane ring, a cyclooctane ring and the like.

The "aromatic five-membered heterocyclic ring" refers to a monocyclic aromatic five-membered heterocyclic ring having one or more heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom in the ring. Specific examples thereof include a pyrrole ring, a pyrazole ring, an imidazole ring and a [1,2,3] triazole ring, each having a nitrogen atom in the ring; a furan ring, which has an oxygen atom in the ring; a thiophene ring, which has a sulfur atom in the ring; an oxazole ring and an isoxazole ring, each having a nitrogen atom and an oxygen atom in the ring; and a thiazole ring and an isothiazole ring, each having a nitrogen atom and a sulfur atom in the ring. A pyrazole ring, a furan ring or a thiophene ring is preferred, and a thiophene ring is particularly preferred.

The "aromatic five-membered heterocyclic ring fused with a cycloalkane ring" refers to a bicyclic ring in which an aromatic five-membered heterocyclic ring is condensed with a cycloalkane ring.

The "aromatic six-membered heterocyclic ring" refers to a monocyclic aromatic six-membered heterocyclic ring having one or more nitrogen atoms in the ring. Specific examples thereof include a pyridine ring, a pyridazine ring, a pyrimidine ring, a pyrazine ring, a [1,2,3] triazine ring, a [1,2,4] triazine ring and a ring of [1,2,3,4] tetrazine. A pyridine ring or a pyrazine ring is preferred, and a pyridine ring is particularly preferred.

The "aromatic six-membered heterocyclic ring fused with a cycloalkane ring" refers to a bicyclic ring in which an aromatic six-membered heterocyclic ring is condensed with a cycloalkane ring.

"Alkylene" refers to straight or branched chain alkylene having 1 to 8 carbon atoms. Specific examples thereof include methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, heptamethylene, octamethylene, methylmethylene, dimethylmethylene, propylene, 2-methyltrimethylene and the like.

"Alkoxy" refers to straight or branched chain alkoxy having 1 to 6 carbon atoms. Specific examples thereof include methoxy, ethoxy, n-propoxy, n-butoxy, n-pentoxyl, n-hexyloxy, isopropoxy, isobutoxy, sec-butoxy, tert-butoxy, isopentoxy and the like.

"Alkyl" refers to straight or branched chain alkyl having 1 to 6 carbon atoms. Specific examples thereof include methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl and the like.

"Cycloalkyl" refers to cycloalkyl having 3 to 8 carbon atoms. In addition, a saturated polycyclic hydrocarbon formed by the condensation of 2 or 3 cycloalkane rings is also included in the "cycloalkyl" of the present invention. Specific examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like. Specific examples of saturated polycyclic hydrocarbon include adamantyl and the like.

"Aryl" refers to a monocyclic aromatic hydrocarbon or a bicyclic or tricyclic fused polycyclic aromatic hydrocarbon having from 6 to 14 carbon atoms. In addition, a condensed polycyclic hydrocarbon formed by condensation thereof with a cycloalkane ring is also included in the "aryl" of the present invention. A specific example of the monocyclic aromatic hydrocarbon is phenyl, specific examples of the condensed polycyclic aromatic hydrocarbon include naphthyl, antryl, phenanthryl and the like, and specific examples of the condensed polycyclic hydrocarbon include indanyl, tetrahydronaphthyl, tetrahydroantranyl and the like.

The "aryloxy" refers to a monocyclic aromatic hydrocarburoxyl or condensed polycyclic aromatic hydrocarburoxyl having from 6 to 14 carbon atoms, or a condensed polycyclic hydrocarburoxyl formed by condensation thereof with a cycloalkane ring. A specific example of the monocyclic aromatic hydrocarburoxyl is phenoxy, specific examples of the condensed polycyclic aromatic hydrocarburoxyl include naphthyloxy, antriloxy, phenanthryloxy and the like, and specific examples of the condensed polycyclic hydrocarbonuroxy include indathyloxy, tetrahydronaphthyloxy, and similar tetrahydroanthranyl.

The "heterocyclic ring" refers to a saturated or unsaturated monocyclic heterocyclic ring, or bicyclic or tricyclic fused polycyclic heterocyclic ring having one or more heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom in the ring .

Specific examples of the saturated monocyclic heterocyclic ring include aziridine, azetidine, pyrrolidine, pyrazolidine, imidazolidine, triazolidine, piperidine, hexahydropyridazine, hexahydropyrimidine, piperazine, homopiperidine, homopiperazine and the like, each having a ring of nitrogen; oxirane, tetrahydrofuran, tetrahydropyran and the like, each having an oxygen atom in the ring; tetrahydrothiophene, tetrahydrothiopyran and the like, each having a sulfur atom in the ring; oxazolidine, isoxazolidine, morpholine and the like, each having a nitrogen atom and an oxygen atom in the ring; and thiazolidine, isothiazolidine, thiomorpholine and the like, each having a nitrogen atom and a sulfur atom in the ring.

In addition, a monocyclic saturated heterocyclic ring of this type can be condensed with a benzene ring or the like to form a heterocyclic ring condensed polycyclic such as dihydroindole, dihydroindazole, dihydrobenzimidazol, tetrahydroquinoline, tetrahydroisoquinoline, tetrahidrocinolina, tetrahidroftalazina, tetrahydroquinazoline, tetrahydroquinoxaline, dihydrobenzofuran, dihydroisobenzofuran, chromane, isochroman, dihydrobenzothiophene, dihydroisobenzothiophene, thiochroman, isothiochroman, dihydrobenzoxazole, dihydrobenzisoxazole, dihydrobenzoxazine, dihydrobenzothiazole, dihydrobenzoisothiazole, dihydrobenzothiazine, 4-carzothiazine, perozoazine, 4-carzothiazine, perhydrobenzothiazine, perhydrobenzothiazine, perhydrobenzothiazine, perhydrobenzothiazine, perhydrobenzothiazole.

Specific examples of the monocyclic unsaturated heterocyclic ring include dihydropyrrole, pyrrole, dihydropyrazole, pyrazole, dihydroimidazole, imidazole, dihidrotriazol, triazole, tetrahydropyridine, dihydropyridine, pyridine, tetrahydropyridazine, dihydropyridazine, pyridazine, tetrahydropyrimidine, dihydropyrimidine, pyrimidine, tetrahydropyrazine, dihydropyrazine, pyrazine and the like , each presenting a nitrogen atom in the ring; dihydrofuran, furan, dihydropyran, pyran and the like, each having an oxygen atom in the ring; dihydrothiophene, thiophene, dihydrothiopyran, thiopyran and the like, each having a sulfur atom in the ring; dihydrooxazole, oxazole, dihydroisoxazole, isoxazole, dihydrooxazine, oxazine and the like, each having a nitrogen atom and an oxygen atom in the ring; dihydrotiazole, thiazole, dihydroisothiazole, isothiazole, dihydrotiazine, thiazine and the like, each having a nitrogen atom and a sulfur atom in the ring.

In addition, an unsaturated monocyclic heterocyclic ring of this type can be condensed with a benzene ring or the like to form a condensed polycyclic heterocyclic ring such as indole, indazole, benzimidazole, benzotriazole, dihydroquinoline, quinoline, dihydroisoquinoline, isoquinoline, phenanthridine, dihydrocinoline, cinoline, dihydrophthalazine, phthalazine, dihydroquinazoline, quinazoline, dihydroquinoxaline, quinoxaline, benzofuran, isobenzofuran, chromene, isochromene, benzothiophene, isobenzothiophene, thiochromene, isotiocromeno, benzoxazole, benzisoxazole, benzoxazine, benzothiazole, benzisothiazole, benzothiazine, phenoxazine  -carbolina,

carbazole, phenanthridine, acridine, phenanthroline, phenazine, phenothiazine or phenoxazine.

"Alkylamino" refers to monoalkylamino having 1 to 6 carbon atoms or dialkylamino having 2 to 12 carbon atoms. Specific examples of monoalkylamino include methylamino, ethylamino, hexylamino and the like, and specific examples of dialkylamino include ethylmethylamino, dimethylamino, diethylamino, dihexylamino and the like.

The "arylamino" refers to monoarylamino having 6 to 20 carbon atoms or diarylamino having 12 to 28 carbon atoms. Specific examples of monoarylamino include phenylamino, naphthylamino, ethylphenylamino and the like, and specific examples of diarylamino include diphenylamino, diantrylamino and the like.

"Acyl" refers to hydrocarbonyl, alkylcarbonyl, cycloalkylcarbonyl, arylcarbonyl or heterocyclic carbonyl. Specific examples of hydrocarbonyl include formyl, specific examples of alkylcarbonyl include acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, monochloroacetyl, trifluoroacetyl and the like, specific examples of cycloalkylcarbonyl include cyclopentanecarbonyl, cyclohexane specific examples, and the like, arylcarbonyl include benzoyl, naphthoyl, toluoyl and the like, and specific examples of heterocyclic carbonyl include furoyl, tenoyl, picolinoyl, nicotinoyl, isonicotinoyl and the like.

"Alkenyl" refers to straight or branched chain alkenyl having from 2 to 8 carbon atoms. Specific examples thereof include vinyl, allyl, 1-propenyl, 3-butenyl, 3-pentenyl, 4-hexenyl, 5-heptenyl, 7octenyl, 1-methylvinyl and the like.

"Alkynyl" refers to straight or branched chain alkynyl having 2 to 8 carbon atoms. Specific examples thereof include ethynyl, 2-propynyl, 2-butynyl, 3-pentinyl, 4-hexinyl, 5-heptinyl, 7-octinyl, 2-methylbutyl and the like.

"Halogen" refers to a fluorine atom, chlorine atom, bromine atom or iodine atom.

"Carboxyl group ester" refers to an ester with an alkyl alcohol, an aryl alcohol or the like. Specific examples of alkyl alcohol include methanol, ethanol, propanol, butanol, benzyl alcohol, phenethyl alcohol and the like. Specific examples of aryl alcohol include phenol, naphthol, antrol, cresol, xylenol and the like.

"Carboxyl group amide" refers to an amide with alkylamine, cycloalkylamine, arylamine, heterocyclic amine or the like. Specific examples of alkylamine include methylamine, ethylamine, ethylmethylamine, dimethylamine, diethylamine, benzylamine and the like, specific examples of cycloalkylamine include cyclopentylamine, cyclohexylamine, cyclohexylmethylamine and the like, specific examples of arylamine include aniline, naphthylamine, diphenylamine, ethylphenylamine, anisphenylamine, anisphenylamine toluidine and the like, and specific examples of heterocyclic amine include benzofuranamine, quinolilamine and the like.

"Alkylcarbonyl" refers to straight or branched chain alkylcarbonyl having from 2 to 7 carbon atoms. Specific examples thereof include methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, n-butylcarbonyl, n-pentylcarbonyl, n-hexylcarbonyl, isopropylcarbonyl, isobutylcarbonyl, sec-butylcarbonyl, tert-butylcarbonyl, isopentylcarbonyl and the like.

"Arylcarbonyl" refers to monocyclic aromatic hydrocarboncarbonyl or condensed polycyclic aromatic hydrocarboncarbon having 7 to 15 carbon atoms, or condensed polycyclic hydrocarboncarbonyl formed by condensation thereof with a cycloalkane ring. A specific example of the monocyclic aromatic hydrocarboncarbonyl is phenylcarbonyl, specific examples of the condensed polycyclic aromatic hydrocarboncarbonyl include naphthylcarbonyl, antrylcarbonyl, phenanthrylcarbonyl, and the like, and specific examples of the condensed polycyclic hydrocarboncarbonyl, indanylcarbonyl, tetrahydronylcarbonyl, similar tetrahydronylcarbonyl, similar tetrahydronylcarbonylcarbonylcarbonyl, tetrahydronylcarbonyl, similar tetrahydronylcarbonylcarbonyl, tetrahydronylcarbonyl, similar tetrahydronylcarbonyl form.

The "heterocyclic carbonyl" refers to saturated or unsaturated monocyclic heterocyclic carbonyl, or bicyclic or tricyclic fused polycyclic heterocyclic carbonyl, each having one or more heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom in the ring.

"Alkylsulfonyl" refers to straight or branched chain alkylsulfonyl having 1 to 6 carbon atoms. Specific examples thereof include methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, n-butylsulfonyl, npentylsulfonyl, n-hexylsulfonyl, isopropylsulfonyl, isobutyl sulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, isopentylsulfonyl and the like.

"Arylsulfonyl" refers to monocyclic aromatic hydrocarbonsulfonyl or condensed polycyclic aromatic hydrocarbonsulfonyl having from 6 to 14 carbon atoms, or condensed polycyclic hydrocarbonsulfonyl formed by condensation thereof with a cycloalkane ring. A specific example of the monocyclic aromatic hydrocarbonsulfonyl is phenylsulfonyl, specific examples of the condensed polycyclic aromatic hydrocarbonsulfonyl include naphthylsulfonyl, antrylsulfonyl, phenanthrylsulfonyl and the like, and specific examples of the condensed polycyclic hydrocarbonsulfonyl and inronyl sulfonyl, tetrahydronulfyl, tetrahydronulfyl, tetrahydronulfyl, tetrahydronylsulfonyl, tetrahydronyl sulfonyl, tetrahydronylsulfonyl, tetrahydronylsulfonyl, tetrahydronylsulfonyl, tetrahydronylsulfonyl, tetrahydronylsulfonyl.

"Alkylthio" refers to straight or branched chain alkylthio having 1 to 6 carbon atoms. Specific examples thereof include methylthio, ethylthio, n-propylthio, n-butylthio, n-pentylthio, n-hexylthio, isopropylthio, isobutylthio, secbutylthio, tert-butylthio, isopentylthio and the like.

"Arylthio" refers to monocyclic aromatic hydrocarbon, or bicyclic or tricyclic condensed polycyclic aromatic hydrocarbon having from 6 to 14 carbon atoms. In addition, it refers to a bicyclic or tricyclic condensed polycyclic hydrocarbon formed by condensing it with a cycloalkane ring. A specific example of the monocyclic aromatic hydrocarbon is phenylthio, specific examples of the condensed polycyclic aromatic hydrocarbon include naphthylthio, antrylthio, phenanthrylthio and the like, and specific examples of the condensed polycyclic hydrocarbonoth include indanylthio, tetrahydronaphthylthio, tetrahydroantriltium and the like.

"Halogenoalkoxy" refers to an alkoxy group having one or more same or different halogen atoms as substituents.

"Hydroxyalkoxy" refers to an alkoxy group having one or more hydroxyl groups as substituents.

"Alkoxyalkoxy" refers to an alkoxy group having one or more same or different alkoxy groups as substituents.

"Aryloxyalkoxy" refers to an alkoxy group having one or more same or different aryloxy groups as substituents.

"Halogenoalkyl" refers to an alkyl group having one or more same or different halogen atoms as substituents.

"Hydroxyalkyl" refers to an alkyl group having one or more hydroxyl groups as substituents.

"Alkoxyalkyl" refers to an alkyl group having one or more same or different alkoxy groups as substituents.

"Aryloxyalkyl" refers to an alkyl group having one or several same or different aryloxy groups as substituents.

"Hydroxyaryl" refers to an aryl group having one or more hydroxyl groups as substituents.

"Alkoxyaryl" refers to an aryl group having one or more same or different alkoxy groups as substituents.

The "substituted alkoxy group" refers to an alkoxy group having one or more groups as substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, an alkoxy group substituted with an aryl group, an aryloxy group, a group cycloalkyl, an aryl group, an aryl group substituted with an alkoxy group, a heterocyclic group, an amino group, an alkylamino group, an arylamino group, a mercapto group, an alkylthio group, an arylthio group, a carboxyl group or an ester of the same or an amide thereof, a cyano group and a nitro group.

The "substituted aryloxy group" refers to an aryloxy group having one or more groups as substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, an aryloxy group, an alkyl group, a cycloalkyl group, an aryl group , a heterocyclic group, an amino group, an alkylamino group, an arylamino group, a mercapto group, an alkylthio group, an arylthio group, a carboxyl group or an ester thereof or an amide thereof, a formyl group, an alkylcarbonyl group , an arylcarbonyl group, a cyano group and a nitro group.

The "substituted alkyl group" refers to an alkyl group having one or more groups as substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, an aryloxy group, a cycloalkyl group, an alkenyl group, an aryl group , an aryl group substituted with a halogen atom, a heterocyclic group, an amino group, an alkylamino group, an arylamino group, a mercapto group, an alkylthio group, an arylthio group, a carboxyl group or an ester thereof or an amide thereof, a formyl group, an alkylcarbonyl group, an arylcarbonyl group, a cyano group and a nitro group.

The "substituted cycloalkyl group" refers to a cycloalkyl group having one or more groups as substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, an aryloxy group, an alkyl group, a cycloalkyl group, an aryl group , a heterocyclic group, an amino group, an alkylamino group, an arylamino group, a mercapto group, an alkylthio group, an arylthio group, a carboxyl group or an ester thereof or an amide thereof, a formyl group, an alkylcarbonyl group , an arylcarbonyl group, a cyano group and a nitro group.

The "substituted aryl group" refers to an aryl group having one or more groups as substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, an alkoxy group substituted with a halogen atom, an aryloxy group, a alkyl group, an alkyl group substituted with a halogen atom, a cycloalkyl group, an aryl group, a heterocyclic group, an amino group, an alkylamino group, an arylamino group, a mercapto group, an alkylthio group, an arylthio group, a carboxyl group or an ester thereof or an amide thereof, a formyl group, an alkylcarbonyl group, an arylcarbonyl group, a cyano group and a nitro group, or an aryl group having one or more carbonyl groups or thiocarbonyl groups in the ring .

The "substituted heterocyclic ring" refers to a heterocyclic ring having one or more groups as substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, an alkoxy group substituted with a halogen atom, an aryloxy group, a alkyl group, an alkyl group substituted with a halogen atom, a cycloalkyl group, an aryl group, a heterocyclic group, an amino group, an alkylamino group, an arylamino group, a mercapto group, an alkylthio group, an arylthio group, a carboxyl group or an ester thereof or an amide thereof, a formyl group, an alkylcarbonyl group, an arylcarbonyl group, a cyano group and a nitro group, or a heterocyclic ring having one or more carbonyl groups or thiocarbonyl groups in the ring .

The "substituted alkylamino group" refers to an alkylamino group having one or more alkyl groups as substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, an aryloxy group, a cycloalkyl group, an aryl group , a heterocyclic group, an amino group, an alkylamino group, an arylamino group, a mercapto group, an alkylthio group, an arylthio group, a carboxyl group or an ester thereof or an amide thereof, a formyl group, an alkylcarbonyl group , an arylcarbonyl group, a cyano group and a nitro group.

The "substituted arylamino group" refers to an arylamino group having one or more aryl groups as substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, an aryloxy group, an alkyl group, a cycloalkyl group , an aryl group, a heterocyclic group, an amino group, an alkylamino group, an arylamino group, a mercapto group, an alkylthio group, an arylthio group, a carboxyl group or an ester thereof or an amide thereof, a formyl group , an alkylcarbonyl group, an arylcarbonyl group, a cyano group and a nitro group, or an arylamino group having one or more carbonyl groups or thiocarbonyl groups in the ring.

The "substituted acyl group" refers to an acyl group having one or more groups as substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, an aryloxy group, a cycloalkyl group, an aryl group, a heterocyclic group , an amino group, an alkylamino group, an arylamino group, a mercapto group, an alkylthio group, an arylthio group, a carboxyl group or an ester thereof or an amide thereof, a formyl group, an alkylcarbonyl group, an arylcarbonyl group , a cyano group and a nitro group.

The "substituted alkenyl group" refers to an alkenyl group having one or more groups as substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, an aryloxy group, a cycloalkyl group, an aryl group, a heterocyclic group , an amino group, an alkylamino group, an arylamino group, a carboxyl group or an ester thereof or an amide thereof, a formyl group, an alkylcarbonyl group, an arylcarbonyl group, a cyano group and a nitro group.

The "substituted alkynyl group" refers to an alkynyl group having one or more groups as substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, an aryloxy group, a cycloalkyl group, an aryl group, a heterocyclic group , an amino group, an alkylamino group, an arylamino group, a carboxyl group or an ester thereof or an amide thereof, a formyl group, an alkylcarbonyl group, an arylcarbonyl group, a cyano group and a nitro group.

The "substituted alkylcarbonyl group" refers to an alkylcarbonyl group having one or more groups as substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, an aryloxy group, a cycloalkyl group, an alkenyl group, an aryl group , an aryl group substituted with a halogen atom, a heterocyclic group, an amino group, an alkylamino group, an arylamino group, a mercapto group, an alkylthio group, an arylthio group, a carboxyl group or an ester thereof or an amide thereof, a formyl group, an alkylcarbonyl group, an arylcarbonyl group, a cyano group and a nitro group.

The "substituted arylcarbonyl group" refers to an arylcarbonyl group having one or more groups as substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, an alkoxy group substituted with a halogen atom, an aryloxy group, a alkyl group, an alkyl group substituted with a halogen atom, a cycloalkyl group, an aryl group, a heterocyclic group, an amino group, an alkylamino group, an arylamino group, a mercapto group, an alkylthio group, an arylthio group, a carboxyl group or an ester thereof or an amide thereof, a formyl group, an alkylcarbonyl group, an arylcarbonyl group, a cyano group and a nitro group, or an arylcarbonyl group having one or more carbonyl groups or thiocarbonyl groups in the ring .

The "substituted heterocyclic carbonyl group" refers to a heterocyclic carbonyl group having one or more groups as substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, an alkoxy group substituted with a halogen atom, an aryloxy group , an alkyl group, an alkyl group substituted with a halogen atom, a cycloalkyl group, an aryl group, a heterocyclic group, an amino group, an alkylamino group, an arylamino group, a mercapto group, an alkylthio group, an arylthio group , a carboxyl group or an ester thereof or an amide thereof, a formyl group, an alkylcarbonyl group, an arylcarbonyl group, a cyano group and a nitro group, or a heterocyclic carbonyl group having one or more carbonyl groups or thiocarbonyl groups in the ring

The "substituted alkylthio group" refers to an alkylthio group having one or more groups as substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, an alkoxy group substituted with an aryl group, an aryloxy group, a group cycloalkyl, an aryl group, an aryl group substituted with an alkoxy group, a heterocyclic group, an amino group, an alkylamino group, an arylamino group, a carboxyl group or an ester thereof or an amide thereof, a formyl group, a alkylcarbonyl group, an arylcarbonyl group, a cyano group and a nitro group.

The "substituted arylthio group" refers to an arylthio group having one or more groups as substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, an aryloxy group, an alkyl group, a cycloalkyl group, an aryl group , a heterocyclic group, an amino group, an alkylamino group, an arylamino group, a carboxyl group or an ester thereof or an amide thereof, a formyl group, an alkylcarbonyl group, an arylcarbonyl group, a cyano group and a nitro group , or an arylthio group having one or more carbonyl groups or thiocarbonyl groups in the ring.

When the compound of the present invention has a free hydroxyl group, a free amino group, a free alkylamino group, a free arylamino group or a free mercapto group as a substituent, these substituents can be protected with a protective group. When the heterocyclic group has a free nitrogen atom, the nitrogen atom can also be protected with a protective group.

The "protecting group for the free hydroxyl group" refers to one widely used as a protecting group such as a substituted or unsubstituted alkyl group, or an unsubstituted alkenyl group such as a methyl group, a methoxymethyl group, a benzyl group, a 4-methoxyphenylmethyl group or an allyl group; a substituted heterocyclic group

or unsubstituted such as 3-bromotetrahydropyranyl group, a tetrahydropyranyl group or a tetrahydrofuranyl group; a substituted or unsubstituted alkylcarbonyl group or a substituted or unsubstituted arylcarbonyl group such as an acetyl group, a trifluoroacetyl group, a benzoyl group or a 4-chlorobenzoyl group; a substituted alkyloxycarbonyl group

or unsubstituted, an unsubstituted alkenyloxycarbonyl group, or a substituted or unsubstituted aryloxycarbonyl group such as a methoxycarbonyl group, an ethoxycarbonyl group, an isobutoxycarbonyl group, a tert-butoxycarbonyl group, a benzyloxycarbonyl group, a p-methoxybenzyloxycarbonyl group, -fluorenylmethoxycarbonyl, a vinyloxycarbonyl group, an aryloxycarbonyl group, a phenyloxycarbonyl group or a p-nitrophenyloxycarbonyl group; or a substituted silyl group such as a trimethylsilyl group, a triethylsilyl group, a triisopropylsilyl group, a tert-butyldimethylsilyl group or a tert-butyldiphenylsilyl group.

The "protecting group for the free amino group, the free alkylamino group, the free arylamino group, or the free nitrogen atom in the case where the heterocyclic group has a nitrogen atom in its ring" refers to one widely used as a protecting group such as an unsubstituted alkenyl group such as an allyl group; a hydrocarbonyl group such as a formyl group; a substituted or unsubstituted alkylcarbonyl group, a substituted or unsubstituted arylcarbonyl group, or an unsubstituted heterocyclic carbonyl group such as an acetyl group, a trichloroacetyl group, a trifluoroacetyl group, a benzoyl group, a 4-chlorobenzoyl group or a picolinoyl group ; a substituted or unsubstituted alkyloxycarbonyl group, or a substituted or unsubstituted aryloxycarbonyl group such as a methoxycarbonyl group, an isobutoxycarbonyl group, a tert-butoxycarbonyl group, a 2,2,2-trichloroethoxycarbonyl group, a benzyloxycarbonyl group, a diphenylmethoxycarbonyl group, a group phenoxycarbonyl or an m-nitrophenoxycarbonyl group; or a substituted or unsubstituted alkylsulfonyl group, or a substituted or unsubstituted arylsulfonyl group such as a methylsulfonyl group, a benzylsulfonyl group, a phenylsulfonyl group, 4-chlorophenylsulfonyl group, a tolylsulfonyl group or 2,4,6-trimethylphenylsulfonyl group.

The "protecting group for the free mercapto group" refers to one widely used as a protecting group such as a substituted or unsubstituted alkyl group, or an unsubstituted alkenyl group such as a methyl group, a methoxymethyl group, a benzyl group, a 4-methoxyphenylmethyl group or an allyl group; a substituted heterocyclic group

or unsubstituted such as 3-bromotetrahydropyranyl group, a tetrahydropyranyl group or a tetrahydrofuranyl group; a substituted or unsubstituted alkylcarbonyl group, or a substituted or unsubstituted arylcarbonyl group such as an acetyl group, a trifluoroacetyl group, a benzoyl group or a 4-chlorobenzoyl group; or a substituted or unsubstituted alkyloxycarbonyl group, an unsubstituted alkenyloxycarbonyl group, or a substituted or unsubstituted aryloxycarbonyl group such as a methoxycarbonyl group, an ethoxycarbonyl group, an isobutoxycarbonyl group, a tert-butoxycarbonyl group, a benzyloxycarbonyl group, a p-methoxycarbonyl group, a p-methoxycarbonyl group , 9-fluorenylmethoxycarbonyl group, a vinyloxycarbonyl group, an aryloxycarbonyl group, a phenyloxycarbonyl group or a p-nitrophenyloxycarbonyl group.

The "various groups" as used herein may be either the same or different, respectively.

In addition, in the "group" as used herein, the respective atoms and rings are also included.

The "salt" in the compound of the present invention is not particularly limited as long as it is a pharmaceutically acceptable salt, and examples thereof include salts with an inorganic acid such as hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, acid. sulfuric acid or phosphoric acid; salts with an organic acid such as acetic acid, fumaric acid, maleic acid, succinic acid, citric acid, tartaric acid, adipic acid, lactic acid, methanesulfonic acid, trifluoromethanesulfonic acid or p-toluenesulfonic acid; salts with an alkali metal such as lithium, sodium or potassium; salts with an alkaline earth metal such as calcium or magnesium; and quaternary salts with ammonia, methyl iodide and the like.

In the case where there are geometric isomers or optical isomers in the compound of the present invention, these isomers are also included within the scope of the present invention.

In addition, the compound of the present invention may be in the form of a hydrate or a solvate.

Furthermore, in the case where there is protonic tautomerism in the compound of the present invention, the tautomeric isomers thereof are also included within the scope of the present invention.

(a) Preferred examples of the compound of the present invention include compounds that satisfy the following definitions and salts thereof.

In the general formula (1),

(a1) ring A represents a benzene ring, a thiophene ring or a pyridine ring; I

(a2) R1 represents an alkyl group, a cycloalkyl group, an aryl group or a heterocyclic ring; I

(a3) in the case where R1 is an alkyl group, the alkyl group may have one or more substituents selected from an aryl group, a hydroxyaryl group and an alkoxyaryl group; I

(a4) in the case where R1 is an aryl group, the aryl group may have one or more substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, a halogenoalkoxy group, a hydrocarbonyloxy group, an alkylcarbonyloxy group , an arylcarbonyloxy group, an alkyl group, halogenoalkyl group and an aryl group; I

(a5) R2 represents a hydrogen atom, an alkyl group or an aryl group; I

(a6) in the case where R2 is an alkyl group, the alkyl group may have one or more substituents selected from a carboxyl group, an alkoxycarbonyl group and an aryloxycarbonyl group; I

(a7) R3 represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic ring or Z-R5; I

(a8) in the case where R3 is an alkyl group, the alkyl group may have one or more substituents selected from a hydroxyl group, an alkoxy group, an aryloxy group, an amino group, an alkylamino group and an arylamino group; I

(a9) in the case where R3 is a heterocyclic ring, the heterocyclic ring may have one or more cyano groups as substituents; I

(a10) R3 and R4 can be linked together to form a heterocyclic ring; I

(a11) in the case where R3 and R4 join together to form a heterocyclic ring, the heterocyclic ring may have one or more substituents selected from a hydroxyl group, an alkoxyl group, an aryloxy group, an alkyl group, a hydroxyalkyl group, an alkoxyalkyl group, an aryloxyalkyl group, an aryl group, an amino group, an alkylamino group, an arylamino group, a carboxyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, a hydrocarbonyl group, an alkylcarbonyl group, an arylcarbonyl group , an aminocarbonyl group, an alkylaminocarbonyl group and an arylaminocarbonyl group, in addition, the heterocyclic ring may have a carbonyl group in the ring; I

(a12) R4 represents a hydrogen atom, an alkyl group, an aryl group, a hydrocarbonyl group, an alkylcarbonyl group or an arylcarbonyl group; I

(a13) in the case where R4 is an alkylcarbonyl group, the alkylcarbonyl group may have one or more alkylcarbonyloxy groups as substituents; I

(a14) Z represents CO, CS, CO-B2-O, CS-B2-O, CO-B2-NR6, CS-B2-NR6, CO-B2-NR6SO2, CS-B2-NR6SO2 or SO2; I

(a15) R5 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group, a heterocyclic ring, a carboxyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, a hydrocarbonyl group, an alkylcarbonyl group, an arylcarbonyl group, a heterocyclic carbonyl group, an aminocarbonyl group, an alkylaminocarbonyl group, or an arylaminocarbonyl group; I

(a16) in the case where R5 is an alkyl group, the alkyl group may have one or more substituents selected from a halogen atom, a hydroxyl group, an alkoxyl group, a hydroxyalkoxy group, alkoxyalkoxy group, an aryloxyalkoxy group, a cycloalkyl group, an aryl group, a heterocyclic ring, a carboxyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, a hydrocarbonyl group, an alkylcarbonyl group, an arylcarbonyl group, an amino group, an alkylamino group, an arylamino group, a group alkoxycarbonylamino, an aryloxycarbonylamino group, a hydrocarbonylamino group, an alkylcarbonylamino group, an arylcarbonylamino group, a mercapto group, an alkylthio group, an arylthio group and a cyano group; I

(a17) in the case where R5 is an aryl group, the aryl group may have one or more halogen atoms as substituents; I

(a18) in the case where R5 is a heterocyclic ring, the heterocyclic ring may have one or more substituents selected from an alkyl group and an aryl group; I

(a19) in the case where R5 is an alkylcarbonyl group, the alkylcarbonyl group may have one or more substituents selected from a carboxyl group, a hydrocarbonyloxy group, an alkylcarbonyloxy group, an arylcarbonyloxy group, an amino group, an alkylamino group and an arylamino group; I

(a20) R5 and R6 can be linked together to form a heterocyclic ring; I

(a21) in the case where R5 and R6 join together to form a heterocyclic ring, the heterocyclic ring may have one or more substituents selected from a hydroxyl group, an alkoxyl group, an aryloxy group, an alkyl group, a hydroxyalkyl group, an alkoxyalkyl group, an aryloxyalkyl group, a carboxyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, a carbonyl group, a hydrocarbonyl group, an alkylcarbonyl group and an arylcarbonyl group, in addition, the heterocyclic ring may have a carbonyl group in the ring; I

(a22) R6 represents a hydrogen atom, an alkyl group or an aryl group; I

(a23) X and Y, which are the same or different, represent one or more groups selected from a hydrogen atom, a halogen atom and an alkyl group; I

(a24) B1 represents an alkylene group; I

(a25) B2 represents a single bond or an alkylene group; I

(a26) p represents 0, 1 or 2; I

(a27) q represents 0 or 1.

That is, preferred examples thereof include in the compounds represented by the general formula (1), compounds that satisfy one or a combination of two or more selected from the above (a1), (a2), (a3), ( a4), (a5), (a6), (a7), (a8), (a9), (a10), (a11), (a12), (a13), (a14), (a15), (a16) , (a17), (a18), (a19), (a20), (a21), (a22), (a23), (a24), (a25), (a26) and (a27) and salts thereof.

(b) The most preferred examples of the compound of the present invention include compounds that satisfy the following definitions and salts thereof.

In the general formula (1),

(b1) ring A represents a benzene ring, a thiophene ring or a pyridine ring; I

(b2) R1 represents an alkyl group, a cycloalkyl group, an aryl group or a heterocyclic ring; I

(b3) in the case where R1 is an alkyl group, the alkyl group may have one or more alkoxyaryl groups as substituents; I

(b4) in the case where R1 is an aryl group, the aryl group may have one or more substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, a halogenoalkoxy group, an alkylcarbonyloxy group, an alkyl group and a halogenoalkyl group; I

(b5) R2 represents a hydrogen atom or an alkyl group; I

(b6) in the case where R2 is an alkyl group, the alkyl group may have one or more substituents selected from a carboxyl group and an alkoxycarbonyl group; I

(b7) R3 represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic ring or Z-R5; I

(b8) in the case where R3 is an alkyl group, the alkyl group may have one or more substituents selected from a hydroxyl group and an alkylamino group; I

(b9) in the case where R3 is a heterocyclic ring, the heterocyclic ring may have one or more cyano groups as substituents; I

(b10) R3 and R4 can be linked together to form a heterocyclic ring; I

(b11) in the case where R3 and R4 join together to form a heterocyclic ring, the heterocyclic ring may have one or more substituents selected from a hydroxyl group, an alkyl group, a hydroxyalkyl group, an alkylamino group, a alkoxycarbonyl group, an alkylcarbonyl group and an alkylaminocarbonyl group, in addition, the heterocyclic ring may have a carbonyl group in the ring; I

(b12) R4 represents a hydrogen atom, an alkyl group or an alkylcarbonyl group; I

(b13) in the case where R4 is an alkylcarbonyl group, the alkylcarbonyl group may have one or more alkylcarbonyloxy groups as substituents; I

(b14) Z represents CO, CO-B2-O, CO-B2-NR6, CS-B2-NR6, CO-B2-NR6SO2 or SO2; I

(b15) R5 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group, a heterocyclic ring, an alkoxycarbonyl group, an alkylcarbonyl group, a heterocyclic carbonyl group or an alkylaminocarbonyl group ; I

(b16) in the case where R5 is an alkyl group, the alkyl group may have one or more substituents selected from a halogen atom, a hydroxyl group, an alkoxyl group, a hydroxyalkoxy group, an alkoxyalkoxy group, a cycloalkyl group , a heterocyclic ring, a carboxyl group, an alkoxycarbonyl group, an amino group, an alkylamino group, an alkoxycarbonylamino group, an alkylcarbonylamino group, an alkylthio group and a cyano group; I

(b17) in the case where R5 is an aryl group, the aryl group may have one or more halogen atoms as substituents; I

(b18) in the case where R5 is a heterocyclic ring, the heterocyclic ring may have one or more alkyl groups as substituents; I

(b19) in the case where R5 is an alkylcarbonyl group, the alkylcarbonyl group may have one or more substituents selected from a carboxyl group, an alkylcarbonyloxy group and an alkylamino group; I

(b20) R5 and R6 can be linked together to form a heterocyclic ring; I

(b21) in the case where R5 and R6 join together to form a heterocyclic ring, the heterocyclic ring may have one or more substituents selected from a hydroxyl group, an alkyl group, a hydroxyalkyl group, an alkoxycarbonyl group and a alkylcarbonyl group, moreover, the heterocyclic ring may have a carbonyl group in the ring; I

(b22) R6 represents a hydrogen atom or an alkyl group; I

(b23) X and Y represent a hydrogen atom; I

(b24) B1 represents an alkylene group; I

(b25) B2 represents a single bond or an alkylene group; and / or (b26) p represents 0 or 1; I

(b27) q represents 0.

That is, the most preferred examples thereof include in the compounds represented by the general formula (1), compounds that satisfy one or a combination of two or more selected from the above (b1), (b2), (b3) , (b4), (b5), (b6), (b7), (b8), (b9), (b10), (b11), (b12), (b13), (b14), (b15), ( b16), (b17), (b18), (b19), (b20), (b21), (b22), (b23), (b24), (b25), (b26) and (b27) and salts of the same.

(c) Additional more preferred examples of the compound of the present invention include compounds that They satisfy the following definitions and salts thereof. In the general formula (1), (c1) ring A represents a benzene ring, a thiophene ring or a pyridine ring; I

(c2) R1 represents an aryl group or a heterocyclic ring; and / or (c3) in the case where R1 is an aryl group, the aryl group may have one or more substituents selected from a halogen atom, a halogenoalkoxy group, an alkyl group and a halogenoalkyl group; I

(c4) R2 represents a hydrogen atom; I

(c5) R3 represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic ring or Z-R5; and / or (c6) in the case where R3 is an alkyl group, the alkyl group may have one or more alkylamino groups

as substituents; I

(c7) in the case where R3 is a heterocyclic ring, the heterocyclic ring may have one or more cyano groups as substituents; and / or (c8) R3 and R4 can be linked together to form a heterocyclic ring; and / or (c9) in the case where R3 and R4 join together to form a heterocyclic ring, the heterocyclic ring can

presenting one or more substituents selected from an alkyl group and an alkylcarbonyl group; and / or (c10) R4 represents a hydrogen atom or an alkyl group; and / or (c11) Z represents CO, CO-B2-O, CO-B2-NR6, CO-B2NR6SO2 or SO2; and / or (c12) R5 represents a hydrogen atom, an alkyl group, an aryl group, an alkylcarbonyl group or a group

alkylaminocarbonyl; and / or (c13) in the case where R5 is an alkyl group, the alkyl group may have one or more substituents

selected from a halogen atom, a hydroxyl group, a heterocyclic ring, an alkylamino group and an alkylcarbonylamino group; and / or (c14) in the case where R5 is an aryl group, the aryl group may have one or more halogen atoms

as substituents; I

(c15) in the case where R5 is an alkylcarbonyl group, the alkylcarbonyl group may have one or more carboxyl groups as substituents; and / or (c16) R5 and R6 can be linked together to form a heterocyclic ring; and / or (c17) in the case where R5 and R6 join together to form a heterocyclic ring, the heterocyclic ring can

present one or more hydroxyalkyl groups as substituents; and / or (c18) R6 represents a hydrogen atom or an alkyl group; and / or (c19) X and Y represent a hydrogen atom; and / or (c20) B1 represents an alkylene group; and / or (c21) B2 represents a single bond or an alkylene group; I

(c22) p represents 0; I

5 (c23) q represents 0.

That is, additional more preferred examples thereof include in compounds represented by the general formula (1), compounds that satisfy one or a combination of two or more selected from the above (c1), (c2), (c3) , (c4), (c5), (c6), (c7), (c8), (c9), (c10), (c11), (c12), (c13), (c14), (c15), ( c16), (c17), (c18),

10 (c19), (c20), (c21), (c22) and (c23), and salts thereof.

(d) Preferred examples of the compound of the present invention in terms of pharmacological activity include compounds that meet the definitions described in any one of the above (a) through (c) and in which in the general formula (1), the Ring A is a pyridine ring or a thiophene ring or salts thereof, and preferred

Particularly compounds in which ring A is a pyridine ring and salts thereof.

(e) The most preferred examples of the compound of the present invention in terms of pharmacological activity include compounds that meet the definitions described in any one of the above (a) to (d) and those in the general formula (1), a partial structure (C):

and a partial structure (D):

25 bind to adjacent carbon atoms in ring A, and salts thereof.

(f) Additional most preferred examples of the compound of the present invention in terms of activity

Pharmacological agents include compounds that meet the definition described in the previous one (d) and the definition described in the previous one (e) and in which the partial structure (C) or (D) is attached to the carbon atom located in position α with respect to a heteroatom in ring A and salts thereof.

(g) Particularly preferred examples of the compound of the present invention include compounds that

35 satisfy the definitions described in any one of the above (a) through (f) and also satisfy the definitions described below and salts thereof.

In the general formula (1),

40 (g1) R3 represents Z-R5; I

(g2) Z represents CO, CO-B2-O, CO-B2-NR6 or CO-B2-NR6SO2; I

(g3) R5 represents a hydrogen atom, an alkyl group, an aryl group, an alkylcarbonyl group or an alkylaminocarbonyl group; I

(g4) in the case where R5 is an alkyl group, the alkyl group may have one or more substituents selected from a halogen atom, a hydroxyl group, a heterocyclic ring, an alkylamino group and an alkylcarbonylamino group; I

50 (g5) in the case where R5 is an aryl group, the aryl group may have one or more halogen atoms as substituents; I

(g6) in the case where R5 is an alkylcarbonyl group, the alkylcarbonyl group may have one or more carboxyl groups as substituents; I

(g7) R5 and R6 can be linked together to form a heterocyclic ring; I

(g8) in the case where R5 and R6 join together to form a heterocyclic ring, the heterocyclic ring may have one or more hydroxyalkyl groups as substituents; I

(g9) R6 represents a hydrogen atom or an alkyl group; I

(g10) B2 represents a single bond or an alkylene group. That is, particularly preferred examples thereof include in compounds that meet the definitions described in any one of the above (a) to (f) and are represented by the general formula (1), compounds that satisfy one or a combination of two or more selected from the above (g1), (g2), (g3), (g4), (g5), (g6), (g7), (g8), (g9) and (g10), and salts of the same.

Specific preferred examples of the compound of the present invention are given below.

•

N- (3,5-Dimethylphenyl) -2- [2- (4-methylpiperazin-1-yl) pyridin-4-ylmethylthio] pyridin-3-carboxamide

•

2- (2-Cyclopropylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide

•

2- [2- (N- (2-Dimethylaminoethyl) -N-methylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide

•

N- (3,5-Dimethylphenyl) -2- (2-morpholinopyridin-4-ylmethylthio) pyridine-3-carboxamide

•

N- (3,5-Dimethylphenyl) -2- [2- (piperidin-1-yl) pyridin-4-ylmethylthio] pyridin-3-carboxamide

•

2- [2- (4-Acetylpiperazin-1-yl) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide

•

N- (Indan-5-yl) -2- (2-morpholinopyridin-4-ylmethylthio) pyridin-3-carboxamide

•

2- [2- (4-Acetylpiperazin-1-yl) pyridin-4-ylmethylthio] -N- (indan-5-yl) pyridin-3-carboxamide

•

N- (3,5-Dimethylphenyl) -2- (2-n-pentylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide

•

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide

•

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridine-3-carboxamide

•

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (indan-5-yl) pyridin-3-carboxamide

•

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) pyridine-3-carboxamide

•

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) pyridin-3-carboxamide

•

2- [2- (N-tert-Butoxycarbonyl-N-methylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide

•

2- [2- (5-Cyanothiazol-2-ylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridin-3-carboxamide

•

2- (2-Aminopyridin-9-ylmethylthio) -N- (indan-5-yl) pyridin-3-carboxamide

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (9-tert-butylphenyl) pyridin-3-carboxamide

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) pyridin-3-carboxamide

•

N- (3,5-Dimethylphenyl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide

•

N- (Indan-5-yl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide

•

2- (2-Methylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridin-3-carboxamide

•

2- (2-Aminopyridin-9-ylmethylthio) -N- (9-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) pyridin-3-carboxamide

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) benzamide

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) benzamide

•

3- (2-Aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) thiophene-2-carboxamide

•

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide • - (3,5-Dimethylphenyl) -2- (2-propionylaminopyridin-4-ylmethylthio) pyridin-3 -carboxamide

•

N- (3,5-Dimethylphenyl) -2- (2-trifluoroacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide

•

N- (3,5-Dimethylphenyl) -2- (2-isobutyrylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide

•

N- (3,5-Dimethylphenyl) -2- (2-pivaloylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide

•

N- (3,5-Dimethylphenyl) -2- (2-trifluoromethanesulfonylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide

•

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridin-3-carboxamide

•

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

2- [2- (N-Acetyl-N-methylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide

•

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) pyridin-3-carboxamide

•

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethyl-4-hydroxyphenyl) pyridine-3-carboxamide

•

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) benzamide

•

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (9-tert-butylphenyl) benzamide

•

3- (2-Acetylaminopyridin-9-ylmethylthio) -N- (3,5-dimethylphenyl) thiophene-2-carboxamide

•

3- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) thiophene-2-carboxamide

•

N- (3,5-Dimethylphenyl) -2- [2- (N’-n-propylureido) pyridin-4-ylmethylthio] -pyridin-3-carboxamide

•

2- [2- (N’-tert-Butylureido) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) -pyridin-3-carboxamide

•

2- [2- (N’-4-Chlorophenylureido) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide

•

N- (3,5-Dimethylphenyl) -2- (2-formylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide

•

N- (3,5-Dimethylphenyl) -2- (2-phenylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide

•

N- (3,5-Dimethylphenyl) -2- [2- (N’-methylureido) pyridin-4-ylmethylthio] pyridin-3-carboxamide

•

2- [2- (N’-Methylureido) pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide

•

N- (4-Chlorophenyl) -2- [2- (N’-methylureido) pyridin-4-ylmethylthio] pyridin-3-carboxamide

•

N- (4-Difluoromethoxyphenyl) -2- [2- (N’-methylureido) pyridin-4-ylmethylthio] pyridin-3-carboxamide

•

2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide

•

2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

2- (2-Aminoacetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide

•

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

N- (3,5-Dimethylphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide

•

N- (4-Chlorophenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide

•

N- (3,5-Dimethyl-9-hydroxyphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide

•

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (3-methylphenyl) pyridin-3-carboxamide

•

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethylphenyl) pyridine-3-carboxamide

•

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) pyridin-3-carboxamide

•

N- (3-Chlorophenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide

•

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (indan-5-yl) pyridin-3-carboxamide

•

N- (3-Chloro-4-trifluoromethoxyphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide

•

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridine-3-carboxamide

•

N- (4-Difluoromethoxyphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide

•

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (3-trifluoromethylphenyl) pyridine-3-carboxamide

•

2- [2- (3-Hydroxycarbonylpropionyloxy) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

N- (3,5-Dimethylphenyl) -2- (2-methanesulfonylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide

•

2- (2-Dimethylaminocarbonyloxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

2- (2-Isopropylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

2- (2-Dimethylaminoacetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethyl-phenyl) pyridin-3-carboxamide

•

2- (2-Dimethylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

2- (2-Morpholinoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

2- [2- (2-Morpholinoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

2- [2- (3-Hydroxypropyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

N- (4-Chlorophenyl) -2- [2- (2-dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide

•

2- (2-Aminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

2- [2- (N- (2-Dimethylaminoethyl) -N-methylamino) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3carboxamide

•

2- [2- (2-Hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (9-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

2- [2- (Piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

N- (9-Difluoromethoxyphenyl) -2- (2-dimethylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide

•

2- [2- (2-Acetylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

N- (4-Chlorophenyl) -2- [2- (piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] pyridin-3-carboxamide

•

2- [2- (2-Hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3-methylphenyl) pyridin-3-carboxamide

•

N- (4-Difluoromethoxyphenyl) -2- [2- (2-dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide

•

N- (4-Difluoromethoxyphenyl) -2- [2- (2-hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide

•

2- [2- (2-Acetylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-difluoromethoxyphenyl) pyridine-3-carboxamide

•

N- (9-Difluoromethoxyphenyl) -2- [2- (N- (2-dimethylaminoethyl) -N-methyl-amino) acetylaminopyridin-4-ylmethylthio] pyridine-3carboxamide

•

2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethylphenyl) pyridine-3-carboxamide

•

2- [2- (4- (2-Hydroxyethyl) piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

N- (4-Difluoromethoxyphenyl) -2- [2- (piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide

•

N- (4-Difluoromethoxyphenyl) -2- (2-isopropylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide

•

2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide

•

N- (3,5-Dimethylphenyl) -2- (2-isopropylaminoacetylaminopyridin-9-ylmethylthio) pyridine-3-carboxamide

•

N- (3,5-Dimethylphenyl) -2- [2- (3-hydroxypropyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide

•

N- (3,5-Dimethylphenyl) -2- [2- (2-morpholinoethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide

•

2- (2-Ethylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

2- (2-Aminoacetylaminopyridin-4-ylmethylthio) -N- (4-difluoromethoxyphenyl) pyridin-3-carboxamide

•

2- (3-Aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide

•

2- (3-Acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide

•

N- (3,5-Dimethylphenyl) -2- (2-morpholinoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide

•

2- [2- (3-Dimethylaminopropyl) aminoacetylamino] pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide

•

2- (2-Dimethylaminoacetylaminopyridin-4-ylmethylthio) -N- (3-methylphenyl) pyridin-3-carboxamide

•

2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3-methylphenyl) pyridin-3-carboxamide

•

N- (3-Methylphenyl) -2- [2- (piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] pyridin-3-carboxamide

•

2- [2- (Piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethylphenyl) pyridine-3-carboxamide

•

N- (4-Difluoromethoxyphenyl) -2- [2- (N- (2-hydroxyethyl) -N-methylamino) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide

The compounds of the present invention can be prepared by the following procedures. Each specific process for preparing the present compounds will be described in detail in the following examples (under the point of preparation examples). The term "Hal" used in the following synthetic routes represents a halogen atom, the term "Boc" represents a tert-butoxycarbonyl group, and the term "TBS" represents a tert-butyldimethylsilyl group. When an oxygen atom, a nitrogen atom, a sulfur atom or the like are included in R1, R2, R3, R4, R5 or R6 of the following formulas, protection and deprotection can be carried out according to widely used procedures.

The processes for preparing the compounds of the present invention are broadly divided into the procedures described below, and the appropriate procedure can be chosen according to the class of substituent.

1) The compound of the present invention (Ia) (R3, R4; alkyl, aryl, hydrogen or the like) can be synthesized according to the synthesis route 1. Specifically, the compound of the present invention (Ia) can be provided by the reaction of the compound (IIa) with the amine (III) without solvent or in an organic solvent such as tributylamine at 100 ° C to 200 ° C for 1 hour to 12 hours.

10 Synthesis path 1

Compound (II) (Hal; F, Cl, Br) including compound (IIa) can be synthesized according to synthesis route 1-1.

Specifically, the compound (II) can be provided by reacting the compound (IV) with the amine (V) in an organic solvent such as dichloromethane or N, N-dimethylformamide (hereinafter referred to as DMF) in the presence of a condensing agent such as N, N'-dicyclohexylcarbodiimide (hereinafter referred to as DCC), O- (7-azabenzotriazol-1-yl) -1,1,3,3-tetramethyluronium hexafluorophosphate (referred to below as HATU memory) or N-benzyl-N'-cyclohexylcarbodiimide

20 bound to polymer and in the presence of a base such as N, N-diisopropylethylamine at room temperature at 50 ° C for 1 hour to 24 hours.

Synthesis Path 1-1

The compound (IV) can be synthesized according to the synthetic route 1-2. Specifically, the compound (IV) can be provided by reacting the compound (VI) with the compound (VII) in an organic solvent such as DMF in the presence of a base such as triethylamine at 0 ° C at room temperature for 1 hour to 12 hours.

Synthesis path 1-2

The compound (VII) can be synthesized according to the synthesis route 1-3. Specifically, the compound (VII) can be provided by treating the compound (VIII) in an organic solvent such as acetonitrile and in the presence of a radical initiator such as benzoyl peroxide and a halogenating agent such as N-chlorosuccinimide or N-bromosuccinimide a reflux for 1 hour to 12 hours. R7 and R8 used in the following synthesis route represents a hydrogen atom, an alkyl group or the like.

10 Synthesis Route 1-3

2) The compound of the present invention (Ib) (R3; alkyl, aryl, hydrogen atom: R4; alkyl, aryl, hydrogen atom, COR5, CONR5R6 or the like) can be synthesized according to the synthetic route 2. Specifically, it can be provided by the reaction of compound (IIb), obtained according to synthesis route 1-1, with the compound

(III) (amine, amide or urea) in the presence of a transition metal catalyst such as palladium acetate or tris (dibenzylidenacetone) dipaladium (0), in the presence of a base such as cesium carbonate, in the presence of a

Catalytic ligand such as 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene and in an organic solvent such as 1,4-dioxane at 80 ° C to 150 ° C for 1 hour to 12 hours.

Synthesis Path 2

3) The compound of the present invention (Ic) (Z; CO, SO2 or the like) can be synthesized according to the synthetic route 3. Specifically, the compound of the present invention (Ic) can be provided by the reaction of the compound of the present invention (Id) with the acid anhydride (IX) such as acetic anhydride or the acid halide (X) such as pivaloyl chloride in the presence of an organic solvent such as pyridine at 0 ° C to 80 ° C for 1 hour to 12 hours.

10 Synthesis path 3

4) The compound of the present invention (Ie) (Z; CO, CS or the like) can be synthesized according to the synthesis route 4. Specifically, the compound of the present invention (Ie) can be provided by the reaction of the compound of the present invention (Id) with isocyanate (XI) such as n-propyl isocyanate or isothiocyanate (XII) such as methyl isothiocyanate in an organic solvent such as DMF at room temperature at 100 ° C for 1 hour to 12 hours.

Synthesis Route 4

5 5) The compound of the present invention (Ib) (R3; alkyl, aryl, hydrogen atom: R4; alkyl, aryl, hydrogen atom, COR5, CONR5R6 or the like) can be synthesized according to the synthetic route 5. Specifically, The compound of the present invention (Ib) can be provided by reacting the compound (XIII) with the amine (V) in an organic solvent such as methylene chloride or DMF in the presence of a condensing agent such as DCC, HATU or N -benzyl-N'-cyclohexylcarbodiimide polymer bound and in the presence of a

10 base such as N, N-diisopropylethylamine at room temperature at 50 ° C for 1 hour to 12 hours.

Synthesis Route 5

The compound (XIII) can be synthesized according to the synthesis route 5-1. Specifically, the compound (XIII) can be provided by the reaction of the compound (VI) with the compound (XIV) (W; a leaving group such as a halogen atom, a methanesulfonyloxy group, a toluenesulfonyloxy group or the like) in an organic solvent such as DMF and in the presence of a base such as triethylamine at 0 ° C at room temperature for

20 from 1 hour to 12 hours.

Synthesis path 5-1

5 The compound (XIVa) can be synthesized according to synthesis route 5-2. Specifically, the compound (XIVa) can be provided by reacting the compound (XV) with a halogenating agent such as carbon tetrabromide-triphenylphosphine in an organic solvent such as methylene chloride at 0 ° C at room temperature for 1 hour to 4 hours.

10 Synthesis path 5-2

The compound (XIVb) can be synthesized according to the synthesis route 5-3. Specifically, the compound (XIVb) can

15 provided by reacting compound (XV) with methanesulfonyl chloride in an organic solvent such as methylene chloride and in the presence of a base such as N, N-diisopropylethylamine at 0 ° C at room temperature for 30 minutes to 3 hours.

Synthesis route 5-3 20

6) The compound of the present invention (If) can be synthesized according to the synthesis route 6. Specifically, the compound of the present invention (If) can be provided by the reaction of the compound of the present invention (Id) with an agent of formylation such as N-formylbenzotriazole in an organic solvent such as tetrahydrofuran at reflux for 3 hours to 24 hours.

Synthesis Route 6

7) The compound of the present invention (Ig) (R2; alkyl or the like) can be synthesized according to the synthetic route 7. Specifically, the compound of the present invention (Ig) can be provided by the reaction of the compound of the present invention (Ih) with halide of R2 (XVI) (R2; alkyl or the like) in an organic solvent such as tetrahydrofuran or DMF and in the presence of a base such as sodium hydride at 0 ° C at temperature

10 room for 30 minutes to 3 hours.

Synthesis Route 7

8) The compound of the present invention (Ii) can be synthesized according to the synthetic route 8. Specifically, the compound of the present invention (Ii) can be provided by the reaction of the compound of the present invention (Id) with R3 halide (XVII) (R3; substituted or unsubstituted aryl and the like) in an organic solvent such as tetrahydrofuran or 1,4-dioxane, in the presence of a transition metal catalyst such as acetate

20 palladium or tris (dibenzylidene ketone) dipaladium (0), in the presence of a catalytic ligand such as triphenylphosphine, 1,4bis (diphenylphosphino) butane or 9,5-bis (diphenylphosphino) -9,9-dimethylxanthene and in the presence of a base such as cesium carbonate at 50 ° C to 120 ° C for 3 hours to 24 hours.

Synthesis route 8 25 9) The compound of the present invention (Ij) (p = 0, 1 or 2, q = 0 or 1) can be synthesized according to the synthesis route 9. Specifically, the compound of the present invention (Ij ), in which the sulfur atom or the nitrogen atom of the compound (Ib) (R3; alkyl, aryl or hydrogen atom: R4; alkyl, aryl, hydrogen atom, COR5, CONR5R6 or

5) is oxidized, can be provided by treating the compound (Ib) in an organic solvent such as chloroform and in the presence of an oxidizing agent such as m-chloroperbenzoic acid or hydrogen peroxide at 0 ° C at room temperature for 1 hour 12 hours

Synthesis path 9 10

10) The compound of the present invention (Ik) (B2; alkylene or the like: R7, R8; alkyl, hydrogen atom or the like) can be synthesized according to the synthetic route 10. Specifically, the compound of the present invention (Ik)

15 may be provided by reacting the compound of the present invention (I1) (B2; alkylene or the like: W; halogen atom or the like) with the amine (XVIII) without solvent or in an organic solvent such as DMF or methanol to room temperature at 100 ° C for 10 minutes to 12 hours.

Synthesis path 10 20

11) The compound of the present invention (Il) (B2; alkylene or the like) can be synthesized according to the synthesis route

11. Specifically, the compound of the present invention (I1) can be provided by the reaction of the

Compound of the present invention (Im) with a halogenating agent such as thionyl chloride in an organic solvent such as methylene chloride at 0 ° C to 50 ° C for 10 minutes to 12 hours.

Synthesis Path 11

10 minutes to 24 hours.

Synthesis Path 12

The compound (XIX) can be synthesized according to the synthesis route 12-1. Specifically, the compound (XIX) can be provided by reacting the amine (V) with the compound (VIa) in an organic solvent such as DMF and in the presence of a condensing agent such as DCC, HATU or carbonyldiimidazole and in the presence of a base such as N, N-diisopropylethylamine at 0 ° C to 50 ° C for 1 hour to 12 hours.

20 Synthesis path 12-1

The compound (XIVc) can be synthesized according to the synthesis route 12-2. Specifically, the compound (XIVc) can be provided by reacting the compound (XV) with a halogenating agent such as an aqueous solution of hydrobromide in water or an organic solvent such as methylene chloride or DMF at 0 ° C to 100 ° C for 3 hours to 12 hours

Synthesis Route 12-2

13. Specifically, the compound of the present invention (Io) can be provided by treating the compound of the present invention (Ip) in the presence of a base such as hydrazine monohydrate or an aqueous solution of sodium hydroxide and in an organic solvent such as methanol or 1,4-dioxane at room temperature at 100 ° C for 1 hour to 24 hours.

10 Synthesis path 13

To discover the usefulness of the compounds of the present invention, the following pharmacological tests 1 to 4 were performed, and the pharmacological effects of the compounds of the present invention were evaluated. Details will be described in the following examples (under the point of pharmacological tests). In pharmacological test 1 (in vitro), the compounds of the present invention showed excellent inhibitory action of cell proliferation, and an angiogenesis inhibitory effect was discovered, and then an inhibitory effect was suggested.

20 of vascular hyperpermeability. In addition, the compounds of the present invention showed an excellent tumor growth inhibitory action, a leg edema inhibitory action and a choroidal neovascularization inhibitory effect in pharmacological tests 2 to 4 (in vivo) using disease animal models specific, and it was found that the compounds of the present invention are useful as a therapeutic agent for a specific disease in which angiogenesis or hyperpermeability is involved

25 vascular.

1. Evaluation test of the angiogenesis inhibitory effect

A test of the inhibitory action of cell proliferation of the compounds of the present invention was performed

30 using a VEFG-induced HUVEC proliferation evaluation system (HUVEC stands for normal human umbilical vein endothelial cells), which is one of the widely used procedures for evaluating the inhibitory effects of drug in vitro angiogenesis.

2. Test of evaluation of the anticancer effect

A test of the tumor growth inhibitory action of the compounds of the present invention was performed using a tumor growth model in mice, which is one of the widely used methods of evaluating the in vivo effects of anticancer drugs.

3.

Antiarthritic effect evaluation test

A test of the leg edema inhibitory action of the compounds of the present invention was performed using an adjuvant arthritis model in rats, which is one of the widely used methods of evaluating the in vivo antiarthritic effects of drugs.

Four.

Evaluation test of the choroidal neovascularization inhibitory effect

A neovascularization incidence test of the compounds of the present invention was performed using a choroidal neovascularization model in rats, which is one of the widely used methods of evaluating the inhibitory effects of choroidal neovascularization in vivo of drugs.

As shown in tests 1 to 4, the compounds of the present invention are useful as a therapeutic agent for a disease in which angiogenesis and / or vascular hyperpermeability is (s) involved, specifically they are very useful as therapeutic agent for cancer, rheumatoid arthritis, age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal venous occlusion, polypoid choroidal angiopathy, diabetic macular edema, vulgar psoriasis or atherosclerosis.

The compound of the present invention can be administered orally or parenterally. Examples of the pharmaceutical form for administration include a tablet, a capsule, a granule, a powder, an injection, an ophthalmic solution and the like. A preparation of this type can be prepared by a widely used technique.

For example, oral preparations such as a tablet, a capsule, a granule and a powder can be prepared by the optional addition of an excipient such as lactose, mannitol, starch, crystalline cellulose, light silicic anhydride, calcium carbonate or calcium hydrogen phosphate, a lubricant such as stearic acid, magnesium stearate or talc, a binder such as starch, hydroxypropylcellulose, hydroxypropylmethylcellulose or polyvinylpyrrolidone, a disintegrant such as carboxymethylcellulose, low-substituted hydroxypropylmethylcellulose or calcium citrate, hydroxypropyl coating agent such as macropropyl a silicone resin, a stabilizer such as ethyl p-hydroxybenzoate or benzyl alcohol, a corrector such as a sweetener, a bitter agent or an aroma, or the like.

Parenteral preparations such as an injection and an ophthalmic solution can be prepared by the optional addition of a tonicity agent such as sodium chloride, concentrated glycerin, propylene glycol, polyethylene glycol, potassium chloride, sorbitol or mannitol, a buffer such as sodium phosphate, sodium hydrogen phosphate, sodium acetate, citric acid, glacial acetic acid or trometamol, a surfactant such as polyoxyethylene sorbitan monooleate, polyoxyl stearate 40 or hydrogenated castor oil-polyoxyethylene, a stabilizer such as sodium citrate or disodium edetate , a preservative such as benzalkonium chloride, paraben, benzethonium chloride, p-hydroxybenzoate, sodium benzoate or chlorobutanol, a pH adjusting agent such as hydrochloric acid, citric acid, phosphoric acid, glacial acetic acid, sodium hydroxide, sodium carbonate or sodium hydrogen carbonate, a soothing agent such as benzyl alcohol, or the like beef.

The dosage of the compound of the present invention can be appropriately selected depending on the symptoms, the age of the patients, the pharmaceutical form and the like. For example, in the case of an oral preparation, the compound of the present invention can be administered in an amount of generally 0.01 to 1,000 mg, preferably 1 to 100 mg daily, which can be provided in a single dose or several doses. divided. In addition, in the case of an ophthalmic solution, one containing the compound of the present invention can be administered at a concentration of 0.0001 to 10% (w / v), preferably 0.01 to 5% (w / v) one to several times a day.

Best way to practice the invention

Hereinafter, preparation examples, formulation examples and pharmacological test results of the compounds of the present invention will be provided. These examples are intended to make the present invention more clearly understood, and do not limit the scope of the present invention.

[Preparation examples]

Reference Example 1

4-Chloromethyl-2-fluoropyridine (reference compound No. 1-1)

N-Chlorosuccinimide (8.8 g, 66 mmol), acetic acid (0.15 ml) and benzoyl peroxide (220 mg, 0.91 mmol) were added to a solution of 2-fluoro-4-picoline (5, 0 g, 45 mmol) in acetonitrile (25 ml) at room temperature, and the mixture was refluxed for 2 hours. The reaction mixture was cooled to room temperature, water (200 ml) was added thereto, and then the mixture was extracted with ethyl acetate (300 ml). The organic phase was washed with brine (200 ml) and dried over anhydrous magnesium sulfate. The organic phase was evaporated under reduced pressure, hexane / ethyl acetate (1: 1) was added to the resulting residue, and then the insoluble material was filtered off. The filtrate was evaporated under reduced pressure to provide 6.5 g of the title reference compound as a crude product.

1H-NMR (500 MHz, DMSO-d6) 10 δ 4.83 (s, 2H), 7.26 (s, 1H), 7.43 (d, J = 5.2 Hz, 1H), 8.27 (d, J = 5.2 Hz, 1H)

As described below, the reference compounds (# 1-2) were obtained using the corresponding compounds selected from commercially available compounds or known compounds according to the synthesis procedure of the reference compound (# 1-1). ).

2-Bromo-4-chloromethylpyridine (reference compound # 1-2) 1 H-NMR (500 MHz, DMSO-d6)

δ 4.51 (s, 2H), 7.28 (s, 1H), 7.52 (d, J = 5.2 Hz, 1H), 8.36 (d, J = 5.2 Hz, 1H) twenty

Reference Example 2

2- (2-fluoropyridin-4-ylmethylthio) pyridin-3-carboxylic acid (reference compound # 2-1)

A solution of triethylamine (7.0 ml, 50 mmol) in N, N-dimethylformamide (20 ml) was added to a solution of 4-chloromethyl-2-fluoropyridine (reference compound No. 1-1, 5.5 g , 38 mmol) and 2-mercaptonicotinic acid (6.2 g, 40 mmol) in N, N-dimethylformamide (40 ml) with ice cooling, then the mixture was stirred for 12 hours at room temperature. Ethyl acetate (50 ml) was added to the reaction mixture, the whole was extracted with 0.1 N aqueous solution of sodium hydroxide (100 ml). 1 N hydrochloric acid was added to the aqueous phase to adjust

30 at pH 5, and the precipitated crystal was filtered off. The crystal was dried at 80 ° C under reduced pressure to provide 5.3 g of the title reference compound as a brown solid. (53% yield)

1 H-NMR (500 MHz, DMSO-d6) δ4.43 (s, 2H), 7.20 (s, 1H), 7.23 (dd, J = 7.9.4.9 Hz, 1H), 7.39 (d, J = 5.2Hz, 1H), 8.13 (d, J = 5.2Hz, 1H), 8.24 (dd, J = 7.9.1.8 Hz, 1H), 8.64 (dd, J = 4.9, 1.8 Hz, 1H), 14.60 (sa, 1H)

As described below, the reference compound (# 2-2) was obtained using the corresponding 40 compounds selected from the reference compound (# 1-2), commercially available compounds or known compounds according to the process of synthesis of the reference compound (# 2-1).

2- (2-Bromopyridin-4-ylmethylthio) pyridin-3-carboxylic acid (reference compound No. 2-2)

45 1H-NMR (500 MHz, DMSO-d6) δ4.37 (s, 2H), 7.28 (dd, J = 7.8.4.7 Hz, 1H), 7.48 (dd, J = 4 , 9, 1.9 Hz, 1H), 7.69 (dd, J = 1.4.0.4 Hz, 1H), 8.23 (dd, J = 7.8.1.7 Hz, 1H) , 8.27 (dd, J = 4.9.0.4 Hz, 1H), 8.63 (dd, J = 4.7.1.7 Hz, 1H), 13.55 (s, 1H)

Reference Example 3

N- (3,5-Dimethylphenyl) -2- (2-fluoropyridin-4-ylmethylthio) pyridin-3-carboxamide (reference compound No. 3-1)

5 O- (7-Azabenzotriazol-1-yl) -N, N, N ', N'-tetramethyluronium hexafluorophosphate (3.0 g, 7.9 mmol) was added to a solution of 2- (2-fluoropyridine acid) -4-ylmethylthio) pyridine-3-carboxylic (reference compound No. 2-1, 1.5 g, 5.7 mmol), 3,5-xylidine (0.90 g, 7.4 mmol) and N , N-diisopropylethylamine (2.0 ml, 11 mmol) in N, N-dimethylformamide (20 ml) at room temperature, and the mixture was stirred for 12 hours. Ethyl acetate (30 ml) was added to the reaction mixture, the whole was washed with brine (50 ml), and then the organic phase was dried over magnesium sulfate.

10 anhydrous The organic phase was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to provide 0.91 g of the title reference compound as a colorless solid. (44% yield)

15 1H-NMR (500 MHz, DMSO-d6)

δ2.26 (s, 6H), 4.46 (s, 2H), 6.76 (s, 1H), 7.18 (s, 1H), 7.29 (dd, J = 7.3.4, 6Hz, 1H), 7.32 (s, 2H), 7.38 (d, J = 5.2 Hz, 1H), 7.94 (dd, J = 7.3.1.5 Hz, 1H), 8.13 (d, J = 5.2 Hz, 1H), 8.58 (dd, J = 4.6.1.5 Hz, 1H), 10.32 (s, 1H)

As described below, the reference compounds (# 3-2-7) were obtained using the corresponding compounds selected from the reference compound (# 2-1), the reference compound (# 2-2), commercially available compounds or known compounds according to the synthesis procedure of the reference compound (# 3-1).

2- (2-Fluoropyridin-4-ylmethylthio) -N- (indan-5-yl) pyridin-3-carboxamide (reference compound No. 3-2)

1H-NMR (500 MHz, DMSO-d6)

30 δ 1.98-2.06 (m, 2H), 2.79-2.90 (m, 4H), 4.46 (s, 2H), 7.16-7.20 (m, 2H), 7.29 (dd, J = 7.3.4.9 Hz, 1H), 7.38 (dd, J = 4.6.1.5 Hz, 2H), 7.61 (s, 1H), 7 , 95 (dd, J = 7.3.1.5 Hz, 1H), 8.13 (d, J = 5.2 Hz, 1H), 8.58 (dd, J = 4.9, 1.5 Hz, 1H), 10.35 (s, 1H)

2- (2-Fluoropyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (reference compound No. 3-3)

35 1H-NMR (500 MHz, DMSO-d6)

δ 4.47 (s, 2H), 7.18 (s, 1H), 7.32 (dd, J = 7.6.4.9 Hz, 1H), 7.35-7.40 (m, 3H ), 7.81 (d, J = 8.2 Hz, 2H), 8.00 (dd, J = 7.6.1.8 Hz, 1H), 8.13 (d, J = 5.2 Hz , 1H), 8.61 (dd, J = 4.9, 1.8 Hz, 1H), 10.67 (s, 1H)

2- (2-Bromopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (reference compound No. 3-4)

1H-NMR (400 MHz, DMSO-d6)

δ 2.26 (s, 6H), 4.41 (s, 2H), 6.76 (s, 1H), 7.29 (dd, J = 7.6.4.9 Hz, 1H), 7, 32 (s, 2H), 7.47 (dd, J = 5.1, 1.5 Hz, 1H), 7.67 45 (d, J = 0.7 Hz, 1H), 7.94 (dd, J = 7.6.1.7 Hz, 1H), 8.27 (dd, J = 5.1.0.7 Hz, 1H), 8.58 (dd, J = 4.9, 1.7 Hz , 1H), 10.32 (s, 1H)

2- (2-Bromopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (reference compound No. 3-5)

1H-NMR (500 MHz, DMSO-d6)

50 δ 4.42 (s, 2H), 7.32 (dd, J = 7.6.4.9 Hz, 1H), 7.38 (d, J = 8.7 Hz, 2H), 7.47 (d, J = 5.1 Hz, 1H), 7.67 (s, 1H), 7.80 (d, J = 8.7 Hz, 2H), 8.00 (dd, J = 7.6, 1.7 Hz, 1H), 8.27 (dd, J = 5.1 Hz, 1H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 10.68 (s, 1H) 2- (2-Bromopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridin-3-carboxamide (reference compound No. 3-6)

1H-NMR (400 MHz, DMSO-d6)

5 δ 4.41 (s, 2H), 7.31 (dd, J = 7.6.9.9 Hz, 1H), 7.42 (d, J = 9.0 Hz, 2H), 7.47 (dd, J = 5,0,1,5 Hz, 1H), 7,67 (d, J = 0,7 Hz, 1H), 7,73 (d, J = 9,0 Hz, 2H), 8 , 00 (dd, J = 7,6,1,7 Hz, 1H), 8,27 (dd, J = 5,0,0,7 Hz, 1H), 8,60 (dd, J = 4,9 , 1.7 Hz, 1H), 10.61 (s, 1H)

2- (2-Bromopyridin-4-ylmethylthio) -N- (4-difluoromethoxyphenyl) pyridin-3-carboxamide (reference compound No. 3-7) 10 1 H-NMR (400 MHz, DMSO-d6)

δ 4.41 (s, 2H), 7.16 (t, J = 74.2 Hz, 1H), 7.19 (d, J = 8.8 Hz, 2H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.47 (dd, J = 5.1, 1.5 Hz, 1H), 7.67 (s, 1H), 7.73 (d, J = 8 , 8 Hz, 2H), 7.99 (dd, J = 7.6.1.7 Hz, 1H), 8.27 (d, J = 5.1 Hz, 1H), 8.59 (dd, J = 4.9, 1.7 15 Hz, 1H), 10.56 (s, 1H)

Reference Example 4

(2-tert-Butoxycarbonylaminopyridin-4-yl) methanol (reference compound No. 4-1)

Di-tert-butyl dicarbonate (7.1 g, 32 mmol) was added to a solution of (2-aminopyridin-4-yl) methanol (3.0 g, 24 mmol) in tert-butanol (60 ml) at room temperature, and the mixture was stirred for 12 hours. The reaction mixture was evaporated under reduced pressure, ethyl acetate (20 ml) was added to the resulting residue, and then the insoluble material was filtered off. The filtrate was evaporated under reduced pressure, and the resulting residue was purified by

25 silica gel column chromatography providing 3.6 g of the title reference compound as a colorless crystal. (60% yield)

30 1 H-NMR (500 MHz, CDCl3)

δ 1.56 (s, 9H), 1.86 (t, J = 6.1 Hz, 1H), 4.73 (d, J = 6.1 Hz, 2H), 7.00 (d, J = 5.2 Hz, 1H), 7.53 (sa, 1H), 7.92 (s, 1H), 8.21 (d, J = 5.2 Hz, 1H)

35 Reference Example 5

2-tert-Butoxycarbonylamino-4- (tert-butyldimethylsilyloxymethyl) pyridine (reference compound No. 5-1)

Imidazole (2.1 g, 31 mmol) and tert-butyldimethylsilyl chloride (4.4 g, 29 mmol) were added to a solution of (2-tert

Butoxycarbonylaminopyridin-4-yl) methanol (reference compound No. 4-1, 6.2 g, 28 mmol) in N, N-dimethylformamide (120 ml) at room temperature, and the mixture was stirred for 2 hours. Ethyl acetate (300 ml) was added to the reaction mixture, then the mixture was washed with water (750 ml) and brine (200 ml), and then the mixture was dried over anhydrous magnesium sulfate. The organic phase was evaporated under reduced pressure to provide 9.0 g of the title reference compound as a colorless solid.

45 (96% yield)

1H-NMR (400 MHz, DMSO-d6)

δ 0.09 (s, 6H), 0.92 (s, 9H), 1.46 (s, 9H), 4.72 (s, 2H), 6.93 (dd, J = 4.9.0 , 9Hz, 1H), 7.78 (s, 1H), 8.16 (d, J = 4.9Hz, 1H), 5 9.67 (s, 1H)

Reference Example 6

2- (N-tert-Butoxycarbonyl-N-methylamino) -4- (tert-butyldimethylsilyloxymethyl) pyridine (reference compound No. 6-1)

10 60% sodium hydride (310 mg, 7.6 mmol) was washed with hexane (5.0 ml), and the residue was suspended in N, N-dimethylformamide (20 ml). 2-tert-Butoxycarbonylamino-4- (tert-butyldimethylsilyloxymethyl) pyridine (reference compound No. 5-1, 1.3 g, 3.7 mmol) was added dropwise to the suspension for 15 minutes with ice cooling , and methyl iodide (2.4 ml, 39 mmol) was added thereto, and then the mixture was stirred overnight to

15 room temperature Water (70 ml) was added to the reaction suspension, and the whole was extracted with ethyl acetate (100 ml). The organic phase was washed with saturated aqueous sodium hydrogen carbonate solution (50 ml) and brine (100 ml), and dried over anhydrous magnesium sulfate. The organic phase was evaporated under reduced pressure to provide 1.4 g of the mixture that included the title reference compound as an orange red oil.

1H-NMR (500 MHz, CDCl3)

δ 0.11 (s, 6H), 0.95 (s, 9H), 1.51 (s, 9H), 3.39 (s, 3H), 4.73 (s, 2H), 7.01 ( d, J = 5.2 Hz, 1H), 7.57 (s, 1H), 8.31 (d, J = 5.2 25 Hz, 1H)

Reference Example 7

[2- (N-tert-Butoxycarbonyl-N-methylamino) pyridin-4-yl] methanol (reference compound No. 7-1)

A solution of tetra-n-butylammonium trihydrate fluoride (1.3 g, 4.2 mmol) in tetrahydrofuran (20 ml) was added to a solution of 2- (N-tert-butoxycarbonyl-N-methylamino) -4 - (tert-Butyldimethylsilyloxymethyl) pyridine (reference compound No. 6-1, 1.4 g, 3.7 mmol) in tetrahydrofuran (20 ml) for 5 minutes at room temperature, and the mixture was stirred for 15 minutes. Ethyl acetate (50 ml) and water (100 ml) were added to the reaction mixture,

The whole was separated, and then the aqueous phase was extracted with ethyl acetate (50 ml). These organic phases were combined, then washed with brine (100 ml) and dried over anhydrous magnesium sulfate. The organic phase was evaporated under reduced pressure, then the resulting residue was purified by silica gel column chromatography to provide 450 mg of the title reference compound as a reddish brown solid. (50% yield)

1H-NMR (500MH, CDCl3)

Δ1.53 (s, 9H), 1.93 (t, J = 5.6 Hz, 1H), 3.40 (s, 3H), 4.73 (d, J = 5.6Hz, 2H), 7.02 (d, J = 5.1 Hz, 1H), 7.70 (s, 1H), 8.34 (d, J = 5.1 Hz, 1H)

Reference Example 8

4-Bromomethyl-2-tert-butoxycarbonylaminopyridine (reference compound No. 8-1)

5 Triphenylphosphine (970 mg, 3.7 mmol) and carbon tetrabromide (1.5 g, 4.6 mmol) were added to a solution of (2-tert-butoxycarbonylaminopyridin-4-yl) methanol (reference compound No. 4 -1, 690 mg, 3.1 mmol) in methylene chloride (20 ml) with ice cooling, and the mixture was stirred for 2 hours at room temperature. Ethyl acetate (30 ml) was added to the reaction mixture, the whole was washed with saturated aqueous sodium hydrogen carbonate solution (20 ml) and brine (20 ml), and then dried over anhydrous magnesium sulfate. Be

The organic phase was evaporated under reduced pressure, and the resulting solid was filtered off with ethyl acetate to give 550 mg of the title reference compound as a colorless solid. (62% yield)

15 1H-NMR (400 MHz, CDCl3)

δ 1.54 (s, 9H), 4.38 (s, 2H), 6.99 (d, J = 5.1 Hz, 1H), 7.61 (sa, 1H), 7.98 (s, 1H), 8.22 (d, J = 5.1 Hz, 1H)

As described below, the reference compounds (# 8-2 ~ 3) were obtained using the corresponding 20 compounds selected from the reference compound (# 7-1), commercially available compounds or known compounds according to Synthesis procedure of the reference compound (No. 8-1).

4-Bromomethyl-2- (N-tert-butoxycarbonyl-N-methylamino) pyridine (reference compound No. 8-2)

25 1H-NMR (500 MHz, DMSO-d6)

δ 1.48 (s, 9H), 3.29 (s, 3H), 4.67 (s, 2H), 7.17 (d, J = 5.1Hz, 1H), 7.70 (s, 1H ), 8.35 (d, J = 5.1 Hz, 1H)

4-Bromomethyl-2-phthaloylaminopyridine (reference compound No. 8-3) 30 1 H-NMR (500 MHz, CDCl 3)

δ 4.48 (s, 2H), 7.39 (dd, J = 5.2.1.5 Hz, 1H), 7.48 (s, 1H), 7.80-7.84 (m, 2H ), 7.96-8.00 (m, 2H), 8.67 (d, J = 5.2 Hz, 1H)

35 Reference Example 9

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) pyridine-3-carboxylic acid (reference compound No. 9-1)

A solution of triethylamine (0.75 ml, 5.4 mmol) in N, N-dimethylformamide (2.0 ml) was added to a solution of 4

Bromomethyl-2-tert-butoxycarbonylaminopyridine (reference compound No. 8-1, 500 mg, 1.7 mmol) and 2mercaptonicotinic acid (270 mg, 1.7 mmol) in N, N-dimethylformamide (3.0 ml ) with ice cooling, and the mixture was stirred for 12 hours at room temperature. Ethyl acetate (20 ml) was added to the reaction mixture, and the whole was extracted with 0.1 N aqueous solution of sodium hydroxide (50 ml). 1 N hydrochloric acid was added to the aqueous phase to adjust to pH 5, and the precipitated crystal was filtered off. The crystal was dried under reduced pressure at

45 60 ° C providing 560 mg of the title reference compound as a colorless crystal. (88% yield)

1H-NMR (500 MHz, DMSO-d6)

δ 1.46 (s, 9H), 4.35 (s, 2H), 7.05 (d, J = 5.2 Hz, 1H), 7.26 (dd, J = 7.9, 4.9 Hz, 1H), 7.87 (s, 1H), 8.12 (d, J = 5.2 Hz, 1H),

8.23 (dd, J = 7.9.1.8 Hz, 1H), 8.63 (dd, J = 4.9, 1.8 Hz, 1H), 9.67 (s, 1H), 13 , 50 (sa, 1H) As described below, the reference compounds (# 9-2 ~ 6) were obtained using the corresponding compound selected from the reference compound (# 8-2), the reference compound (# 83), commercially available compounds or known compounds according to the synthesis process of the reference compound (# 9-1).

2- [2- (N-tert-Butoxycarbonyl-N-methylamino) pyridin-4-ylmethylthio] pyridine-3-carboxylic acid (reference compound No. 92)

1H-NMR (500 MHz, DMSO-d6) δ 1.40 (s, 9H), 3.25 (s, 3H), 4.38 (s, 2H), 7.17 (dd, J = 5.2.1.5 Hz, 1H), 7, 27 (dd, J = 7.6.4.9 Hz, 1H), 7.61 (s, 1H), 8.218.26 (m, 2H), 8.63 (dd, J = 4.9, 1, 8 Hz, 1H), 13.49 (sa, 1H)

2- (2-Phthaloylaminopyridin-4-ylmethylthio) pyridin-3-carboxylic acid (reference compound No. 9-3) 1H-NMR (400 MHz, DMSO-d6) δ 4.46 (s, 2H), 7.27 (dd, J = 7.7.4.8 Hz, 1H), 7.56 (d, J = 5.1 Hz, 1H) 7.61 (s , 1H), 7.91-8.00 (m, 4H), 8.23 (dd, J = 7.7.1.8

Hz, 1H), 8.52 (d, J = 5.1 Hz, 1H), 8.63 (dd, J = 4.8.1.8 Hz, 1H), 13.55 (s a, 1H) 2- [2- (5-Cyanothiazol-2-ylamino) pyridin-4-ylmethylthio] pyridin-3-carboxylic acid (reference compound No. 9-4) 1H-NMR (400 MHz, DMSO-d6) δ 4.39 (s, 2H), 7.12 (d, J = 5.1 Hz, 1H), 7.21 (s, 1H), 7.27 (dd, J = 7.8.4.6 Hz, 1H), 8.23 (dd, J = 7.8.1.7 Hz, 1H), 8.25

(s, 1H), 8.29 (d, J = 5.1 Hz, 1H), 8.62 (dd, J = 4.6.1.7Hz, 1H), 12.19 (s, 1H), 13.52 (sa, 1 H) 2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) benzoic acid (reference compound No. 9-5) 1H-NMR (500 MHz, DMSO-d6) δ 1.47 (s, 9H), 4.22 (s, 2H), 7.09 (d, J = 5.2 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H) , 7.42 (d, J = 7.6 Hz, 1H), 7.47 (t, J = 7.6

Hz, 1H), 7.88 (s, 1H), 7.89 (d, J = 7.6 Hz, 1H), 8.16 (d, J = 5.2 Hz, 1H), 9.74 ( s, 1H), 13.10 (sa, 1H) 3- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) thiophene-2-carboxylic acid (reference compound No. 9-6) 1H-NMR (400 MHz, DMSO-d6) δ 1.47 (s, 9H), 4.33 (s, 2H), 7.09 (d, J = 5.1 Hz, 1H), 7.17 (d, J = 5.1 Hz, 1H) , 7.85 (d, J = 5.1 Hz, 1H), 7.90 (s, 1H), 8.17

(d, J = 5.1 Hz, 1H), 9.76 (s, 1H), 13.04 (s a, 1H)

Reference Example 10

N- (3,5-Dimethylphenyl) -2-thioxo-1,2-dihydropyridin-3-carboxamide (reference compound No. 10-1)

2-Mercaptonicotinic acid (90 g, 0.58 mol) was suspended in N, N-dimethylformamide (660 ml), and carbonyldiimidazole (110 g, 0.70 mol) was added thereto with ice cooling, and then stirred the mixture at room temperature for 2 hours. Water (5.4 ml) was added thereto, the whole was stirred for 40 minutes. 3,5-Xylidine (76 ml, 0.61 mol) was added thereto, and the mixture was stirred for 16 hours at 60 ° C. The mixture was allowed to stand, water (1.3 L) was added thereto, and then the precipitated solid was filtered off. The solid was dried under reduced pressure at 45 ° C to provide 130 g of the title reference compound as a yellow solid. (89% yield) 1 H-NMR (500 MHz, DMSO-d6)

δ 2.27 (s, 6H), 6.77 (s, 1H), 7.10 (dd, J = 7.6.6.0 Hz, 1H), 7.34 (s, 2H), 8, 03 (dd, J = 6.0.1.8 Hz, 1H), 8.55 (dd, J = 7.6.1.8 Hz, 1H), 12.90 (s, 1H), 14.18 (s, 1H) As described below, the reference compounds (# 10-2 ~ 10) were obtained using the

corresponding compounds selected from commercially available compounds or known compounds according to the synthesis procedure of the reference compound (No. 10-1). 2-Thioxo-N- (4-trifluoromethoxyphenyl) -1,2-dihydropyridin-3-carboxamide (reference compound No. 10-2)

1H-NMR (500 MHz, DMSO-d6) δ 7.08 (dd, J = 7.5.5.8 Hz, 1H), 7.39 (d, J = 8.8 Hz, 2H), 7.82 (d, J = 8.8 Hz, 2H), 8.03 (dd, J = 5.8.1.8 Hz, 1H), 8.48 (dd, J = 7.5.1.8 Hz, 1H), 12.91 (s, 1H), 14.19 (s, 1H)

N- (4-Chlorophenyl) -2-thioxo-1,2-dihydropyridin-3-carboxamide (reference compound No. 10-3) 1H-NMR (400 MHz, DMSO-d6) δ 7.08 (dd, J = 7.6.6.1 Hz, 1H), 7.43 (d, J = 8.7Hz, 2H), 7.74 (d, J = 8.7 Hz, 2H ), 8.03 (dd, J = 6.1, 1.8 Hz, 1H), 8.48 (dd, J

= 7.6.1.8 Hz, 1H), 12.90 (s, 1H), 14.19 (s, 1H) N- (Indan-5-yl) -2-thioxo-1,2-dihydropyridin-3-carboxamide (reference compound 10-4) 1H-NMR (400 MHz, DMSO-d6) δ 1.98-2.06 (m, 2H), 2.81-2.89 (m, 4H), 7.09 (dd, J = 7.6.4.8 Hz, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.43 (dd, J = 8.1.2.0

Hz, 1H), 7.62 (s, 1H), 8.03 (dd, J = 4.8.1.7 Hz, 1H), 8.55 (dd, J = 7.6.1.7 Hz , 1H), 12.93 (s, 1H), 14.18 (s, 1H) N- (4-tert-Butylphenyl) -2-thioxo-1,2-dihydropyridine-3-carboxamide (reference compound No. 10-5) 1H-NMR (400 MHz, DMSO-d6) δ 1.28 (s, 9H), 7.09 (dd, J = 7.6.5.9 Hz, 1H), 7.39 (d, J = 8.8 Hz, 2H), 7.62 ( d, J = 8.8 Hz, 2H), 8.03 (dd, J = 5.9.1.9

Hz, 1H), 8.55 (dd, J = 7.6.1.9 Hz, 1H), 12.90 (s, 1H), 14.19 (s, 1H) N- (3-Methylphenyl) -2-thioxo-1,2-dihydropyridin-3-carboxamide (reference compound No. 10-6) 1H-NMR (400 MHz, DMSO-d6) δ 2.32 (s, 3H), 6.95 (d, J = 7.6Hz, 1H), 7.10 (dd, J = 7.6.5.9 Hz, 1H), 7.25 (t , J = 7.6 Hz, 1H), 7.52-7.55 (m, 2H), 8.03 (dd, J

= 5.9.2.0 Hz, 1H), 8.54 (dd, J = 7.6.2.0 Hz, 1H), 12.91 (s, 1H), 14.19 (s, 1H) 2-Thioxo-N- (4-trifluoromethylphenyl) -1,2-dihydropyridine-3-carboxamide (reference compound No. 10-7) 1H-NMR (500 MHz, DMSO-d6) δ 7.09 (dd, J = 7.6.5.8 Hz, 1H), 7.74 (d, J = 8.4 Hz, 2H), 7.92 (d, J = 8.4 Hz, 2H), 8.04 (dd, J = 5.8.1.8Hz, 1H), 8.47 (dd, J =

7.6.1.8 Hz, 1H), 13.04 (s, 1H), 14.20 (s at, 1H) N- (3-Chlorophenyl) -2-thioxo-1,2-dihydropyridin-3-carboxamide (reference compound No. 10-8) 1H-NMR (500 MHz, DMSO-d6) δ 7.08 (dd, J = 7.6.5.8 Hz, 1H), 7.19 (d, J = 7.9 Hz, 1H), 7.40 (t, J = 7.9 Hz, 1H), 7.52 (d, J = 7.9 Hz, 1H), 7.96 (t, J = 2.0

Hz, 1H), 8.03 (dd, J = 5.8.1.8 Hz, 1H), 8.46 (dd, J = 7.6.1.8 Hz, 1H), 12.90 (s , 1H), 14.19 (sa, 1H) N- (4-Difluoromethoxyphenyl) -2-thioxo-1,2-dihydropyridine-3-carboxamide (reference compound No. 10-9) 1H-NMR (500 MHz, DMSO-d6) δ 7.09 (dd, J = 7.5.4.8 Hz, 1H), 7.18 (t, J = 74.6 Hz, 1H), 7.20 (d, J = 9.1 Hz, 2H), 7.75 (d, J = 9.1 Hz, 2H), 8.03 (dd, J =

4.8.1.9 Hz, 1H), 8.51 (dd, J = 7.5.1.9 Hz, 1H), 12.90 (s, 1H), 14.18 (s, 1H)

N- (Isoquinolin-3-yl) -2-thioxo-1,2-dihydropyridin-3-carboxamide (reference compound No. 10-10)

1H-NMR (400 MHz, DMSO-d6)

5 δ 7.15 (dd, J = 7.8.6.1 Hz, 1H), 7.58 (t, J = 7.5 Hz, 1H), 7.75 (t, J = 7.0 Hz , 1H), 7.97 (d, J = 8.1 Hz, 1H), 8.08-8.10 (m, 2H), 8.69-8.72 (m, 2H), 9.19 ( s, 1H), 13.71 (s, 1H), 14.24 (s, 1H)

Reference Example 11

10 4-Acetoxymethyl-2-acetylaminopyridine (reference compound No. 11-1)

(2-Aminopyridin-4-yl) methanol (5.0 g, 40 mmol) was suspended in pyridine (20 ml), acetic anhydride (11 ml, 120 mmol) was added thereto with ice cooling, and the mixture was stirred Mix for 5 hours at room temperature. Ethyl acetate (150 ml) was added to the reaction mixture, and then the mixture was washed with water (150 ml), solution

Saturated aqueous sodium hydrogen carbonate (150 ml) and brine (150 ml) successively. The organic phase was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting solid was filtered off with hexane, then dried under reduced pressure at 40 ° C to provide 6.7 g of the title reference compound as a colorless solid. (79% yield)

1H-NMR (500 MHz, DMSO-d6)

δ 2.09 (s, 3H), 2.11 (s, 3H), 5.11 (s, 2H), 7.04 (d, J = 5.2 Hz, 1H), 8.05 (s, 1H), 8.27 (d, J = 5.2 Hz, 1H), 10.51 (s, 1H) 25

Reference Compound No. 12

(2-Acetylaminopyridin-4-yl) methanol (reference compound No. 12-1)

4-Acetoxymethyl-2-acetylaminopyridine (reference compound No. 11-1.6.6 g, 32 mmol) was dissolved in tetrahydrofuran (20 ml), and a 2N aqueous solution of hydroxide was added dropwise. sodium (19 ml, 38 mmol) thereto with ice cooling. The mixture was stirred for 40 minutes at room temperature, and water (100 ml) was added thereto. The whole was extracted with ethyl acetate (80 ml) six times, and then the organic phase was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the

The resulting solid was mixed with the mixed solvent of ethyl acetate and hexane, and then the solid was dried under reduced pressure at 40 ° C to give 4.5 g of the title reference compound as a colorless solid. (86% yield)

40 1H-NMR (400 MHz, DMSO-d6)

δ 2.08 (s, 3H), 4.50 (d, J = 5.9 Hz, 2H), 5.40 (t, J = 5.9 Hz, 1H), 7.01 (d, J = 4.9 Hz, 1H), 8.05 (s, 1H), 8.20 (d, J = 4.9 Hz, 1H), 10.38 (s, 1H)

45 Reference Example 13

2-Acetylamino-4-methanesulfonyloxymethylpyridine (reference compound No. 13-1)

A solution of triethylamine (1.7 ml, 12 mmol) and methanesulfonyl chloride (0.70 ml, 9.0 mmol) in anhydrous tetrahydrofuran (3.0 ml) was added to a solution of (2-acetylaminopyridine-4 -il) methanol (reference compound no.

12-1, 1.0 g, 6.0 mmol) in anhydrous tetrahydrofuran (9.0 ml) with ice cooling, and the mixture was stirred for 20 minutes. Water (30 ml) was added to the reaction mixture, the whole was extracted with ethyl acetate (40 ml) three times, and then the organic phase was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting solid was filtered off with hexane. The solid was dried under reduced pressure at 40 ° C to provide 1.3 g of the title reference compound as a pale yellow solid. (87% yield)

1H-NMR (400 MHz, CDCl3) 10 δ 2.22 (s, 3H), 3.08 (s, 3H), 5.25 (s, 2H), 7.10 (dd, J = 5.2, 1.8 Hz, 1H), 8.18 (s, 1H), 8.23 (s, 1H), 8.30 (d, J = 5.2 Hz, 1H)

Reference Example 14

2-Amino-4-bromomethylpyridine hydrobromide (reference compound No. 14-1)

(2-Aminopyridin-4-yl) methanol (15 g, 12 mmol) was suspended in a 47% aqueous solution of hydrobromic acid (120 ml, 72 mmol) at room temperature, and the mixture was stirred for 6 hours at temperature outside of 120ºC. The mixture was stirred for 15 hours at room temperature, then the precipitated solid was filtered off and

20 washed with ethyl acetate. The solid was dried under reduced pressure to provide 23 g of the title reference compound as a gray solid. (71% yield)

25 1H-NMR (400 MHz, DMSO-d6)

δ 44.69 (s, 2H), 6.88 (dd, J = 6.8.1.7 Hz, 1H), 7.04 (s, 1H), 7.94 (d, J = 6.8 Hz, 1H), 8.13 (sa, 2H), 13.28 (sa, 1H)

Example 1

30 N- (3,5-Dimethylphenyl) -2- [2- (4-methylpiperazin-1-yl) pyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 1-1)

N-methylpiperazine (2.0 ml) was added to N- (3,5-dimethylphenyl) -2- (2-fluoropyridin-4-ylmethylthio) pyridine-3-carboxamide (reference compound No. 3-1, 100 mg, 0.27 mmol) at room temperature, then the vessel was sealed and

The reaction mixture was stirred for 3 hours at 150 ° C. The mixture was cooled to room temperature, ethyl acetate (20 ml) was added to the reaction mixture, and then the whole was washed with brine (20 ml) and dried over anhydrous magnesium sulfate. The organic phase was evaporated under reduced pressure, and the resulting solid was filtered off with ethyl acetate to give 39 mg of the objective compound as a colorless crystal. (32% yield)

1H-NMR (500 MHz, DMSO-d6) δ 2.19 (s, 3H), 2.25 (s, 6H), 2.35 (t, J = 5.0 Hz, 4H), 3.42 (t, J = 5.0Hz, 4H), 4.31 (s, 2H), 6.64 (dd, J = 5.2.1.2 Hz, 1H), 6.76

(s, 1H), 6.84 (s, 1H), 7.28 (dd, J = 7.5.4.9 Hz, 1H), 7.32 (s, 2H), 7.91 (dd, J = 7.5.1.8 Hz, 1H), 7.99 (d, J = 5.2 Hz, 1H), 8.59 (dd, J = 4.9, 1.8 Hz, 1H), 10.30 (s, 1H) As described below, the compounds (# 1-2 ~ 21) were obtained using the corresponding ones.

compounds selected from the reference compounds (# 3-1 ~ 3), commercially available compounds or known compounds according to the compound synthesis procedure (No. 1-1). 2- (2-Cyclopropylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound # 1-2)

1H-NMR (500 MHz, CDCl3) δ 0.48-0.53 (m, 2H), 0.73-0.77 (m, 2H), 2.32 (s, 6H), 2.46 (m, 1H), 4.41 (s , 2H), 5.20 (sa, 1H), 6.67 (d, J = 5.2 Hz, 1H), 6.79 (s, 1H), 6.81 (s, 1H), 7.13 (dd, J = 7.6.4.9 Hz, 1H), 7.24 (s, 2H), 7.88 -7.91 (m, 2H), 7.93 (d, J = 5.2 Hz, 1H), 8.91 (dd, J = 4.9, 1.8 Hz, 1H)

2- [2- (N- (2-Dimethylaminoethyl) -N-methylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (compound No. 1-3)

1H-NMR (500 MHz, DMSO-d6) δ 2.13 (s, 6H), 2.25 (s, 6H), 2.33 (t, J = 7.0 Hz, 2H), 2.94 (s, 3H), 3.56 (t, J = 7.0 Hz, 2H), 4.30 (s, 2H), 6.53 (d, J = 5.2 Hz, 1H), 6.60 (s, 1H), 6.76 (s, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H), 7.31 (s, 2H ), 7.90 (dd, J = 7.6.1.5 Hz, 1H), 7.93 (d, J = 5.2 Hz, 1H), 8.59 (dd, J = 4.9, 1.5 Hz, 1H), 10.30 (s, 1H)

N- (3,5-Dimethylphenyl) -2- (2-morpholinopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound # 1-4) 1H-NMR (500 MHz, CDCl3) δ 2.32 (s, 6H), 3.47 (t, J = 4.9 Hz, 4H), 3.80 (t, J = 4.9 Hz, 4H), 4.40 (s, 2H) , 6.70 (s, 1H), 6.72 (d, J = 5.2 Hz, 1H), 6.82

(s, 1H), 7.15 (dd, J = 7.6.4.8 Hz, 1H), 7.24 (s, 2H), 7.76 (s, 1H), 7.90 (dd, J = 7.6.1.5 Hz, 1H), 8.10 (d, J = 5.2 Hz, 1H), 8.54 (dd, J = 4.8, 1.5 Hz, 1H) N- (3,5-Dimethylphenyl) -2- [2- (piperidin-1-yl) pyridin-4-ylmethylthio] pyridin-3-carboxamide (compound # 1-5)

1H-NMR (500 MHz, DMSO-d6) δ 1.46-1.60 (m, 6H), 2.25 (s, 6H), 3.46 (t, J = 5.2 Hz, 4H), 4.30 (s, 2H), 6, 58 (d, J = 6.1 Hz, 1H), 6.76 (s, 1H), 6.82 (s, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H), 7.32 (s, 2H), 7.91 (m, 1H), 7.96 (m, 1H), 8.58 (dd, J = 4.9, 1.8 Hz, 1H), 10.30 (s, 1H)

2- [2- (4-Acetylpiperazin-1-yl) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound # 1-6) 1H-NMR (500 MHz, CDCl3) δ 2.13 (s, 3H), 2.32 (s, 6H), 3.46-3.49 (m, 2H), 3.54-3.56 (m, 2H), 3.59-3 , 61 (m, 2H), 3.70-3.73 (m, 2H), 4.39 (s, 2H), 6.72

(m, 1H), 6.82 (s, 1H), 7.00 (s, 1H), 7.15 (dd, J = 7.6.4.8 Hz, 1H), 7.24 (s, 2H), 7.75 (s, 1H), 7.89 (dd, J = 7.6.1.7 Hz, 1H),

8.09 (dd, J = 4.6.1.2 Hz, 1H), 8.54 (dd, J = 4.8.1.7 Hz, 1H) 2- [2- (4-tert-Butoxycarbonylpiperazin -1-yl) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound # 17)

1H-NMR (400 MHz, CDCl3) δ 1.47 (s, 9H), 2.29 (s, 6H), 3.49 (sa, 8H), 4.36 (s, 2H), 6.68 (d, J = 5.3 Hz, 1H), 6.70 (s, 1H), 6.80 (s, 1H), 7.08 (dd, J =

7.6.4.9 Hz, 1H), 7.29 (s, 2H), 7.85 (dd, J = 7.6.1.7 Hz, 1H), 8.05 (s, 1H), 8.07 (d, J = 5.3 Hz, 1H), 8.51 (dd, J = 4.9, 1.7 Hz, 1H) N- (3,5-Dimethylphenyl) -2- [2- (N- (2-hydroxyethyl) -N-methylamino) pyridin-4-ylmethylthio] pyridine-3-carboxamide (compound # 1-8) 1H-NMR (500 MHz, CDCl3) δ 2.17 (s, 1H), 2.32 (s, 6H), 3.02 (s, 3H), 3.66 (t, J = 5.0 Hz, 2H), 3.79 (t, J = 5.0 Hz, 2H), 4.38 (s, 2H), 6.59 (s, 1H), 6.63

(dd, J = 5,2,1,8 Hz, 1H), 6,81 (s, 1H), 7,13 (dd, J = 7,6, 4,9 Hz, 1H), 7,24 ( s, 2H), 7.87 (s, 1H), 7.89 (dd, J = 7.6.1.5 Hz, 1H), 7.94 (d, J = 5.2 Hz, 1H), 8.53 (dd, J = 4.9, 1.5 Hz, 1H) N- (3,5-Dimethylphenyl) -2- [2- (4-hydroxypiperidin-1-yl) pyridin-4-ylmethylthio] pyridin-3-carboxamide (compound # 1-9)

1H-NMR (500 MHz, CDCl3) δ 1.43 (s, 1H), 1.48-1.61 (m, 2H), 1.92-1.98 (m, 2H), 2.32 (s, 6H), 3.09-3 , 14 (m, 2H), 3.90 (m, 1H), 4.01-4.06 (m, 2H), 4.38 (s, 2H), 6.69 (dd, J = 5.1, 1.1 Hz, 1H), 6.73 (s, 1H), 6.82 (s, 1H), 7.14 (dd, J = 7.6.4.8Hz, 1H), 7.24 (s, 2H), 7.79 (s, 1H), 7.90 (d, J = 4.8 Hz, 1H), 8.08 (d, J = 5.1 Hz, 1H), 8.55 (dd, J = 4.8, 1.8 Hz, 1H)

N- (Indan-5-yl) -2- (2-morpholinopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound # 1-10) 1H-NMR (500 MHz, CDCl3) δ 2.03-2.13 (m, 2H), 2.85-2.94 (m, 4H), 3.47 (t, J = 4.9 Hz, 4H), 3.80 (t, J = 4.9Hz, 4H), 4.39 (s, 2H), 6.68-6.72 (m, 2H),

7.15 (dd, J = 7.6.4.8 Hz, 1H), 7.19 (d, J = 8.3 Hz, 1H), 7.24 (s, 1H), 7.58 (s , 1H), 7.81 (s, 1H), 7.91 (d, J = 7.6 Hz, 1H), 8.10 (d, J = 5.2 Hz, 1H), 8.54 (dd, J = 4.8.1.8 Hz, 1H) 2- [2- (4-Acetylpiperazin-1-yl) pyridin-4-ylmethylthio] -N- (indan-5-yl) -pyridin-3-carboxamide (compound No. 1-11)

1H-NMR (500 MHz, CDCl3) δ 2.09 (t, J = 7.3Hz, 2H), 2.13 (s, 3H), 2.87-2.94 (m, 4H), 3.47 (t, J = 5.2 Hz , 2H), 3.53-3.58 (m, 2H), 3.59-3.62 (m, 2H), 3.72 (t, J = 5.2 Hz, 2H), 4.39 (s, 2H), 6.72 (m, 2H), 7.15 (dd, J = 7.6.4.8 Hz , 1H), 7.19 (d, J = 8.9 Hz, 1H), 7.24 (s, 1H), 7.58 (s, 1H), 7.80 (s, 1H), 7.91 (d, J = 6.7 Hz, 1H), 8.09 (m, 1H), 8.54 (dd, J = 4,8,1,8 Hz, 1H)

2- (2-Morpholinopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound # 1-12) 1H-NMR (500 MHz, DMSO-d6) δ 3.38 (t, J = 4.8 Hz, 4H), 3.66 (t, J = 4.8 Hz, 4H), 4.33 (s, 2H), 6.70 (dd, J = 5.2.1.2 Hz, 1H), 6.86 (s, 1H), 7.31 (dd, J =

7.6.4.9 Hz, 1H), 7.37 (d, J = 8.6Hz, 2H), 7.80 (d, J = 8.6 Hz, 2H), 7.97 (dd, J = 7.6.1.8 Hz, 1H), 8.01 (d, J = 5.2 Hz, 1H), 8.62 (dd, J = 4.9, 1.8 Hz, 1H), 10.66 (s, 1H) 2- [2- (4-Acetylpiperazin-1-yl) pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (compound No. 1-13)

1H-NMR (400 MHz, CDCl3) δ 2.05 (s, 3H), 3.44-3.49 (m, 2H), 3.52-3.57 (m, 2H), 3.59-3.63 (m, 2H), 3 , 68-3.73 (m, 2H), 4.40 (s, 2H), 6.70-6.73 (m, 2H), 7.17 (dd, J = 7.6.4.9 Hz, 1H), 7.23 (d, J = 8.3 Hz, 2H), 7.64 (d, J = 8.3 Hz, 2H), 7.92 (dd, J = 7.6.1.7 Hz, 1H), 7.98 (s, 1H), 8.10 (dd, J = 5.1.0.7 Hz, 1H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H)

N- (3,5-Dimethylphenyl) -2- [2- (4-ethoxycarbonylpiperazin-1-yl) pyridin-4-ylmethylthio] pyridine-3-carboxamide (compound No. 1-14) 1H-NMR (400 MHz, DMSO-d6) δ 1.15-1.21 (m, 3H), 2.25 (s, 6H), 3.18-3.40 (m, 2H), 3.41-3.48 (m, 6H), 4 , 03-4.09 (m, 2H), 4.32 (s, 2H), 6.68 (d, J = 5.0

Hz, 1H), 6.76 (s, 1H), 6.88 (s, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H), 7.32 (s, 2H ), 7.91 (dd, J = 7.6.1.7 Hz, 1H), 8.00 (d, J = 5.0 Hz, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.31 (s, 1H) N- (3,5-Dimethylphenyl) -2- (2-thiomorpholinopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 1-15) 1H-NMR (400 MHz, DMSO-d6)

δ 2.25 (s, 6H), 2.49-2.56 (m, 4H), 3.84-3.87 (m, 4H), 4.30 (s, 2H), 6.62 (d , J = 5.3 Hz, 1H), 6.76 (s, 1H), 6.86 (s, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H), 7 , 32 (s, 2H), 7.91 (dd, J = 7.6.1.7 Hz, 1H), 7.98 (d, J = 5.3 Hz, 1H), 8.59 (dd, J = 4.9, 1.7Hz, 1H), 10.31 (s, 1H)

N- (3,5-Dimethylphenyl) -2- [2- (3-hydroxymethylpiperidin-1-yl) pyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 1-16)

1H-NMR (500 MHz, DMSO-d6)

δ 1.14 (m, 1H 1.37-1.74 (m, 4H), 2.25 (s, 6H), 2.71-2.77 (m, 2H), 3.24-3.35 (m, 2H), 4.12 (d, J = 13.1Hz, 1H), 4.24 (d, J-13.1 Hz, 1H), 4.29 (s, 2H), 4.54 ( t, J = 5.2 Hz, 1H), 6.58 (d, J = 5.2 Hz, 1H), 6.76 (s, 1H), 6.82 (s, 1H), 7.27 ( dd, J = 7.6.4.9 Hz, 1H) 7.32 (s, 2H), 7.91 (dd, J = 7.6.1.6 Hz, 1H), 7.95 (d, J = 5.2 Hz, 1H), 8.59 (dd, J = 4.9, 1.6 Hz, 1H), 10.30 (s, 1H)

2- [2 - ((2S) -Dimethylaminocarbonylpyrrolidin-1-yl) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (compound No. 1-17)

1H-NMR (400 MHz, DMSO-d6)

δ 1.90-2.00 (m, 2H), 2.25 (s, 6H), 2.76 (s, 3H), 3.08 (s, 3H), 3.20-3.45 (m , 4H), 4.27 (d, J = 13.6Hz, 1H), 4.33 (d, J =, 13.6 Hz, 1H), 4.87 (m, 1H), 6.41 (s , 1H) 6.53 (dd, J = 5.4, 1.3 Hz, 1H), 6.75 (s, 1H), 7.27 (dd, J = 7.5.4.9 Hz, 1H ), 7.32 (s, 2H), 7.87 (d, J = 5.4 Hz, 1H), 7.89 (dd, J = 7.5.1.7 Hz, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.32 (s, 1H)

2- [2- (3-Dimethylaminopyrrolidin-1-yl) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound # 1-18)

1H-NMR (400 MHz, DMSO-d6)

δ 1.75 (m, 1H), 2.11 (m, 1H), 2.17 (s, 6H), 2.25 (s, 6H), 2.74 (m, 1H) 3.04 (m , 1H), 3.28 (m, 1H), 3.50 (t, J = 8.5 Hz, 1H), 3.60 (dd, J = 9.8.7.1 Hz, 1H) 4, 30 (s, 2H), 6.48 (s, 1H), 6.54 (dd, J = 5.1, 1.2 Hz, 1H), 6.76 (s, 1H), 7.27 (dd , J = 7.8.5.0 Hz, 1H), 7.32 (s, 2H), 7.89-7.93 (m, 2H), 8.59 (dd, J = 5.0.1 , 7 Hz, 1H), 10.30 (s, 1H)

N- (3,5-Dimethylphenyl) -2- [2- (2-hydroxyethylamino) pyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 1-19)

1H-NMR (400 MHz, CDCl3)

δ 2.32 (s, 6H), 2.88 (s, 1H), 3.43 (t, J = 4.6 Hz, 2H), 3.74 (t, J = 4.6 Hz, 2H) , 4.34 (s, 2H), 5.08 (s, 1H), 6.52 (s, 1H), 6.63 (dd, J = 5.4.1.2 Hz, 1H), 6, 81 (d, J = 0.8 Hz, 1H), 7.11 (dd, J = 7.8.4.8 Hz, 1H), 7.24 (s, 2H), 7.83-7.93 (m, 3H), 8.51 (dd, J = 4.8.1.7 Hz, 1H)

N- (3,5-Dimethylphenyl) -2- (2-n-pentylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 1-20)

1H-NMR (500 MHz, CDCl3)

δ 0.86-0.92 (m, 3H), 1.20-1.38 (m, 4H), 1.55-1.60 (m, 2H), 2.31 (s, 6H), 3 , 18-3.20 (m, 2H), 4.35 (s, 2H), 4.57 (s, 1H), 6.41 (s, 1H), 6.58 (dd, J = 5.2 , 1.5Hz, 1H), 6.80 (s, 1H), 7.09 (dd, J = 7.6.4.9 Hz, 1H), 7.24 (s, 2H), 7.86 ( dd, J = 7.6.1.7 Hz, 1H), 7.94 (d, J = 5.2 Hz, 1H), 8.02 (s, 1H), 8.51 (dd, J = 4 , 9, 1.7 Hz, 1H)

N- (3,5-Dimethylphenyl) -2- [2- (4-ethoxycarbonylpiperidin-1-yl) pyridin-4-ylmethylthio] pyridine-3-carboxamide (compound # 1-21)

1H-NMR (500 MHz, DMSO-d6)

δ 1.18 (t, J = 7.0Hz, 3H), 1.48-1.51 (m, 2H), 1.82-1.86 (m, 2H), 2.25 (s, 6H) , 2.57 (m, 1H), 2.86-2.93 (m, 2H), 4.06 (q, J = 7.0 Hz, 2H), 4.13-4.16 (m, 2H ), 4.30 (s, 2H), 6.62 (dd, J = 5.2.1, 1 Hz, 1H), 6.76 (s, 1H), 6.87 (s, 1H), 7 , 28 (dd, J = 7.6.4.9 Hz, 1H), 7.32 (s, 2H), 7.91 (dd, J = 7.6.1.7 Hz, 1H), 7, 98 (d, J = 5.2 Hz, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.31 (s, 1H)

Example 2

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (compound # 2-1)

O- (7-Azabenzotriazol-1-yl) -N, N, N ', N'-tetramethyluronium hexafluorophosphate (630 mg, 1.7 mmol) was added to a solution of 2- (2-tert-butoxycarbonylaminopyridine) 4-ylmethylthio) pyridine-3-carboxylic acid (reference compound No. 9-1, 500 mg, 1.4 mmol), 3,5-xylidine (180 mg, 1.5 mmol) and N, N-diisopropylethylamine ( 0.72 ml, 4.1 mmol) in N, N-dimethylformamide (7 ml) at room temperature, and the mixture was stirred for 12 hours. Ethyl acetate (30 ml) was added to the reaction mixture, then the whole was washed with brine (50 ml) and dried over anhydrous magnesium sulfate. The organic phase was evaporated under reduced pressure, then the resulting residue was purified by silica gel column chromatography to provide 670 mg of the objective compound quantitatively as a colorless solid.

1H-NMR (500 MHz, DMSO-d6) δ 1.45 (s, 9H), 2.25 (s, 6H), 4.38 (s, 2H), 6.76 (s, 1H), 7.03 (d, J = 5.2Hz, 1H ), 7.28 (dd, J = 7.6.4.9Hz, 1H), 7.32 (s, 2H), 7.87

(s, 1H), 7.92 (dd, J = 7.6.1.8 Hz, 1H), 8.11 (d, J = 5.2 Hz, 1H), 8.57 (dd, J = 4.9, 1.8 Hz, 1H), 9.66 (s, 1H), 10.30 (s a, 1H) As described below, the compounds (No. 2-2 ~ 36) were obtained using the corresponding ones.

compounds selected from the reference compounds (# 9-1 ~ 6), commercially available compounds or known compounds according to the method of synthesis of the compound (No. 2-1). 2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridine-3-carboxamide (compound No. 2-2)

1H-NMR (500 MHz, DMSO-d6) δ 1.20 (d, J = 7.0 Hz, 6H), 1.45 (s, 9H), 2.86 (m, 1H), 4.39 (s, 2H), 7.00 (d, J = 7.6 Hz, 1H), 7.04 (dd, J = 4.9, 1.5 Hz, 1H), 7.24-7.30 (m, 2H), 7.51 (d, J = 7.6 Hz, 1H), 7.59 (s, 1H), 7.87 (s, 1H), 7.96 (dd, J = 7.6.1.5Hz, 1H), 8.11 (m, 1H), 8.58 (dd, J = 4.9, 1.5 Hz, 1H), 9.66 (s, 1H), 10.39 (s, 1H)

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (indan-5-yl) pyridin-3-carboxamide (compound # 2-3) 1H-NMR (500 MHz, DMSO-d6) δ1.45 (s, 9H), 1.98-2.04 (m, 2H), 2.80-2.89 (m, 4H), 4.38 (s, 2H), 7.03 (dd, J = 4.9, 1.5 Hz, 1H), 7.17 (d, J = 8.2 Hz, 1H),

7.28 (dd, J = 7.6.4.9Hz, 1H), 7.38 (d, J = 8.2Hz, 1H), 7.61 (s, 1H), 7.87 (s, 1H ), 7.93 (dd, J = 7.6.1.5 Hz, 1H), 8.11 (d, J = 4.9 Hz, 1H), 8.57 (dd, J = 4.9, 1.5 Hz, 1H), 9.67 (s, 1H), 10.33 (s, 1H) 2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound # 2-4)

1H-NMR (500 MHz, DMSO-d6) δ1.45 (s, 9H), 4.39 (s, 2H), 7.03 (d, J = 5.2 Hz, 1H), 7.30 (dd, J = 7.6.4.9 Hz , 1H), 7.37 (d, J = 8.2 Hz, 2H), 7.81 (d, J = 8.2 Hz, 2H), 7.87 (s, 1H), 7.98 (dd, J = 7.6.1.8 Hz, 1H), 8.11 (d, J = 5.2 Hz, 1H), 8.60 (dd, J = 4.9, 1.8 Hz, 1H), 9.67 (s, 1H), 10.66 (s, 1 H)

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) pyridine-3-carboxamide (compound No. 2-5) 1H-NMR (500 MHz, DMSO-d6) δ 1.27 (s, 9H), 1.45 (s, 9H), 4.38 (s, 2H), 7.03 (d, J = 5.2 Hz, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H), 7.36 (d, J = 8.8 Hz, 2H),

7.60 (d, J = 8.8Hz, 2H), 7.87 (s, 1H), 7.94 (dd, J = 7.6.1.5Hz, 1H), 8.11 (d, J = 5.2 Hz, 1H), 8.58 (dd, J = 4.9, 1.5 Hz, 1H), 9.67 (s, 1H), 10.39 (s, 1H) 2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) pyridin-3-carboxamide (compound No. 2-6)

1H-NMR (500 MHz, DMSO-d6) δ 1.45 (s, 9H), 4.40 (s, 2H), 7.04 (d, J = 5.2 Hz, 1H), 7.24 (d, J = 8.3 Hz, 1H) , 7.31 (dd, J = 7.6.4.9Hz, 1H), 7.69 (d, J = 8.3 Hz, 1H), 7.87 (s, 1H), 7.97-8.00 (m, 2H), 8.11 (d, J = 5.2 Hz, 1H), 8.21 (s, 1H ), 8.60 (dd, J = 4.9, 1.6 Hz, 1H), 9.68 (s, 1H), 10.60 (s, 1H), 12.95 (s, 1H)

2- [2- (N-tert-Butoxycarbonyl-N-methylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (compound No. 2-7)

1H-NMR (500 MHz, DMSO-d6) δ 1.41 (s, 9H), 2.25 (s, 6H), 3.24 (s, 3H), 4.41 (s, 2H), 6.76 (s, 1H), 7.15 ( d, J = 5.2 Hz, 1H), 7.28 (dd, J = 7.6.4.9Hz, 1H), 7.31 (s, 2H), 7.64 (s, 1H), 7.93 (dd, J = 7.6.1.5Hz, 1H), 8.25 (d, J = 5.2 Hz, 1H), 8.58 (dd, J = 4.9, 1.5 Hz, 1H), 10.29 (s, 1H)

2- [2- (N-tert-Butoxycarbonyl-N-methylamino) pyridin-4-ylmethylthio] -N- (indan-5-yl) pyridin-3-carboxamide (compound # 2-8) 1H-NMR (500 MHz, DMSO-d6) δ 1.41 (s, 9H), 2.01 (t, J = 7.3 Hz, 2H), 2.80-2.86 (m, 4H), 3.24 (s, 3H), 4, 41 (s, 2H), 7.14-7.18 (m, 2H), 7.28 (dd, J =

7.6.4.9 Hz, 1H), 7.38 (d, J = 8.6 Hz, 1H), 7.61 (s, 1H), 7.64 (s, 1H), 7.92 ( dd, J = 7.6.1.8 Hz, 1H), 8.24 (d, J = 4.9 Hz,

1H), 8.58 (dd, J = 4.9, 1.8 Hz, 1H), 10.33 (s, 1H) 2- [2- (N-tert-Butoxycarbonyl-N-methylamino) pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound # 2-9)

1H-NMR (500 MHz, DMSO-d6) δ 1.40 (s, 9H), 3.24 (s, 3H), 4.43 (s, 2H), 7.15 (dd, J = 5.2.1.5 Hz, 1H), 7, 31 (dd, J = 7.6, 4.9 Hz, 1H), 7.37 (d, J = 8.6

Hz, 2H), 7.63 (s, 1H), 7.80 (d, J = 9.2Hz, 2H), 7.99 (dd, J = 7.6.1.8 Hz, 1H), 8 , 23 (d, J-5.2 Hz, 1H), 8.60 (dd, J = 4.9, 1.8Hz, 1H), 10.65 (s, 1H) 2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridine-3-carboxamide (compound No. 2-10) 1H-NMR (500 MHz, DMSO-d6) δ 1.45 (s, 9H), 4.39 (s, 2H), 7.03 (d, J = 5.2 Hz, 1H), 7.29 (dd, J = 7.6.4.9 Hz, 1H), 7.41 (d, J = 8.9Hz, 2H), 7.72 (d, J = 8.9

Hz, 2H), 7.87 (s, 1H), 7.98 (dd, J = 7.6.1.5Hz, 1H), 8.10 (d, J = 5.2 2Hz, 1H), 8 , 59 (dd, J = 4.9, 1.5 Hz, 1H), 9.66 (s, 1H), 10.60

(s, 1H) 2- [2- (N-tert-Butoxycarbonyl-N-ethylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (compound No. 211)

1H-NMR (400 MHz, CDCl3) 1.19 (t, J = 6.9 Hz, 3H), 1.47 (s, 9H), 2.31 (s, 6H), 3.94 (q, J = 6.9 Hz, 2H), 4.45 (s, 2H), 6.79 (s, 1H), 7.04 (dd, J = 5.1,

1.4Hz, 1H), 7.14 (dd, J = 7.6.4.9 Hz, 1H), 7.22 (s, 2H), 7.56 (s, 1H), 7.86 (dd , J = 7.6.1.8Hz, 1H), 7.97 (s, 1H), 8.25 (d, J = 5.1Hz, 1H), 8.55 (dd, J = 4.9, 1.8Hz, 1H) 2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3-chlorophenyl) pyridine-3-carboxamide (compound No. 2-12) 1H-NMR (500 MHz, DMSO-d6) δ 1.45 (s, 9H), 4.39 (s, 2H), 7.03 (d, J = 5.2 Hz, 1H), 7.19 (d, J = 8.2Hz, 1H), 7.30 (dd, J = 7.6.4.9Hz, 1H), 7.38 (t, J =

8.1Hz, 1H), 7.59 (d, J = 8.2Hz, 1H), 7.87 (s, 1H), 7.89 (s, 1H), 7.99 (dd, J = 7 , 6.1.8 Hz, 1H), 8.11 (d, J = 5.2 Hz, 1H), 8.60 (dd, J = 4.9, 1.8 Hz, 1H), 9.67 (s, 1H), 10.64 (s, 1H 2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) pyridin-3-carboxamide (compound No. 2-13)

1H-NMR (400 MHz, DMSO-d6) δ 1.45 (s, 9H), 4.40 (s, 2H), 7.05 (dd, J = 5.2.1.5 Hz, 1H), 7.28 (dd, J = 7.6 , 4.9 Hz, 1H), 7.58 (ddd, J = 7.1.6.8.1.0 Hz, 1H), 7.75 (ddd, J = 7.1.6.8.1.0 Hz, 1H), 7.88 (sa, 1H), 7.98 (d, J = 7.1 Hz, 1H), 8 , 06 (dd, J = 7.6.1.7 Hz, 1H), 8.08 (sa, 1H), 8.11 (d, J = 5.2Hz, 1H), 8.59 (dd, J = 4.9, 1.7Hz, 1H), 8.59 (d, J = 1.0Hz, 1H), 9.19 ( s, 1H), 9.68 (s, 1H), 11.16 (s, 1H)

2- [2- (N-tert-Butoxycarbonyl-N-methylamino) pyridin-4-ylmethylthio] -N- (4-chlorophenyl) pyridine-3-carboxamide (compound No. 214)

1H-NMR (400 MHz, DMSO-d6) δ 1.40 (s, 9H), 3.24 (s, 3H), 4.42 (s, 2H), 7.15 (dd, J = 5.2.1.7 Hz, 1H), 7, 30 (dd, J = 7.6, 4.9 Hz, 1H), 7.41 (d, J = 8.9 Hz, 2H), 7.63 (s, 1H), 7.72 (d, J = 8.9Hz, 2H), 7.98 (dd, J = 7.6.1.7 Hz, 1H), 8 , 24 (d, J = 5.2 Hz, 1H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 10.58 (s, 1H)

2- [2- (N-tert-Butoxycarbonyl-N-methylamino) pyridin-4-ylmethylthio] -N- (3-chlorophenyl) pyridin-3-carboxamide (compound No. 215)

1H-NMR (400 MHz, DMSO-d6) δ 1.40 (s, 9H), 3.24 (s, 3H), 4.43 (s, 2H), 7.16-7.18 (m, 2H), 7.31 (dd, J = 7 , 6.4.9 Hz, 1H), 7.38 (t, J = 8.1 Hz, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.63 (s, 1H), 7.88 (t, J = 2.0 Hz, 1H), 7.99 (dd, J = 7.6, 1.7 Hz, 1H), 8.24 (dd, J = 5.0.0.6 Hz, 1H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 10.63 (s, 1H)

2- [2- (N-tert-Butoxycarbonyl-N-methylamino) pyridin-4-ylmethylthio] -N- (4-tert-butylphenyl) pyridine-3-carboxamide (compound No. 2-16)

1H-NMR (400 MHz, DMSO-d6) δ 1.27 (s, 9H), 1.40 (s, 9H), 3.24 (s, 3H), 4.41 (s, 2H), 7.15 (dd, J = 5.2.1 , 6 Hz, 1H), 7.29 (dd, J = 7.6.4.9 Hz, 1H), 7.36 (d, J = 8.8 Hz, 2H), 7.60 (d, J = 8.8 Hz, 2H), 7.63 (s, 1H), 7.94 (dd, J = 7.6, 1.7 Hz, 1H), 8.24 (d, J = 5.1 Hz, 1H), 8.58 (dd, J = 4.9, 1.7 Hz, 1H), 10.37 (s, 1H)

2- [2- (N-tert-Butoxycarbonyl-N-methylamino) pyridin-4-ylmethylthio] -N- (isoquinolin-3-yl) pyridin-3-carboxamide (compound No. 2-17)

1H-NMR (500 MHz, DMSO-d6) δ 1.39 (s, 9H), 3.24 (s, 3H), 4.43 (s, 2H), 7.16 (dd, J = 5.2.1.5 Hz, 1H), 7, 28 (dd, J = 7.6, 4.9 Hz, 1H), 7.58 (t, J = 7.6 Hz, 1H), 7.64 (s, 1H), 7.75 (t, J = 8.1 Hz, 1H), 7.97 (d, J = 8.1 Hz, 1H), 8.05- 8.10 (m, 2H), 8.25 (d, J = 5.2 Hz, 1H), 8,598.60 (m, 2H), 9.19 (s, 1H), 11.15 (s, 1H )

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- [2- (4-methoxyphenyl) ethyl] pyridin-3-carboxamide (compound # 2-18) 1H-NMR (500 MHz, DMSO-d6) δ 1.46 (s, 9H), 2.75 (t, J = 7.3 Hz, 2H), 3.35-3.41 (m, 2H), 3.71 (s, 3H), 4, 33 (s, 2H), 6.83 (d, J = 8.5 Hz, 2H), 7.02 (dd, J =

4.9, 1.2 Hz, 1H), 7.15 (d, J = 8.5 Hz, 2H), 7.21 (dd, J = 7.6.4.9 Hz, 1H), 7, 73 (dd, J = 7.6.1.7 Hz, 1H), 7.87 (sa, 1H), 8.11 (d, J = 4.9Hz, 1H), 8.52 (dd, J = 4.9, 1.7Hz, 1H), 8.58 (t, J = 5.4Hz, 1H), 9.68 ( s, 1H) N- (Adamantan-1-yl) -2- (2-tert-butoxycarbonylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 2-19)

1H-NMR (400 MHz, DMSO-d6) δ 1.47 (s, 9H), 1.64 (sa, 6H), 2.03 (sa, 9H), 4.35 (s, 2H), 7.03 (dd, J = 5.4.1 , 5 Hz, 1H), 7.17 (dd, J = 7.6.4.9 Hz, 1H), 7.67 (dd, J = 7.6.1.7 Hz, 1H), 7.85-7.92 (m, 2H), 8.11 (d, J = 5.4 Hz, 1H), 8.48 ( dd, J = 4.9, 1.7 Hz, 1H), 9.68 (s, 1H)

2- [2- (N-tert-Butoxycarbonyl-N-methylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) -N-methylpyridine-3-carboxamide (compound # 2-20)

1H-NMR (400 MHz, DMSO-d6) δ 1.44 (s, 9H), 2.04 (s, 6H), 3.25 (s, 3H), 3.32 (s, 3H), 4.43 (s, 2H), 6.73- 6.78 (m, 3H), 6.98 (m, 1H), 7.10 (d, J = 5.1 Hz, 1H), 7.41 (m, 1H), 7.67 (s, 1H), 8.25 (d, J = 5.1 Hz, 1H), 8.33 (m, 1H)

N- (3,5-Dimethylphenyl) -2- (2-phthaloylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 2-21) 1H-NMR (900 MHz, DMSO-d6) δ 2.25 (s, 6H), 4.50 (s, 2H), 6.76 (s, 1H), 7.29 (dd, J = 7.6.4.9 Hz, 1H), 7, 32 (s, 2H), 7.56 (d, J = 5.1 Hz, 1H), 7.61 (s, 1H),

7.94-8.00 (m, 5H), 8.52 (d, J = 5.1 Hz, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10 , 32 (s, 1H) N- (4-Chlorophenyl) -2- [2- (5-cyanothiazol-2-ylamino) pyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 2-22) 1H-NMR (400 MHz, DMSO-d6) δ 4.43 (s, 2H), 7.11 (d, J = 5.1 Hz, 1H), 7.21 (s, 1H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.42 (d, J = 8.8 Hz, 2H), 7.73

(d, J = 8.8Hz, 2H), 7.99 (dd, J = 7.6.1.7 Hz, 1H), 8.25 (s, 1H), 8.28 (d, J = 5 , 1Hz, 1H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 10.60 (s, 1H), 12.20 (s, 1H)

2- [2- (5-Cyanothiazol-2-ylamino) pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (compound No. 2-23) 1H-NMR (400 MHz, DMSO-d6) δ 4.43 (s, 2H), 7.11 (d, J = 5.1Hz, 1H), 7.22 (s, 1H), 7.32 (dd, J = 7.6.4.9 Hz , 1H), 7.38 (d, J = 8.3 Hz, 2H), 7.81 (d, J = 8.3

Hz, 2H), 8.00 (dd, J = 7.6.1.7Hz, 1H), 8.25 (s, 1H), 8.28 (d, J = 5.1Hz, 1H), 8, 61 (dd, J = 4.9, 1.7 Hz, 1H), 10.67 (s, 1H), 12.21 (s, 1H) 2- [2- (5-Cyanothiazol-2-ylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound No. 2-24)

1H-NMR (500 MHz, DMSO-d6) δ 2.25 (s, 6H), 4.42 (s, 2H), 6.76 (s, 1H), 7.11 (d, J = 5.2 Hz, 1H), 7.21 (s, 1H), 7.29 (dd, J = 7.6.4.9Hz, 1H), 7.32 (s, 2H), 7.94 (dd, J = 7.6.1.5 Hz, 1H), 8.25 (s, 1H), 8.28 (d, J = 5.2 Hz, 1H), 8.58 (dd , J = 4.9, 1.5 Hz, 1H), 10.31 (s, 1H), 12.21 (s, 1H)

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) benzamide (compound No. 2-25) 1H-NMR (500 MHz, DMSO-d6) δ 1.45 (s, 9H), 4.22 (s, 2H), 6.99 (d, J = 5.2 Hz, 1H), 7.30 (t, J = 7.6 Hz, 1H) , 7.40 (d, J = 8.6 Hz, 2H), 7.42 (t, J = 7.6

Hz, 1H), 7.48 (d, J = 7.6 Hz, 1H), 7.52 (d, J = 7.6 Hz, 1H), 7.75 (d, J = 8.6 Hz, 2H), 7.83 (s, 1H), 8.11 (d, J = 5.2 Hz, 1H), 9.68 (s, 1 H), 10.48 (s, 1 H) 2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) benzamide (compound No. 2-26)

1H-NMR (500 MHz, DMSO-d6) δ 1.27 (s, 9H), 1.45 (s, 9H), 4.22 (s, 2H), 7.00 (d, J = 5.2 Hz, 1H), 7.28 (t, J = 7.6 Hz, 1H), 7.34 (d, J = 8.6 Hz, 2H), 7.40 (t, J = 7.6 Hz, 1H), 7.46 (d, J = 7.6Hz, 1H), 7.49 (d, J = 7.6Hz, 1H), 7.62 (d, J = 8.6 Hz, 2H), 7.84 (s, 1H), 8.11 (d, J = 5.2 Hz, 1H), 9.70 (s, 1H), 10.27 (s, 1H)

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) benzamide (compound No. 2-27) 1H-NMR (500 MHz, DMSO-d6) δ 1.45 (s, 9H), 4.23 (s, 2H), 6.99 (d, J = 5.2 Hz, 1H), 7.30 (t, J = 7.6 Hz, 1H) , 7.35 (d, J = 8.6 Hz, 2H), 7.43 (t, J = 7.6 Hz,

1H), 7.49 (d, J = 7.6 Hz, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.83 (d, J = 8.6 Hz, 2H) , 7.84 (s, 1H), 8.11 (d, J = 5.2 Hz, 1H), 9.68 (s, 1H), 10.55 (s, 1H) 2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) benzamide (compound No. 2-28)

1H-NMR (400 MHz, DMSO-d6) δ 1.44 (s, 9H), 4.24 (s, 2H), 7.01 (d, J = 5.1 Hz, 1H), 7.30 (d, J = 7.3 Hz, 1H) , 7.43 (t, J = 8.3 Hz, 1H), 7.47 (d, J = 7.1 Hz, 1H), 7.57 (t, J = 8.3 Hz, 1H), 7.61 (d, J = 7.3 Hz, 1H), 7.74 (t, J = 8.3 Hz, 1H), 7.84 (sa, 1H), 7.97 (d, J = 8.3 Hz, 1H), 8.08 (d, J = 8.3 Hz, 1H), 8.11 (d, J = 5.1 Hz, 1H), 8.60 (s, 1H), 9.18 (s, 1H) 9.71 (s, 1H) 10.96 (s, 1H)

2- (2-tert-Butoxycarbonylaminopyridin-9-ylmethylthio) -N- (3-isopropylphenyl) benzamide (compound No. 2-29) 1H-NMR (500 MHz, DMSO-d6) δ 1.20 (d, J = 6.7 Hz, 6H), 1.45 (s, 9H), 2.86 (m, 1H), 4.23 (s, 2H), 6.98 (d, J = 7.6 Hz, 1H), 7.01 (d, J = 5.2 Hz, 1H), 7.24

(t, J = 7.6 Hz, 1H), 7.28 (t, J = 7.6 Hz, 1H), 7.41 (t, J = 7.6 Hz, 1H), 7.46 (d , J = 7.6 Hz, 1H), 7.50-7.55 (m, 2H), 7.62 (s a, 1H), 7.84 (s, 1H), 8.12 (d, J = 5.2 Hz, 1H), 9.70 (s, 1H), 10.28 (s, 1H) 2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (4-chloro-3-methylphenyl) benzamide (compound # 2-30)

1H-NMR (500 MHz, DMSO-d6) δ 1.45 (s, 9H), 2.32 (s, 3H), 4.25 (s, 2H), 6.99 (d, J = 5.2 Hz, 1H), 7.29 (t, J = 7.3 Hz, 1H), 7.36 (t, J = 8.6 Hz, 1H), 7.45 (m, 1H), 7.51 (d, J = 7.3Hz, 1H), 7.54 (d, J = 8.6Hz, 1H), 7.72-7.80 (m, 2H), 7 , 84 (sa, 1H), 8.11 (d, J = 5.2 Hz, 1H), 9.70 (s, 1H), 10.41 (s, 1H)

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) benzamide (compound # 2-31)

1H-NMR (500 MHz, DMSO-d6) δ 1.44 (s, 9H), 4.24 (s, 2H), 7.00 (d, J = 5.2 Hz, 1H), 7.26 (d, J = 8.6 Hz, 1H) , 7.30 (t, J = 8.6 Hz, 1H), 7.43 (t, J = 8.6 Hz,

1H), 7.48 (d, J = 7.3 Hz, 1H), 7.54 (d, J = 7.3Hz, 1H), 7.68 (d, J = 8.6 Hz, 1H), 7.84 (s, 1H), 7.99 (sa, 1H), 8.11 (d, J = 5.2 Hz, 1H), 8.25 (s, 1H), 9.69 (s, 1H), 10.49 (s, 1H), 12.93 (s, 1H) 2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) benzamide (compound No. 2-32) 1H-NMR (500 MHz, DMSO-d6) δ 1.45 (s, 9H), 2.25 (s, 6H), 4.22 (s, 2H), 6.74 (s, 1H), 7.00 (dd, J = 4.91.2Hz , 1H), 7.28 (t, J = 7.3Hz, 1H), 7.35 (s, 2H), 7.41

(m, 1H), 7.45 (s, 1H), 7.48 (t, J = 7.3Hz, 1H), 7.84 (s, 1H), 8.12 (d, J = 4.9 Hz, 1H), 9.69 (s, 1H), 10.18 (s, 1H) 3- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) thiophene-2-carboxamide (compound No. 2-33) 1H-NMR (400 MHz, DMSO-d6) δ 1.45 (s, 9H), 2.25 (s, 6H), 4.26 (s, 2H), 6.74 (s, 1H), 6.95 (d, J = 5.1 Hz, 1H), 7.24 (s, 2H), 7.24 (d, J = 5.1 Hz, 1H), 7.82

(s, 1H), 7.83 (s, 1H), 8.11 (d, J = 5.1 Hz, 1H), 9.71 (s, 1H), 9.82 (s, 1H)

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3,5-dimethyl-4-hydroxyphenyl) pyridine-3-carboxamide (compound No. 234) 1H-NMR (400 MHz, DMSO-d6) δ1.46 (s, 9H), 2.15 (s, 6H), 4.37 (s, 2H), 7.03 (dd, J = 5.0.1.3 Hz, 1H), 7.23 (s, 2H), 7.26 (dd, J = 7.6.4.9 Hz, 1H), 7.87

(s, 1H), 7.90 (dd, J = 7.6.1.6 Hz, 1H), 8.10-8.12 (m, 2H), 8.56 (dd, J = 4.9 , 1.6 Hz, 1H), 9.68 (s, 1H), 10.09 (s, 1H)

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3-chloro-4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 2-35) 1H-NMR (500 MHz, DMSO-d6) δ 1.45 (s, 9H), 4.40 (s, 2H), 7.03 (dd, J = 5.2.1.5 Hz, 1H), 7.32 (dd, J = 7.6 , 4.9 Hz, 1H), 7.58 (dd, J = 8.9.1.2 Hz, 1H), 7.71

(dd, J = 8.9.2.4 Hz, 1H), 7.87 (s, 1H), 8.01 (dd, J = 7.6.1.8 Hz, 1H), 8.08 ( d, J = 2.4Hz, 1H), 8.10 (d, J = 5.2Hz, 1H), 8.61 (dd, J = 4.9, 1.8 Hz, 1H), 9.67 (s, 1H), 10.81 (s, 1H) 2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3-trifluoromethylphenyl) pyridine-3-carboxamide (compound No. 2-36)

1H-NMR (500 MHz, DMSO-d6) δ 1.45 (s, 9H), 4.40 (s, 2H), 7.04 (d, J = 5.2 Hz, 1H) 7.32 (dd, J = 7.6.4.9 Hz , 1H), 7.48 (d, J = 7.9Hz, 1H), 7.60 (t, J = 7.9 Hz, 1H), 7.88 (s, 1H), 7.91 (d, J = 7.9Hz, 1H), 8.03 (dd, J = 7.6.1.8 Hz, 1H), 8 , 11 (d, J = 5.2 Hz, 1H), 8.18 (s, 1H), 8.61 (dd, J = 4.9, 1.8 Hz, 1H), 9.67 (s, 1H), 10.79 (s, 1H)

Example 3

2- (2-Aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide monohydrochloride (compound # 3-1)

A solution of 4 N hydrochloric acid in 1,4-dioxane (5.0 ml) was added to a solution of 2- (2-tert-butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3- Carboxamide (compound No. 2-1, 420 mg, 0.90mmol) in 1,4-dioxane (5.0mL) at room temperature, and the mixture was stirred for 12 hours. Ethanol (6.0 ml) was added to the reaction mixture, and the precipitated solid was filtered off. The solid was dried under reduced pressure at 60 ° C to provide 320 mg of the objective compound as a colorless crystal.

(Yield 88%) Or as described below, a free base of compound # 3-1 was synthesized.

N- (3,5-dimethylphenyl) -2-thioxo-1,2-dihydropyridine-3-carboxamide (reference compound No. 10-1, 100 g, 0.39 mol) and 2-amino hydrobromide were dissolved -4-Bromomethylpyridine (reference compound No. 14-1, 110 g, 0.40 mol) in N, N-dimethylformamide (840 ml) with ice cooling, then triethylamine (160 ml, 1) was added dropwise , 2 mol) thereto, and the mixture was stirred for 6 hours at room temperature. The reaction mixture was poured into water (2.5 L), and then the precipitated solid was filtered off and dried under reduced pressure at 45 ° C to provide 140 g of the free base of the objective compound quantitatively as a pale yellow solid.

1H-NMR (500 MHz, DMSO-d6)

δ 2.26 (s, 6H), 4.44 (s, 2H), 6.77 (s, 1H), 6.89 (d, J = 6.7 Hz, 1H), 7.03 (s, 1H), 7.32 (dd, J = 7.6, 4.9Hz, 1H), 7.34 (s, 2H), 7.84 (d, J = 6.7Hz, 1H), 7.97 (sa, 2H), 8.00 (dd, J = 7.6, 1.8 Hz, 1H), 8.56 (dd, J = 4.9, 1.8 Hz, 1H), 10.35 ( s, 1H), 13.40 (sa, 1H)

As described below, the compounds (No. 3-2-37) were obtained using the corresponding compounds selected from the reference compounds (No. 2-1-36), commercially available compounds or known compounds according to the compound synthesis procedure (# 3-1).

2- (2-Aminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridine-3-carboxamide monohydrochloride (compound No. 3-2)

1H-NMR (500 MHz, DMSO-d6)

δ 1.21 (d, J = 6.7 Hz, 6H), 2.87 (m, 1H), 4.41 (s, 2H), 6.89 (d, J = 6.7Hz, 1H), 7.00-7.03 (m, 2H), 7.27 (m, 1H), 7.32 (dd, J = 7.6.4.9 Hz, 1H), 7.53 (d, J = 7.3 Hz, 1H), 7.60 (s, 1H), 7.84 (d, J = 6.7 Hz, 1H), 7.95 (s, 2H), 8.04 (d, J = 7.6 Hz, 1H), 8.56 (d, J = 4.9 Hz, 1H), 10.44 (s, 1H) 13.33 (sa, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (indan-5-yl) pyridin-3-carboxamide monohydrochloride (compound # 3-3)

1H-NMR (500 MHz, DMSO-d6)

δ 1.91-2.05 (m, 2H), 2.81-2.90 (m, 4H), 4.40 (s, 2H), 6.89 (m, 1H), 7.03 (s , 1H), 7.19 (d, J = 7.6 Hz, 1H), 7.31 (dd, J = 7.6.4.9Hz, 1H), 7.41 (d, J = 7.6 Hz, 1H), 7.63 (s, 1H), 7.84 (d, J = 6.7 Hz, 1H), 8.00-8.05 (m, 3H), 8.56 (dd, J = 4.9, 1.5 Hz, 1H), 10.40 (s, 1H), 13.50 (sa, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) pyridine-3-carboxamide monohydrochloride (compound # 3-4)

1H-NMR (500 MHz, DMSO-d6)

δ 1.28 (s, 9H), 4.40 (s, 2H), 6.89 (dd, J = 7.7.1.5 Hz, 1H 7.03 (s, 1H), 7.32 ( dd, J = 7.7.4.9Hz, 1H), 7.37 (d, J = 8.8Hz, 2H), 7.62 (d, J = 8.8Hz, 2H), 7.84 (d, J = 6.4 Hz, 1H), 7.97 (s, 2H), 8.02 (dd, J = 7.7.1.5 Hz, 1H), 8.56 (dd, J = 4.9, 1.5 Hz, 1H), 10.44 (s, 1H), 13.42 (sa, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) pyridin-3-carboxamide monohydrochloride (compound 3-5)

1H-NMR (500 MHz, DMSO-d6)

δ 94.42 (s, 2H), 6.39 (sa, 1H), 6.89 (d, J = 6.4Hz, 1H), 7.06 (s, 1H), 7.29-7.36 (m, 2H), 7.70 (d, J = 8.5Hz, 1H), 7.85 (d, J = 6.4Hz, 1H), 8.02 (s, 1H), 8.02-8 , 16 (m, 3H), 8.23 (s, 1H), 8.58 (dd, J = 4.9, 1.5 Hz, 1H), 10.70 (s, 1H), 13.71 ( sa, 1H)

N- (3,5-dimethylphenyl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide monohydrochloride (compound # 3-6)

1H-NMR (500 MHz, DMSO-d6) δ 2.26 (s, 6H), 2.91 (d, J = 4.9Hz, 3H), 4.41 (s, 2H), 5.98 (sa, 1H), 6.77 (s, 1H ), 6.87 (dd, J = 7.7.1.5Hz, 1H), 7.10 (s, 1H),

7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.35 (s, 2H), 7.81 (d, J = 7.7 Hz, 1H), 8.00 (dd , J = 7.6.1.5 Hz, 1H), 8.57 (dd, J = 4.9, 1.5Hz, 1H), 10.39 (s, 1H), 13.48 (s at, 1H) N- (indan-5-yl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide monohydrochloride (compound # 3-7) 1H-NMR (400 MHz, DMSO-d6) δ 1.98-2.06 (m, 2H), 2.81-2.87 (m, 4H), 2.91 (d, J = 4.9 Hz, 3H), 4.40 (s, 2H ), 6.87 (dd, J = 6.8.1.5 Hz, 1H), 7.10 (s, 1H),

7.18 (d, J = 8.3Hz, 1H), 7.31. (Dd, J = 7.6.4.9Hz, 1H), 7.42 (d, J = 8.8Hz, 1H) , 7.63 (s, 1H), 7.80 (d, J = 6.6Hz, 1H), 8.01

(dd, J = 7.6.1.7 Hz, 1H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 8.97 (sa, 1H), 10.44 ( s, 1H), 13.43 (sa, 1H) 2- (2-Methylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide monohydrochloride (compound No. 3-8)

1H-NMR (500 MHz, DMSO-d6) δ 2.91 (d, J = 4.9Hz, 3H), 4.42 (s, 2H), 6.87 (dd, J = 6.7.1.5Hz, 1H), 7.09 (s, 1H), 7.33 (dd, J = 7.6.4.9 Hz, 1H), 7.38 (d, J =

8.2 Hz, 2H), 7.80-7.85 (m, 3H), 8.07 (dd, J = 7.6.1.8 Hz, 1H) 8.59 (dd, J = 4, 9, 1.8 Hz, 1H), 8.90 (sa, 1H), 10.77 (s, 1H), 13.32 (s a, 1H) 2- (2-Aminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridine-3-carboxamide monohydrochloride (compound # 3-9) 1H-NMR (500 MHz, DMSO-d6) δ 4.41 (s, 2H), 6.89 (d, J = 6.4 Hz, 1H), 7.03 (s, 1H), 7.33 (dd, J = 7.6.4.9 Hz, 1H), 7.43 (d, J = 8.6Hz, 2H), 7.75

(d, J = 8.6Hz, 2H), 7.84 (d, J = 6.4Hz, 1H), 7.96 (s, 2H), 8.06 (dd, J = 7.6.1, 5 Hz, 1H), 8.57 (dd, J = 4.9, 1.5 Hz, 1H), 10.66 (s, 1H), 13.40 (s a, 1H) 2- (2-Aminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (compound # 3-10)

1H-NMR (500 MHz, DMSO-d6) δ 4.25 (s, 2H), 5.83 (s, 2H), 6.45 (s, 1H), 6.48 (dd, J = 5.2.1.3 Hz, 1H), 7, 30 (dd, J = 7.8.4.8 Hz, 1H), 7.37 (d, J = 8.2 Hz, 2H), 7.77 (dd, J = 5.2 Hz, 1H), 7.81 (d, J = 8.2 Hz, 2H), 7.97 (d, J = 7.8.1 , 8 Hz, 1H), 8.60 (dd, J = 4,8,1,8 Hz, 1H), 10.67 (s, 1 H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (3-chlorophenyl) pyridin-3-carboxamide monohydrochloride (compound # 3-11) 1 H-NMR (400 MHz, DMSO-d6) δ 4.41 (s, 2H), 6.88 (d, J = 6.6 Hz, 1H), 7.05 (s, 1H), 7.19 (d, J = 8.1 Hz, 1H), 7.33 (dd, J = 7.6.4.9 Hz, 1H), 7.40

(t, J = 8.1Hz, 1H), 7.64 (d, J = 8.1Hz, 1H), 7.85 (d, J = 6.6Hz, 1H), 7.93 (s, 1H), 8.04 (sa, 2H), 8.08 (dd, J = 7.6.1.7 Hz, 1H), 8.58 (dd, J = 4.9, 1.7 Hz, 1H), 10.78 (s, 1H), 13.64 (s a, 1H) N- (3,5-Dimethylphenyl) -2- (2-ethylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 3-12)

1H-NMR (400 MHz, DMSO-d6) δ 1.08 (t, J = 7.2 Hz, 3H), 2.25 (s, 6H), 3.15-3.22 (m, 2H), 4.24 (s, 2H), 6, 39 (t, J = 5.5 Hz, 1H), 6.42-6.46 (m, 2H), 6.76 (s, 1H), 7.27 (dd, J = 7.4.4.8 Hz, 1H), 7.32 (s, 2H), 7.83 (d, J = 5.4 Hz, 1H) , 7.90 (dd, J = 7.4.1.5Hz, 1H), 8.57 (dd, J = 4,8,1,5 Hz, 1H), 10,30 (s, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) pyridin-3-carboxamide (compound No. 3-13) 1H-NMR (500 MHz, DMSO-d6) δ 4.25 (s, 2H), 5.83 (s, 2H), 6.46 (s, 1H), 6.49 (dd, J = 5.2.1.5 Hz, 1H), 7, 28 (dd, J = 7.6.4.9 Hz, 1H), 7.58 (ddd,

J = 7,9,7,9,1,2 Hz, 1H), 7.75 (ddd, J = 7,9,7,9,1,2Hz, 1H), 7.78 (d, J = 5 , 2Hz, 1H), 7.98 (d, J = 7.9 Hz, 1H), 8.04 (dd, J = 7.6.1.8 Hz, 1H), 8.09 (d, J 7 , 9 Hz, 1H), 8.59 (dd, J = 5.2.1.5 Hz, 1H), 8.59 (sa, 1H), 9.19 (sa, 1H), 11.15 (s , 1H) N- (4-Chlorophenyl) -2- (2-methylaminopyridin-9-ylmethylthio) pyridine-3-carboxamide (compound # 3-14) 1 H-NMR (400 MHz, DMSO-d6)

δ 2.71 (d, J = 4.9 Hz, 3H), 4.26 (s, 2H), 6.46-6.49 (m, 3H), 7.29 (dd, J = 7.6 , 4.9 Hz, 1H), 7.41 (dd, J = 6.7.2.1 Hz, 2H), 7.73 (d, J = 8.8 Hz, 2H), 7.85 (d, J = 5.1 Hz, 1H), 7.96 (dd, J = 7.6.1.7 Hz, 1H), 8 , 59 (dd, J = 4.9, 1.7 Hz, 1H), 10.60 (s, 1H) N- (3-Chlorophenyl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 3-15) 1H-NMR (400 MHz, DMSO-d6) δ 2.71 (d, J = 4.9 Hz, 3H), 4.26 (s, 2H), 6.42-6.49 (m, 3H), 7.18 (ddd, J = 8.1 , 2,0,0,9 Hz, 1H), 7,30 (dd, J = 7,6,4,9Hz, 1H),

7.39 (t, J = 8.1 Hz, 1H), 7.58 (d, J = 8.1 Hz, 1H), 7.85 (d, J = 5.1 Hz, 1H), 7, 89 (t, J = 2.0 Hz, 1H), 7.97 (dd, J = 7.6.1.7 Hz, 1H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 10.65 (s, 1H) N- (4-tert-Butylphenyl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound # 3-16)

1H-NMR (400 MHz, DMSO-d6) δ 1.27 (s, 9H), 2.71 (d, J = 4.9 Hz, 3H), 4.25 (s, 2H), 6.40-6.49 (m, 3H), 7, 28 (dd, J = 7.6.4.9 Hz, 1H), 7.36 (d, J = 8.8 Hz, 2H), 7.60 (d, J = 8.8Hz, 2H), 7.85 (d, J = 4.9 Hz, 1H), 7.92 (dd, J = 7.6.1.7 Hz , 1H), 8.58 (dd, J = 4.9, 1.7 Hz, 1H), 10.39 (s, 1H)

N- (Isoquinolin-3-yl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound # 3-17) 1H-NMR (400 MHz, DMSO-d6) δ 2.71 '(d, J = 4.9 Hz, 3H), 4.27 (s, 2H), 6.39-6.50 (m, 3H), 7.27 (dd, J = 7, 6.4.8 Hz, 1H), 7.58 (m, 1H), 7.75 (m, 1H), 7.85

(d, J = 5.4 Hz, 1H), 7.98 (d, J = 8.1Hz, 1H), 8.04 (dd, J = 7.6.1.7Hz, 1H), 8.09 (d, J = 8.3 Hz, 1H), 8.58-8.60 (m, 2H), 9.19 (s, 1H), 11.16 (s, 1H) N- (Adamantan-1-yl) -2- (2-aminopyridin-4-ylmethylthio) pyridine-3-carboxamide monohydrochloride (compound # 3-18)

1H-NMR (400 MHz, DMSO-d6) δ 1.65 (sa, 6H), 2.04 (sa, 9H), 4.36 (s, 2H), 6.87 (d, J = 6.7 Hz, 1H), 6.99 (s, 1H), 7.21 (dd, J = 7.6.4.9 Hz, 1H), 7.74 (dd, J = 7.6.1.2 Hz, 1H), 7.84 (d, J = 6.7 Hz, 1H), 7.87 (sa, 2H), 7.92 (s, 1H 8 , 47 (dd, J = 4.9, 1.2 Hz, 1H), 13.34 (s, 1H)

N- (3,5-dimethylphenyl) -2- [2- (piperazin-1-yl) pyridin-4-ylmethylthio] pyridin-3-carboxamide dihydrochloride (compound No. 3-19) 1H-NMR (400 MHz, DMSO-d6) δ 2.25 (s, 6H), 3.50-4.30 (m, 8H), 4.39 (s, 2H), 6.76 (s, 1H), 6.92 (s, 1H), 7.23 (s, 1H), 7.30 (dd, J = 7.7.4.8 Hz, 1H), 7.33

(s, 2H), 7.41 (s, 1H), 7.98 (d, J = 5.8 Hz, 1H), 8.02 (d, J = 5.8. Hz, 1H), 8, 60 (dd, J = 4,8,1,8 Hz, 1H), 9,20 (s, 2H), 10,35 (s, 1H) 2- (2-Aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) benzamide monohydrochloride (compound No. 3-20)

1H-NMR (400 MHz, DMSO-d6) δ 2.26 (s, 6H), 4.25 (s, 2H), 6.75 (s, 1H), 6.82 (m, 1H), 6.85 (s, 1H), 7.28- 7.35 (m, 3H), 7.40-7.45 (m, 2H), 7.52 (d, J = 7.3 Hz, 1H), 7.84 (d, J = 6.6 Hz, 1H), 7.95 (s at, 2H), 10.21 (s, 1H), 13.43 (s at, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) benzamide monohydrochloride (compound No. 3-21) 1H-NMR (500 MHz, DMSO-d6) δ 4.25 (s, 2H), 6.81 (dd, J = 6.7.1.5Hz, 1H), 6.85 (s, 1H), 7.35 (t, J = 8.6 Hz , 1H), 7.41 (d, J = 8.6 Hz, 2H), 7.45 (t, J = 8.6

Hz, 1H), 7.46 (d, J = 1.5 Hz, 1H), 7.56 (d, J = 8.6 Hz, 1H), 7.75 (d, J = 8.6 Hz, 2H), 7.83 (d, J = 6.7 Hz, 1H), 7.92 (s a, 2H), 10.51 (s, 1H), 13.33 (s a, 1H) 2- (2-Aminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) benzamide monohydrochloride (compound No. 3-22)

1H-NMR (400 MHz, DMSO-d6) δ 1.28 (s, 9H), 4.25 (s, 2H), 6.82 (d, J = 6.6 Hz, 1H), 6.84 (s, 1H), 7.33 (t, J = 6.6 Hz, 1H), 7.35 (d, J = 8.8Hz, 2H), 7.40-7.47 (m, 2H), 7.53 (d, J = 6.6Hz, 1H), 7.63 (d, J = 8.8Hz, 2H), 7.83 (d, J = 6.6Hz, 1H), 7.90 (sa, 2H), 10.29 (s, 1H), 13.36 (s a, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) benzamide monohydrochloride (compound No. 3-23) 1H-NMR (400 MHz, DMSO-d6) δ 4.25 (s, 2H), 6.81 (d, J = 6.7 Hz, 1H), 6.84 (s, 1H), 7.35 (m, 1H), 7.37 (d, J = 8.9Hz, 2H), 7.43-7.49 (m, 2H), 7.57 (d, J =

6.7 Hz, 1H), 7.83 (s, 1H), 7.83 (d, J = 8.9Hz, 2H), 7.88 (sa, 2H), 10.57 (s, 1H), 13.41 (sa, 1 H) 2- (2-Aminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) benzamide monohydrochloride (compound No. 3-24) 1H-NMR (400 MHz, DMSO-d6) δ 4.27 (s, 2H), 6.83 (d, J = 6.7 Hz, 1H), 6.87 (s, 1H), 7.35 (m, 1H), 7.44-7, 46 (m, 2H), 7.58 (d, J = 8.2 Hz, 1H), 7.64

(d, J = 7.0 Hz, 1H), 7.76 (t, J = 7.0 Hz, 1H), 7.84 (d, J = 6.7 Hz, 1H), 7.97 (d , J = 8.2 Hz, 1H), 8.00 (sa, 2H), 8.09 (d, J = 8.2 Hz, 1H), 8.59 (s, 1H), 9.20 (s, 1H), 10.99 (s, 1H), 13.51 (s at, 1H) 2- (2-Aminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) benzamide (compound # 3-25)

1H-NMR (500 MHz, DMSO-d6) δ 1.20 (d, J = 7.0 Hz, 6H), 2.86 (m, 1H), 4.06 (s, 2H), 5.86 (s, 2H), 6.43 (s, 1H), 6.49 (d, J = 5.2 Hz, 1H), 6.98 (d, J = 7.6 Hz, 1H), 7.29 (t, J = 7.6 Hz, 1H), 7.28 (d, J = 8.2 Hz, 1H), 7.42 (t, J = 8.2 Hz, 1H), 7.43 (d, J = 7.6Hz, 1H), 7.51 (d, J = 7.6Hz, 1H), 7.54 (d, J = 8.2Hz, 1H), 7.64 (sa, 1H), 7.79 (d, J = 5.2Hz, 1H) , 10.28 (s, 1 H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-chloro-3-methylphenyl) benzamide (compound No. 3-26) 1H-NMR (500 MHz, DMSO-d6) δ 2.32 (s, 3H), 4.06 (s, 2H), 5.87 (s, 2H), 6.42 (s, 1H), 6.48 (d, J = 5.2 Hz, 1H), 7.28 (t, J = 7.6 Hz, 1H), 7.37 (d, J = 8.6

Hz, 1H), 7.43 (t, J = 7.6 Hz, 1H), 7.44 (d, J = 7.6 Hz, 1H), 7.51 (d, J = 7.6 Hz, 1H), 7.55 (d, J = 8.6 Hz, 1H), 7.75 (sa, 1H), 7.79 (d, J = 5.2 Hz, 1H), 10.42 (s, 1H) 2- (2-Aminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) benzamide (compound No. 3-27)

1H-NMR (500 MHz, DMSO-d6) δ 4.08 (s, 2H), 5.86 (s, 2H), 6.43 (s, 1H), 6.49 (d, J = 5.2 Hz, 1H), 7.26 (d, J = 8.6 Hz, 1H), 7.30 (t, J = 7.3 Hz, 1H), 7.43 (t, J = 7.6 Hz, 1H), 7.46 (d, J = 7.6 Hz, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.68 (d , J = 8.6 Hz, 1H), 7.85 (d, J = 5.2 Hz, 1H), 7.99 (s at, 1H), 8.26 (s at, 1H), 10.50 (s, 1H), 12.93 (s, 1H)

3- (2-Aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) thiophene-2-carboxamide (compound No. 3-28) 1H-NMR (400 MHz, DMSO-d6) δ 2.25 (s, 6H), 4.10 (s, 2H), 5.88 (s, 2H), 6.40 (s, 1H) 6.46 (d, J = 5.1 Hz, 1H ), 6.74 (s, 1H), 7.20 (d, J = 5.1 Hz, 1H), 7.26

(s, 2H), 7.79 (d, J = 5.1 Hz, 1H), 7.82 (d, J = 5.1 Hz, 1H), 9.83 (s, 1H) 2- (3-Aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound No. 3-29) 1H-NMR (500 MHz, CDCl3) δ 2.30 (s, 6H), 4.15-4.60 (sa, 2H), 4.38 (s, 2H), 6.81 (s, 1H), 7.09 (d, J = 4 , 9Hz, 1H), 7.13 (dd, J = 7.6, 4.9Hz, 1H), 7.24 (s,

2H), 7.86-7.88 (m, 2H), 7.97 (s, 1H), 8.13 (s, 1H), 8.53 (dd, J = 4.9, 1.8 Hz , 1 HOUR) 2- (2-Aminopyridin-4-ylmethylthio) -N- (3,5-dimethyl-4-hydroxyphenyl) pyridin-3-carboxamide (compound # 3-30) 1H-NMR (500 MHz, DMSO-d6) δ 2.15 (s, 6H), 4.23 (s, 2H), 5.85 (s, 2H), 6.45 (s, 1H), 6.48 (dd, J = 5.2.1 , 2 Hz, 1H), 7.23-7.27 (m, 3H), 7.77 (d, J = 5.2

Hz, 1H), 7.88 (dd, J = 7.6.1.5 Hz, 1H), 8.09 (s, 1H), 8.55 (dd, J = 4.9, 1.5 Hz , 1H), 10.09 (s, 1H) 2- (2-Aminopyridin-4-ylmethylthio) -N- (4-difluoromethoxyphenyl) pyridin-3-carboxamide (compound # 3-31) 1H-NMR (500 MHz, DMSO-d6)

δ 4.24 (s, 2H), 5.83 (s, 2H), 6.45 (d, J = 0.6 Hz, 1H), 6.48 (dd, J = 5.2,1.5 Hz, 1H), 7.18 (d, J = 8.8 Hz, 2H), 7.18 (t, J = 74.1 Hz, 1H), 7.29 (dd, J = 7.6.4 , 8 Hz, 1H), 7.73 (d, J = 8.8 Hz, 2H), 7.77 (dd, J = 5.2.0.6 Hz, 1H), 7.96 (dd, J = 7.6.1.7 Hz, 1H), 8.59 (dd, J = 4.8.1.7 Hz, 1H), 10.55 (s, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) pyridin-3-carboxamide (compound # 3-32) 1H-NMR (400 MHz, DMSO-d6) δ 1.27 (s, 9H), 4.24 (s, 2H), 5.83 (s, 2H), 6.45 (s, 1H), 6.48 (dd, J = 5.2.1 , 5 Hz, 1H), 7.28 (dd, J = 7.6, 4.9 Hz, 1H), 7.36

(d, J = 8.5 Hz, 2H), 7.61 (d, J = 8.5 Hz, 2H), 7.77 (d, J = 5.2 Hz, 1H), 7.92 (dd , J = 7.6, 1.7 Hz, 1H), 8.58 (dd, J = 4.9, 1.7 Hz, 1H), 10.40 (s, 1H) 2- (2-Aminopyridin-4-ylmethylthio) -N- (3-methylphenyl) pyridin-3-carboxamide (compound # 3-33)

1H-NMR (400 MHz, DMSO-d6) δ 2.30 (s, 3H), 4.24 (s, 2H), 5.84 (s, 2H), 6.45 (s, 1H), 6.48 (dd, J = 5.2, 1 , 6 Hz, 1H), 6.93 (d, J = 7.8Hz, 1H), 7.22 (t, J = 7.8 Hz, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H), 7.46 (d, J = 7.8 Hz, 1H), 7.56 (s, 1H), 7.77 (d, J = 5.2 Hz, 1H), 7.93 (dd, J = 7.6, 1.7 Hz, 1H), 8.58 (dd, J = 4.9, 1.7 Hz, 1H), 10.39 (s, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-trifluoromethylphenyl) pyridin-3-carboxamide (compound # 3-34) 1 H-NMR (400 MHz, DMSO-d6 δ 4.25 (s, 2H), 5.84 (s, 2H), 6.45 (s, 1H), 6.48 (dd, J = 5.4.1.5 Hz, 1H), 7.31 (dd, J = 7 , 6.4.9 Hz, 1H), 7.73 (d, J = 8.3

Hz, 2H), 7.77 (d, J = 5.4 Hz, 1H), 7.92 (d, J = 8.3 Hz, 2H), 8.00 (dd, J = 7.6.1 , 7 Hz, 1H), 8.61 (dd, J = 4.9, 1.7 Hz, 1H), 10.83 (s, 1 H) 2- (2-Aminopyridin-4-ylmethylthio) -N- (3-chloro-4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 3-35)

1H-NMR (500 MHz, DMSO-d6) δ 4.25 (s, 2H), 5.83 (s, 2H), 6.45 (s, 1H), 6.48 (d, J = 5.1 Hz, 1H), 7.31 (dd, J = 7.6, 4.9 Hz, 1H), 7.59 (d, J = 8.9 Hz, 1H), 7.72 (dd, J = 8.9, 2.9 Hz, 1H), 7.77 (d, J = 5.1 Hz, 1H), 8.00 (dd, J = 7 , 6.1.8 Hz, 1H), 8.09 (d, J = 2.4 Hz, 1H), 8.61 (dd, J = 4.9, 1.8 Hz, 1H), 10.82 (s, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (3-trifluoromethylphenyl) pyridin-3-carboxamide (compound # 3-36) 1H-NMR (400 MHz, DMSO-d6) δ 4.25 (s, 2H), 5.84 (s, 2H), 6.45 (s, 1H), 6.48 (d, J = 5.1 Hz, 1H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.48 (d, J = 7.1 Hz, 1H),

7.61 (dd, J = 8.1.7.1Hz, 1H), 7.77 (d, J = 5.1Hz, 1H), 7.91 (d, J = 8.1Hz, 1H), 8 , 02 (dd, J = 7.6.1.7 Hz, 1H), 8.19 (s, 1H) 8.61 (dd, J = 4.9, 1.7 Hz, 1H), 10.80 (s, 1H) 2- (2-Aminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridin-3-carboxamide (compound # 3-37)

1H-NMR (500 MHz, DMSO-d6) δ 1.20 (d, J = 7.0 Hz, 6H), 2.87 (m, 1H), 4.24 (s, 2H), 5.83 (s, 2H), 6.45 (s, 1H), 6.48 (d, J = 5.2 Hz, 1H), 7.00 (d, J = 7.6 Hz, 1H), 7.26 (t, J = 7.6 Hz, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H), 7.52 (d, J = 7 , 6 Hz, 1H), 7.60 (s, 1H), 7.77 (d, J = 5.2 Hz, 1H), 7.94 (dd, J = 7.6.1.5 Hz, 1H), 8.58 (dd, J = 4.9, 1.5 Hz, 1H), 10.40 (s, 1H )

Example 4

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound No. 4-1)

Acetic anhydride (1.0 ml, 10 mmol) was added to a solution of 2- (2-aminopyridin-4-ylmethylthio) N- (3,5-dimethylphenyl) pyridine-3-carboxamide monohydrochloride (compound # 3 -1.0 g, 2.5 mmol) in pyridine (10 ml) at room temperature, and the mixture was stirred for 4 hours. Ethyl acetate (30 ml) was added to the reaction mixture, then the whole was washed with water (20 ml) and brine (20 ml), and then the organic phase was dried over anhydrous magnesium sulfate. The organic phase was evaporated under reduced pressure, and the resulting solid was filtered off with hexane / ethyl acetate (1: 1) to give 770 mg of the objective compound as a colorless crystal (76% yield).

Or the compound was also synthesized in the following procedure. N- (3,5-dimethylphenyl) -2-thioxo-1,2-dihydropyridin-3-carboxamide (reference compound No. 10-1, 200 mg, 0.77 mmol) and 2-acetylamino-4-methanesulfonyloxymethylpyridine (compound Reference No. 13-1, 190 mg, 0.77 mmol) in N, N-dimethylformamide (2.0 ml) with ice cooling and under nitrogen atmosphere, then triethylamine (0.22 ml, 1) was added , 5 mmol) thereto, and then the mixture was stirred for 2 hours at room temperature. Ethyl acetate (40 ml) was added to the reaction mixture, and then the whole was washed with water (30 ml) and brine (20 ml). The organic phase was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting solid was filtered off with the solvent mixture consisting of diisopropyl ether and ethyl acetate and dried under reduced pressure at 40 ° C to afford 250 mg of the objective compound as a pale yellow solid. (81% yield)

1H-NMR (500 MHz, DMSO-d6)

2.05 (s, 3H), 2.25 (s, 6H), 4.39 (s, 2H), 6.76 (s, 1H), 7.09 (dd, J = 5.2.1, 5 Hz, 1H), 7.28 (m, 1H), 7.32 (s, 2H), 7.92 (dd, J = 7.6.1.8 Hz, 1H), 8.15-8, 18 (m, 2H), 8.57 (dd, J = 5.2, 1.5 Hz, 1H), 10.29 (s, 1H), 10.40 (s, 1H)

As described below, the compounds (No. 4-2 ~ 68) were obtained using the corresponding compounds selected from the compounds (No. 3-1 ~ 37), commercially available compounds or known compounds according to the process of Synthesis of the compound (No. 4-1).

N- (3,5-Dimethylphenyl) -2- (2-propionylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 4-2)

1H-NMR (500 MHz, DMSO-d6)

δ 1.05 (t, J = 7.3 Hz, 3H), 2.25 (s, 6H), 2.36 (q, J = 7.3 Hz, 2H), 9.39 (s, 2H) , 6.76 (s, 1H), 7.09 (d, J = 5.1 Hz, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H), 7.32 ( s, 2H), 7.93 (dd, J = 7.6, 1.5 Hz, 1H), 8.16 (s, 1H), 8.17 (s, 1H), 8.58 (dd, J = 4.9, 1.5 Hz, 1H), 10.30 (s, 1H), 10.35 (s, 1H)

N- (3,5-Dimethylphenyl) -2- (2-trifluoroacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 4-3)

1H-NMR (400 MHz, DMSO-d6)

δ 2.25 (s, 6H), 4.45 (s, 2H), 6.76 (s, 1H), 7.27-7.32 (m, 4H), 7.93 (dd, J = 7 , 6.1.7 Hz, 1H), 8.03 (s, 1H), 8.31 (d, J = 4.9Hz, 1H), 8.58 (dd, J = 4.9, 1.7 Hz, 1H), 10.30 (s, 1H), 11.97 (sa, 1H)

N- (3,5-Dimethylphenyl) -2- (2-isobutyrylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 4-4)

1H-NMR (500 MHz, DMSO-d6)

δ 1.06 (d, J = 6.7 Hz, 6H), 2.25 (s, 6H), 2.72 (m, 1H), 4.40 (s, 2H), 6.76 (s, 1H), 7.10 (dd, J = 4.9, 1.8Hz, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H), 7.32 (s, 2H) , 7.93 (dd, J = 7.6.1.8 Hz, 1H), 8.17-8.19 (m, 2H), 8.58 (dd, J = 4.9, 1.8 Hz , 1H), 10.30 (s, 1H), 10.34 (s, 1H)

N- (3,5-Dimethylphenyl) -2- (2-pivaloylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 4-5)

1H-NMR (400 MHz, CDCl3)

δ 1.30 (s, 9H), 2.32 (s, 6H), 4.49 (s, 2H), 6.80 (d, J = 0.7 Hz, 1H), 7.07-7, 13 (m, 2H), 7.29 (s, 2H), 7.86 (dd, J = 7.6.1.7 Hz, 1H), 8.00 (sa, 1H), 8.11-8 , 15 (m, 2H), 8.31 (d, J = 0.7 Hz, 1H), 8.51 (dd, J = 4.9, 1.7 Hz, 1H)

N- (3,5-Dimethylphenyl) -2- (2-trifluoromethanesulfonylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 4-6) 1 H-NMR (400 MHz, DMSO-d6)

δ 2.26 (s, 6H), 4.43 (s, 2H), 6.77 (s, 1H), 7.14 (d, J = 6.3 Hz, 1H), 7.28-7, 32 (m, 3H), 7.72 (s, 1H), 7.95-7.99 (m, 2H), 8.53 (dd, J = 4.9, 1.7 Hz, 1H), 10.29 (s, 1H), 13.99 (s at, 1H) N- (3,5-Dimethylphenyl) -2- (2-methanesulfonylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 4-7) 1H-NMR (500 MHz, CDCl3) δ 2.32 (s, 6H), 2.94 (s, 3H), 4.42 (s, 2H), 6.81 (s, 1H), 6.85 (dd, J = 6.1, 1 , 5 Hz, 1H), 7.13 (dd, J = 7.6, 4.9 Hz, 1H), 7.28

(s, 2H), 7.46 (s, 1H), 7.83 (dd, J = 7.6, 1.5 Hz, 1H), 7.91 (s, 1H), 8.03 (d, J = 6.1 Hz, 1H), 8.51 (dd, J = 4.9, 1.5 Hz, 1H), 11.80 (s a, 1H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridin-3-carboxamide (compound # 4-8)

1H-NMR (400 MHz, DMSO-d6) δ 1.20 (d, J = 6.8 Hz, 6H), 2.06 (s, 3H), 2.87 (m, 1H), 4.39 (s, 2H), 7.00 (d, J = 7.6 Hz, 1H), 7.10 (dd, J = 5.1, 1.7 Hz, 1H), 7.23-7.30 (m, 2H), 7.51 (d, J = 7.8 Hz, 1H), 7.59 (s, 1H), 7.96 (d, J = 5.9 Hz , 1H), 8.15-8.18 (m, 2H), 8.58 (dd, J = 4.9, 1.7 Hz, 1H), 10.39 (s, 1H), 10.40 (s, 1H)

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (indan-5-yl) pyridin-3-carboxamide (compound No. 4-9) 1H-NMR (400 MHz, DMSO-d6) δ 1.97-2.06 (m, 2H), 2.06 (s, 3H), 2.79-2.87 (m, 4H), 4.39 (s, 2H), 7.09 (d , J = 5.1, 1.5 Hz, 1H), 7.17 (d, J = 7.8 Hz, 1H),

7.28 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.3 Hz, 1H), 7.61 (s, 1H), 7.93 (d , J = 5.9 Hz, 1H) 8.15-8.18 (m, 2H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 10.33 (s, 1H), 10.40 (s, 1H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridin-3-carboxamide (compound No. 4-10)

1H-NMR (500 MHz, DMSO-d6) δ 2.06 (s, 3H), 4.40 (s, 2H), 7.09 (d, J = 5.2 Hz, 1H), 7.29 (dd, J = 7.6.4.9 Hz, 1H), 7.41 (d, J = 8.6 Hz, 2H), 7.72 (d, J = 8.6 Hz, 2H), 7.98 (dd, J = 7.6.1.8 Hz, 1H), 8.16 (s, 1H), 8.17 (d, J = 5.2Hz, 1H), 8 , 59 (dd, J = 4.9, 1.8 Hz, 1H), 10.40 (s, 1H), 10.59 (s, 1 H)

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 4-11) 1H-NMR (400 MHz, DMSO-d6) δ 2.06 (s, 3H), 4.40 (s, 2H), 7.10 (dd, J = 5.2.1.6 Hz, 1H), 7.30 (dd, J = 7.6 , 4.8 Hz, 1H), 7.37 (d, J = 8.6 Hz, 2H), 7.80 (d, J

= 8.6 Hz, 2H), 7.98 (dd, J = 7.6.1.7 Hz, 1H), 8.14-8.18 (m, 2H), 8.60 (dd, J = 4.8.1.7 Hz, 1H), 10.41 (s, 1H), 10.66 (s, 1H) 2- [2- (N-Acetyl-N-methylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound No. 4-12) 1H-NMR (500 MHz, DMSO-d6) δ 1.96 (s, 3H), 2.25 (s, 6H), 3.22 (s, 3H), 4.43 (s, 2H), 6.76 (s, 1H), 7.27- 7.30 (m, 2H), 7.32 (s, 2H), 7.52 (s, 1H), 7.93 (dd,

J = 7.6.1.5 Hz, 1H), 8.34 (d, J = 4.9 Hz, 1H), 8.58 (dd, J = 4.9, 1.8 Hz, 1H), 10.31 (s, 1 H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (quinolin-6-yl) pyridin-3-carboxamide (compound No. 4-13) 1H-NMR (400 MHz, DMSO-d6) δ 2.06 (s, 3H), 4.42 (s, 2H), 7.11 (d, J = 5.2 Hz, 1H), 7.33 (dd, J = 7.6, 4.9Hz , 1H), 7.51 (dd, J = 8.2.4.3Hz, 1H), 7.89

(dd, J = 9.2.2.4 Hz, 1H), 8.00 (d, J = 9.2 Hz, 1H), 8.05 (dd, J = 7.6.1.5 Hz, 1H), 8.15-8.20 (m, 2H), 8.34 (d, J = 7.6Hz, 1H), 8.51 (d, J = 2.4 Hz, 1H), 8.62 (dd, J = 4.9, 1.5 Hz, 1H), 8.81 (dd, J = 4.3.1, 5 Hz, 1H), 10.40 (s, 1H), 10.80 (s, 1H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3-chloro-4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 4-14)

1H-NMR (400 MHz, DMSO-d6) δ 2.06 (s, 3H), 4.41 (s, 2H), 7.10 (d, J = 4.9 Hz, 1H), 7.32 (dd, J = 7.6.4.9 Hz, 1H), 7.58 (d, J = 9.0.Hz, 1H), 7.71 (d, J = 9.0 Hz, 1H), 8.01 (dd, J = 7.6.1.7 Hz, 1H), 8.08 (s, 1H), 8.16 (s, 1H), 8.17 ( d, J = 4.9 Hz, 1H), 8.61 (dd, J = 4.9, 1.7 Hz, 1H), 10.41 (s, 1H), 10.80 (s, 1H)

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) pyridin-3-carboxamide (compound No. 4-15) 1H-NMR (400 MHz, DMSO-d6) δ 2.05 (s, 3H), 4.40 (s, 2H), 7.11 (dd, J = 5.1, 1.5 Hz, 1H), 7.28 (dd, J = 7.6 , 4.9 Hz, 1H), 7.58 (m, 1H), 7.75 (m, 1H),

7.97 (d, J = 8.0 Hz, 1H), 8.06 (dd, J = 7.6, 1.7 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H ), 8.15-8.20 (m, 2H), 8.58-8.60 (m, 2H), 9.19 (s, 1H), 10.42 (s, 1H), 11.16 (s, 1H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3-chlorophenyl) pyridin-3-carboxamide (compound No. 4-16)

1H-NMR (500 MHz, DMSO-d6) δ 2.06 (s, 3H), 4.40 (s, 2H), 7.10 (dd, J = 5.1, 1.5 Hz, 1H), 7.18 (dd, J = 8.1 , 1.1 Hz, 1H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.38 (t, J = 8.1 Hz, 1H), 7.58 (dd, J = 8.1, 1.1 Hz, 1H), 7.88 (s, 1H), 7.99 (dd , J = 7.6.1.8 Hz, 1H), 8.16 (s, 1H), 8.17 (d, J = 5.2 Hz, 1H) 8.60 (dd, J = 4.9, 1.8 Hz, 1H), 10.40 (s, 1H), 10.64 (s, 1H)

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) pyridin-3-carboxamide (compound No. 4-17) 1H-NMR (400 MHz, DMSO-d6) δ 1.27 (s, 9H), 2.06 (s, 3H), 9.39 (s, 2H), 7.10 (d, J = 5.1 Hz, 1H), 7.28 (dd, J = 7.7, 4.9 Hz, 1H), 7.36 (d, J = 8.7 Hz, 2H),

7.60 (d, J = 8.7 Hz, 2H), 7.94 (dd, J = 7.7, 1.8 Hz, 1H), 8.15-8.17 (m, 2H), 8 , 57 (dd, J = 4.9, 1.8Hz, 1H), 10.39 (s, 1H), 10.41 (s, 1 H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-fluoro-3-methylphenyl) pyridin-3-carboxamide (compound No. 4-18)

1H-NMR (400 MHz, DMSO-d6) δ 2.06 (s, 3H), 2.23 (d, J = 1.5 Hz, 3H), 4.39 (s, 2H), 7.09-7.14 (m, 2H), 7, 29 (dd, J = 7.6, 4.9 Hz, 1H), 7.48 (m, 1H), 7.63 (d, J = 5.6 Hz, 1H), 7.95 (dd, J = 7.6.1.7 Hz, 1H), 8.16-8.17 (m, 2H), 8.58 ( dd, J = 4.9, 1.7 Hz, 1H), 10.41 (s, 1H), 10.44 (s, 1H)

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3-fluoro-4-methylphenyl) pyridin-3-carboxamide (compound No. 4-19) 1H-NMR (400 MHz, DMSO-d6) δ 2.06 (s, 3H), 2.20 (d, J = 1.2 Hz, 3H), 4.40 (s, 2H), 7.09 (dd, J = 5.1, 1.5 Hz, 1H), 7.24 (t, J = 8.4 Hz, 1H), 7.29 (dd, J =

7.6.4.7 Hz, 1H), 7.34 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 13.7 Hz, 1H), 7.96 (dd, J = 7.6.1.7 Hz, 1H), 8.15-8.17 (m, 2H), 8.59 (dd, J = 4,7,1,7 Hz, 1H), 10,41 (s, 1H), 10,56 (s, 1H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3-methylphenyl) pyridin-3-carboxamide (compound No. 4-20)

1H-NMR (400 MHz, DMSO-d6) δ 2.06 (s, 3H), 2.30 (s, 3H), 4.40 (s, 2H), 6.93 (d, J = 8.1Hz, 1H), 7.10 (dd, J = 5.1, 1.5 Hz, 1H), 7.22 (t, J = 8.1 Hz, 1H), 7.29 (dd, J = 7.6.4.9Hz, 1H), 7.45 (d, J = 8.1Hz, 1H), 7.56 (s, 1H), 7.96 (dd, J = 7.6.1.7 Hz, 1H), 8.16-8.17 (m, 2H), 8.58 (dd, J = 4.9, 1.7 Hz, 1H) 10.39 (s, 1H), 10.41 (s, 1H)

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (1H-indazol-5-yl) pyridin-3-carboxamide (compound No. 4-21) 1H-NMR (400 MHz, DMSO-d6) δ 2.06 (s, 3H), 4.40 (s, 2H), 7.10 (dd, J = 5.1, 1.5 Hz, 1H), 7.30 (dd, J = 7.6 , 4.9 Hz, 1H), 7.50-7.55 (m, 2H), 7.98 (dd, J =

7.6.1.7 Hz, 1H), 8.05 (s, 1H), 8.15-8.18 (m, 2H), 8.22 (s, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.41 (s, 1H), 10.47 (s, 1H), 13.03 (s, 1 H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) pyridin-3-carboxamide (compound No. 4-22)

1H-NMR (400 MHz, DMSO-d6) δ 2.06 (s, 3H), 4.41 (s, 2H), 7.10 (dd, J = 5.2.1.6 Hz, 1H), 7.24 (dd, J = 8.8 , 1.7 Hz, 1H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.70 (d, J = 8.8 Hz, 1H), 7.97-8.00 (m, 2H), 8.16-8.18 (m, 2H), 8.21 (s, 1H), 8, 60 (dd, J = 4.9, 1.7 Hz, 1H), 10.41 (s, 1H), 10.60 (s, 1H), 12.97 (s, 1H)

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3,4-dimethylphenyl) pyridin-3-carboxamide (compound No. 4-23)

1H-NMR (400 MHz, DMSO-d6) δ 2.06 (s, 3H), 2.18 (s, 3H), 2.20 (s, 3H), 4.40 (s, 2H), 7.08-7.10 (m, 2H), 7.27 (dd, J = 7.6.4.9 Hz, 1H), 7.39 (d, J = 8.1

Hz, 1H), 7.48 (s, 1H), 7.93 (dd, J = 7.6.1.6 Hz, 1H), 8.16-8.17 (m, 2H), 8.57 (dd, J = 4.9, 1.6 Hz, 1H), 10.29 (s, 1H), 10.40 (s, 1H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3,5-dichlorophenyl) pyridin-3-carboxamide (compound No. 4-24) 1H-NMR (400 MHz, DMSO-d6) δ 2.06 (s, 3H), 4.41 (s, 2H), 7.10 (dd, J = 5.1, 1.7 Hz, 1H), 7.32 (dd, J = 7.6 , 4.9 Hz, 1H), 7.36 (t, J = 2.0 Hz, 1H), 7.77

(s, 2H), 8.01 (dd, J = 7.6, 1.7 Hz, 1H), 8.17 (s, 1H), 8.17 (d, J = 5.1 Hz, 1H) , 8.61 (dd, J = 4.9, 1.7 Hz, 1H), 10.41 (s, 1H), 10.77 (s, 1H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethylphenyl) pyridin-3-carboxamide (compound No. 4-25)

1H-NMR (400 MHz, DMSO-d6) δ 2.06 (s, 3H), 4.41 (s, 2H), 7.10 (dd, J = 5.1, 1.6 Hz, 1H), 7.31 (dd, J = 7.6 , 4.9 Hz, 1H), 7.73 (d, J = 8.5 Hz, 2H), 7.92 (d, J = 8.5 Hz, 2H), 8.01 (dd, J = 7.6.1.7 Hz, 1H), 8.16 (s, 1H), 8.17 (d, J = 5.1 Hz , 1H), 8.61 (dd, J = 4.9, 1.7 Hz, 1H), 10.41 (s, 1H), 10.81 (s, 1H)

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-n-propylphenyl) pyridin-3-carboxamide (compound No. 4-26) 1H-NMR (400 MHz, DMSO-d6) δ 0.88 (t, J = 7.3 Hz, 3H), 1.52-1.60 (m, 2H), 2.06 (s, 3H), 2.50-2.53 (m, 2H ), 4.39 (s, 2H), 7.09 (dd, J = 5.1, 1.5 Hz, 1H),

7.16 (d, J = 8.4 Hz, 2H), 7.28 (dd, J = 7.6.4.9 Hz, 1H), 7.59 (d, J = 8.4Hz, 2H) , 7.94 (dd, J = 7.6.1.7 Hz, 1H), 8.16 (s, 1H), 8.16 (d, J = 5.1 Hz, 1H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 10.38 (s, 1H), 10.90 (s , 1 HOUR) 2- [2- (N-Acetyl-N-methylamino) pyridin-4-ylmethylthio] -N- (4-chlorophenyl) pyridin-3-carboxamide (compound No. 4-27)

1H-NMR (500 MHz, DMSO-d6) δ 1.95 (s, 3H), 3.22 (s, 3H), 4.43 (s, 2H), 7.29-7.31 (m, 2H), 7.42 (dd, J = 6 , 7, 2.1Hz, 2H), 7.52 (s, 1H), 7.72 (d, J = 8.9 Hz, 2H), 7.99 (dd, J = 7.6.1.5 Hz, 1H), 8.34 (d, J = 5.2 Hz, 1H), 8.60 (dd, J = 4 , 9, 1.8 Hz, 1H), 10.60 (s, 1H)

2- [2- (N-Acetyl-N-methylamino) pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (compound No. 4-28) 1H-NMR (400 MHz, DMSO-d6) δ 1.95 (s, 3H), 3.22 (s, 3H), 4.44 (s, 2H), 7.30-7.32 (m, 2H), 7.38 (d, J = 8 , 3 Hz, 2H), 7.52 (s, 1H), 7.80 (d, J = 8.3 Hz, 2H),

7.99 (dd, J = 7.6.1.7 Hz, 1H), 8.34 (d, J = 5.1 Hz, 1H), 8.60 (dd, J = 4.9, 1, 7 Hz, 1H), 10.66 (s, 1H) 2- [2- (N-Acetyl-N-methylamino) pyridin-4-ylmethylthio] -N- (4-tert-butylphenyl) pyridin-3-carboxamide (compound No. 4-29) 1H-NMR (900 MHz, DMSO-d6) δ 1.27 (s, 9H), 1.95 (s, 3H), 3.22 (s, 3H), 4.43 (s, 2H), 7.28-7.30 (m, 2H), 7.36 (d, J = 8.5 Hz, 2H), 7.51 (s, 1H), 7.60 (d, J =

8.5 Hz, 2H), 7.95 (d, J = 6.1 Hz, 1H), 8.34 (d, J = 5.1 Hz, 1H) 8.58 (dd, J = 4.9 , 1.7 Hz, 1H), 10.39 (s, 1H) 2- [2- (N-Acetyl-N-methylamino) pyridin-4-ylmethylthio] -N- (isoquinolin-3-yl) pyridin-3-carboxamide (compound No. 4-30) 1H-NMR (400 MHz, DMSO-d6) δ 1.95 (s, 3H), 3.22 (s, 3H), 4.45 (s, 2H), 7.28-7.31 (m, 2H), 7.52 (s, 1H), 7.58 (m, 1H), 7.75 (m, 1H), 7.98 (d, J = 8.1

Hz, 1H), 8.06-8.09 (m, 2H), 8.35 (d, J = 5.1 Hz, 1H), 8.58-8.60 (m, 2H), 9.20 (s, 1H), 11.17 (s, 1H) 2- [2- (N-Methyl-N-propionylamino) pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (compound No. 4-31) 1H-NMR (500 MHz, DMSO-d6) δ 0.93 (t, J = 7.3 Hz, 3H), 2.22 (q, J = 7.3 Hz, 2H), 3.21 (s, 3H), 4.44 (s, 2H) , 7.30-7.32 (m, 2H), 7.37 (d, J = 8.6 Hz, 2H),

7.50 (s, 1H), 7.81 (d, J = 8.9Hz, 2H), 8.00 (dd, J = 7.6, 1.8Hz, 1H), 8.35 (d, J = 4.9Hz, 1H), 8.60 (dd, J = 4.7.1.8Hz, 1H), 10.66 (s, 1H)

N- (3-Chlorophenyl) -2- [2- (N-methyl-N-propionylamino) pyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 4-32) 1H-NMR (500 MHz, DMSO-d6) δ 0.93 (t, J = 7.4 Hz, 3H), 2.22 (q, J = 7.4 Hz, 2H), 3.21 (s, 3H), 4.44 (s, 2H) , 7.19 (ddd, J = 7,9,2,1,0,9Hz, 1H), 7.31-7.32

(m, 2H), 7.39 (t, J = 8.2 Hz, 1H), 7.51 (s, 1H), 7.58 (dd, J = 8.2.1.2 Hz, 1H) , 7.89 (t, J = 1.8 Hz, 1H), 8.00 (dd, J = 7.6.1.8 Hz, 1H), 8.35 (d, J = 5.5 Hz, 1H), 8.60 (dd, J = 4.9, 1.8 Hz, 1H), 10.64 (s, 1H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (2,2-dimethylpropyl) pyridin-3-carboxamide (compound No. 4-33)

1H-NMR (500 MHz, DMSO-d6) δ 0.90 (s, 9H), 2.06 (s, 3H), 3.04 (d, J = 6.4 Hz, 2H), 4.36 (s, 2H), 7.08 (dd, J = 5.2.1.5 Hz, 1H), 7.21 (dd, J = 7.6.4.9 Hz, 1H), 7.77 (dd, J = 7.6.1.8 Hz, 1H), 8.14 (sa, 1H), 8.16 (d, J = 5.2 Hz, 1H), 8.43 (t, J = 6.4 Hz, 1H), 8.51 (dd, J = 4.9, 1.8 Hz, 1H), 10.40 (s, 1H)

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- [2- (4-methoxyphenyl) ethyl] pyridin-3-carboxamide (compound No. 4-34) 1H-NMR (500 MHz, DMSO-d6) δ 2.06 (s, 3H), 2.75 (t, J = 7.3 Hz, 2H), 3.35-3.41 (m, 2H), 3.71 (s, 3H), 4, 34 (s, 2H), 6.83 (d, J = 8.6 Hz, 2H), 7.08 (dd, J

= 5.2.1.5 Hz, 1H), 7.15 (d, J = 8.6 Hz, 2H), 7.21 (dd, J = 7.6, 4.9 Hz, 1H), 7 , 73 (dd, J = 7.6, 1.8Hz, 1H), 8.15 (sa, 1H), 8.17 (d, J = 5.2Hz, 1H), 8.52 (dd, J = 4.9, 1.8Hz, 1H), 8.57 (t, J = 5.5Hz, 1H), 10 , 41 (s, 1H) 2- (2-Acetylaminopyridin-9-ylmethylthio) -N- (2-chlorophenyl) pyridin-3-carboxamide (compound No. 4-35)

1H-NMR (400 MHz, DMSO-d6) δ 2.06 (s, 3H), 4.40 (s, 2H), 7.11 (dd, J = 4.9, 1.5 Hz, 1H), 7.24-7.33 (m, 2H ), 7.39 (m, 1H), 7.55 (dd, J = 8.0.1.5 Hz, 1H), 7.60 (d, J = 7.3 Hz, 1H), 8.04 (d, J = 6.3 Hz, 1H), 8.16-8.19 (m, 2H), 8.60 (dd , J = 4,6,1,7 Hz, 1H), 10,23 (s, 1H), 10,42 (s, 1H)

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (5-chloro-2,4-di methoxyphenyl) pyridine-3-carboxamide (compound No. 4-36) 1H-NMR (400 MHz, DMSO-d6) δ 2.06 (s, 3H), 3.85 (s, 3H), 3.90 (s, 3H), 4.38 (s, 2H), 6.87 (s, 1H), 7.10 ( dd, J = 5.1, 1.5 Hz, 1H), 7.26 (m, 1H), 7.76

(s, 1H), 7.96 (d, J = 6.6 Hz, 1H), 8.15-8.18 (m, 2H), 8.57 (d, J = 3.7 Hz, 1H) , 9.71 (s, 1H), 10.41 (s, 1H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethyl-4-hydroxyphenyl) pyridine-3-carboxamide (compound No. 4-37) 1H-NMR (400 MHz, DMSO-d6) δ 2.06 (s, 3H), 2.15 (s, 6H), 4.38 (s, 2H), 7.10 (dd, J = 5.1, 1.5 Hz, 1H), 7, 23-7.28 (m, 3H), 7.90 (dd, J = 7.6.1.7 Hz, 1H),

8.09 (s, 1H), 8.15-8.18 (m, 2H), 8.56 (dd, J = 4.8, 1.7 Hz, 1H), 10.08 (s, 1H) , 10.41 (s, 1 H) N- (3,5-Dimethylphenyl) -2- [2- (2,5-dioxopyrrolidin-1-yl) pyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 4-38) 1H-NMR (500 MHz, DMSO-d6) δ 2.26 (s, 6H), 2.80 (s, 4H), 4.48 (s, 2H), 6.76 (s, 1H), 7.28 (dd, J = 7.6.4 , 9Hz, 1H), 7.32 (s, 2H), 7.40 (s, 1H), 7.52

(d, J = 4.9Hz, 1H), 7.94 (dd, J = 7.6.1.5 Hz, 1H), 8.47 (d, J = 4.9Hz, 1H), 8, 57 (dd, J = 4.9, 1.5 Hz, 1H), 10.31 (s, 1H) N- (3,5-Dimethylphenyl) -2- (2-methoxycarbonylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 4-39) 1H-NMR (400 MHz, DMSO-d6) δ 2.25 (s, 6H), 3.65 (s, 3H), 4.39 (s, 2H), 6.76 (s, 1H), 7.06 (m, 1H), 7.27- 7.33 (m, 3H), 7.91-7.94 (m, 2H), 8.13 (d, J =

5.4 4 Hz, 1H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 10.10 (s, 1H), 10.30 (s, 1H) 2- [2- (4-Chlorophenyl) sulfonylaminopyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound No. 4-40) 1H-NMR (400 MHz, DMSO-d6)

δ 2.26 (s, 6H), 4.34 (s, 2H), 6.77 (s, 1H), 6.85 (m, 1H), 7.27-7.31 (m, 2H), 7.34 (s, 2H), 7.51 (d, J = 7.6 Hz, 2H), 7.77-7.80 (m, 3H), 7.97 (d, J = 6.3 Hz, 1H), 8.50 (m, 1H), 10.31 (s, 1H) N- (3,5-Dimethylphenyl) -2- [2- (1-oxo-3-buten-1-ylamino) pyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 4-41)

1H-NMR (400 MHz, DMSO-d6) δ 2.25 (s, 6H), 3.16-3.20 (m, 2H), 4.40 (s, 2H), 5.10-5.19 (m, 2H), 5.98 (m , 1H), 6.76 (s, 1H), 7.11 (dd, J = 5.1, 1.5 5 Hz, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H), 7.32 (s, 2H), 7.92 (dd, J = 7.6.1.7 Hz , 1H), 8.15 (s, 1H), 8.18 (d, J = 5.1 Hz, 1H), 8.57 (m, 1H), 10.29 (s, 1H), 10.44 (s, 1H)

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) benzamide (compound No. 4-42) 1H-NMR (500 MHz, DMSO-d6) δ 2.06 (s, 3H), 4.24 (s, 2H), 7.05 (d, J = 5.2 Hz, 1H), 7.30 (t, J = 7.3 Hz, 1H) , 7.39 (d, J = 8.9 Hz, 2H), 7.44 (t, J = 7.3

Hz, 1H), 7.48 (d, J = 7.3 Hz, 1H), 7.52 (d, J = 7.3 Hz, 1H), 7.75 (d, J = 8.9 Hz, 2H), 8.11 (s, 1H), 8.17 (d, J = 5.2 Hz, 1H), 10.43 (s, 1H), 10.98 (s, 1H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) benzamide (compound No. 4-43)

1H-NMR (500 MHz, DMSO-d6) δ 2.07 (s, 3H), 2.25 (s, 6H), 4.23 (s, 2H), 6.74 (s, 1H), 7.06 (dd, J = 4.9, 1 , 5 Hz, 1H), 7.28 (m, 1H), 7.35 (s, 2H), 7.40 (m, 1H), 7.45 (d, J = 9.2 Hz, 1H), 7.48 (m, 1H), 8.11 (s, 1H), 8.18 (dd, J = 5, 2.0.6 Hz, 1H), 10.18 (s, 1H), 10.44 (s, 1H)

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) benzamide (compound No. 4-44) 1H-NMR (500 MHz, DMSO-d6) δ 1.27 (s, 9H), 2.07 (s, 3H), 4.23 (s, 2H), 7.06 (d, J = 4.9 Hz, 1H), 7.28 (t, J = 7.3 Hz, 1H), 7.35 (d, J = 8.6 Hz, 2H), 7.41

(t, J = 7.3 Hz, 1H), 7.47 (d, J = 7.3Hz, 1H), 7.50 (d, J = 7.3Hz, 1H), 7.63 (d, J = 8.6 Hz, 2H), 8.11 (s, 1H), 8.18 (d, J = 4.9 Hz, 1H), 10.26 (s, 1H), 10.43 (s, 1H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) benzamide (compound No. 4-45)

1H-NMR (500 MHz, DMSO-d6) δ 2.06 (s, 3H), 4.24 (s, 2H), 7.06 (d, J = 5.2 Hz, 1H), 7.30 (t, J = 7.6 Hz, 1H) , 7.35 (d, J = 8.6 Hz, 2H), 7.43 (t, J = 7.6 Hz, 1H), 7.49 (d, J = 7.6 Hz, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.83 (d, J = 8.6 Hz, 2H), 8.11 (s, 1H), 8.17 (d, J = 5.2 Hz, 1H), 10.43 (s, 1H), 10.54 (s, 1H)

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) benzamide (compound No. 4-46) 1H-NMR (500 MHz, DMSO-d6) δ 2.06 (s, 3H), 4.24 (s, 2H), 7.07 (d, J = 4.9 Hz, 1H), 7.29 (t, J = 7.6 Hz, 1H) , 7.43 (t, J = 7.6 Hz, 1H), 7.48 (d, J = 7.6 Hz,

1H), 7.57 (t, J = 7.6 Hz, 1H), 7.61 (d, J = 7.6 Hz, 1H), 7.74 (t, J = 7.6 Hz, 1H) , 7.97 (d, J = 7.6 Hz, 1H), 8.08 (d, J = 7.6 Hz, 1H), 8.11 (s, 1H), 8.17 (d, J = 4.9 Hz, 1H), 8.60 (s, 1H), 9.18 (s, 1H), 10, 43 (s, 1H), 10.95 (s, 1H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) benzamide (compound No. 4-47)

1H-NMR (500 MHz, DMSO-d6) δ 1.20 (d, J = 7.0 Hz, 6H), 2.07 (s, 3H), 2.86 (m, 1H), 4.24 (s, 2H), 6.98 (d, J = 7.6 Hz, 1H), 7.07 (d, J = 5.2 Hz, 1H), 7.24 (t, J = 7.6 Hz, 1H), 7.28 (t, J = 7.6Hz, 1H), 7.41 (t, J = 7.6Hz, 1H), 7.46 (d, J = 7.6 Hz, 1H), 7.52 (d, J = 7.6 Hz, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.62 (s, 1H), 8.11 (s, 1H), 8.18 (d, J = 5.2 Hz, 1H), 10.27 (s, 1H) , 10.44 (s, 1 H)

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-chloro-3-methylphenyl) benzamide (compound No. 4-48) 1H-NMR (500 MHz, DMSO-d6) δ 2.06 (s, 3H), 2.32 (s, 3H), 4.23 (s, 2H), 7.06 (d, J = 5.2 Hz, 1H), 7.29 (t, J = 7.6 Hz, 1H), 7.36 (d, J = 8.6 Hz, 1H), 7.42

(t, J = 7.6 Hz, 1H), 7.48 (d, J = 7.6 Hz, 1H), 7.51 (d, J = 7.6 Hz, 1H), 7.53 (m , 1H), 7.74 (s, 1H), 8.11 (s, 1H), 8.18 (d, J = 5.2 Hz, 1H), 10.40 (s, 1H), 10.43 (s, 1H)

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) benzamide (compound No. 4-49) 1H-NMR (500 MHz, DMSO-d6) δ 2.06 (s, 3H), 4.25 (s, 2H), 7.07 (d, J = 5.2 Hz, 1H), 7.26 (d, J = 8.6 Hz, 1H) , 7.31 (t, J = 7.3 Hz, 1H), 7.42 (t, J = 7.3

Hz, 1H), 7.49 (d, J = 7.3 Hz, 1H), 7.55 (d, J = 7.3 Hz, 1H), 7.68 (d, J = 8.6 Hz, 1H), 7.99 (s, 1H), 8.11 (s, 1H), 8.17 (d, J = 5.2 Hz, 1H), 8.25 (s, 1H), 10.43 (s, 1H), 10.49 (s, 1H), 12.93 (s, 1H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (2,2-dimethylpropyl) benzamide (compound No. 4-50)

1H-NMR (500 MHz, DMSO-d6) δ 0.91 (s, 9H), 2.07 (s, 3H), 3.04 (d, J = 6.4 Hz, 2H), 4.20 (s, 2H), 7.05 (dd, J = 4.9, 1.8 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 7.31-7.37 (m, 2H), 7.40 (d, J = 7.6 Hz, 1H), 8.09 (sa, 1H), 8.18 (d, J = 5.2 Hz , 1H), 8.25 (t, J = 6.4 Hz, 1H), 10.43 (s, 1 HOUR)

3- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) thiophene-2-carboxamide (compound No. 4-51) 1H-NMR (500 MHz, DMSO-d6) δ 1.27 (s, 9H), 2.06 (s, 3H), 4.27 (s, 2H), 6.99 (d, J = 4.9 Hz, 1H), 7.24 (d, J = 5.2 Hz, 1H), 7.34 (d, J = 8.9 Hz, 2H), 7.52

(d, J = 8.9 Hz, 2H), 7.83 (d, J = 5.2 Hz, 1H), 8.11 (s, 1H), 8.16 (d, J = 4.9 Hz , 1H), 9.90 (s, 1H), 10.43 (s, 1H) 3- (2-Acetylaminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) thiophene-2-carboxamide (compound No. 4-52) 1H-NMR (500 MHz, DMSO-d6) δ 2.04 (s, 3H), 4.28 (s, 2H), 7.01 (d, J = 4.9 Hz, 1H), 7.20 (d, J = 8.6 Hz, 1H) , 7.27 (d, J = 5.2 Hz, 1H) 7.68 (d, J = 8.6

Hz, 1H), 7.85 (d, J = 5.2 Hz, 1H), 7.99 (sa, 1H), 8.09 (s, 1H), 8.10 (s, 1H), 8, 16 (d, J = 4.9 Hz, 1H), 10.12 (s, 1H), 10.41 (s, 1H), 12.94 (s, 1H) 3- (2-Acetylaminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) thiophene-2-carboxamide (compound No. 4-53)

1H-NMR (500 MHz, DMSO-d6) δ 1.96 (s, 3H), 4.31 (s, 2H), 6.92 (d, J = 5.2 Hz, 1H), 7.32 (d, J = 5.2 Hz, 1H) , 7.57 (t, J = 7.6 Hz, 1H), 7.75 (t, J = 7.6 Hz, 1H), 7.91 (d, J = 5.2 Hz, 1H), 7.93 (d, J = 7.6 Hz, 1H), 8.03 (s, 1H), 8.08 ( d, J = 5.2 Hz, 1H), 8.10 (d, J = 7.6 Hz, 1H), 8.45 (s, 1H), 9.17 (s, 1H), 10.32 (s, 1H), 10.55 (s, 1H)

3- (2-Acetylaminopyridin-4-ylmethylthio) -N- (2,2-dimethylpropyl) thiophene-2-carboxamide (compound No. 4-54) 1H-NMR (500 MHz, DMSO-d6) δ 0.85 (s, 9H), 2.07 (s, 3H), 3.01 (d, J = 6.1 Hz, 2H), 4.24 (s, 2H), 6.88 (d, J = 5.1, 1.7 Hz, 1H), 7.23 (d, J = 5.1 Hz, 1H),

7.75 (d, J = 5.1 Hz, 1H), 7.94 (d, J = 6.1 Hz, 1H), 8.04 (sa, 1H), 8.16 (d, J = 5 , 1 Hz, 1H), 10.45 (s, 1H) 3- (2-Acetylaminopyridin-4-ylmethylthio) -N- [2- (4-methoxyphenyl) ethyl] thiophene-2-carboxamide (compound No. 4-55) 1H-NMR (500 MHz, DMSO-d6) δ 2.06 (s, 3H), 2.71 (t, J = 7.3 Hz, 2H), 3.33-3.38 (m, 2H), 3.71 (s, 3H), 4, 19 (s, 2H), 6.85 (d, J = 8.6 Hz, 2H), 6.95 (dd, J

= 4.9, 1.5 Hz, 1H), 7.14 (d, J = 8.6 Hz, 2H), 7.15 (d, J = 5.2 Hz, 1H), 7.71 (d , J = 5.2Hz, 1H), 8.06 (t, J = 5.5Hz, 1H), 8.08 (s a, 1H), 8.18 (d, J = 4.9 Hz, 1H), 10.46 (s, 1H) 3- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) thiophene-2-carboxamide (compound No. 4-56)

1H-NMR (400 MHz, DMSO-d6) δ 2.05 (s, 3H), 2.25 (s, 6H), 4.27 (s, 2H), 6.74 (s, 1H), 6.97 (dd, J = 5.1, 1 , 5 Hz, 1H), 7.22-7.27 (m, 3H), 7.83 (d, J = 5.1Hz, 1H), 8.11 (s, 1H), 8.16 (d, J = 5.1 Hz, 1H), 9.82 (s, 1H), 10.43 (s, 1H)

3- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) thiophene-2-carboxamide (compound No. 4-57) 1H-NMR (500 MHz, CDCl3)

δ 2.11 (s, 3H), 3.96 (s, 2H), 6.44 (dd, J = 6.7, 1.9 Hz, 1H), 7.16 (d, J = 5.2 Hz, 1H), 7.26 (d, J = 8.9 Hz, 2H), 7.46 (d, J = 8.9 Hz, 2H), 7.57 (d, J = 5.2 Hz, 1H), 8.00 (d, J = 6.7 Hz, 1H), 8.03 (s, 1H), 8.07 (s, 1H), 9.79 (s, 1H) 3- (2- Acetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) thiophene-2-carboxamide (compound No. 4-58)

1H-NMR (900 MHz, CDCl3) δ 2.10 (s, 3H), 3.98 (s, 2H), 6.48 (dd, J = 5.1, 1.7Hz, 1H), 7.15 (d, J = 0.7Hz, 1H), 7.17 (d, J = 5.1Hz, 2H), 7.54 (dd, J = 7.8.2.2Hz, 1H), 7.58 ( d, J = 5.1 Hz, 2H), 8.00-8.02 (m, 2H), 8.09 (s, 1H), 9.84 (s, 1H)

N- (3,5-Dimethylphenyl) -2- (2-methoxyacetylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 4-59) 1H-NMR (500 MHz, DMSO-d6) δ 2.25 (s, 6H), 3.35 (s, 3H), 4.04 (s, 2H), 4.42 (s, 2H), 6.76 (s, 1H), 7.15 ( dd, J = 5,2,1,5 Hz, 1H), 7.28 (dd, J = 7,6,4,9

Hz, 1H), 7.32 (s, 2H), 7.93 (dd, J = 7.6.1.8 Hz, 1H), 8.17 (s, 1H), 8.19 (d, J = 4.9 Hz, 1H), 8.58 (dd, J = 4.9, 1.5 5 Hz, 1H), 9.89 (s, 1H), 10.30 (s, 1H) 2- (2-Methoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 4-60)

1H-NMR (500 MHz, DMSO-d6) δ 3.35 (s, 3H), 4.03 (s, 2H), 4.43 (s, 2H), 7.15 (dd, J = 5.2.1.5 Hz, 1H), 7, 31 (dd, J = 7.6, 4.9 Hz, 1H), 7.37 (d, J = 8.6 Hz, 2H), 7.80 (d, J = 8.6Hz, 2H), 7.99 (dd, J = 7.6, 1.5 Hz, 1H), 8.17 (s, 1H), 8 , 19 (dd, J = 5,2,0,6 Hz, 1H), 8,60 (dd, J = 4.9, 1.8 Hz, 1H), 9.89 (s, 1H), 10.66 (s, 1H)

N- (3,5-Dimethylphenyl) -2- (2-phenoxyacetylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 4-61) 1H-NMR (500 MHz, DMSO-d6) δ 2.25 (s, 6H), 4.41 (s, 2H), 4.76 (s, 2H), 6.76 (s, 1H), 7.03-7.09 (m, 3H), 7.16 (d, J = 4.9 Hz, 1H), 7.27 (dd, J = 7.6.4.9

Hz, 1H), 7.28-7.30 (m, 3H), 7.31 (s, 1H), 7.92 (dd, J = 7.6, 1.8 Hz, 1H), 8.15 (s, 1H), 8.22 (d, J = 4.9 Hz, 1H), 8.56 (dd, J = 4.9, 1.8 Hz, 1H), 10.30 (s, 1H), 10.43 (s, 1H) 2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (4-chloro phenyl) pyridin-3-carboxamide (compound No. 4-62)

1H-NMR (500 MHz, DMSO-d6) δ 2.10 (s, 3H), 4.41 (s, 2H), 4.68 (s, 2H), 7.14 (d, J = 5.2 Hz, 1H), 7.29 (dd, J 7.6.4.9 Hz, 1H), 7.41 (d, J = 8.6 Hz, 2H), 7.72 (d, J = 8.6 Hz, 2H), 7.98 (dd, J = 7.6.1.5 Hz, 1H), 8.10 (sa, 1H), 8.20 (d , J = 5.2 Hz, 1H), 8.58 (dd, J = 4.9, 1.5Hz, 1H), 10.59 (s, 1 H), 10.60 (s, 1 H)

N- (3,5-Dimethylphenyl) -2- (3-methanesulfonylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 4-63) 1H-NMR (500 MHz, CDCl3) δ 2.32 (s, 6H), 3.07 (s, 3H), 4.36 (s, 2H), 6.83 (s, 1H), 7.21-7.25 (m, 4H), 7.90 (d, J = 6.4 Hz, 1H), 7.94 (s, 1H), 8.33 (d, J =

4.9 Hz, 1H), 8.72 (dd, J = 4.5.1.5 Hz, 1H), 8.78 (s, 1H), 10.64 (s, 1H) 2- (3-Acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound No. 4-64) 1H-NMR (400 MHz, CDCl3) δ 2.19 (s, 3H), 2.30 (s, 6H), 4.31 (s, 2H), 6.81 (s, 1H), 7.16-7.22 (m, 2H), 7.25 (s, 2H), 7.87 (d, J = 7.6 Hz, 1H), 8.18 (d, J

= 5.1 Hz, 1H), 8.48-8.52 (m, 2H), 8.94 (s, 1H), 9.38 (s, 1H) N- (4-Acetoxy-3,5-dimethylphenyl) -2- (2-acetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 4-65) 1H-NMR (500 MHz, DMSO-d6) δ 2.06 (s, 3H), 2.07 (s, 6H), 2.33 (s, 3H), 4.39 (s, 2H), 7.10 (dd, J = 5.2.1 , 5 Hz, 1H), 7.29 (dd, J = 7.6.4.9 Hz, 1H) 7.42

(s, 2H), 7.94 (dd, J = 7.6.1.8 Hz, 1H), 8.16-8.18 (m, 2H), 8.58 (dd, J = 4.9 , 1.8 Hz, 1H), 10.38 (s, 1H), 10.41 (s, 1H) 2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3-trifluoromethylphenyl) pyridin-3-carboxamide (compound No. 4-66) 1H-NMR (400 MHz, DMSO-d6)

δ 2.06 (s, 3H), 4.41 (s, 2H), 7.10 (dd, J = 5.1, 1.6 Hz, 1H), 7.32 (dd, J = 7.6 , 4.9 Hz, 1H), 7.48 (d, J = 7.6 Hz, 1H), 7.61 (dd, J = 8.3.7.6 Hz, 1H), 7.91 (d , J = 8.3 Hz, 1H), 8.03 (dd, J = 7.6.1.7 Hz, 1H), 8.16-8.18 (m, 3H), 8.61 (dd, J = 4.9, 1.7 Hz, 1H), 10.41 (s, 1H), 10.79 (s, 1H)

5 2- [2- (4-Hydroxycarbonylbutyryl) aminopyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound No. 4-67)

1H-NMR (400 MHz, DMSO-d6)

10 δ 1.73-1.82 (m, 2H), 2.24 (t, J = 7.6 Hz, 2H), 2.25 (s, 6H), 2.39 (t, J = 7, 3 Hz, 2H), 4.39 (s, 2H), 6.76 (s, 1H), 7.10 (d, J = 6.6 Hz, 1H), 7.28 (dd, J = 7, 6.4.9 Hz, 1H), 7.32 (s, 2H), 7.92 (dd, J = 7.6.1.7 Hz, 1H), 8.17 (d, J = 6.6 Hz, 1H), 8.17 (s, 1H), 8.58 (dd, J = 4.9, 1.7 Hz, 1H), 10.31 (s, 1H), 10.40 (s, 1H ), 12.04 (sa, 1 H)

2- [2- (3,5-Dioxomorpholin-4-yl) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound No. 4-68)

15 1H-NMR (400 MHz, DMSO-d6)

δ 2.25 (s, 6H), 4.48 (s, 2H), 4.54 (s, 4H), 6.76 (s, 1H), 7.29 (dd, J = 7.6.4 , 9 Hz, 1H), 7.33 (s, 2H), 7.45 (s, 1H), 7.53 (d, J = 4.9 Hz, 1H), 7.94 (dd, J = 7 , 6.1.7 Hz, 1H), 8.46 (d, J = 4.9 Hz, 1H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 10.33 (s, 1H)

20 Example 5

N- (3,5-Dimethylphenyl) -2- [2- (N’-n-propylureido) pyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 5-1)

N-Propyl isocyanate (20 mg, 0.23 mmol) was added to a solution of 2- (2-aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (The free base of compound No. 3-1, 28 mg, 0.077 mmol) in N, N-dimethylformamide (0.60 ml) at room temperature, and the mixture was stirred for 4 hours at 80 ° C. Ethyl acetate (10 ml) was added to the reaction mixture, the whole was washed with water (15 ml) and brine (15 ml), and then the organic phase was dried over anhydrous magnesium sulfate. The organic phase was evaporated under reduced pressure, and the residue was purified

30 resulting by silica gel column chromatography providing 12 mg of the objective compound as a colorless solid (Yield 33%).

35 1H-NMR (500 MHz, DMSO-d6)

δ 0.87 (t, J = 7.6 Hz, 3H), 1.46 (m, 2H), 2.25 (s, 6H), 3.11 (m, 2H), 4.33 (s, 2H), 6.76 (s, 1H), 6.93 (d, J = 5.2 Hz, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H), 7, 32 (s, 2H), 7.37 (s, 1H), 7.93 (dd, J = 7.6, 1.5 Hz, 1H), 8.05 (d, J = 5.2 Hz, 1H ), 8.23 (sa, 1H), 8.57 (dd, J = 4.9, 1.5 Hz, 1H), 9.13 (s, 1H), 10.29 (s, 1H)

As described below, the compounds (N.5-2 ~ 6) were obtained using the corresponding compounds selected from the reference compounds (No. 3-1-37), commercially available compounds or known compounds according to Compound synthesis procedure (No. 5-1).

45 2- [2- (N’-tert-Butylureido) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound No. 5-2)

1H-NMR (500 MHz, DMSO-d6)

δ 1.30 (s, 9H), 2.25 (s, 6H), 4.33 (s, 2H), 6.76 (s, 1H), 6.91 (d, J = 5.2Hz, 1H ), 7.28 (dd, J = 7.6.4.9Hz, 1H), 7.32 (s, 2H), 7.42 50 (s, 1H), 7.93 (dd, J = 7, 6, 1.5 Hz, 1H), 8.03 (d, J = 5.2 Hz, 1H), 8.06 (sa, 1H), 8.57 (dd, J = 4.9, 1.5 Hz, 1H), 8.91 (s, 1H), 10.30 (s, 1H)

2- [2- (N’-4-Chlorophenylureido) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound # 5-3)

1H-NMR (400 MHz, DMSO-d6)

δ 2.25 (s, 6H), 4.38 (s, 2H), 6.76 (s, 1H), 7.05 (d, J = 5.2 Hz, 1H), 7.27-7, 50 (m, 4H), 7.53-7.56 (m, 4H), 7.94 (dd, J = 7.6, 1.7 Hz, 1H), 8.16 (d, J = 5, 2 Hz, 1H), 8.58 (dd, J = 4.9, 1.7 Hz, 1H), 9.48 (s, 1H), 10.30 (s, 1H), 10.69 (s, 1H) 5 N- (3,5-Dimethylphenyl) -2- [2- (N'-methylthioureido) pyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 5-4)

1H-NMR (500 MHz, DMSO-d6)

10 δ 2.26 (s, 6H), 3.05 (d, J = 4.6 Hz, 3H), 4.35 (s, 2H), 6.76 (s, 1H), 7.05 (dd , J = 5.5,1.5 Hz, 1H), 7.21 (s, 1H), 7.29 (dd, J = 7.6, 4.9 Hz, 1H), 7.32 (s, 2H), 7.94 (dd, J = 7.6.1.5Hz, 1H), 8.10 (d, J = 5.5 Hz, 1H), 8.58 (dd, J = 4.9, 1.5 Hz, 1H), 10.29 (s, 1H), 10.54 (s, 1H), 11.49 (d, J = 4.6 Hz, 1H)

N- (4-Chlorophenyl) -2- [2- (N'-n-propylureido) pyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 5-5) 15 1 H-NMR (400 MHz, DMSO -d6)

δ 0.87 (t, J = 6.3 Hz, 3H), 1.40-1.50 (m, 2H), 3.10 (q, J = 6.8 Hz, 2H), 4.34 ( s, 2H), 6.93 (d, J = 5.4 Hz, 1H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (s, 1H), 7.42 (d, J = 9.0 Hz, 2H), 7.73 (d, J = 9.0 Hz, 2H), 7.98 (dd, J = 7.6.1.7 Hz, 1H ), 8.05 (d, J =

20 5. Hz, 1H), 8.24 (sa, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 9.14 (s, 1H), 10.59 ( s, 1H)

2- [2- (N’-n-Propylureido) pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (compound # 5-6)

1H-NMR (500 MHz, DMSO-d6)

25 δ 0.87 (t, J = 6.3 Hz, 3H), 1.43-1.48 (m, 2H), 3.11 (q, J = 7.0 Hz, 2H), 4.35 (s, 2H), 6.93 (d, J = 4.9 Hz, 1H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.36-7.38 ( m, 3H), 7.81 (d, J = 8.6 Hz, 2H), 7.99 (dd, J = 7.6, 1.5 Hz, 1H), 8.05 (d, J = 4 , 9 Hz, 1H), 8.23 (sa, 1H), 8.60 (dd, J = 4.9, 1.5 Hz, 1H), 9.13 (s, 1H), 10.65 (s ,1 HOUR)

30 Example 6

N- (3,5-Dimethylphenyl) -2- (2-formylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 6-1)

2- (2-Aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (the free base of compound # 3) was dissolved

1.50 mg, 0.14 mmol) in anhydrous tetrahydrofuran (0.20 ml), a solution of N-formylbenzotriazole (19 mg, 0.13 mmol) in anhydrous tetrahydrofuran (0.2 ml) was added thereto , and then the mixture was refluxed for 16 hours. The mixture was diluted with dichloromethane (15 ml), and then the whole was washed with 2N aqueous solution of sodium hydroxide (4.0 ml) twice and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to provide 60 mg of the objective compound quantitatively as a colorless solid.

1H-NMR (400 MHz, DMSO-d6)

45 δ 2.25 (s, 6H), 3.30 (s, 1H), 4.37 (s, 2H), 6.76 (s, 1H), 6.97 (s, 1H), 7.13 (m, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H), 7.32 (s, 2H), 7.93 (d, J = 7.6 Hz, 1H) 8.16 (m, 1H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 10.30 (s, 1H), 10.54 (s, 1H)

Example 7

2- (2-Aminopyridin-4-ylmethylthio) -N- (tert-butoxycarbonylmethyl) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (compound No. 71)

5 A solution of 2- (2-aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (the free base of compound No. 3-1, 50 mg) was added dropwise , 0.14 mmol) in anhydrous N, N-dimethylformamide (2 ml) to a suspension of 60% sodium hydride (13 mg, 0.30 mmol) in anhydrous N, N-dimethylformamide (1.0 ml) with cooling with ice, and the mixture was stirred for 5 minutes. Bromoacetic acid tert-butyl ester (22 µL, 0.15 mmol) was added to the

10 reaction mixture, and the mixture was stirred for 30 minutes at room temperature. The mixture was poured into ice water (15 ml), and the whole was extracted with ethyl acetate (15 ml). The organic phase was washed with saturated aqueous sodium hydrogen carbonate solution (30 ml) and brine (30 ml), and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give 45 mg of the objective compound as a colorless amorphous solid. (Performance of

15 69%)

1H-NMR (500 MHz, DMSO-d6)

20 δ 1.42 (s, 9H), 2.05 (s, 6H), 4.27 (s, 2H), 4.38 (s, 2H), 5.85 (s, 2H), 6.45 -6.46 (m, 2H), 6.77-6.79 (m, 3H), 6.95 (s, 1H), 7.28 (s, 1H), 7.78 (dd, J = 4 , 9.0.9 Hz, 1H), 8.33 (s, 1H)

Example 8

N- (3,5-Dimethylphenyl) -2- (2-phenylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 8-1)

While nitrogen was bubbling, 2- (2-aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (the free base of compound No. 3-1, 63 mg, 0.18 was added mmol), cesium carbonate (130 mg, 0.38 mmol), 30 iodobenzene (37 µl, 0.33 mmol), 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene (8.1 mg, 0.014mmol ) and tris (dibenzylideneacetone) dipaladium (0) (4.3 mg, 0.0047 mmol) to 1,4-dioxane (2.0 ml). The mixture was stirred for 20 hours at 90 ° C in the sealed tube, the mixture was diluted with ethyl acetate (30 ml), and then the whole was washed with saturated aqueous sodium hydrogen carbonate solution (30 ml). The organic phase was dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The resulting residue was purified by chromatography on

35 silica gel column. The resulting solid was filtered off with diethyl ether and dried under reduced pressure to provide 31 mg of the objective compound as a colorless solid. (31% yield)

1H-NMR (500 MHz, DMSO-d6)

5 δ 2.25 (s, 6H), 4.34 (s, 2H), 6.75-6.76 (m, 2H), 6.85-6.87 (m, 2H), 7.22 ( t, J = 7.8 Hz, 2H), 7.29 (dd, J = 7.3, 4.9 Hz, 1H), 7.33 (s, 2H), 7.61 (d, J = 7 , 6 Hz, 2H), 7.93 (d, J = 7.6 Hz, 1H), 8.03 (d, J = 5.5 Hz, 1H), 8.58 (d, J = 4.9 Hz, 1H), 8.97 (s, 1H), 10.31 (s, 1H)

Example 9

10 N- (3,5-Dimethylphenyl) -2- [2- (N’-methylureido) pyridin-4-ylmethylthio] pyridin-3-carboxamide (compound # 9-1)

While nitrogen was bubbling, 2- (2-bromopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (reference compound No. 3-4, 100 mg, 0.23 mmol) was added , cesium carbonate (91 mg, 0.28 mmol), N15 methylurea (52 mg, 0.70 mmol), 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene (8.1 mg, 0.014 mmol) and tris (dibenzylideneacetone) dipaladium (0) (4.3 mg, 0.0047 mmol) to 1,4-dioxane (2.0 ml). The mixture was stirred for 5 hours at 100 ° C in the sealed tube, the mixture was diluted with ethyl acetate (30 ml), and then the whole was washed with saturated aqueous sodium hydrogen carbonate solution (30 ml) twice. The organic phase was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by

20 silica gel column chromatography. The resulting solid was filtered off with ethyl acetate and dried under reduced pressure to give 21 mg of the objective compound as a colorless solid. (22% yield)

25 1H-NMR (500 MHz, DMSO-d6)

δ 2.25 (s, 6H), 2.71 (d, J = 4.6 Hz, 3H), 4.33 (s, 2H), 6.76 (s, 1H), 6.93 (dd, J = 5.3.1.4 Hz, 1H), 7.28 (dd, J = 7.5.4.7 Hz, 1H), 7.33 (m, 3H), 7.92 (dd, J = 7.5.1.5 Hz, 1H), 8.05 (d, J = 5.3 Hz, 1H), 8.15 (s, 1H), 8.57 (dd, J = 4.7, 1.5 Hz, 1H), 9.20 (s, 1H), 10.29 (s, 1H)

As described below, the compounds (No. 9-2 ~ 4) were obtained using the corresponding compounds selected from the compounds (No. 3-4 ~ 7), commercially available compounds or known compounds according to the process of synthesis of the compound (No. 9-1).

2- [2- (N’-Methylureido) pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (compound No. 9-2)

1H-NMR (500 MHz, DMSO-d6) δ 2.70 (d, J = 4.6 Hz, 3H), 4.34 (s, 2H), 6.93 (dd, J = 5.5.1 , 5 Hz, 1H), 7.30 (dd, J = 7.6, 4.8 Hz, 1H), 7.33 (s, 1H), 7.37 (d, J = 8.9Hz, 2H) , 7.80 (d, J = 8.9 Hz, 2H), 7.99 (dd, J = 7.6.1.7 Hz, 1H), 8.05 (d, J = 5.5 Hz, 1H), 8.15 (s, 1H), 8.60 (dd, J = 4.8.1.7 Hz, 1H), 9.21 (s, 1H), 10.66 (s, 1H)

5 N- (9-Chlorophenyl) -2- [2- (N’-methylureido) pyridin-9-ylmethylthio] pyridin-3-carboxamide (compound # 9-3)

1H-NMR (400 MHz, DMSO-d6)

52.71 (d, J = 4.6 Hz, 3H), 4.34 (s, 2H), 6.93 (dd, J = 5.1, 1.4 Hz, 1H), 7.28-7 , 33 (m, 2H), 7.41 (d, J = 8.9 Hz, 2H), 7.72

10 (d, J = 8.9 Hz, 2H) 7.98 (dd, J = 7.6, 1.7 Hz, 1H), 8.04 (d, J = 5.1 Hz, 1H), 8 , 16 (s, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 9.21 (s, 1H), 10.60 (s, 1H)

N- (4-Difluoromethoxyphenyl) -2- [2- (N’-methylureido) pyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 9-4)

15 1H-NMR (400 MHz, DMSO-d6)

δ 2.70 (d, J = 4.6Hz, 3H), 4.34 (s, 2H), 6.93 (dd, J = 5.1, 1.3 Hz, 1H), 7.17 (t , J = 74.1 Hz, 1H), 7.18 (d, J = 8.9Hz, 2H), 7.28-7.33 (m, 2H), 7.72 (d, J = 8.9 Hz, 2H), 7.97 (dd, J = 7.8.1.7 Hz, 1H), 8.04 (d, J = 5.1 Hz, 1H), 8.17 (s, 1H) 8 , 59 (dd, J = 4.8, 1.7 Hz, 1H), 9.22 (s, 1H), 10.55 (s, 1H)

Example 10

2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound # 10-1)

While nitrogen was bubbling, 2- (2-bromopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (reference compound No. 3-4, 1.9 g, 4, 7 mmol), cesium carbonate (1.8 g, 5.6 mmol), acetoxyacetamide (1.6 g, 5.6 mmol), 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene (810 mg, 1.4 mmol) and tris (dibenzylideneacetone) dipaladium (0) (430 mg, 0.47 mmol) to 1,4-dioxane (20 ml). The mixture was stirred for 3 hours at 100 ° C in the sealed tube and diluted with ethyl acetate (300 ml), and then the whole was washed with solution.

30 saturated aqueous sodium hydrogen carbonate (300 ml). The organic phase was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to provide 1.0 g of the objective compound as a pale yellow solid. (47% yield)

Or the compound was also synthesized as described below.

Acetoxyacetic acid (1.2 g, 10 mmol) was dissolved in pyridine (12 ml) at room temperature,

Acetoxyacetyl (1.1 ml, 10 mmol) thereto, and the mixture was stirred for 4 hours at room temperature. In addition, 2- (2-aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (the free base of compound No. 3-1, 1.0 g, 2, was added, 5 mmol) thereto, and the mixture was stirred for 15 hours. Ethyl acetate (100 ml) was added to the reaction mixture, and the whole was washed with 1 N hydrochloric acid (150 ml) three times, saturated aqueous sodium hydrogen carbonate solution (150 ml) twice and brine (150 ml ). The organic phase was dried over sulfate of

45 anhydrous sodium. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography. The resulting solid was filtered off with ethyl acetate, and then dried under reduced pressure to provide 0.97 g of the objective compound as a brown solid. (77% yield)

50 1H-NMR (400 MHz, DMSO-d6)

δ 2.10 (s, 3H), 2.25 (s, 6H), 4.40 (s, 2H), 4.68 (s, 2H), 6.76 (s, 1H), 7.14 ( dd, J = 5.1, 1.5 Hz, 1H), 7.28 (dd, J = 7.6.4.8 Hz, 1H), 7.32 (s, 2H), 7.92 (dd , J = 7.6, 1.8 Hz, 1H), 8.10 (s, 1H), 8.20 (d, J = 5.1 1Hz, 1H), 8.57 (dd, J = 4, 8, 1.8 Hz, 1H), 10.30 (s, 1H), 10.60 (s, 1H)

As described below, the compounds (# 10-2 ~ 21) were obtained using the corresponding compounds selected from the reference compounds (# 3-4.5), the compounds (# 3- 1 ~ 37), commercially available compounds or known compounds according to the compound synthesis procedure (# 10-1).

2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 10-2) 1H-NMR (900 MHz, DMSO-d6) δ 2.09 (s, 3H), 4.41 (s, 2H), 9.68 (s, 2H), 7.14 (dd, J = 5.2.1.5 Hz, 1H), 7, 30 (dd, J = 7.6, 4.8 Hz, 1H), 7.36 (d, J = 8.3

Hz, 2H), 7.80 (d, J = 8.3Hz, 2H), 7.98 (dd, J = 7.6.1.8Hz, 1H), 8.10 (s, 1H), 8, 20 (d, J = 5.2Hz, 1H), 8.59 (dd, J = 4.8.1.8 Hz,

1H), 10.59 (s, 1H), 10.65 (s, 1H) 2- (2-tert-Butoxycarbonylaminoacetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (compound No. 10-3)

1H-NMR (500 MHz, DMSO-d6) δ 1.39 (s, 9H), 2.25 (s, 6H), 3.75 (d, J = 6.3 Hz, 2H), 4.40 (s, 2H), 6.76 (s, 1H), 7.03 (m, 1H), 7.12 (dd, J = 5.1, 1.7 Hz, 1H),

7.28 (m, 1H), 7.32 (s, 2H), 7.92 (dd, J = 7.6.1.7 Hz, 1H), 8.14 (d, J = 0.7 Hz , 1H), 8.18 (dd, J = 5.1, 0.7 Hz, 1H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 10.30 (s, 1H), 10.31 (s, 1H) 2- [2- (2-Acetoxypropionylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound No. 10-4) 1H-NMR (400 MHz, CDCI3) δ 1.55 (d, J = 6.7 Hz, 3H), 2.19 (s, 3H), 2.32 (s, 6H), 4.50 (s, 2H), 5.31 (q, J = 6.7 Hz, 1H), 6.81 (s, 1H), 7.11-7.14 (m, 2H),

7.27 (s, 2H), 7.85 (dd, J = 7.6.1.8 Hz, 1H), 8.03 (s, 1H), 8.17 (d, J = 5.2 Hz , 1H), 8.29 (s, 1H), 8.43 (s, 1H), 8.52 (dd, J = 4.9, 1.8 Hz, 1H) N- (3,5-Dimethylphenyl) -2- [2- (3-methoxypropionyl) aminopyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 10-5)

1H-NMR (400 MHz, DMSO-d6) δ 2.25 (s, 6H), 2.60 (t, J = 6.2 Hz, 2H), 3.21 (s, 3H), 3.59 (t, J = 6.2 Hz, 2H) , 4.40 (s, 2H), 6.76 (s, 1H), 7.11 (dd, J = 5.2, 1.4 Hz, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H), 7.32 (s, 2H), 7.92 (dd, J = 7.6, 1 , 7 Hz, 1H), 8.17 (s, 1H), 8.18 (s, 1H), 8.58 (dd, J = 9.9, 1.7 Hz, 1H), 10.31 (s, 1H), 10.42 (s, 1H)

2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (indan-5-yl) pyridin-3-carboxamide (compound No. 10-6) 1H-NMR (400 MHz, DMSO-d6) δ 2.02-2.06 (m, 2H), 2.10 (s, 3H), 2.79-2.87 (m, 4H), 4.40 (s, 2H), 4.68 (s , 2H), 7.14 (dd, J = 5.1, 1.5 Hz, 1H), 7.17 (d, J =

8.1 Hz, 1H), 7.28 (dd, J = 7.6.4.8. Hz, 1H), 7.37 (d, J = 7.3 Hz, 1H), 7.62 (s , 1H), 7.93 (m, 1H), 8.10 (s, 1H), 8.20 (d, J = 5.1 Hz, 1H), 8.57 (dd, J = 4.8, 1.7 Hz, 1H), 10.34 (s, 1H), 10.60 (s, 1H) 2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (3-methylphenyl) pyridin-3-carboxamide (compound No. 10-7)

1H-NMR (400 MHz, DMSO-d6) δ 2.10 (s, 3H), 2.30 (s, 3H), 9.91 (s, 2H), 4.69 (s, 2H), 6.93 (d, J = 7.8 Hz, 1H), 7.15 (dd, J = 5.1, 1.5 Hz, 1H), 7.22 (t, J = 7.8 Hz, 1H), 7.29 (dd, J = 7.6, 4.9 Hz, 1H), 7.46 (d, J = 7.8 Hz, 1H), 7.57 (m, 1H), 7.94 (dd, J = 7.6.1.7 Hz, 1H), 8.11 (s, 1H), 8.20 (d, J = 5.1 Hz, 1H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 10.39 (s, 1H) , 10.60 (s, 1 H)

2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethylphenyl) pyridin-3-carboxamide (compound No. 10-8) 1H-NMR (400 MHz, DMSO-d6) δ 2.10 (s, 3H), 4.42 (s, 2H), 4.72 (s, 2H), 7.15 (dd, J = 5.1, 1.5 Hz, 1H), 7, 31 (dd, J = 7.6, 4.9 Hz, 1H), 7.73 (d, J = 8.8 Hz,

2H), 7.91 (d, J = 8.8 Hz, 2H), 8.02 (dd, J = 7.6.1.7Hz, 1H), 8.11 (s, 1H), 8.20 (d, J = 5.1Hz, 1H), 8.60 (dd, J = 4.9, 1.7Hz, 1H), 10.60 (s, 1H), 10.82 (s, 1H) N- (4-Chlorophenyl) -2- (2-methoxyacetylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 10-9) 1H-NMR (400 MHz, DMSO-d6)

δ 3.35 (s, 3H), 4.04 (s, 2H), 4.42 (s, 2H), 7.15 (dd, J = 5.1, 1.5 Hz, 1H), 7, 30 (dd, J = 7.6, 4.9 Hz, 1H), 7.41 (d, J = 8.8 Hz, 2H), 7.73 (d, J = 8.8 Hz, 2H), 7.98 (dd, J = 7.6.1.7Hz, 1H), 8.17 (s, 1H), 8.19 (d, J = 5.1 Hz, 1H), 8.60 (dd, J = 9.9.1.7 Hz, 1H), 9.90 (s, 1H), 10.60 (s, 1H)

2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) pyridine-3-carboxamide (compound No. 10-10) 1H-NMR (400 MHz, DMSO-d6) δ 1.27 (s, 9H), 2.10 (s, 3H), 4.40 (s, 2H), 4.68 (s, 2H), 7.14 (d, J = 5.1 Hz, 1H), 7.28 (dd, J = 7.6.4.9Hz, 1H), 7.36 (d, J

= 8.5 Hz, 2H), 7.60 (d, J = 8.5 Hz, 2H), 7.94 (d, J = 7.6 Hz, 1H), 8.10 (sa, 1H), 8.20 (d, J = 5.1 Hz, 1H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 10.39 (s, 1H), 10.60 (s, 1H) 2- [2- (3-Methoxypropionyl) aminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 10-11)

1H-NMR (400 MHz, DMSO-d6) δ 2.60 (t, J = 6.1 Hz, 2H), 3.22 (s, 3H), 3.59 (t, J = 6.1 Hz, 2H), 4.41 (s, 2H) , 7.11 (dd, J = 5.1, 1.5 Hz, 1H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.7Hz, 2H), 7.81 (d, J = 8.7Hz, 2H), 7.99 (dd, J = 7.6.1.7 Hz, 1H) 8.18 (d, J = 5.1 Hz, 1H), 8.18 (s, 1H), 8.60 (d, J = 4.9, 1.7 Hz, 1H), 10.42 (s, 1H), 10.66 (s, 1H)

2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (3-chloro-4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 1012)

1H-NMR (400 MHz, DMSO-d6) δ 2.10 (s, 3H), 4.42 (s, 2H), 4.68 (s, 2H), 7.15 (d, J = 5.1 Hz, 1H), 7.32 (d, J = 7.6, 4.9 Hz, 1H), 7.59 (d, J = 9.0 Hz, 1H), 7.71 (dd, J = 9.0.2.4 Hz, 1H), 8.01 (dd, J = 7.6.1.7 Hz, 1H), 8.08 (d, J = 2, 4 4Hz, 1H), 8.10 (sa, 1H), 8.20 (d, J = 5.1 Hz, 1H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 10.61 (s, 1H), 10.81 (s, 1H)

2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (3-trifluoromethylphenyl) pyridin-3-carboxamide (compound No. 20-13) 1H-NMR (400 MHz, DMSO-d6) δ 2.10 (s, 3H), 4.42 (s, 2H), 4.68 (s, 2H), 7.15 (d, J = 5.1 Hz, 1H), 7.32 (d, J = 7.6, 4.9 Hz, 1H), 7.48 (d, J = 1.8 Hz, 1H),

7.60 (t, J = 8.1 Hz, 1H), 7.91 (d, J = 8.1 Hz, 1H), 8.03 (dd, J = 7.6.1.7 Hz, 1H ), 8.11 (sa, 1H), 8.18 (s, 1H), 8.20 (d, J = 5.1 Hz, 1H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 10.61 (s, 1H), 10.79 (s, 1H) 2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridine-3-carboxamide (compound No. 10-14)

1H-NMR (900 MHz, DMSO-d6) δ 1.20 (d, J = 6.8 Hz, 6H), 2.13 (s, 3H), 2.85 (m, 1H), 4.40 (s, 2H), 4.68 (s, 2H), 7.15 (d, J = 5.1 Hz, 1H), 7.23-7.30 (m, 2H), 7.50 (m, 1H), 7.58-7.60 (m, 2H), 7.96 (dd, J = 7.6.1.7 Hz, 1H), 8, 10 (sa, 1H), 8.20 (d, J = 5.1 Hz, 1H), 8.57 (dd, J = 4.6, 1.7 Hz, 1H), 10.40 (s, 1H), 10.60 (s, 1H)

2- (2-Ethoxycarbonylacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 10-15) 1H-NMR (400 MHz, DMSO-d6) δ 1.19 (t, J = 7.1 Hz, 3H), 3.53 (s, 2H), 4.10 (q, J = 7.1 Hz, 2H), 4.42 (s, 2H) , 7.15 (dd, J = 5.1, 1.1 Hz, 1H), 7.31 (dd, J =

7.6.4.9 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.81 (d, J = 8.8 Hz, 2H), 7.99 (dd, J = 7.6.1.7 Hz, 1H), 8.16 (s, 1H), 8.20 (d, J = 5.1

Hz, 1H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 10.63 (s, 1H), 10.66 (s, 1H) 2- [2- (3-tert-Butoxycarbonylaminopropionylamino) pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 10-16)

1H-NMR (500 MHz, CDCI3) δ 1.42 (s, 9H), 2.59 (t, J = 5.7 Hz, 2H), 3.42-3.50 (m, 2H), 4.53 (s, 2H), 5, 05 (s, 1H), 7.09 (dd, J = 5.2.1.5Hz, 1H), 7.16 (dd, J

= 7.6.4.8Hz, 1H), 7.22 (d, J = 8.9Hz, 2H), 7.70 (d, J = 8.9Hz, 2H), 7.90 (dd, J = 7.6.1.8Hz, 1H), 7.98 (s, 1H), 8.15 (d, J = 5.2 Hz, 1H), 8.24 (s, 1H), 8.28 (s, 1H), 8.54 (dd, J = 4.8.1.8 Hz, 1H) 2- [2 - ((4S) -terc-Butoxycarbonylamino-5-hydroxypentanoyl) aminopyridin-9-ylmethylthio] -N- (9-trifluoromethoxyphenyl) pyridin-3

carboxamide (compound No. 10-17) 1H-NMR (400 MHz, DMSO-d6)

δ 1.36 (s, 9H), 1.42 (m, 1H), 1.82 (m, 1H), 2.32-2.39 (m, 4H), 3.22 (m, 1H), 4.40 (s, 2H), 4.61 (m, 1H), 6.47 (m, 1H), 7.09 (m, 1H), 7.29 (dd, J = 7.6.4, 8 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 8.8 Hz, 2H), 7.98 (dd, J = 7.6, 1.8 Hz, 1H), 8.16 (s, 1H), 8.17 (s, 1H), 8.60 (dd, J = 4.8.1.8 Hz, 1H), 10.34 ( s, 1H), 10.66 (s, 1H)

5 2- [2- (2-Oxopyrrolidin-1-yl) pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (compound No. 10-18)

1H-NMR (400 MHz, DMSO-d6)

10 δ 1.97-2.05 (m, 2H), 2.51-2.57 (m, 2H), 3.94 (t, J = 7.1 Hz, 2H), 4.42 (s, 2H), 7.15 (dd, J = 5.1, 1.5 Hz, 1H), 7.30 (dd, J = 7.6.4.8 Hz, 1H), 7.37 (d, J = 8.7 Hz, 2H), 7.80 (d, J = 8.7 Hz, 2H), 7.99 (dd, J = 7.6, 1.7 Hz, 1H), 8.25 (d , J = 5.1 Hz, 1H), 8.40 (s, 1H), 8.60 (dd, J = 4.8.1.7 Hz, 1H), 10.65 (s, 1H)

2- (2-Cyanoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (compound No. 10-19) 15 1 H-NMR (500 MHz, CDCl3)

δ 3.66 (s, 2H), 4.55 (s, 2H), 7.16 (dd, J = 7.6.4.9Hz, 1H), 7.23 (d, J = 8.6 Hz , 2H), 7.24-7.29 (m, 2H), 7.75 (d, J = 8.6Hz, 2H), 7.89 (dd, J = 7.6.1.8 Hz, 1H ), 8.16 (d, J = 5.5 Hz, 1H), 8.20 (s, 1H), 8.41 (s, 1H), 8.52 (dd, J = 4.9, 1, 8 Hz, 1H) 2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (4-difluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 10-20)

1H-NMR (4000 MHz, DMSO-d6)

25 δ 2.06 (s, 3H), 3.30 (s, 2H), 4.40 (s, 2H), 7.10 (dd, J = 5.1, 1.5 Hz, 1H), 7 , 16 (t, J = 74.2 Hz, 1H), 7.18 (d, J = 8.8 Hz, 2H), 7.30 (dd, J = 7.6.4.9 Hz, 1H) , 7.72 (d, J = 8.8 Hz, 2H), 7.97 (dd, J = 7.6, 1.7Hz, 1H), 8.16-8.17 (m, 2H), 8 , 59 (dd, J = 4.9, 1.7Hz, 1H), 10.41 (s, 1H), 10.55 (s, 1H)

2- (2-tert-Butoxycarbonylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-difluoromethoxyphenyl) pyridine-3-carboxamide 30 (compound No. 10-21)

1H-NMR (400 MHz, DMSO-d6)

δ 1.39 (s, 9H), 3.75 (d, J = 6.1 Hz, 2H), 4.41 (s, 2H), 7.04 (t, J = 6.1 Hz, 1H) , 7.12 (d, J = 5.2 Hz, 1H), 7.17 (t, J = 74.2 35 Hz, 1H), 7.18 (d, J = 8.8 Hz, 2H), 7.29 (dd, J = 7.6.4.9 Hz, 1H), 7.72 (d, J = 8.8 Hz, 2H), 7.96 (d, J = 7.6.1, 6 Hz, 1H), 8.14 (s, 1H), 8.18 (d, J = 5.2 Hz, 1H), 8.59 (dd, J = 4.9, 1.6 Hz, 1H) , 10.31 (s, 1H), 10.54 (s, 1H)

Example 11

2- (2-Aminopyridin-4-ylmethylthio) -N-carboxymethyl-N- (3,5-dimethylphenyl) pyridine-3-carboxamide monohydrochloride (compound No. 11-1)

2- (2-Aminopyridin-4-ylmethylthio) -N- (tert-butoxycarbonylmethyl) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (compound No. 7-1.40 mg, 0.084 mmol) was dissolved ) in ethyl acetate (1.0 ml), and added 4 N hydrochloric acid in ethyl acetate

45 (1.0 ml) thereto, and then the mixture was stirred for 18 hours at room temperature. The precipitated solid was filtered off with diethyl ether and dried under reduced pressure to provide 30 mg of the objective compound as a colorless solid. (86% yield)

1H-NMR (500 MHz, DMSO-d6) δ 2.04 (s, 6H), 4.44 (sa, 4H), 5.35 (sa, 1H), 6.77 (s, 3H), 6, 87 (d, J = 6.9 Hz, 1H), 6.98 (s, 1H), 7.03 (s, 1H), 7.31 (s, 1H), 7.87 (d, J = 6 , 9 Hz, 1H), 8.02 (s, 2H), 8.32 (s, 1H), 13.52 (s, 1H)

As described below, the compounds (No. 11-2 ~ 3) were obtained using the corresponding 5 compounds selected from the compounds (No. 10-3, 17), commercially available compounds or known compounds according to the process of synthesis of the compound (No. 11-1).

2- (2-Aminoacetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide monohydrochloride (compound No. 11-2) 10 1 H-NMR (500 MHz, DMSO-d6)

δ 2.25 (s, 6H), 3.81 (s, 2H), 4.46 (s, 2H), 6.76 (s, 1H), 7.10 (sa, 1H), 7.23 ( dd, J = 5.2, 1.3 Hz, 1H), 7.29 (dd, J = 7.6.4.9 Hz, 1H), 7.34 (s, 2H), 7.97 (dd , J = 7.6.1.8 Hz, 1H), 8.13 (s, 1H), 8.24 (d, J = 5.2 Hz, 1H), 8.28 (s, 2H), 8 , 57 (dd, J = 15 4.9, 1.5 Hz, 1H), 10.36 (s, 1H), 11.09 (s, 1H)

2- [2 - ((4S) -amino-5-hydroxypentanoyl) aminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3carboxamide monohydrochloride (compound No. 11-3)

20 1H-NMR (500 MHz, DMSO-d6)

δ 1.78-1.86 (m, 2H), 2.26-2.29 (m, 2H), 3.12 (s, 1H), 3.36-3.39 (m, 2H), 3 , 44 (m, 1H), 3.60 (m, 1H), 3.96 (s, 1H), 4.42 (s, 2H), 7.17 (d, J = 5.2 Hz, 1H) , 7.31 (dd, J = 7.6.4.8 Hz, 1H), 7.37 (d, J = 8.5 Hz, 2H), 7.81 (d, J = 8.5 Hz, 2H), 7.83 (s, 1H), 8.01 (dd, J = 7.6, 1.8 Hz, 1H), 8.13 (s, 1H), 8.20 (d, J = 5 , 2 Hz, 1H), 8.60 (dd, J = 4.8.1.8 Hz, 1H), 10.64 (s, 1H),

25 10.68 (s, 1 H)

Example 12

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 12-1)

2- 2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 10-2, 25 mg, 0.048 mmol) was dissolved in the methanol mixture (2, 0 ml) and tetrahydrofuran (1.0 ml), and a 4 N aqueous solution of sodium hydroxide (60 ml) was added thereto with ice cooling. The mixture was stirred for 15 minutes at room temperature and diluted with ethyl acetate (30 ml), and then the whole was washed with

35 saturated aqueous solution of sodium hydrogen carbonate (30 ml) and brine (30 ml). The organic phase was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to provide 23 mg of the objective compound quantitatively as a pale yellow solid.

40 1H-NMR (500 MHz, DMSO-d6)

δ 4.01 (d, J = 5.8 Hz, 2H), 4.43 (s, 2H), 5.72 (t, J = 5.8 Hz, 1H), 7.15 (d, J = 6.7 Hz, 1H), 7.31 (dd, J = 7.6, 4.9 Hz, 1H), 7.37 (d, J = 8.3Hz, 2H), 7.80 (d, J = 8.3Hz, 2H), 7.98 (dd, J = 7.6.1.8 Hz, 1H), 8.19 (s, 1H), 8.20 (s, 1H), 8.60 ( dd, J = 4.9,

45 1.8 Hz, 1H), 9.58 (s, 1H), 10.65 (s, 1H)

As described below, the compounds (No. 12-2 ~ 16) were obtained using the corresponding compounds selected from the compounds (No. 10-1 ~ 21), commercially available compounds or known compounds according to the process of Synthesis of the compound (No. 12-1).

50 N- (3,5-Dimethylphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 12-2)

1H-NMR (500 MHz, DMSO-d6) δ 2.25 (s, 6H), 4.01 (d, J = 6.1 Hz, 2H), 4.42 (s, 2H), 5.73 (t, J = 6.0 Hz, 1H) , 6.76 (s, 1H), 7.15 (d, J = 6.7 Hz, 1H), 7.28

(dd, J = 7.3.4.9 Hz, 1H), 7.32 (s, 2H), 7.93 (d, J = 5.8 Hz, 1H), 8.19-8.20 ( m, 2H), 8.57 (dd, J = 4.9, 1.8 Hz, 1H), 9.58 (s, 1H), 10.30 (s, 1H) N- (4-Chlorophenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 12-3) 1H-NMR (400 MHz, DMSO-d6) δ 4.01 (d, J = 6.1 Hz, 2H), 4.43 (s, 2H), 5.74 (t, J = 6.1 Hz, 1H), 7.15 (d, J = 5.4 Hz, 1H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.41

(d, J = 8.8 Hz, 2H), 7.72 (d, J = 8.8 Hz, 2H), 7.98 (dd, J = 7.6.1.7Hz, 1H), 8, 18-8.20 (m, 2H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 9.59 (s, 1H), 10.60 (s, 1H) N- (3,5-Dimethylphenyl) -2- [2- (2-hydroxypropionylamino) pyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 12-4)

1H-NMR (400 MHz, CDCl3) δ 1.52 (d, J = 6.9 Hz, 3H), 1.64 (s, 1H), 2.31 (s, 6H), 4.37 (q, J = 6.9 Hz, 1H) , 4.49 (s, 2H), 6.80 (d, J = 0.7 Hz, 1H), 7.097.13 (m, 2H), 7.27 (s, 2H), 7.84 (dd, J = 7.6.1.7 Hz, 1H), 8.06 (s, 1H), 8.13 (dd, J = 5.1.0.5 Hz, 1H), 8.34 (s, 1H ), 8.51 (dd, J = 4,8,1,7 Hz, 1H), 9,27 (s, 1H)

N- (3,5-Dimethyl-4-hydroxyphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 12-5) 1H-NMR (500MH2, DMSO-d6) δ 2.15 (s, 6H), 4.01-4.05 (m, 2H), 4.41 (s, 2H), 5.75 (sa, 1H), 7.15 (dd, J = 5 , 3.1.4 Hz, 1H), 7.24 (s, 2H), 7.26 (dd, J =

7.6.4.9 Hz, 1H), 7.90 (dd, J = 7.6, 1.5 Hz, 1H), 8.10 (s, 1H), 8.18-8.20 (m , 2H), 8.56 (dd, J = 4.9, 1.5 Hz, 1H), 9.59 (s, 1H), 10.09 (s, 1H) 2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (3-methylphenyl) pyridin-3-carboxamide (compound No. 12-6)

1H-NMR (500 MHz, DMSO-d6) δ 2.30 (s, 3H), 4.01 (d, J = 6.1 Hz, 2H), 4.42 (s, 2H), 5.74 (t, J = 6.1 Hz, 1H) , 6.93 (d, J = 7.8 Hz, 1H), 7.16 (dd, J = 5.2, 1.5 Hz, 1H), 7.22 (t, J = 7.8 Hz, 1H), 7.29 (dd, J = 7.6, 4.9 Hz, 1H), 7.46 (d, J = 7.8 Hz, 1H), 7.56 (s, 1H), 7.95 (dd, J = 7.6.1.7 Hz, 1H), 8.18-8.20 (m, 2H), 8.58 (dd, J = 4.9, 1.7 Hz, 1H), 9.59 (s , 1H), 10.38 (s, 1H)

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethylphenyl) pyridin-3-carboxamide (compound No. 12-7) 1H-NMR (500 MHz, DMSO-d6) δ 4.01 (d, J = 6.1 Hz, 2H), 4.44 (s, 2H), 5.74 (t, J = 6.1 Hz, 1H), 7.16 (dd, J = 5.2.1.2 Hz, 1H), 7.32 (dd, J = 7.6.4.9 Hz,

1H), 7.73 (d, J = 8.6 Hz, 2H), 7.92 (d, J = 8.6 Hz, 2H), 8.02 (dd, J = 7.6.1.8 Hz, 1H), 8.18-8.20 (m, 2H), 8.61 (dd, J = 4.9, 1.8 Hz, 1H), 9.59 (s, 1H), 10.82 (s, 1H) N- (4-tert-Butylphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 12-8)

1H-NMR (400 MHz, DMSO-d6) δ 1.27 (s, 9H), 4.01 (d, J = 5.5 Hz, 2H), 4.42 (s, 2H), 5.74 (t, J = 5.5Hz, 1H), 7.16 (d, J = 6.6 Hz, 1H), 7.29 (dd, J = 7.6.4.9 Hz, 1H), 7.36 (d, J = 8.5 Hz, 2H), 7.60 (d, J = 8.5 Hz, 2H), 7.94 (d, J = 7.6 Hz, 1H), 8.18-8.20 (m, 2H), 8.58 (dd, J = 4.9, 1.7 Hz, 1H), 9.59 (s at, 1H), 10.40 (s, 1H)

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) pyridin-3-carboxamide (compound No. 12-9) 1H-NMR (500 MHz, DMSO-d6) δ 4.03 (d, J = 5.9 Hz, 2H), 4.44 (s, 2H), 5.74 (t, J = 5.9 Hz, 1H), 7.17 (dd, J = 5.2.1.6 Hz, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H),

7.58 (m, 1H), 7.75 (m, 1H), 7.98 (d, J = 7.6 Hz, 1H), 8.05-8.10 (m, 2H), 8.17 -8.21 (m, 2H), 8.58 (dd, J = 4.9, 1.6 Hz, 1H), 8.60 (s, 1H), 9.19 (s, 1H), 9.60 (s, 1H), 11.16 (s, 1H) N- (3-Chlorophenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide (compound No. 12-10) 1H-NMR (400 MHz, DMSO-d6)

δ 4.01 (d, J = 5.9 Hz, 2H), 4.43 (s, 2H), 5.74 (t, J = 5.9 Hz, 1H), 7.15-7.20 ( m, 2H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.39 (t, J = 7.6 Hz, 1H), 7.58 (m, 1H), 7.88 (d, J = 1.7 Hz, 1H), 7.99 (dd, J = 7.6.1.7 Hz, 1H), 8.16-8.19 (m, 2H), 8 , 60 (dd, J = 4.9, 1.7 Hz, 1H), 9.59 (s, 1H), 10.65 (s, 1H)

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (indan-5-yl) pyridin-3-carboxamide (compound No. 12-11)

1H-NMR (400 MHz, DMSO-d6)

δ 1.99-2.06 (m, 2H), 2.80-2.87 (m, 4H), 4.01 (d, J = 4.9 Hz, 2H), 4.42 (s, 2H ), 5.74 (s, 1H), 7.14-7.18 (m, 2H), 7.28 (dd, J = 7.6.4.9Hz, 1H), 7.38 (d, J = 6.9Hz, 1H), 7.61 (s, 1H), 7.93 (dd, J = 7.6.1.7 Hz, 1H), 8.18-8.21 (m, 2H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 9.58 (s, 1H), 10.34 (s, 1H)

N- (3-Chloro-4-trifluoromethoxyphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 1212)

1H-NMR (400 MHz, DMSO-d6)

δ 4.01 (s, 2H), 4.44 (s, 2H), 5.74 (t, J = 5.6 Hz, 1H), 7.15 (d, J = 5.1 Hz, 1H) , 7.32 (d, J = 7.6.4.9 Hz, 1H), 7.59 (d, J = 8.8 Hz, 1H), 7.71 (dd, J = 8.8.2 , 4 Hz, 1H), 8.01 (dd, J = 7.6.1.7 Hz, 1H), 8.08 (d, J = 2.4 Hz, 1H), 8.19 (s, 1H ), 8.20 (d, J = 5.1 Hz, 1H), 8.61 (dd, J = 4.9, 1.7 Hz, 1H), 9.59 (s, 1H), 10.81 (s, 1H)

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridine-3-carboxamide (compound No. 12-13)

1H-NMR (400 MHz, DMSO-d6)

δ 1.20 (d, J = 6.8 Hz, 6H), 2.88 (m, 1H), 4.01 (d, J = 5.9 Hz, 2H), 4.42 (s, 2H) , 5.74 (t, J = 5.9 Hz, 1H), 7.00 (d, J = 7.6 Hz, 1H), 7.16 (d, J = 6.6 Hz, 1H), 7 , 26 (t, J = 8.2 Hz, 1H), 7.29 (dd, J = 7.6.4.9 Hz, 1H), 7.51 (d, J = 8.2 Hz, 1H) , 7.59 (sa, 1H), 7.96 (d, J = 6.6 Hz, 1H), 8.19 (d, J = 8.2 Hz, 1H), 8.20 (s, 1H) , 8.58 (dd, J = 4.9, 1.7 Hz, 1H), 9.59 (s, 1H), 10.40 (s, 1H)

2- (2-Hydroxycarbonylacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 1214)

1H-NMR (400 MHz, DMSO-d6)

δ 3.42 (s, 2H), 4.42 (s, 2H), 7.14 (dd, J = 5.1, 1.3 Hz, 1H), 7.31 (dd, J = 7.6 , 4.9 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.81 (d, J = 8.8 Hz, 2H), 7.98 (dd, J = 7 , 6.1.7 Hz, 1H), 8.17 (s, 1H), 8.19 (d, J = 5.1 Hz, 1H), 8.60 (dd, J = 4.9, 1, 7 Hz, 1H), 10.58 (s, 1H), 10.67 (s, 1H)

N- (4-Difluoromethoxyphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 12-15)

1H-NMR (400 MHz, DMSO-d6)

δ 4.01 (d, J = 5.9 Hz, 2H), 4.43 (s, 2H), 5.74 (t, J = 5.9 Hz, 1H), 7.14-7.19 ( m, 3H), 7.19 (t, J = 74.6 Hz, 1H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.73 (d, J = 8 , 8 Hz, 2H), 7.97 (dd, J = 7.6.1.7 Hz, 1H), 8.19-8.20 (m, 2H), 8.59 (dd, J = 4, 9, 1.7 Hz, 1H), 9.59 (s, 1H), 10.55 (s, 1H)

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (3-trifluoromethylphenyl) pyridin-3-carboxamide (compound No. 12-16)

1H-NMR (400 MHz, DMSO-d6)

δ 4.01 (d, J = 5.9 Hz, 2H), 4.44 (s, 2H), 5.74 (t, J = 5.9 Hz, 1H), 7.16 (dd, J = 5.4.1.2 Hz, 1H), 7.32 (dd, J = 7.7.4.9 Hz, 1H), 7.48 (d, J = 8.1 Hz, 1H), 7, 61 (t, J = 8.1 Hz, 1H), 7.91 (d, J = 8.1 Hz, 1H), 8.03 (dd, J = 7.7.1.7 Hz, 1H), 8.17-8.20 (m, 3H), 8.61 (dd, J = 4.9, 1.7 Hz, 1H), 9.59 (s, 1H), 10.79 (s, 1H)

Example 13

2- [2-Bis (acetoxyacetyl) aminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 13-1)

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (compound No. 3-11, 800 mg, 1.9 mmol) was dissolved in pyridine (10 ml), and acetoxyacetyl chloride (0.66 ml, 6.1 mmol) was added thereto with ice cooling, and the mixture was stirred for 18 hours at room temperature. The mixture was diluted with ethyl acetate (100 ml), and the whole was washed with saturated aqueous sodium hydrogen carbonate solution (100 ml) and 1 N hydrochloric acid (50 ml) twice successively. The organic phase was washed with saturated aqueous sodium hydrogen carbonate solution (100 ml) again and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The resulting solid was recrystallized from ethyl acetate-hexane to provide 300 mg of the objective compound as a colorless solid. (30% yield)

5 1H-NMR (400 MHz, DMSO-d6)

δ 2.06 (s, 6H), 4.48 (s, 2H), 4.72 (s, 4H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7, 38 (d, J = 8.3 Hz, 2H), 7.57-7.59 (m, 2H), 7.81 (d, J = 9.0 Hz, 2H), 8.01 (dd, J = 7.6.1.7 Hz, 1H), 8.49 (d, J = 5.8 Hz, 1H), 8.56 (dd, J = 4.9, 1.7 Hz, 1H), 10 , 67 (s, 1H)

As described below, the compounds (No. 13-2 ~ 14) were obtained using the corresponding compounds selected from the compounds (No. 3-1 ~ 37), commercially available compounds or known compounds according to the process of synthesis of the compound (No. 13-1).

2- 2- [2-Bis (acetoxyacetyl) aminopyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound No. 13-2)

1H-NMR (400 MHz, DMSO-d6)

δ 2.07 (s, 6H), 2.26 (s, 6H), 4.47 (s, 2H), 4.72 (s, 4H), 6.76 (s, 1H), 7.28 ( dd, J = 7.6.4.Hz, 1H), 7.33 (s, 2H), 7.58 (s, 1H), 7.59 (d, J = 5.6Hz, 1H), 7 , 95 (dd, J = 7.6.1.7Hz, 1H), 8.49 (d, J = 5.6Hz, 1H), 8.54 (dd, J = 4.9, 1.7 Hz, 1H), 10.31 (s, 1H)

N- (3,5-Dimethylphenyl) -2- (2-ethoxycarbonyloxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 13-3)

1H-NMR (500 MHz, DMSO-d6)

25 δ 1.23 (t, J = 7.0 Hz, 3H), 2.25 (s, 6H), 4.15 (q, J = 7.0 Hz, 2H), 4.41 (s, 2H ), 4.73 (s, 2H), 6.76 (s, 1H), 7.15 (dd, J = 5.2.1.6 Hz, 1H), 7.28 (dd, J = 7, 6.4.9 Hz, 1H), 7.32 (s, 2H), 7.92 (dd, J = 7.6.1.6 Hz, 1H), 8.11 (s, 1H), 8, 20 (d, J = 5.2 Hz, 1H), 8.57 (dd, J = 4.9, 1.6 Hz, 1H), 10.30 (s, 1H), 10.65 (s, 1H )

2- 2- [2- (3-Hydroxycarbonylpropionyloxy) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 13-4)

1H-NMR (400 MHz, DMSO-d6)

35 δ 2.49-2.52 (m, 2H), 2.60-2.64 (m, 2H), 4.41 (s, 2H), 4.71 (s, 2H), 7.15 ( dd, J = 5.1, 1.5 Hz, 1H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.3 Hz, 2H ), 7.80 (d, J = 8.3 Hz, 2H), 7.98 (dd, J = 7.6.1.7 Hz, 1H), 8.11 (sa, 1H), 8.20 (d, J = 5.1 Hz, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.59 (s, 1H), 10.67 (s, 1H) , 12.28 (sa, 1 H)

N- (3,5-Dimethylphenyl) -2- (2-methanesulfonylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 1340 5)

1H-NMR (400 MHz, DMSO-d6)

δ 2.25 (s, 6H), 2.96 (s, 3H), 3.89 (s, 2H), 4.41 (s, 2H), 6.76 (s, 1H), 7.14 ( m, 1H), 7.28 (dd, J = 7.6.4.8 Hz, 1H), 7.32 45 (s, 2H), 7.47 (s, 1H), 7.92 (d, J = 7.6Hz, 1H), 8.16 (s, 1H), 8.10 (d, J = 4.5 Hz, 1H), 8.57 (dd, J = 4.8.1.5 Hz , 1H), 10.30 (s, 1H), 10.38 (s, 1H)

2- (2-Diethylaminocarbonyloxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 13-6) 50 1H-NMR (400 MHz, DMSO-d6)

δ 1.02-1.14 (m, 6H), 3.20-3.34 (m, 4H), 4.41 (s, 2H), 4.66 (s, 2H), 7.13 (dd , J = 5.1, 1.5 Hz, 1H), 7.29 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H) , 7.80 (d, J = 8.8 Hz, 2H), 7.98 (dd, J = 7.6.1.7 Hz, 1H), 8.13 (s, 1H), 8.19 ( d, J = 5.1 Hz, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.52 (s, 1H), 10.66 (s, 1H)

2- (2-Dimethylaminocarbonyloxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 13-7)

1H-NMR (400 MHz, DMSO-d6)

δ 2.83 (s, 3H), 2.92 (s, 3H), 4.42 (s, 2H), 4.64 (s, 2H), 7.14 (dd, J = 5.1, 1 , 3 Hz, 1H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.81 (d, J = 8.8 Hz, 2H), 7.99 (dd, J = 7.6.1.7 Hz, 1H), 8.12 (s, 1H), 8.19 (d, J = 5.1Hz, 1H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 10.52 (s, 1H), 10.67 (s, 1H)

2- (2-Morpholinocarbonyloxy-acetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 13-8)

1H-NMR (400 MHz, DMSO-d6)

δ 3.30-3.35 (m, 4H), 3.58 (t, J = 4.9 Hz, 4H), 4.42 (s, 2H), 4.68 (s, 2H), 7, 14 (dd, J = 5.1, 1.5 Hz, 1H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.8Hz, 2H), 7.80 (d, J = 8.8Hz, 2H), 7.99 (dd, J = 7.6.1.7 Hz, 1H), 8.12 (s, 1H), 8.19 (d, J = 5.1 Hz, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.56 (s, 1H), 10.66 (s, 1H)

2- (2-Isobutyryloxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 13-9)

1H-NMR (500 MHz, DMSO-d6)

δ 1.13 (d, J = 7.0 Hz, 6H), 2.64 (m, 1H), 4.41 (s, 2H), 4.70 (s, 2H), 7.14 (dd, J = 5.0.1.2 Hz, 1H), 7.30 (dd, J = 7.5.4.7 Hz, 1H), 7.37 (d, J = 8.9 Hz, 2H), 7.80 (d, J = 8.9 Hz, 2H), 7.98 (dd, J = 7.5.1.7 Hz, 1H), 8.11 (s, 1H), 8.20 (dd , J = 5.0.0.6 Hz, 1H), 8.59 (dd, J = 4.7.1.7 Hz, 1H), 10.60 (s, 1H), 10.66 (s, 1 HOUR)

2- [2- (4-Hydroxycarbonylbutyryl) oxiacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 13-10)

1H-NMR (400 MHz, DMSO-d6)

δ 1.75-1.79 (m, 2H), 2.31 (t, J = 7.3 Hz, 2H), 2.44 (t, J = 7.3 Hz, 2H), 4.41 ( s, 2H), 4.70 (s, 2H), 7.14 (d, J = 5.1 Hz, 1H), 7.30 (dd, J = 7.6.4.9Hz, 1H), 7 , 37 (d, J = 8.3 Hz, 2H), 7.80 (d, J = 8.3 Hz, 2H), 7.98 (dd, J = 7.6.1.7 Hz, 1H) , 8.11 (s, 1H), 8.20 (d, J = 5.1 Hz, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.61 ( s, 1H), 10.67 (s, 1H), 12.17 (sa, 1H)

2- (2-Acetoxyacetoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 1311)

1H-NMR (400 MHz, DMSO-d6)

δ 2.11 (s, 3H), 4.42 (s, 2H), 4.77 (s, 2H), 4.79 (s, 2H), 7.15 (dd, J = 5.1, 1 , 5 Hz, 1H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 8.8 Hz, 2H), 7.98 (dd, J = 7.6.1.7 Hz, 1H), 8.11 (s, 1H), 8.20 (d, J = 5.1 Hz , 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.64 (s, 1H), 10.66 (s, 1H)

2- (2-Methoxyethoxyethoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 1312)

1H-NMR (400 MHz, DMSO-d6)

δ 3.22 (s, 3H), 3.44-3.47 (m, 2H), 3.53-3.58 (m, 4H), 3.64-3.67 (m, 2H), 4 , 11 (s, 2H), 4.43 (s, 2H), 7.16 (d, J = 5.1 Hz, 1H), 7.31 (dd, J = 7.6, 4.9 Hz, 1H), 7.37 (d, J = 8.9 Hz, 2H), 7.81 (d, J = 8.9 Hz, 2H), 7.99 (dd, J = 7.6.1.7 Hz, 1H), 8,188.20 (m, 2H), 8.60 (dd, J = 4.9, 1.7 7 Hz, 1H), 9.78 (s, 1H), 10.66 (s, 1 HOUR)

2- (2-Dimethylaminoacetylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 13-13)

1H-NMR (400 MHz, DMSO-d6)

δ 2.25 (s, 6H), 2.92 (s, 2H), 3.95 (d, J = 5.9 Hz, 2H), 4.41 (s, 2H), 7.12 (dd, J = 5.1, 1.5 Hz, 1H), 7.29 (dd, J = 7.7.4.8 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 8.8 Hz, 2H), 7.98 (dd, J = 7.7.1.6 Hz, 1H), 8.01 (s, 1H), 8.13 (s , 1H), 8.19 (dd, J = 5.1.0.5 Hz, 1H), 8.59 (dd, J = 4.8.1.6Hz, 1H), 10.45 (s, 1H ), 10.66 (s, 1 H)

N- (4-Difluoromethoxyphenyl) -2- (2-dimethylaminocarbonyloxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 13-14)

1H-NMR (400 MHz, DMSO-d6)

5 δ 2.83 (s, 3H), 2.92 (s, 3H), 4.41 (s, 2H), 4.64 (s, 2H), 7.13-7.20 (m, 3H) , 7.17 (t, J = 74.0 Hz, 1H), 7.29 (dd, J = 7.6, 4.9 Hz, 1H), 7.73 (d, J = 8.8 Hz, 2H), 7.97 (dd, J = 7.6.1.7 Hz, 1H), 8.11 (s, 1H), 8.19 (d, J = 4.9 Hz, 1H), 8, 59 (dd, J = 4.9, 1.7 Hz, 1H), 10.52 (s, 1H), 10.55 (s, 1H)

10 Example 14

N- (4-tert-Butylphenyl) -2- (2-dimethylaminopyridin-4-ylmethylthio) benzamide (compound No. 14-1)

Triethylamine (61 µl, 0.44 mmol) was added to a solution of 4-chloromethyl-2-dimethylaminopyridine (36 mg, 0.21 mmol) and

15 N- (4-tert-Butylphenyl) -2-mercaptobenzamide (36 mg, 0.13 mmol) in N, N-dimethylformamide (1.0 ml) at room temperature, and the mixture was stirred for 68 hours. The mixture was diluted with ethyl acetate (30 ml), the whole was washed with saturated aqueous sodium hydrogen carbonate solution (30 ml) and brine (30 ml) successively, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give 19 mg of the target compound as

20 a pale yellow oil. (22% yield)

1H-NMR (400 MHz, DMSO-d6)

25 δ 1.27 (s, 9H), 2.95 (s, 6H), 4.12 (s, 2H), 6.55 (dd, J = 5.1, 1.2 Hz, 1H) 6, 58 (s, 1H), 7.29 (m, 1H), 7.35 (d, J = 8.8 Hz, 2H), 7.42 (m, 1H), 7.48-7.51 (m , 2H), 7.63 (d, J = 8.5Hz, 2H), 7.95 (dd, J = 5.1.0.7 Hz, 1H), 10.27 (s, 1H)

As described below, the compound (# 14-2) was obtained using the corresponding compounds

30 selected from the reference compound (# 10-1), commercially available compounds or known compounds according to the method of synthesis of the compound (# 14-1).

2- (2-Dimethylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound No. 14-2)

35 1H-NMR (500 MHz, DMSO-d6)

δ 2.28 (s, 6H), 2.96 (s, 6H), 4.35 (s, 2H), 6.55 (dd, J = 5.2.1.2 Hz, 1H), 6, 60 (s, 2H), 6.62 (s, 1H), 6.83 (s, 1H), 7.23 (dd, J = 7.6.4.9 Hz, 1H), 7.60 (dd , J = 7.6.1.8 Hz, 1H), 7.96 (d, J = 5.2 Hz, 1H), 8.53 (dd, J = 4.9, 1.8 Hz, 1H) , 9.78 (s, 1 H)

40 Example 15

2- (2-Acetylaminopyridin-4-ylmethylsulfinyl) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound No. 15-1)

M-Chloroperbenzoic acid (75%, 60 mg, 0.26 mmol) was added to a solution of 2- (2-acetylaminopyridine-4

Ilmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (compound No. 4-1, 60 mg, 0.15 mmol) in methylene chloride (3 ml) with ice cooling, and Stir the mixture for 1 hour. The reaction mixture was diluted with ethyl acetate (30 ml), the whole was washed with saturated aqueous sodium hydrogen carbonate solution (10 ml) twice and brine (10 ml), and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the precipitated solid was filtered off with ethyl acetate to give 30 mg of the objective compound as a

50 colorless solid. (48% yield) 1H-NMR (400 MHz, DMSO-d6)

δ 2.08 (s, 3H), 2.29 (s, 6H), 4.20 (d, J = 12.2 Hz, 1H), 4.48 (d, J = 12.2 Hz, 1H) , 6.80 (s, 1H), 6.94 (dd, J = 4.9, 1.7 Hz, 1H), 7.36 (s, 2H), 7.74 (dd, J = 7.8 , 4.9 Hz, 1H), 8.05 (s, 1H), 8.23 (d, J = 4.9 Hz, 1H), 8.29 (dd, J = 7.8.1.5 Hz , 1H), 8.86 (dd, J = 4.9, 1.5 Hz, 1H), 10.49 (s, 1H), 10.56 (s, 1H)

Example 16

N- (4-tert-Butylphenyl) -2- (2-chloroacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 16-1)

N- (4-tert-Butylphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 128, 250 mg, 0.55mmol) was suspended in anhydrous dichloromethane (5.0 ml ) with ice cooling, and thionyl chloride (80 µl, 1.1 mmol) was added thereto. The mixture was stirred for 6 hours at room temperature, and the solvent was evaporated under reduced pressure. The resulting solid was filtered off with ethyl acetate and washed with diethyl ether to afford 270 mg of the objective compound quantitatively as a pale yellow solid.

1H-NMR (400 MHz, DMSO-d6)

δ 1.27 (s, 9H), 4.37 (s, 2H), 4.45 (s, 2H), 7.27 (d, J = 5.4 Hz, 1H), 7.30 (dd, J = 7.6.4.8 Hz, 1H), 7.36 (d, J = 8.8 Hz, 2H), 7.61 (d, J = 8.8 Hz, 2H), 7.97 ( d, J = 7.6 Hz, 1H), 8.09 (s, 1H), 8.24 (d, J = 5.4 Hz, 1H), 8.58 (dd, J = 4.8.1 , 7 Hz, 1H), 10.43 (s, 1H), 11.19 (s, 1H)

As described below, the compounds (No. 16-2 ~ 9) were obtained using the corresponding compounds selected from the compounds (No. 12-1 ~ 16), commercially available compounds or known compounds according to the process of Synthesis of the compound (No. 16-1).

2- (2-Chloroacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 16-2)

1H-NMR (400 MHz, DMSO-d6)

δ 4.32 (s, 2H), 4.43 (s, 2H), 7.17 (dd, J = 5.1, 1.7 Hz, 1H), 7.31 (dd, J = 7.8 , 4.9 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.81 (d, J = 8.8Hz, 2H), 7.99 (dd, J = 7, 8.1.7Hz, 1H), 8.15 (s, 1H), 8.21 (d, J = 5.1 Hz, 1H), 8.60 (dd, J = 4.9, 1.7 Hz , 1H), 10.66 (s, 1H), 10.75 (s, 1H)

2- (2-Chloroacetylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridin-3-carboxamide (compound No. 16-3)

1H-NMR (400 MHz, DMSO-d6)

δ 4.32 (s, 2H), 4.43 (s, 2H), 7.17 (dd, J = 5.1, 1.5 Hz, 1H), 7.30 (dd, J = 7.6 , 4.9 Hz, 1H), 7.41 (d, J = 8.8 Hz, 2H), 7.73 (d, J = 8.8Hz, 2H), 7.98 (dd, J = 7, 6.1.7 Hz, 1H), 8.15 (s, 1H), 8.21 (dd, J = 5.1, 1.5 Hz, 1H), 8.60 (dd, J = 4.9 , 1.7 Hz, 1H), 10.60 (s, 1H), 10.75 (s, 1H)

2- (2-Chloroacetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound No. 16-4)

1H-NMR (400 MHz, DMSO-d6)

δ 2.25 (s, 6H), 4.32 (s, 2H), 4.42 (s, 2H), 6.76 (s, 1H), 7.17 (dd, J = 5.1, 1 , 5 Hz, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H), 7.32 (s, 2H), 7.93 (dd, J = 7.6.1, 7Hz, 1H), 8.15 (s, 1H), 8.21 (dd, J = 5.1,0.7 Hz, 1H), 8.58 (dd, J = 4.9, 1.7 Hz , 1H), 10.30 (s, 1H), 10.75 (s, 1H)

2- (2-Chloroacetylaminopyridin-4-ylmethylthio) -N- (4-difluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 16-5)

1H-NMR (400 MHz, DMSO-d6)

δ 4.32 (s, 2H), 4.43 (s, 2H), 7.17 (t, J = 74.2 Hz, 1H), 7.17-7.17 (m, 3H), 7, 30 (dd, J = 7.6.4.8 Hz, 1H), 7.73 (d, J = 9.0 Hz, 2H), 7.97 (dd, J = 7.6.1.7 Hz , 1H), 8.15 (s, 1H), 8.19 (d, J = 5.1 Hz, 1H), 8.59 (dd, J = 4.8.1.7 Hz, 1H), 10 , 55 (s, 1H), 5 10.75 (s, 1H)

2- (2-Chloroacetylaminopyridin-4-ylmethylthio) -N- (3-methylphenyl) pyridin-3-carboxamide (compound No. 16-6)

1H-NMR (400 MHz, DMSO-d6)

10 δ 2.30 (s, 3H), 4.32 (s, 2H), 9.42 (s, 2H), 6.93 (d, J = 7.8 Hz, 1H), 7.17 (dd , J = 5.1, 1.3 Hz, 1H), 7.22 (t, J = 7.8 Hz, 1H), 7.29 (dd, J = 7.7.4.9Hz, 1H), 7.46 (d, J = 7.8Hz, 1H), 7.56 (s, 1H), 7.95 (dd, J = 7.7.1.6 Hz, 1H), 8.15 (s, 1H), 8.22 (d, J = 5.1 Hz, 1H), 8.58 (dd, J = 4.9, 1.6 Hz, 1H), 10.38 (s, 1H), 10, 75 (s, 1H)

2- (2-Chloroacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethylphenyl) pyridin-3-carboxamide (compound No. 16-7)

1H-NMR (400 MHz, DMSO-d6)

δ 4.32 (s, 2H), 4.44 (s, 2H), 7.17 (d, J = 5.1, 1.0Hz, 1H), 7.32 (dd, J = 7.7, 4.9Hz, 1H), 7.73 (d, J = 8.5Hz, 2H), 7.92 (d, J = 8.5

20 Hz, 2H), 8.02 (dd, J = 7.7.1.7Hz, 1H), 8.15 (s, 1H), 8.22 (d, J = 5.1Hz, 1H), 8 , 61 (dd, J = 4.9, 1.7 Hz, 1H), 10.75 (s, 1H), 10.82 (s, 1H)

2- (2-Chloroacetylaminopyridin-4-ylmethylthio) -N- (3-trifluoromethylphenyl) pyridin-3-carboxamide (compound No. 16-8)

25 1H-NMR (400 MHz, DMSO-d6)

δ 4.32 (s, 2H), 4.44 (s, 2H), 7.18 (d, J = 5.1, 1.2Hz, 1H), 7.33 (dd, J = 7.6, 4.8 Hz, 1H), 7.48 (d, J = 8.1 Hz, 1H), 7.61 (t, J = 8.1Hz, 1H), 7.92 (d, J = 8.1Hz , 1H), 8.04 (dd, J = 7.6.1.7Hz, 1H), 8.16 (s, 1H), 8.19 (s, 1H), 8.22 (d, J = 5 , 1 Hz, 1H), 8.62 (dd, J = 4.8.1.7 Hz, 1H), 10.76 (s, 1H), 10.80 (s, 1H)

2- (2-Chloroacetylaminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridine-3-carboxamide (compound No. 16-9)

1H-NMR (500 MHz, DMSO-d6)

35 δ 1.20 (d, J = 6.7 Hz, 6H), 2.87 (m, 1H), 4.32 (s, 2H), 4.42 (s, 2H), 7.00 (d , J = 7.6 Hz, 1H), 7.17 (dd, J = 5.0.1.5 Hz, 1H), 7.24-7.30 (m, 2H), 7.51 (d, J = 7.6Hz, 1H), 7.59 (s, 1H), 7.96 (dd, J = 7.6.1.5 Hz, 1H), 8.15 (s, 1H), 8.21 (dd, J = 5.0.0.6 Hz, 1H), 8.58 (dd, J = 4.9, 1.5 Hz, 1H), 10.39 (s, 1H), 10.75 ( s, 1H)

Example 17

40 N- (4-tert-Butylphenyl) -2- (2-morpholinoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 17-1)

N- (4-tert-Butylphenyl) -2- (2-chloroacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 16-1, 50 mg, 0.11 mmol) was suspended in morpholine (1, 0ml), and the mixture was stirred for 2 hours at 80 ° C in the sealed tube. Was added

To the reaction mixture, ethyl acetate (50 ml) was washed with water (50 ml) and brine (50 ml), and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, the resulting solid was filtered off with diethyl ether and dried under reduced pressure to provide 17 mg of the objective compound as a pale yellow solid. (32% yield)

1H-NMR (500 MHz, CDCl3)

δ 1.32 (s, 9H), 2.60 (t, J = 4.6 Hz, 4H), 3.14 (s, 2H), 3.78 (t, J = 4.6 Hz, 4H) , 4.51 (s, 2H), 7.10 (dd, J = 5.2.1.5Hz, 1), 7.13 (dd, J = 7.6.4.9Hz, 1H), 7, 38 (d, J = 8.7Hz, 2H), 7.56 (d, J = 8.7Hz, 2H), 7.87 (d, J = 7.6Hz, 1H), 8.11 (sa , 1H), 8.18 (d, J = 5.2 Hz, 1H), 8.29 (s, 1H), 8.54 (dd, J = 4.9, 1.7 Hz, 1H), 9 , 48 (s, 1H)

As described below, the compounds (No. 17-2 ~ 88) were obtained using the corresponding compounds selected from the compounds (No. 16-1 ~ 9), commercially available compounds or known compounds according to the process of Synthesis of the compound (No. 17-1).

2- (2-Isopropylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-2) 1H-NMR (400 MHz, DMSO-d6) δ 0.99 (d, J = 6.3 Hz, 6H), 2.71 (m, 1H), 3.27 (s, 2H), 4.43 (s, 2H), 7.14 (dd, J = 5.2.1.6 Hz, 1H), 7.31 (dd, J = 7.6.4.9

Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.81 (d, J = 8.8 Hz, 2H), 7.99 (dd, J = 7.6.1 , 7 Hz, 1H), 8.17-8.20 (m, 2H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 10.12 (s, 1H), 10.66 (s, 1H) N- (3,5-Dimethylphenyl) -2- (2-morpholinoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound # 17-3)

1H-NMR (400 MHz, CDCl3) δ 2.32 (s, 6H), 2.60 (t, J = 4.6 Hz, 4H), 3.14 (s, 2H), 3.78 (t, J = 4.6Hz, 4H), 4.51 (s, 2H), 6.81 (s, 1H), 7.10 (dd, J = 5.1, 1.5Hz, 1H), 7.13 (dd, J = 7.6.4.9Hz, 1H), 7.27 (s, 2H), 7.67 (m, 1), 7.87 (dd, J = 7.6.1.7Hz, 1H), 8.19 (d, J = 5.1Hz, 1H), 8.30 (s, 1H), 8.55 (dd, J = 4.9, 1.7 Hz, 1H), 9.48 (s, 1H)

2- (2-Dimethylaminoacetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound No. 17-4) 1H-NMR (400 MHz, CDCl3) δ 2.32 (s, 6H), 2.36 (s, 6H), 3.07 (s, 2H), 4.51 (s, 2H), 6.80 (s, 1H), 7.08 ( dd, J = 5,2,1,6 Hz, 1H), 7,12 (dd, J = 7,5,4,8

Hz, 1H), 7.27 (s, 2H), 7.86 (dd, J = 7.5.1.8 Hz, 1H), 8.12 (s, 1H), 8.18 (d, J = 5.2 Hz, 1H), 8.29 (s, 1H), 8.53 (dd, J = 4.8.1.8 Hz, 1H), 9.64 (s, 1H) 2- (2-Dimethylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-5)

1H-NMR (500 MHz, CDCl3) δ 2.36 (s, 6H), 3.07 (s, 2H), 4.53 (s, 2H), 7.07 (dd, J = 5.2.1.5 Hz, 1H), 7, 15 (dd, J = 7.6, 4.9 Hz, 1H), 7.21 (d, J = 8.2 Hz, 2H), 7.70 (d, J = 8.2 Hz, 2H), 7.88 (dd, J = 7.6.1.9 Hz, 1H), 8.18 (dd, J = 5 , 2.0.6Hz, 1H), 8.28 (d, J = 0.6Hz, 1H), 8.44 (s, 1H), 8.54 (dd, J = 4.9, 1.9 Hz, 1H), 9.66 (s, 1H)

2- (2-Morpholinoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-6) 1H-NMR (500 MHz, CDCl3) δ 2.60 (t, J = 4.6 Hz, 4H), 3.13 (s, 2H), 3.78 (t, J = 4.6 Hz, 4H), 4.53 (s, 2H) , 7.09 (dd, J = 5.2.1.8 Hz, 1H), 7.15 (dd, J =

7.6.4.9 Hz, 1H), 7.22 (d, J = 8.3 Hz, 2H), 7.69 (d, J = 8.3Hz, 2H), 7.89 (dd, J = 7.6.1.5 Hz, 1H), 8.19 (d, J = 5.2 Hz, 1H), 8.28 (s, 1H), 8.36 (s, 1H), 8.54 (dd, J = 4.9, 1.5 Hz, 1H), 9.50 (s, 1H) N- (4-tert-Butylphenyl) -2- (2-cyclopropylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 17-7)

1H-NMR (500 MHz, CDCl3) δ 0.46-0.49 (m, 4H), 1.32 (s, 9H), 2.15 (sa, 1H), 2.27 (m, 1H), 3.49 (s, 2H), 4.51 (s, 2H), 7.07 (dd, J = 4.9, 1.4Hz, 1H), 7.13 (dd, J = 7.3.4.9Hz, 1H), 7.38 (d, J = 8.4Hz, 2H), 7.56 (d, J = 88.4Hz, 2H), 7 , 88 (d, J = 7.3Hz, 1H), 8.15-8.17 (m, 2H), 8.28 (s, 1H), 8.54 (dd, J = 4.9, 1.8 Hz, 1H), 9.41 (s, 1H)

N- (4-tert-Butylphenyl) -2- [2- (N-methyl-N- (1-methylpiperidin-4-yl) amino) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (compound # 17-8)

1H-NMR (500 MHz, CDCl3) δ 1.26 (s, 9H), 1.77-1.80 (m, 2H), 1.86-2.01 (m, 4H), 2.26 (s, 3H), 2.37 (s , 3H), 2.80-2.91 (m, 3H), 3.17 (s, 2H), 4.51 (s, 2H), 7.07 (dd, J = 5.2.1.8 Hz, 1H), 7.13 (dd, J = 7.5, 4.9 Hz, 1H), 7.38 ( d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz, 2H), 7.87 (d, J = 7.5 Hz, 1H), 8.17 (s, 1H), 8.17 (dd, J = 5.2.0.8Hz, 1H), 8.29 (d, J = 0 , 8 Hz, 1H), 8.54 (dd, J = 4.9, 1.8 Hz, 1H), 9.75 (s, 1H)

N- (4-tert-Butylphenyl) -2- [2- (2-methylthioethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (compound No. 17-9)

1H-NMR (400 MHz, CDCl3)

δ 1.31 (s, 9H), 2.10 (s, 3H), 2.68 (t, J = 6.1 Hz, 2H), 2.86 (t, J = 6.1Hz, 2H), 3.40 (s, 2H), 4.51 (s, 2H), 7.08 (dd, J = 5.1, 1.5Hz, 1H), 7.13 (dd, J = 7.6.4 , 9 Hz, 1H), 7.38 (d, J = 8.7 Hz, 2H), 7.56 (d, J = 8.7Hz, 2H), 7.87 (dd, J = 7.6, 1.7 Hz, 1H), 8.17-8.18 (m, 2H), 8.29 (s, 1H), 8.53 (dd, J = 4.9, 1.7 HZ, 1H), 9.75 (S, 1H)

2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-10)

1H-NMR (400 MHz, CDCl3)

δ 2.22 (s, 6H), 2.41-2.44 (m, 2H), 2.69-2.73 (m, 2H), 3.38 (s, 2H), 4.53 (s , 2H), 7.06 (dd, J = 5.1, 1.7 Hz, 1H), 7.14 (dd, J = 7.7.4.9 Hz, 1H), 7.22 (d, J = 8.5 Hz, 2H), 7.71 (d, J = 8.5 Hz, 2H), 7.87 (dd, J = 7.7.1.8 Hz, 1H), 8.18 ( dd, J = 5,1,0,7Hz, 1H), 8,28 (d, J = 0,7 Hz, 1H), 8,51 (s, 1H), 8,53 (dd, J = 4, 9, 1.8 Hz, 1H), 9.93 (s, 1H)

2- [2- (2-Morpholinoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-11)

1H-NMR (400 MHz, CDCl3)

δ 2.41-2.43 (m, 4H), 2.48-2.51 (m, 2H), 2.73-2.76 (m, 2H), 3.38 (s, 2H), 3 , 63-3.66 (m, 4H), 4.53 (s, 2H), 7.06 (dd, J = 5.1, 1.7 Hz, 1H), 7.15 (dd, J = 7 , 6.4.9 Hz, 1H), 7.21 (d, J = 9.0 Hz, 2H), 7.70 (d, J = 9.0 Hz, 2H), 7.86 (dd, J = 7.6.1.7 Hz, 1H), 8.17 (dd, J = 5.1.0.9Hz, 1H), 8.29 (d, J = 0.9Hz, 1H), 8.50 (s, 1H), 8.55 (dd, J = 4.9, 1.7 Hz, 1H), 9.84 (s, 1H)

2- [2- (N-Methyl-N- (1-methylpiperidin-4-yl) amino) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3carboxamide (compound # 17-12)

1H-NMR (400 MHz, CDCl3)

δ 1.54-1.65 (m, 2H), 1.76-1.79 (m, 2H), 1.88-1.96 (m, 2H), 2.26 (s, 3H), 2 , 37 (s, 3H), 2.39 (m, 1H), 2.88-2.92 (m, 2H), 3.16 (s, 2H), 4.53 (s, 2H), 7, 06 (dd, J = 5.1, 1.5 Hz, 1H), 7.14 (dd, J = 7.6.4.9 Hz, 1H), 7.22 (d, J = 8.9Hz, 2H), 7.70 (d, J = 8.9Hz, 2H), 7.88 (dd, J = 7.6.1.7Hz, 1H), 8.17 (d, J = 5.1Hz, 1H ), 8.28 (s, 1H), 8.48 (s, 1H), 8.54 (dd, J = 4.9, 1.7 Hz, 1H), 9.76 (s, 1H)

2- [2- (3-Methoxypropyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-13)

1H-NMR (400 MHz, DMSO-d6)

δ 1.60-1.67 (m, 2H), 2.55 (t, J = 7.0 Hz, 2H), 3.20 (s, 3H), 3.26 (s, 2H) 3.37 (t, J = 6.3 Hz, 2H), 4.42 (s, 2H), 7.14 (dd, J = 5.1, 1.5 Hz, 1H), 7.31 (dd, J = 7.7.4.9 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.81 (d, J = 8.8 Hz, 2H), 7.99 (dd, J = 7.7.1.7 Hz, 1H), 8.18 (d, J = 5.1 Hz, 1H), 8.21 (s, 1H), 8.60 (dd, J = 4.9 , 1.7 Hz, 1H), 10.08 (s, 1H), 10.66 (s, 1H)

2- [2- (3-Hydroxypropyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-14)

1H-NMR (500 MHz, DMSO-d6)

δ 1.53-1.59 (m, 2H), 2.57 (t, J = 6.9Hz, 2H), 3.26 (s, 2H), 3.46 (t, J = 6.3 Hz , 2H), 4.41 (sa, 1H), 4.42 (s, 2H), 7.14 (dd, J = 5.2.1.5 Hz, 1H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.6 Hz, 2H), 7.80 (d, J = 8.6 Hz, 2H), 7.99 (dd, J = 7.6.1.8 Hz, 1H), 8.18 (d, J = 5.2 Hz, 1H), 8.21 (s, 1H), 8.60 (dd, J = 4.9 , 1.8 Hz, 1H), 10.08 (s, 1H), 10.66 (s, 1H)

2- [2- (Tetrahydropyran-4-yl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-15)

1H-NMR (400 MHz, DMSO-d6)

δ 1.20-1.30 (m, 2H), 1.72-1.75 (m, 2H), 2.59 (m, 1H), 3.22-3.32 (m, 4H), 3 , 79-3.82 (m, 2H), 4.42 (s, 2H), 7.14 (dd, J = 5.1, 1.5 Hz, 1H), 7.31 (dd, J = 7 , 6, 4.9 Hz, 1H), 7.37 (d, J = 9.0 Hz, 2H) 7.81 (d, J = 9.0 Hz, 2H), 7.99 (dd, J = 7.6.1.7 Hz, 1H), 8.19 (d, J = 5.1Hz, 1H), 8.20 (s, 1H), 8.60 (dd, J = 4.9, 1, 7 Hz, 1H), 10.11 (sa, 1H), 10.66 (s, 1H)

2- [2- (4-Hydroxypiperidin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-16)

1H-NMR (400 MHz, DMSO-d6) δ 1.42-1.47 (m, 2H), 1.72-1.75 (m, 2H), 2.23-2.28 (m, 2H), 2.71-2.75 (m, 2H), 3.11 (s, 2H), 3.47 (m, 1H), 4.42 (s, 2H),

4.59 (d, J = 4.2 Hz, 1H), 7.15 (d, J = 6.6 Hz, 1H), 7.31 (dd, J = 7.6.4.9 Hz, 1H ), 7.37 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 8.8 Hz, 2H), 7.99 (dd, J = 7.6.1.7 Hz, 1H), 8.18-8.19 (m, 2H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 9.82 (s, 1H), 10.66 (s, 1H) 2- [2- (1,4-trans-4-Hydroxycyclohexan-1-yl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3

carboxamide (compound # 17-17) 1H-NMR (500 MHz, DMSO-d6) δ 1.00-1.15 (m, 4H), 1.74-1.82 (m, 4H), 2.31 (m, 1H), 3.27 (s, 2H), 3.34 (m , 1H), 4.42 (s, 2H), 4.47 (d, J = 4.6Hz, 1H), 7.14

(d, J = 5,2,1,5 Hz, 1H), 7.31 (dd, J = 7,6,4,9Hz, 1H), 7,37 (d, J = 8,2 Hz, 2H ), 7.81 (d, J = 8.2 Hz, 2H), 7.99 (dd, J = 7.6.1.8

Hz, 1H), 8.17-8.20 (m, 2H), 8.60 (dd, J = 4.9, 1.8 Hz, 1H), 10.08 (s, 1H), 10.65 (s, 1H) 2- [2- (4-Ethoxycarbonylpiperidin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound # 17-18)

1H-NMR (500 MHz, DMSO-d6) δ 1.17 (t, J = 77.0 Hz, 3H), 1.57-1.66 (m, 2H), 1.80-1.84 (m, 2H), 2.20-2.37 (m, 3H), 2.78-2.83 (m, 2H), 3.13 (s, 2H), 4.07 (q, J = 7.0 Hz, 2H), 4.42 (s, 2H), 7.15 (d, J = 5.2.1.2 Hz, 1H), 7.31 (dd, J = 7.6.4.9Hz, 1H), 7.37 (d, J = 8.6Hz, 2H), 7.81 (d, J

= 8.6 Hz, 2H), 7.99 (dd, J = 7.6.1.8 Hz, 1H), 8.18 (s, 1H), 8.19 (d, J = 1.8 Hz , 1H), 8.60 (dd, J = 4.9, 1.8 Hz, 1H), 9.84 (s, 1H), 10.66 (s, 1H) 2- (2-Diethylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-19) 1H-NMR (400 MHz, DMSO-d6) δ 1.00 (t, J = 7.1 Hz, 6H), 2.59 (q, J = 7.1 Hz, 4H), 3.16 (s, 2H), 4.43 (s, 2H) , 7.16 (dd, J = 5.1, 1.5 Hz, 1H), 7.31 (dd, J =

7.8.4.9 Hz, 1H), 7.37 (d, J = 8.9 Hz, 2H), 7.81 (d, J = 8.9 Hz, 2H), 7.99 (dd, J = 7.8.1.7Hz, 1H), 8.17-8.19 (m, 2H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 9.82 (s, 1H), 10.66 (s, 1H) 2- [2- (Pyrrolidin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (compound No. 17-20)

1H-NMR (500 MHz, DMSO-d6) δ 1.71-1.77 (m, 4H), 2.55-2.59 (m, 4H), 3.27 (s, 2H), 4.42 (s, 2H), 7.14 (dd , J = 5,2,1,5 Hz, 1H), 7,31 (dd, J = 7,6,4,9 Hz, 1H), 7.37 (d, J = 8.6 Hz, 2H), 7.80 (d, J = 8.6 Hz, 2H), 7.99 (dd, J = 7.6.1 , 8 Hz, 1H), 8.18 (d, J = 5.2 Hz, 1H), 8.18 (s, 1H), 8.60 (dd, J = 4.9, 1.8 Hz, 1H), 9.81 (s, 1H), 10.66 (s, 1H)

N- (4-Chlorophenyl) -2- (2-dimethylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 17-21) 1H-NMR (400 MHz, DMSO-d6) δ 2.28 (s, 6H), 3.09 (s, 2H), 4.42 (s, 2H), 7.14 (d, J = 6.6 Hz, 1H), 7.30 (dd, J = 7.7.4.8 Hz, 1H), 7.41 (d, J = 8.8 Hz, 2H),

7.73 (d, J = 8.8 Hz, 2H), 7.98 (dd, J = 7.7.1.6 Hz, 1H), 8.17 (s, 1H), 8.19 (s , 1H) 8.59 (dd, J = 4.8.1.6 Hz, 1H), 9.81 (s, 1H), 10.60 (s, 1H) N- (4-Chlorophenyl) -2- (2-morpholinoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 17-22)

1H-NMR (500 MHz, DMSO-d6) δ 2.45-2.55 (m, 4H), 3.16 (s, 2H), 3.61 (t, J = 4.9 Hz, 4H), 4.42 (s, 2H), 7, 15 (d, J = 4.9 Hz, 1H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.41 (d, J = 8.9 Hz, 2H), 7.72 (d, J = 8.9 Hz, 2H), 7.98 (dd, J = 7.6.1.5 Hz, 1H), 8.19 (s, 1H), 8.19 (d, J = 4.9 Hz, 1H), 8.59 (dd, J = 4.9, 1.5 Hz, 1H), 9.89 (s, 1H), 10.59 (s, 1H)

N- (4-Chlorophenyl) -2- [2- (2-dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (compound No. 1723)

1H-NMR (400 MHz, DMSO-d6) δ 2.13 (s, 6H), 2.31 (t, J = 6.1Hz, 2H), 2.60 (t, J = 6.1Hz, 2H), 3.30 (s, 2H), 4 , 42 (s, 2H), 7.13 (d, J = 5.1 Hz, 1H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.41 (d, J = 9.0 Hz, 2H), 7.72 (d, J = 9.0 Hz, 2H), 7.98 (dd , J = 7.6.1.7 Hz, 1H), 8.18 (d, J = 5.1Hz, 1H), 8.20 (s, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.25 (s at, 1H), 10.60 (s, 1H)

N- (4-Chlorophenyl) -2- [2- (pyridin-2-yl) methylaminoacetylaminopyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 17-24) 1H-NMR (500 MHz, DMSO-d6) δ 3.36 (s, 2H), 3.84 (s, 2H), 4.42 (s, 2H), 7.13 (d, J = 4.9 Hz, 1H), 7.24 (m, 1H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.40-7.44

(m, 3H), 7.71-7.78 (m, 3H), 7.98 (dd, J = 7.6.1.8 Hz, 1H), 8.17-8.20 (m, 2H ), 8.50 (d, J = 4.9Hz, 1H), 8.59 (dd, J = 4.9, 1.8

Hz, 1H), 10.20 (s, 1H), 10.59 (s, 1H) N- (4-Chlorophenyl) -2- [2- (pyridinium-1-yl) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide bromide (compound No. 1725)

1H-NMR (400 MHz, DMSO-d6) δ 4.40 (s, 2H), 5.70 (s, 2H), 7.20 (d, J = 5.1 Hz, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H), 7.41 (d, J = 8.8 Hz, 2H), 7.73 (d, J = 8.8

Hz, 2H), 8.01 (dd, J = 7.6.1.5 Hz, 1H), 8.07 (s, 1H), 8.19-8.27 (m, 3H), 8.55 (dd, J = 4.9, 1.5 Hz, 1H), 8.69 (t, J = 7.7 Hz, 1H), 9.06 (d, J = 5.6 Hz, 2H), 10.68 (s, 1H), 11.27 (s, 1H) 2- (2-Aminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (compound No. 17-26) 1H-NMR (400 MHz, DMSO-d6) δ 3.27 (s, 2H), 4.42 (s, 2H), 7.13 (dd, J = 5.2.1.5 Hz, 1H), 7.31 (dd, J = 7.6 , 4.9 Hz, 1H), 7.37 (d, J = 8.5 Hz, 2H), 7.81 (d, J

= 8.5 Hz, 2H), 7.99 (dd, J = 7.6.1.8 Hz, 1H), 8.18 (dd, J = 5.2.0.8 Hz, 1H), 8 , 21 (s, 1H), 8.60 (dd, J = 4.9, 1.8 Hz, 1H), 10.66 (s, 1 H) 2- (2-Methylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-27)

1H-NMR (400 MHz, DMSO-d6) δ 2.29 (s, 3H), 3.24 (s, 2H), 4.42 (s, 2H), 7.14 (dd, J = 5.1, 1.5 Hz, 1H), 7, 31 (dd, J = 7.7, 4.8 Hz, 1H), 7.37 (d, J = 9.0 Hz, 2H), 7.80 (d, J = 9.0 Hz, 2H), 7.99 (dd, J = 7.7.1.6 Hz, 1H), 8.18 (d, J = 5 , 1 Hz, 1H), 8.21 (s, 1H), 8.60 (dd, J = 4,8,1,6 Hz, 1H), 10.66 (s, 1H)

2- [2- (N- (2-Dimethylaminoethyl) -N-methylamino) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound # 17-28)

1H-NMR (500 MHz, DMSO-d6) δ 2.13 (s, 6H), 2.33 (s, 3H), 2.35 (t, J = 6.4 Hz, 2H), 2.55 (t, J = 6.4 Hz, 2H) , 3.17 (s, 2H), 4.42 (s, 2H), 7.12 (d, J = 5.0 Hz, 1H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.7 Hz, 2H), 7.80 (d, J = 8.7 Hz, 2H), 7.99 (dd, J = 7.6.1.7 Hz, 1H), 8.18 (d, J = 5.0 Hz, 1H), 8.21 (s, 1H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 10.37 (s, 1H) , 10.65 (s, 1 H)

2- [2- (N- (2-Diethylaminoethyl) -N-ethylamino) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound # 17-29)

1H-NMR (400 MHz, DMSO-d6) δ 0.91 (t, J = 7.2Hz, 6H), 0.98 (t, J = 7.1Hz, 3H), 2.43-2.51 (m, 6H), 2.61 (q, J = 7.2Hz, 4H), 3.20 (s, 2H), 4.42 (s, 2H), 7.12 (d, J = 5.1 Hz, 1H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7 , 81 (d, J = 8.8 Hz, 2H), 7.99 (dd, J = 7.6.1.7 Hz, 1H), 8.18 (d, J = 5.1 Hz, 1H), 8.20 (s, 1H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 10.40 (s, 1H), 10.66 (s, 1H)

2- [2- (3-Dimethylaminopropyl) aminoacetylamino] pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-30)

1H-NMR (500 MHz, DMSO-d6) δ 1.50-1.56 (m, 2H), 2.09 (s, 6H), 2.23 (t, J = 7.0 Hz, 2H), 2.45-2.50 (m, 2H ), 3.26 (s, 2H), 3.30 (sa, 1H), 4.42 (s, 2H), 7.13 (d, J = 5,2,1,5Hz, 1H), 7.31 (dd, J = 7.6,4,9Hz, 1H), 7.37 (d, J = 8.9Hz, 2H), 7.81 (d, J = 8.9Hz, 2H), 7.99 (dd, J = 7.6.1.8Hz, 1H), 8.18 (d, J = 5.2 Hz, 1H), 8.20 (s, 1H), 8.60 (dd, J = 4.9, 1, 8 Hz, 1H), 10.09 (s, 1H), 10.66 (s, 1H)

2- [2- (2-Hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-31) 1H-NMR (500 MHz, DMSO-d6)

δ 2.60 (t, J = 5.7 Hz, 2H), 3.31 (s, 2H), 3.43-3.47 (m, 2H), 4.42 (s, 2H), 4, 57 (t, J = 5.3 Hz, 1H), 7.14 (d, J = 5.0.1.5Hz, 1H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.7 Hz, 2H), 7.81 (d, J = 8.7Hz, 2H), 7.99 (dd, J = 7.6.1.8Hz, 1H), 8.18 (d, J = 5.0Hz, 1H), 8.21 (s, 1H), 8.60 (dd, J = 4.9, 1.8Hz, 1H), 10.12 (sa, 1H), 10.66 (s, 1H)

2- [2- (2-Ethoxyethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-32)

1H-NMR (400 MHz, DMSO-d6)

δ 1.08 (t, J = 7.0 Hz, 3H), 2.68 (t, J = 5.5 Hz, 2H), 3.30 (s, 2H), 3.36-3.42 ( m, 4H), 4.42 (s, 2H), 7.13 (d, J = 5.1 Hz, 1H), 7.31 (dd, J = 7.7.4.9 Hz, 1H), 7.37 (d, J = 8.8Hz, 2H), 7.81 (d, J = 8.8Hz, 2H), 7.99 (d, J = 7.7 Hz, 1H), 8.18 ( d, J = 5.1 Hz, 1H), 8.21 (s, 1H), 8.60 (dd, J = 4.9, 1.8 Hz, 1H), 10.12 (sa, 1H), 10.66 (s, 1 H)

2- [2- (2- (2-Hydroxyethoxy) ethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-33)

1H-NMR (400 MHz, DMSO-d6)

δ 2.69 (t, J = 5.2 Hz, 2H), 3.30 (s, 2H), 3.40 (t, J = 5.2 Hz, 2H), 3.44-3.49 ( m, 4H), 4.42 (s, 2H), 4.66 (sa, 1H), 7.14 (dd, J = 5.0.1.5 Hz, 1H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.9 Hz, 2H), 7.81 (d, J = 8.9Hz, 2H), 7.99 (dd, J = 7.6.1.7Hz, 1H), 8.17 (d, J = 5.0 Hz, 1H), 8.22 (s, 1H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 10.13 (sa, 1H), 10.66 (s, 1H)

2- [2- (Piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 1734)

1H-NMR (500 MHz, CDCl3)

δ 2.57 (sa, 4H), 2.95-2.98 (m, 4H), 3.11 (s, 2H), 4.53 (s, 2H), 7.08 (d, J = 5 , 2,1,8Hz, 1H), 7.14 (dd, J = 7.6,4,9Hz, 1H), 7.22 (d, J = 8.6Hz, 2H), 7.70 (d, J = 8.6Hz, 2H), 7.88 (dd, J = 7.6.1.7Hz, 1H), 8.19 (dd, J = 5.2.0.6 Hz, 1H), 8, 28 (d, J = 0.6 Hz, 1H), 8.41 (sa, 1H), 8.54 (dd, J = 4.9, 1.7 Hz, 1H), 9.56 (s, 1H )

N- (4-Difluoromethoxyphenyl) -2- (2-dimethylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide monohydrochloride (compound No. 17-35)

1H-NMR (400 MHz, DMSO-d6)

δ 2.86 (s, 6H), 4.18 (s, 2H), 4.44 (s, 2H), 7.18 (t, J = 74.2 Hz, 1H), 7.18-7, 24 (m, 3H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.75 (d, J = 9.1 Hz, 2H), 8.03 (dd, J = 7.6.1.8 Hz, 1H), 8.15 (s, 1H), 8.25 (d, J = 5.1 Hz, 1H), 8.59 (dd, J = 4.9, 1.8 Hz, 1H), 10.02 (s, 1H), 10.63 (s, 1H), 11.20 (s, 1H)

2- [2- (2-Acetylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-36)

1H-NMR (500 MHz, DMSO-d6)

δ 1.79 (s, 3H), 2.57 (t, J = 6.1 Hz, 2H), 3.11 (m, 2H), 3.29 (s, 2H), 4.42 (s, 2H), 7.14 (dd, J = 5.0.1.5 Hz, 1H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.9 Hz, 2H), 7.79-7.84 (m, 3H), 7.99 (dd, J = 7.6.1.8 Hz, 1H), 8.18 (d, J = 5.0 Hz, 1H), 8.20 (s, 1H), 8.60 (dd, J = 4.9, 1.8 Hz, 1H), 10.08 (s, 1H), 10.66 ( s, 1H)

N- (4-Chlorophenyl) -2- [2- (2-hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (compound No. 17-37)

1H-NMR (500 MHz, DMSO-d6)

δ 2.60 (t, J = 5.5 Hz, 2H), 3.30 (s, 2H), 3.44-3.47 (m, 2H), 4.42 (s, 2H), 4, 57 (t, J = 5.2 Hz, 1H), 7.13 (d, J = 4.9 Hz, 1H), 7.30 (dd, J = 7.5.4.9 Hz, 1H) 7 , 41 (d, J = 8.7 Hz, 2H), 7.72 (d, J = 8.7 Hz, 2H), 7.98 (d, J = 7.5 Hz, 1H), 8.18 (d, J = 4.9 Hz, 1H), 8.20 (s, 1H), 8.59 (d, J = 4.9 Hz, 1H), 10.13 (s, 1H), 10.59 (s, 1H)

N- (4-Chlorophenyl) -2- [2- (3-hydroxypropyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (compound No. 17-38)

1H-NMR (500 MHz, DMSO-d6)

δ 1.54-1.59 (m, 2H), 2.57 (t, J = 6.9Hz, 2H), 3.27 (s, 2H), 3.46 (t, J = 6.3 Hz , 2H), 4.42 (s, 2H), 7.14 (d, J = 5.0 Hz, 1H), 7.30 (dd, J = 7.5.5.0 Hz, 1H), 7 , 41 (d, J = 8.7 Hz, 2H), 7.72 (d, J = 8.7 Hz, 2H), 7.98 (d, J = 7.5 Hz, 1H), 8.18 (d, J = 5.0 Hz, 1H), 8.20 (s, 1H), 8.59 (d, J = 5.0 Hz, 1H), 10.07 (s, 1H), 10.59 (s, 1H)

N- (4-Chlorophenyl) -2- [2- (N- (2-hydroxyethyl) -N-methylamino) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (compound No. 17-39)

1H-NMR (500 MHz, DMSO-d6) δ 2.31 (s, 3H), 2.54 (t, J = 5.7 Hz, 2H), 3.19 (s, 2H), 3.46-3.51 (m, 2H), 4, 42 (s, 2H), 4.63 (t, J = 5.2 Hz, 1H), 7.14 (dd, J = 5.0,1.5 Hz, 1H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.41 (d, J = 8.9 Hz, 2H), 7, 72 (d, J = 8.9 Hz, 2H), 7.98 (m, 1H), 8.18 (d, J = 5.0 Hz, 1H), 8.20 (s, 1H), 8.59 (dd, J = 4.9, 1.5 Hz, 1H), 9.95 (s, 1H), 10.59 ( s, 1H)

N- (4-Chlorophenyl) -2- [2- (piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 17-40) 1H-NMR (500 MHz, DMSO-d6) δ 2.43 (sa, 4H), 2.72 (t, J = 4.9Hz, 4H), 3.09 (s, 2H), 4.42 (s, 2H), 7.15 (m, 1H ), 7.30 (dd, J = 7.5.4.9Hz, 1H), 7.41 (d, J =

8.9 Hz, 2H), 7.72 (d, J = 8.9 Hz, 2H), 7.98 (m, 1H), 8.18-8.19 (m, 2H), 8.59 ( dd, J = 4.9, 1.5 Hz, 1H), 9.81 (s, 1H), 10.59

(s, 1H) 2- [2- (2-Acetylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-chlorophenyl) pyridin-3-carboxamide (compound No. 1741)

1H-NMR (500 MHz, DMSO-d6) δ 1.79 (s, 3H), 2.57 (t, J = 6.4Hz, 2H), 3.09-3.13 (m, 2H), 3.29 (d, J = 2.4 Hz , 2H), 4.42 (s, 2H), 7.14 (d, J = 5.2 Hz, 1H),

7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.41 (d, J = 8.9 Hz, 2H), 7.72 (d, J = 8.9 Hz, 2H ), 7.84 (m, 1H), 7.98 (d, J = 7.6 Hz, 1H), 8.18 (d, J = 5.2 Hz, 1H), 8.20 (s, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.08 (s, 1H) , 10.59 (s, 1 H) N- (4-Chlorophenyl) -2- [2- (3-dimethylaminopropyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (compound No.

17-42) 1H-NMR (500 MHz, DMSO-d6) δ 1.51-1.57 (m, 2H), 2.10 (s, 6H), 2.25 (t, J = 7.0 Hz, 2H), 2.52-2.54 (m, 2H ), 3.26 (s, 2H), 4.42 (s, 2H), 7.13 (dd, J =

5.2.1.5 Hz, 1H), 7.30 (dd, J = 7.5.4.7 Hz, 1H), 7.41 (d, J = 8.9 Hz, 2H), 7, 73 (d, J = 8.9 Hz, 2H), 7.98 (dd, J = 7.5.1.7

Hz, 1H), 8.18 (d, J = 5.2 Hz, 1H), 8.20 (s, 1H), 8.59 (dd, J = 4.7.1.7 Hz, 1H) 10 , 09 (s, 1H), 10.59 (s, 1H) 2- (2-Dimethylaminoacetylaminopyridin-4-ylmethylthio) -N- (3-methylphenyl) pyridine-3-carboxamide monohydrochloride (compound No. 17-43)

1H-NMR (400 MHz, DMSO-d6) δ 2.30 (s, 3H), 2.86 (s, 6H), 4.17 (s, 2H), 4.44 (s, 2H), 6.94 (d, J = 7.7 Hz, 1H), 7.20-7.25 (m, 2H), 7.30 (dd, J = 7.6.4.9

Hz, 1H), 7.47 (d, J = 7.7 Hz, 1H), 7.57 (s, 1H), 7.99 (dd, J = 7.6.1.6 Hz, 1H), 8.15 (s, 1H), 8.25 (d, J = 5.4Hz, 1H), 8.58 (dd, J = 4.9, 1.6Hz, 1H), 9.97 (s, 1H), 10.43 (s, 1H), 11.15 (s, 1H) 2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3-methylphenyl) pyridin-3-carboxamide (compound # 17

44) 1H-NMR (400 MHz, DMSO-d6) δ 2.29 (s, 3H), 2.30 (s, 6H), 2.48-2.50 (m, 2H), 2.69 (t, J = 6.3 Hz, 2H), 3, 36-3.38 (m, 2H), 4.41 (s, 2H), 6.94 (d, J = 6.6

Hz, 1H), 7.12-7.31 (m, 3H), 7.45 (d, J = 7.3 Hz, 1H), 7.56 (s, 1H), 7.95 (d, J = 7.6 Hz, 1H), 8.18-8.20 (m, 2H), 8.58 (dd, J = 4.9, 1.7 Hz, 1H), 10.31 (s, 1H), 10.39 (s, 1H) N- (3-Methylphenyl) -2- [2- (piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 17-45)

1H-NMR (400 MHz, DMSO-d6) δ 2.30 (s, 3H), 2.46-2.50 (m, 4H), 2.80 (t, J = 4.6 Hz, 4H), 3.14 (s, 2H), 4, 41 (s, 2H), 6.93 (d, J = 7.9 Hz, 1H), 7.15 (d, J = 6.1 Hz, 1H), 7.22 (t, J = 7.9 Hz, 1H), 7.29 (dd, J = 7.6.4.9 Hz, 1H), 7.46 (d, J = 7 , 9Hz, 1H), 7.56 (s, 1H), 7.96 (dd, J = 7.6.1.7 Hz, 1H), 8.18-8.20 (m, 2H), 8.58 (dd, J = 4.9, 1.7 Hz, 1H), 9.87 (s, 1H), 10.41 (s, 1H)

2- [2- (2-Hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3-methylphenyl) pyridin-3-carboxamide (compound No. 17-46) 1 H-NMR (400 MHz, DMSO-d6)

δ 2.30 (s, 3H), 2.60 (t, J = 5.6 Hz, 2H), 3.30-3.32 (m, 2H), 3.43-3.47 (m, 2H ), 4.41 (s, 2H), 4.58 (t, J = 5.2Hz, 1H), 6.93 (d, J = 7.8Hz, 1H), 7.13 (dd, J = 5 , 1, 1.5Hz, 1H), 7.22 (t, J = 7.8Hz, 1H), 7.29 (dd, J = 7.6.4.9 Hz, 1H), 7.45 (d , J = 7.8Hz, 1H), 7.55 (s, 1H), 7.94 (dd, J = 7.6.1.6Hz, 1H), 8.18 (d, J = 5.1 Hz , 1H), 8.20 (s, 1H), 8.58 (dd, J = 4.9, 1.6 Hz, 1H), 10.1.9 (s, 1H), 10.38 (s, 1H)

N- (4-Difluoromethoxyphenyl) -2- [2- (2-dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (compound No. 17-47)

1H-NMR (400 MHz, DMSO-d6)

δ 2.13 (s, 6H), 2.31 (t, J = 6.2 Hz, 2H), 2.60 (t, J = 6.2 Hz, 2H), 3.30 (s, 2H) , 4.41 (s, 2H), 7.12 (dd, J = 5.1, 1.5 Hz, 1H), 7.18 (d, J = 8.0 Hz, 2H), 7.18 ( t, J = 74.3 Hz, 1H), 7.30 (dd, J = 7.6.4.8 Hz, 1H), 7.72 (d, J = 8.0 Hz, 2H), 7, 97 (dd, J = 7.6.1.7 Hz, 1H), 8.18-8.20 (m, 2H), 8.59 (dd, J = 4.8, 1.7 Hz, 1H) , 10.25 (s, 1H), 10.54 (s, 1H)

N- (4-Difluoromethoxyphenyl) -2- [2- (2-hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (compound No. 17-48)

1H-NMR (400 MHz, DMSO-d6)

δ 2.60 (t, J = 5.6 Hz, 2H), 3.31 (s, 2H), 3.44-3.48 (m, 2H), 4.42 (s, 2H), 4, 58 (t, J = 5.2Hz, 1H), 7.14 (dd, J = 5.1, 1.7Hz, 1H), 7.17 (t, J = 74.2 Hz, 1H), 7, 18 (d, J = 8.8 Hz, 2H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.73 (d, J = 8.8 Hz, 2H), 7.97 (dd, J = 7.6.1.7Hz, 1H), 8.18-8.21 (m, 2H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H ), 10.13 (s, 1H), 10.55 (s, 1H)

2- [2- (2-Acetylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-difluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-49)

1H-NMR (400 MHz, DMSO-d6)

1.79 (s, 3H), 2.57 (t, J = 6.4 Hz, 2H), 3.09-3.13 (m, 2H), 3.29 (s, 2H), 4.42 (s, 2H), 7.14 (dd, J = 5.1, 1.5Hz, 1H), 7.18 (t, J = 74.2Hz, 1H), 7.18 (d, J = 9, 0Hz, 2H), 7.30 (dd, J = 7.6.4.9Hz, 1H), 7.72 (d, J = 9.0Hz, 2H), 7.84 (s, 1H), 7, 97 (dd, J = 7.6.1.6 Hz, 1H), 8.18-8.20 (m, 2H), 8.59 (dd, J = 4.9, 1.6 Hz, 1H) , 10.08 (s, 1H), 10.55 (s, 1H)

N- (4-Difluoromethoxyphenyl) -2- [2- (N- (2-dimethylaminoethyl) -N-methylamino) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (compound No. 17-50)

1H-NMR (400 MHz, DMSO-d6)

δ 2.14 (s, 6H), 2.33 (s, 3H), 2.36 (t, J = 6.4 Hz, 2H), 2.56 (t, J = 6.4Hz, 2H), 3.17 (s, 2H), 4.41 (s, 2H), 7.13 (dd, J = 5.1, 1.1Hz, 1H), 7.17 (t, J = 74.2 Hz, 1H), 7.18 (d, J = 8.8 Hz, 2H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.73 (d, J = 8.8 Hz, 2H), 7.79 (dd, J = 7.6.1.7 Hz, 1H), 8.18-8.20 (m, 2H), 8.59 (dd, J = 4.9, 1.7Hz, 1H), 10.38 (s, 1H), 10.55 (s, 1H)

2- (2-Dimethylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethylphenyl) pyridin-3-carboxamide (compound No. 17-51)

1H-NMR (500 MHz, DMSO-d6)

δ 2.28 (s, 6H), 3.09 (s, 2H), 4.43 (s, 2H), 7.15 (dd, J = 5.2.1.5 Hz, 1H), 7, 32 (dd, J = 7.6, 4.9 Hz, 1H), 7.73 (d, J = 8.7 Hz, 2H), 7.91 (d, J = 8.7 Hz, 2H), 8.02 (dd, J = 7.6.1.7 Hz, 1H), 8.18 (d, J = 5.2 Hz, 1H), 8.18 (s, 1H) 8.61 (dd, J = 4.9, 1.7 Hz, 1H), 9.81 (s, 1H), 10.81 (s, 1H)

2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethylphenyl) pyridine-3-carboxamide (compound No. 17-52)

1H-NMR (400 MHz, DMSO-d6)

δ 2.12 (s, 6H), 2.30 (t, J = 6.1 Hz, 2H), 2.59 (t, J = 6.1 Hz, 2H), 3.30 (s, 2H) , 4.43 (s, 2H), 7.13 (d, J = 5.2, 1.5 Hz, 1H), 7.31 (dd, J = 7.7.4.9Hz, 1H), 7 , 73 (d, J = 8.7 Hz, 2H), 7.91 (d, J = 8.7 Hz, 2H), 8.02 (dd, J = 7.7.1.7 Hz, 1H) , 8.18 (d, J = 5.2 Hz, 1H), 8.21 (s, 1H), 8.61 (dd, J = 4.9, 1.7 Hz, 1H), 10.26 ( sa, 1H), 10.82 (s, 1H)

2- [2- (2-Hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethylphenyl) pyridine-3-carboxamide (compound No. 17-53)

1H-NMR (500 MHz, DMSO-d6)

δ 2.60 (t, J = 5.5 Hz, 2H), 3.30 (s, 2H), 3.43-3.47 (m, 2H), 4.43 (s, 2H), 4, 57 (t, J = 5.2 Hz, 1H), 7.14 (dd, J = 5.2.1.5 Hz, 1H), 7.32 (dd, J = 7.6.4.9 Hz , 1H), 7.73 (d, J = 8.7 Hz, 2H), 7.92 (d, J = 8.7Hz, 2H), 8.02 (dd, J = 7.6.1.8Hz , 1H), 8.18 (d, J = 5.2Hz, 1H), 8.21 (s, 1H), 8.61 (dd, J = 4.9, 1.8 Hz, 1H), 10, 22 (sa, 1H), 10.82 (s, 1H)

2- [2- (Piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethylphenyl) pyridin-3-carboxamide (compound No. 17-54) 1H-NMR (400 MHz, DMSO-d6) δ 2.43 (sa, 4H), 2.70-2.73 (m, 4H), 3.10 (s, 2H), 4.43 (s, 2H), 7.15 (d, J = 5 , 5 Hz, 1H), 7.32 (dd, J = 7.6.4.9 Hz, 1H), 7.73

(d, J = 8.8Hz, 2H), 7.91 (d, J = 8.8Hz, 2H), 8.02 (dd, J = 7.6.1.7Hz, 1H), 8.19 ( d, J-5.5 Hz, 1H), 8.20 (s, 1H), 8.61 (dd, J = 4.9, 1.7 Hz, 1H), 9.82 (s at, 1H), 10.82 (s, 1H) 2- (2-Dimethylaminoacetylaminopyridin-4-ylmethylthio) -N- (3-trifluoromethylphenyl) pyridin-3-carboxamide (compound No. 17-55)

1H-NMR (400 MHz, DMSO-d6) δ 2.28 (s, 6H), 3.09 (s, 2H), 4.43 (s, 2H), 7.15 (dd, J = 5.1, 1.7 Hz, 1H), 7, 32 (dd, J = 7.6.4.9 Hz, 1H), 7.48 (d, J = 7.8 Hz, 1H), 7.61 (t, J = 7.8 Hz, 1H), 7.91 (d, J = 7.8 Hz, 1H), 8.03 (dd, J = 7.6, 1 , 7 Hz, 1H), 8.18 (s, 1H), 8.18 (d, J = 5.1Hz, 1H), 8.19 (s, 1H), 8.61 (dd, J = 4.9, 1.7 Hz, 1H), 9.81 (s, 1H), 10.79 (s ,1 HOUR)

2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3-trifluoromethylphenyl) pyridine-3-carboxamide (compound No. 17-56)

1H-NMR (400 MHz, DMSO-d6) δ 2.13 (s, 6H), 2.31 (t, J = 6.2 Hz, 2H), 2.59 (t, J = 6.2 Hz, 2H), 3.30 (s, 2H) , 4.43 (s, 2H), 7.13 (dd, J = 5.1, 1.5 Hz, 1H), 7.32 (dd, J = 7.7.4.9Hz, 1H), 7.48 (d, J = 7.9 Hz, 1H), 7.61 (t, J = 7.9Hz, 1H), 7.91 (d, J = 7.9Hz, 1H), 8.03 (dd, J = 7.7.1.7 Hz, 1H), 8.18 (s, 1H), 8.18 (d, J = 5.1Hz, 1H), 8.21 (s, 1H), 8.61 (dd, J = 4.9, 1.7 Hz, 1H), 10.26 (sa, 1H), 10.79 (s, 1H)

2- [2- (Piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (3-trifluoromethylphenyl) pyridine-3-carboxamide monohydrochloride (compound No. 17-57)

1H-NMR (400 MHz, DMSO-d6) δ 3.40 (sa, 4H), 3.49 (sa, 4H), 4.14 (sa, 2H), 4.45 (s, 2H), 7.26 (d, J = 5.0 Hz, 1H), 7.33 (dd, J = 7.6.4.9 Hz, 1H), 7.49 (d, J = 7.9 Hz, 1H), 7.61 (t, J = 7.9 Hz, 1H), 7.95 (d, J = 7.9 Hz, 1H), 8.10 (dd , J = 7.6.1.5 Hz, 1H), 8.18 (sa, 1H) 8.22 (s, 1H), 8.27 (d, J = 5.0Hz, 1H), 8.61 (dd, J = 4.9, 1.5 Hz, 1H), 9.70 (sa, 2H), 10.91 (s, 1H), 11.08 (s, 1H)

2- [2- (4- (2-Hydroxyethyl) piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-58)

1H-NMR (400 MHz, DMSO-d6) δ 2.38 (t, J = 6.3 Hz, 2H), 2.45 (sa, 8H), 3.13 (s, 2H), 3.32-3.50 (m, 2H), 4, 38 (t, J = 5.4 Hz, 1H), 4.42 (s, 2H), 7.15 (d, J = 5.1Hz, 1H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.9 Hz, 2H), 7.80 (d, J = 8.9 Hz, 2H), 7.99 (dd, J = 7.6.1.5 Hz, 1H), 8.18-8.19 (m, 2H), 8.60 (dd, J = 4.9, 1.5 Hz, 1H), 9.81 (s, 1H), 10.66 (s, 1H)

2- [2- (4-Acetylpiperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-59)

1H-NMR (400 MHz, DMSO-d6) δ 1.99 (s, 3H), 2.46-2.53 (m, 4H), 3.20 (s, 2H), 3.45-3.47 (m, 4H), 4.43 (s , 2H), 7.15 (dd, J = 5.4.1.2 Hz, 1H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.81 (d, J = 8.8 Hz, 2H), 7.99 (dd, J = 7.6.1.6 Hz, 1H), 8.18-8.20 (m, 2H), 8.60 (dd, J = 4.9, 1.6Hz, 1H) 9.94 (s, 1H), 10.66 (s, 1H)

2- [2- (2-Hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3-isopropylphenyl) pyridin-3-carboxamide (compound No. 17-60) 1H-NMR (500 MHz, DMSO-d6) δ 1.20 (d, J = 7.1Hz, 6H), 2.60 (sa, 2H), 2.86 (m, 1H), 3.30 (s, 2H), 3.45 (t, J = 5.5 Hz, 2H), 4.41 (s, 2H), 7.00 (d, J = 7.8

Hz, 1H), 7.14 (m, 1H 7.23-7.30 (m, 2H), 7.51 (d, J = 8.5 Hz, 1H), 7.59 (s, 1H), 7.96 (d, J = 7.8 Hz, 1H), 8.18 (d, J = 5.4

Hz, 1H), 8.20 (s, 1H), 8.58 (dd, J = 4.9, 1.7 Hz, 1H), 10.15 (s, 1H), 10.39 (s, 1H ) 2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3-isopropylphenyl) pyridine-3-carboxamide (compound No. 17-61)

1H-NMR (400 MHz, CDCl3)

δ 1.25 (d, J = 6.8 Hz, 6H), 2.23 (s, 6H), 2.43 (t, J = 5.7 Hz, 2H), 2.71 (t, J = 5.7 Hz, 2H), 2.91 (m, 1H), 3.32 (m, 1H), 3.38 (s, 2H), 4.50 (s, 2H), 7.03 (d, J = 7.6 Hz, 1H), 7.07 (d, J = 5.0 Hz, 1H), 7.11 (dd, J = 7.6.4.9 Hz, 1H), 7.27 (m, 1H), 7.46 (d, J = 7.6 Hz, 1H), 7.52 (s, 1H), 7.86 (d, J = 7.3 Hz, 1H), 8.17 (d, J = 5.0 Hz , 1H), 8.29 (m, 2H), 8.52 (m, 1H), 9.89 (s, 1H)

2- [2- (4-Methylpiperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-62)

1H-NMR (400 MHz, CDCl3) δ 2.38 (s, 3H), 2.61-2.69 (m, 8H), 3.15 (s, 2H), 4.53 (s, 2H), 7.08 (dd, J = 5 , 1, 1.1 Hz, 1H), 7.15 (dd, J = 7.6.4.8 Hz, 1H), 7.22 (d, J = 8.9 Hz, 2H), 7.70 (d, J = 8.9 Hz, 2H), 7.88 (dd, J = 7.6.1.7 Hz, 1H ), 8.19 (d, J = 5.1 Hz, 1H), 8.28 (s, 1H), 8.39 (s, 1H), 8.54 (dd, J = 4.8.1.7 Hz, 1H), 9.50 (s, 1H)

N- (4-Chlorophenyl) -2- [2- (2-propin-1-yl) aminoacetylaminopyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 17-63) 1H-NMR (400 MHz, DMSO-d6) δ 2.80 (sa, 1H), 3.10 (t, J = 2.4 Hz, 1H), 3.30-3.40 (m, 4H), 4.42 (s, 2H), 7, 12 (d, J = 5.1 Hz, 1H), 7.30 (dd, J = 7.6, 4.9

Hz, 1H), 7.41 (d, J = 8.8 Hz, 2H), 7.73 (d, J = 8.8 Hz, 2H), 7.98 (dd, J = 7.6.1 , 7 Hz, 1H), 8.17-8.20 (m, 2H), 8.59 (dd, J =

4.9, 1.7 Hz, 1H), 10.04 (s, 1H), 10.60 (s, 1H) N- (4-Chlorophenyl) -2- [2- (4- (2-hydroxyethyl) piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (compound No. 17-64)

1H-NMR (400 MHz, DMSO-d6) δ 2.39 (t, J = 6.3 Hz, 2H), 2.40-2.60 (m, 8H), 3.13 (s, 2H), 3.45-3.49 (m, 2H ), 4.38 (t, J = 5.1 Hz, 1H), 4.42 (s, 2H), 7.15

(d, J = 5.9 Hz, 1H), 7.30 (dd, J = 7.6, 4.9 Hz, 1H), 7.41 (d, J = 8.8 Hz, 2H), 7 , 72 (d, J = 8.8 Hz, 2H), 7.98 (m, 1H), 8.18 (s, 1H), 8.19 (d, J = 5.9 Hz, 1H), 8.59 (dd, J = 4.9, 1.5 Hz, 1H), 9.81 (s, 1H) , 10.60 (s, 1 H) N- (4-Difluoromethoxyphenyl) -2- [2- (N- (2-hydroxyethyl) -N-methylamino) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide

(compound No. 17-65) 1H-NMR (400 MHz, DMSO-d6) δ 2.31 (s, 3H), 2.54 (t, J = 5.8 Hz, 2H), 3.19 (s, 2H), 3.47-3.51 (m, 2H), 4, 42 (s, 2H), 4.63 (t, J = 5.3 Hz, 1H), 7.14 (dd, J

= 5,0,1,5Hz, 1H), 7,17 (d, J = 9,0Hz, 2H), 7,17 (t, J = 74,2 Hz, 1H), 7,30 (dd, J = 7.6.4.9 Hz, 1H), 7.72 (d, J = 9.0 Hz, 2H),

7.97 (dd, J = 7.6.1.7 Hz, 1H), 8.16-8.20 (m, 2H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.41 (s, 1H), 10.54 (s, 1H) N- (4-Difluoromethoxyphenyl) -2- [2- (piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (compound No. 1766)

1H-NMR (400 MHz, DMSO-d6) δ 2.42 (sa, 4H), 2.72 (sa, 4H), 3.10 (s, 2H), 4.42 (s, 2H), 7.15 (m, 1H), 7.17 ( t, J = 74.2 Hz, 1H), 7.18 (d, J = 8.9 Hz, 2H),

7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.72 (d, J = 8.9 Hz, 2H), 7.98 (d, J = 7.6Hz, 1H) , 8.18-8.19 (m, 2H), 8.59 (dd, J = 4.9, 1.7Hz, 1H), 9.82 (s, 1H), 10.55 (s, 1H) 2- (2-Aminoacetylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridin-3-carboxamide (compound No. 17-67) 1H-NMR (400 MHz, DMSO-d6) δ 3.33-3.34 (m, 2H), 4.42 (s, 2H), 7.14 (m, 1H), 7.30 (dd, J = 7.6.4.9 Hz, 1H ), 7.41 (d, J = 8.8Hz, 2H), 7.73 (d, J = 8.8Hz, 2H),

7.95-8.01 (m, 2H), 8.19 (m, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.64 (s, 1H) 2- (2-Acetylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridin-3-carboxamide (compound No. 17-68) 1H-NMR (400 MHz, DMSO-d6) δ 1.87 (s, 3H), 3.89 (d, J = 5.9 Hz, 2H), 4.41 (s, 2H), 7.12 (dd, J = 5.1, 1.2 Hz, 1H), 7.29 (dd, J = 7.6.4.9 Hz, 1H), 7.41 (d, J

= 8.8 Hz, 2H), 7.73 (d, J = 8.8 Hz, 2H), 7.97 (dd, J = 7.6.1.7 Hz, 1H), 8.13-8 , 19 (m, 3H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.39 (s, 1 H), 10.60 (s, 1 H) N- (4-Difluoromethoxyphenyl) -2- (2-phthaloylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 17-69) 1H-NMR (400 MHz, DMSO-d6),

δ 4.39 (s, 2H), 4.49 (s, 2H), 7.15-7.19 (m, 3H), 7.18 (t, J = 74.2 Hz, 1H), 7, 27 (dd, J = 7.6.4.9 Hz, 1H), 7.70 (d, J = 9.0 Hz, 2H), 7.83-7.95 (m, 5H), 8.06 (s, 1H), 8.22 (d, J = 5.1 Hz, 1H), 8.55 (dd, J = 4.9, 1.7 Hz, 1H), 10.52 (s, 1H) , 10.90 (s, 1 H)

N- (4-Difluoromethoxyphenyl) -2- [2- (4-methylpiperazin-1-yl) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (compound No. 17-70)

1H-NMR (400 MHz, DMSO-d6)

δ 2.17 (s, 3H), 2.36 (sa, 4H), 2.51 (sa, 4H), 3.14 (s, 2H), 4.42 (s, 2H), 7.14- 7.19 (m, 3H), 7.18 (t, J = 74.2 Hz, 1H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.73 (d , J = 9.0 Hz, 2H), 7.97 (dd, J = 7.6.1.7Hz, 1H), 8.18-8.19 (m, 2H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 9.82 (s, 1H), 10.54 (s, 1H)

N- (4-Difluoromethoxyphenyl) -2- (2-isopropylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 1771)

1H-NMR (400 MHz, DMSO-d6)

δ 0.99 (d, J = 6.1 Hz, 6H), 2.72 (m, 1H), 3.26 (s, 2H), 4.42 (s, 2H), 7.14 (dd, J = 5.1, 1.5 Hz, 1H), 7.17 (t, J = 74.2 Hz, 1H), 7.18 (d, J = 9.0Hz, 2H), 7.30 (dd , J = 7.6.4.9Hz, 1H), 7.72 (d, J = 9.0Hz, 2H), 7.97 (dd, J = 7.6.1.7 Hz, 1H), 8 , 16-8.20 (m, 2H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.10 (s, 1H), 10.54 (s, 1H)

2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide (compound No. 17-72)

1H-NMR (400 MHz, DMSO-d6)

δ 2.15 (s, 6H), 2.25 (s, 6H), 2.33 (t, J = 6.1 Hz, 2H), 2.61 (t, J = 6.1 Hz, 2H) , 3.31 (s, 2H), 4.41 (s, 2H), 6.76 (s, 1H), 7.13 (dd, J = 5.1, 1.5 Hz, 1H), 7, 28 (dd, J = 7.6.4.9 Hz, 1H), 7.32 (s, 2H), 7.92 (dd, J = 7.6.1.7 Hz, 1H), 8.18 -8.20 (m, 2H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 10.26 (s, 1H), 10.29 (s, 1H)

N- (3,5-Dimethylphenyl) -2- (2-isopropylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 17-73)

1H-NMR (400 MHz, DMSO-d6)

δ 0.99 (d, J = 6.1 Hz, 6H), 2.25 (s, 6H), 2.73 (m, 1H), 3.27 (s, 2H), 4.41 (s, 2H), 6.76 (s, 1H), 7.14 (dd, J = 5.1, 1.2Hz, 1H), 7.28 (dd, J = 7.6.4.9 Hz, 1H) , 7.32 (s, 2H), 7.92 (dd, J = 7.6.1.7 Hz, 1H) 8.16-8.20 (m, 2H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H) 10.12 (s, 1H), 10.30 (s, 1H)

2- [2- (2-Propen-1-yl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (compound No. 17-74)

1H-NMR (400 MHz, DMSO-d6)

δ 3.18 (d, J = 5.4 Hz, 2H), 3.27 (s, 2H), 4.42 (s, 2H), 5.07 (d, J = 10.0 Hz, 1H) , 5.17 (d, J = 17.1 Hz, 1H), 5.83 (m, 1H), 7.14 (d, J = 5.0 Hz, 1H), 7.31 (dd, J = 7.7.4.9 Hz, 1H), 7.37 (d, J = 8.7 Hz, 2H), 7.81 (d, J = 8.7 Hz, 2H), 7.99 (d, J = 7.7 Hz, 1H), 8.18 (d, J = 5.0 Hz, 1H), 8.20 (s, 1H), 8.60 (d, J = 4.9 Hz, 1H) , 10.09 (sa, 1H), 10.66 (s, 1H)

2- [2- (2-Methylaziridin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-75)

1H-NMR (400 MHz, DMSO-d6)

δ 1.13 (d, J = 5.4 Hz, 3H), 1.45 (d, J = 6.3 Hz, 1H), 1.54 (d, J = 3.7 Hz, 1H), 1 , 63 (m, 1H), 3.01 (d, J = 15.9 Hz, 1H), 3.10 (d, J = 15.9 Hz, 1H), 4.43 (s, 2H), 7 , 16 (dd, J = 5.1, 1.5 Hz, 1H), 7.31 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.81 (d, J = 8.8 Hz, 2H), 7.99 (dd, J = 7.6.1.Hz, 1H), 8.20 (d, J = 5, 1Hz, 1H), 8.20 (s, 1H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 9.83 (s, 1H), 10.66 (s, 1H )

2- [2- (N-Ethyl-N-methylaminoacetylamino) pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (compound No. 17-76)

1H-NMR (400 MHz, DMSO-d6) δ 1.02 (t, J = 7.1 Hz, 3H), 2.28 (s, 3H), 2.49-2.51 (m, 2H), 3.13 (s, 2H), 4.43 (s, 2H), 7.15 (dd, J = 5.1, 1.5 Hz, 1H), 7.31 (dd, J = 7.6, 4.9Hz, 1), 7.37 (d, J = 8.8 Hz, 2H), 7.81 (d, J = 8.8 Hz, 2H), 7.99 (dd, J = 7.6 , 1.7 Hz, 1H), 8.18 (d, J = 5.1 Hz, 1H), 8.19 (s, 1H), 8.60 (dd, J = 4.9, 1.7 Hz , 1H), 9.80 (s, 1H), 10.66 (s, 1H)

2- [2- (Azetidin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (compound No. 17-77) 1H-NMR (400 MHz, DMSO-d6) δ 1.99-2.06 (m, 2H), 3.21 (s, 2H), 3.28 (t, J = 7.0 Hz, 4H), 4.92 (s, 2H), 7, 19 (d, J = 5.1 Hz, 1H), 7.30 (dd, J = 7.6.4.9

Hz, 1H) 7.37 (d, J = 8.9 Hz, 2H), 7.80 (d, J = 8.9 Hz, 2H), 7.99 (d, J = 7.6 Hz, 1H ), 8.15 (s, 1H), 8.18 (d, J = 5.1 Hz, 1H),

8.60 (dd, J = 4.9, 1.7 Hz, 1H), 9.81 (s, 1H), 10.66 (s, 1H) 2- [2- (2- (Pyrrolidin-1-yl) ethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-78)

1H-NMR (400 MHz, DMSO-d6) δ 1.65-1.67 (m, 4H), 2.41-2.48 (m, 6H), 2.63 (t, J = 6.2 Hz, 2H), 3.32 (s, 2H ), 4.42 (s, 2H), 7.13 (dd, J = 5.1, 1.5 Hz, 1H),

7.30 (dd, J = 7.6, 4.9 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 8.8 Hz, 2H ), 7.99 (dd, J = 7.6, 1.6Hz, 1H), 8.18 (d, J = 5.1 Hz, 1H), 8.20 (s, 1H), 8.60 (dd, J = 4.9, 1.6 Hz, 1H), 10.23 (s, 1H), 10, 66 (s, 1 H) N- (4-Chlorophenyl) -2- [2- (2- (pyrrolidin-1-yl) ethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No.

17-79) 1H-NMR (500 MHz, DMSO-d6) δ 1.65-1.66 (m, 4H), 2.42-2.45 (m, 4H), 2.47-2.52 (m, 2H), 2.62-2.64 (m, 2H), 3.29 (s, 2H), 4.42 (s, 2H), 7.12 (dd, J =

5.2.1.7 Hz, 1H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.41 (d, J = 8.9 Hz, 2H), 7, 72 (d, J = 8.9 Hz, 2H), 7.98 (dd, J = 7.6, 1.7

Hz, 1H), 8.18 (d, J = 5.2 Hz, 1H), 8.20 (s, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.22 (s, 1H), 10.59 (s, 1H) 2- [2- (1,4-Dihydro-4-oxopyridin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide (compound # 17-80)

1H-NMR (400 MHz, DMSO-d6) δ 4.41 (s, 2H), 4.82 (s, 2H), 6.06 (d, J = 7.6 Hz, 2H), 7.16 (d, J = 5.1Hz, 1H), 7.30 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J =

8.9 Hz, 2H), 7.58 (d, J = 7.6 Hz, 2H), 7.80 (d, J = 8.9 Hz, 2H), 7.98 (dd, J = 7, 6, 1.7 Hz, 1H), 8.11 (s, 1H), 8.22 (d, J = 5.1 Hz, 1H), 8.58 (dd, J = 4.9, 1.7 Hz, 1H), 10.65 (s, 1H), 10.83 (s, 1H) N- (4-Chlorophenyl) -2- [2- (4-methylpiperazin-1-yl) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (compound No. 17-81) 1H-NMR (400 MHz, DMSO-d6) δ 2.17 (s, 3H), 2.35 (sa, 6H), 3.14 (s, 2H), 3.32 (s, 2H), 4.42 (s, 2H), 7.15 ( d, J = 6.3Hz, 1H), 7.30 (dd, J = 7.6, 4.9Hz, 1H),

7.41 (d, J = 8.8 Hz, 2H), 7.72 (d, J = 8.8 Hz, 2H), 7.98 (dd, J = 7.6, 1.6 Hz, 1H ), 8.18-8.19 (m, 2H), 8.59 (dd, J = 4.9, 1.6 Hz, 1H), 9.82 (s, 1H), 10.60 (s, 1H) 2- [2- (Imidazol-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-82)

1H-NMR (400 MHz, DMSO-d6) δ 4.41 (s, 2H), 4.94 (s, 2H), 6.88 (d, J = 1.0 Hz, 1H), 7.15-7.16 (m, 2H), 7, 29 (dd, J = 7.6.4.9 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.62 (s, 1H), 7.79 (d, J = 8.8Hz, 2H), 7.98 (dd, J = 7.6, 1.7 Hz, 1H), 8 , 11 (s, 1H), 8.22 (d, J = 5.1Hz, 1H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 10.65 (s, 1H), 10.78 (s, 1H)

N- (4-Chlorophenyl) -2- [2- (azetidin-1-yl) acetylaminopyridin-4-ylmethylthio] pyridin-3-carboxamide (compound No. 17-83) 1H-NMR (400 MHz, DMSO-d6) δ 1.90-2.08 (m, 2H), 3.21 (s, 2H), 3.25-3.34 (m, 4H), 4.41 (s, 2H), 7.14 (d , J = 5.1 Hz, 1H), 7.30 (dd, J = 7.6.4.9 Hz, 1H),

7.41 (d, J = 8.8 Hz, 2H), 7.72 (d, J = 8.8 Hz, 2H), 7.98 (m, 1H), 8.15-8.19 (m , 2H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 9.80

(s, 1H), 10.59 (s, 1H) N- (3,5-Dimethylphenyl) -2- [2- (3-hydroxypropyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (compound # 1784) 1H-NMR (400 MHz, DMSO-d6)

δ 1.50-1.60 (m, 2H), 2.25 (s, 6H), 2.57 (t, J = 6.8 Hz, 2H), 3.27 (s, 2H), 3, 46 (t, J = 6.8 Hz, 2H), 4.40 (sa, 1H), 4.41 (s, 2H), 6.76 (s, 1H), 7.14 (d, J = 5 , 1 Hz, 1H), 7.28 (dd, J = 7.6, 4.9 Hz, 1H), 7.32 (s, 2H), 7.93 (dd, J = 7.6, 1, 7Hz, 1H), 8,178.21 (m, 2H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 10.07 (sa, 1H), 10.59 (s, 1H )

N- (3,5-Dimethylphenyl) -2- [2- (2-morpholinoethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (compound No. 1785)

1H-NMR (400 MHz, DMSO-d6)

δ 2.25 (s, 6H), 2.30-2.40 (m, 6H), 2.63 (t, J = 6.1 Hz, 2H), 3.30 (s, 2H), 3, 54 (t, J = 4.6 Hz, 4H), 4.41 (s, 2H), 6.76 (s, 1H), 7.13 (d, J = 5.1Hz, 1H), 7.28 (dd, J = 7.6, 4.9Hz, 1H), 7.32 (s, 2H), 7.93 (dd, J = 7.6, 1.7Hz, 1H), 8.17-8 , 21 (m, 2H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 10.17 (sa, 1H), 10.30 (s, 1H)

2- (2-Ethylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-86)

1H-NMR (400 MHz, CDCl3)

δ 1.15 (t, J = 7.1Hz, 3H), 2.72 (q, J = 7.1Hz, 2H), 3.39 (s, 2H), 4.52 (s, 2H), 7 , 06 (d, J = 5.1 Hz, 1H), 7.13 (dd, J = 7.6.4.9 Hz, 1H), 7.21 (d, J = 8.3 Hz, 2H) , 7.70 (d, J = 8.3 Hz, 2H), 7.87 (dd, J = 7.6, 1.7 Hz, 1H), 8.18 (d, J = 5.1 Hz, 1H), 8.26 (s, 1H), 8.51-8.54 (m, 2H), 9.82 (sa, 1H)

2- (2-Cyclopropylmethoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (compound No. 17-87)

1H-NMR (400 MHz, DMSO-d6)

δ 0.19-0.23 (m, 2H), 0.46-0.51 (m, 2H), 1.11 (m, 1H), 3.35 (d, J = 6.8 Hz, 2H ), 4.09 (s, 2H), 4.43 (s, 2H), 7.16 (dd, J = 5.0, 1.5Hz, 1H), 7.31 (dd, J = 7.7 , 4.9 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.81 (d, J = 8.8Hz, 2H), 7.99 (dd, J = 7, 7, 1.7Hz, 1H), 8.18 (d, J = 5.0 Hz, 1H), 8.20 (s, 1H), 8.60 (dd, J = 4.9, 1.7 Hz , 1H), 9.74 (s, 1H), 10.66 (s, 1H)

N- (3,5-Dimethylphenyl) -2- (2-phthaloylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 17-88)

1H-NMR (400 MHz, DMSO-d6)

δ 2.24 (s, 6H), 4.38 (s, 2H), 4.50 (s, 2H), 6.74 (s, 1H), 7.15 (d, J = 5.1Hz, 1H ), 7.25 (dd, J = 7.8, 4.9Hz, 1H), 7.30 (s, 2H), 7.83 (s, 1H), 7.88-7.94 (m, 4H ), 8.06 (sa, 1H), 8.22 (d, J = 5.1 Hz, 1H), 8.53 (dd, J = 4.9, 1.7 Hz, 1H), 10.28 (s, 1H), 10.90 (s, 1H)

Example 18

2- (2-Aminoacetylaminopyridin-4-ylmethylthio) -N- (4-difluoromethoxyphenyl) pyridin-3-carboxamide (compound No. 18-1)

N- (4-Difluoromethoxyphenyl) -2- (2-phthaloylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (compound No. 17-69, 50 mg, 0.085 mmol) and hydrazine monohydrate (42 µl, 0,) were suspended 42 mmol) in the mixture of methanol (2.0 ml) and 1,4-dioxane (2.0 ml) at room temperature, then the mixture was stirred for 1 hour at 80 ° C. The mixture was diluted with ethyl acetate (30 ml), and the whole was washed with brine (30 ml) twice and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to provide 11 mg of the objective compound as a colorless solid. (29% yield)

1H-NMR (400 MHz, DMSO-d6)

δ 3.30 (s, 2H), 3.41 (s, 2H), 4.43 (s, 2H), 7.14-7.20 (m, 3H), 7.18 (t, J = 74 , 2 Hz, 1H), 7.30 (dd, J = 7.6, 4.9 Hz, 1H), 7.73 (d, J = 9.0 Hz, 2H), 7.84 (s, 1H ), 7.98 (d, J = 7.6 Hz, 1H), 8.30 (d, J = 5.1 Hz, 1H), 8.60 (d, J = 4.9 Hz, 1H), 10.54 (s, 1 H)

The chemical structures of the compounds of the present invention described above are shown below.

[Formulation examples]

5 Typical formulation examples of the compound of the present invention are shown below.

1) Tablet (in 100 mg)

Compound of the present invention 1 mg Lactose 66.4 mg Corn starch 20 mg Calcium carboxymethylcellulose 6 mg Hydroxypropylcellulose 4 mg Magnesium stearate 0.6 mg

The tablet of the above-mentioned formulation is coated using 2 mg of a coating agent (for example, a conventional coating agent such as hydroxypropyl methylcellulose, macrogol or a silicone resin), obtaining a desired coated tablet. In addition, a desired tablet can be obtained by appropriately changing the classes and / or amounts of the compound of the present invention and / or the additives.

15 2) Capsule

Formulation 2 (in 150 mg) Compound of the present invention 5 mg Lactose 145 mg

A desired capsule can be obtained by appropriately changing the mixing ratio of the compound of the present invention with respect to lactose.

3) Ophthalmic dissolution

Formulation 3 (in 100 ml) Compound of the present invention 100 mg Sodium chloride 900 mg Polysorbate 80 200 mg Sodium hydroxide sufficient quantity Hydrochloric acid sufficient quantity Sterile purified water sufficient quantity

A desired ophthalmic solution can be obtained by appropriately changing the classes and / or amounts of the compound of the present invention and / or the additives.

[Pharmacological tests]

30 1. Evaluation test of the angiogenesis inhibitory effect

As one of the widely used methods of evaluating the inhibitory effects of drug angiogenesis, a test of the inhibitory action of cell proliferation has been reported using a VEGF-induced HUVEC proliferation reaction evaluation system in Cancer Res ., 59, 99-106 (1999). According to the procedure described in the aforementioned document, a test of the inhibitory action was performed

of the cell proliferation of the compounds of the present invention, the rate of inhibition of cell proliferation was calculated, and the angiogenesis inhibitory effect of each of the compounds of the present invention was evaluated using the rate obtained as an index.

(Preparation of the test compound solution)

Each test compound was dissolved in dimethylsulfoxide (abbreviated hereinafter as DMSO), and the solution obtained was diluted with a commercially available phosphoric acid buffer solution (abbreviated hereinafter as PBS), thus preparing a 20 µg / ml solution of test compound.

(Preparation of the HUVEC suspension)

HUVEC was suspended in an F12K medium containing 0.5% fetal bovine serum (abbreviated hereinafter as FBS), thus preparing a HUVEC suspension of 2 x 104 cells / ml.

(Preparation of the VEGF solution)

VEGF was dissolved in PBS containing 0.1% bovine serum albumin, and the solution obtained was diluted with f12K medium containing 0.5% FBS, thus preparing a solution 400 ng / ml of VEGF.

(Test procedure and measurement procedure)

1) The HUVEC suspension was inoculated in an amount of 100 µl in each well of a 96-well plate coated with type I collagen (2 x 103 cells per well).

2) One day after inoculation, the test compound solution was added in an amount of 5 µl per well.

3) One hour after the addition of the test compound solution, the VEGF solution was added in an amount of 5 µl per well.

4) Three days after the addition of the VEGF solution, the WST-8 test kit (Dojin Chemical Co., Ltd.) was added in an amount of 10 µl per well.

5) After 3 hours, the aforementioned plate was connected to an absorber (Multilabel Counter ARVO), and an absorbance at 450nm of each well suspension was measured (hereinafter referred to as test compound suspension).

6) A test was carried out in the same manner as in the previous 1) to 5) except that 1.0% DMSO was used instead of the test compound solution. The result was used as a control.

Incubation was carried out under conditions of 37 ° C, 5% carbon dioxide and 95% oxygen in an incubator throughout all the test stages mentioned above.

(Calculation of the rate of inhibition of cell proliferation)

The rate of inhibition of cell proliferation (%), which was used as an index of an angiogenesis inhibitory effect, was calculated according to the following calculation equation.

(Calculation equation)

Rate of cell proliferation inhibition (%) = 100 - {(absorbance of test compound suspension -A) / (control absorbance - A)} x 100

A: Absorbance of only the cell suspension (cell + medium)

(Test results and discussion)

As an example of the test results, Table 1 shows the rates of cell proliferation inhibition (%) of the test compounds (compound 1-1, compound 1-2, compound 1-3, compound 1-4, compound 1-5, compound 1-6, compound 1-10, compound 1-11, compound 1-20, compound 2-1, compound 2-2, compound 2-3, compound 2-4, compound 2-5, compound 2-6, compound 2-7, compound 2-24, compound 3-1, compound 3-2, compound 3-3, compound 3-4, compound 3-5, compound 3-6, compound 3-7, compound 3-8, compound 3-9, compound 3-10, compound 3-13, compound 3-20, compound 3-21, compound 3-28, compound 4-1, compound 42, compound 4-3, compound 4- 4, compound 4-5, compound 4-6, compound 4-10, compound 4-11, compound 4

12, compound 4-22, compound 4-37, compound 4-42, compound 4-44, compound 4-56, compound 4-57, compound 5-1, compound 5-2, compound 5-3, compound 6- 1, compound 8-1, compound 9-1, compound 9-2, compound 9-3, compound 9-4, compound 10-1, compound 11-2, compound 12-1, compound 12-2, compound 123, compound 12-5, compound 12-6, compound 12-7, compound 12-9, compound 12-10, compound 12-11, 5 compound 12-12, compound 12-13, compound 12-15, compound 12-16 , compound 13-4, compound 13-5, compound 13-7, compound 17-2, compound 17-4, compound 17-5, compound 17-6, compound 17-10, compound 17-11, compound 17-14 , compound 17-23, compound 17-26, compound 17-28, compound 17-31, compound 1734, compound 17-35, compound 17-36, compound 17-40, compound 17-46, compound 17-47, compound 17-48, compound 17-49, compound 17-50, compound 17-52, compound 17-58, compound 17-66, compound 17-71,

Compound 17-72, compound 17-73, compound 17-84, compound 17-85, compound 17-86 and compound 18-1).

Table 1

Compound

Rate of cell proliferation inhibition (%)  Compound Rate of cell proliferation inhibition (%)  Compound Rate of cell proliferation inhibition (%)

1-1

97 4-5 100 12-16 99

1-2

100 4-6 100 13-4 88

1-3

99 4-10 100 13-5 100

1-4

100 4-11 93 13-7 81

1-5

90 4-12 100 17-2 88

1-6

100 4-22 97 17-4 100

1-10

94 4-37 100 17-5 83

1-11

96 4-42 100 17-6 84

1-20

100 4-44 85 17-10 82

2-1

100 4-56 99 17-11 84

2-2

100 4-57 100 17-14 77

2-3

100 5-1 100 17-23 93

2-4

99 5-2 100 17-26 87

2-5

95 5-3 100 17-28 100

2-6

100 6-1 100 17-31 92

2-7

52 8-1 100 17-34 81

2-24

88 9-1 100 17-35 95

3-1

100 9-2 100 17-36 81

3-2

97 9-3 100 17-40 92

3-3

100 9-4 100 17-46 100

3-4

100 10-1 100 17-47 89

3-5

96 11-2 100 17-48 100

3-6

100 12-1 78 17-49 95

3-7

96 12-2 100 17-50 100

3-8

100 12-3 100 17-52 94

3-9

100 12-5 100 17-58 76

3-10

97 12-6 96 17-66 91

3-13

100 12-7 87 17-71 95

3-20

100 12-9 99 17-72 100

3-21

100 12-10 100 17-73 100

(continuation)

3-28

100 12-11 100 17-84 100

4-1

100 12-12 91 17-85 100

4-2

100 12-13 91 17-86 86

4-3

100 12-15 91 18-1 88

4-4

100

As shown in Table 1, the compounds of the present invention showed excellent inhibitory action on cell proliferation. Therefore, the compounds of the present invention have an excellent angiogenesis inhibitory effect.

2. Test of evaluation of the anticancer effect As one of the most widely used methods of evaluation of the anticancer effects of drugs, a test of the tumor growth inhibitory action using cancer models in mice has been reported in 10 Cancer Res., 59 , 5209-5218 (1999). According to the procedure described in the aforementioned document, a test of the tumor growth inhibitory action of the compounds of the present invention was performed, the rate of tumor tissue weight inhibition was calculated, and the anticancer effect of each was evaluated. of the compounds of the present invention using the rate obtained as an index. 15 (Preparation of the test compound suspension) A 1% aqueous solution of methylcellulose was added to each test compound to suspend it with a sonicator, whereby a 10 mg / ml suspension of test compound was prepared. 20 (Preparation of the B16 cell suspension) Physiological saline was added to B16 cells, whereby a B16 cell suspension of 3.3 x 107 cells / ml was prepared. 25 (Test procedure and measurement procedure) 1) The back of each mouse (C57BL / 6N mouse, female, 6 weeks old,) was shaved using a depilatory with Nembutal anesthesia.

30 2) Several days after depilation, the B16 cell suspension (300 µl) was injected intradermally into the back of the mouse with Nembutal anesthesia. 3) From the day of B16 cell injection (ie day 0) to day 10, the oral administration was administered

suspension of test compound (100 mg / kg / day) once a day consecutively. 35 4) Ten days after the injection of the cells, the mouse was sacrificed with CO2 gas. 5) A mouse tumor tissue was enucleated, and the weight of the tumor tissue was measured with an electronic scale. 6) A test was performed in the same manner as in 1) to 5) except that the 1% aqueous solution of methylcellulose was used instead of the test compound suspension, and the result was used as a control. (Calculation of the rate of inhibition of tumor tissue weight) 45 A rate of inhibition of tumor tissue weight (the average of 9 mice per group) was calculated, which was used as an index of the anticancer effect, according to the following calculation equation . (Calculation equation) 50 Tumor tissue weight inhibition rate (%) = 100 - (Mx / Mo) x 100 Mo: Tumor tissue weight of the control group Mx: Tumor tissue weight of the compound solution administration group of test 55 (Test results and discussion)

As an example of the test results, Table 2 shows the rates of tumor tissue weight inhibition (%) of the test compounds (compound 1-4, compound 1-6, compound 3-1, compound 3-2, compound 3-6, compound 3-8, compound 3-10, compound 3-20, compound 4-1, compound 4-2, compound 4-10, compound 4

5 11, compound 4-14, compound 4-16, compound 4-20, compound 4-43, compound 4-56, compound 4-59, compound 9-1, compound 10-1, compound 10-2, compound 11 -2, compound 12-1, compound 12-2, compound 12-3, compound 12-5, compound 12-7, compound 12-9, compound 12-11, compound 12-12, compound 12-15, compound 13 -7, compound 17-2, compound 17-5, compound 17-10, compound 17-11, compound 17-14, compound 17-23 and compound 17-35).

10 Table 2

Compound

Rate of tumor tissue weight inhibition (%)  Compound Rate of tumor tissue weight inhibition (%)  Compound Rate of tumor tissue weight inhibition (%)

1-4

68 4-16 74 12-7 59

1-6

42 4-20 84 12-9 47

3-1

70 4-43 47 12-11 52

3-2

61 4-56 42 12-12 60

3-6

71 4-59 80 12-15 69

3-8

80 9-1 43 13-7 75

3-10

85 10-1 54 17-2 83

3-20

42 10-2 83 17-5 69

4-1

75 11-2 64 17-10 79

4-2

51 12-1 85 17-11 81

4-10

75 12-2 71 17-14 79

4-11

86 12-3 41 17-23 56

4-14

44 12-5 67 17-35 72

As shown in Table 2, the compounds of the present invention showed excellent tumor growth inhibitory action. Therefore, the compounds of the present invention have an excellent anticancer effect.

3. Test of evaluation of the antiarthritic effect

As one of the most widely used procedures for evaluating the antiarthritic effects of drugs, it is known

20 a test of the inhibitory action of leg edema using models of adjuvant arthritis in rats. Therefore, a test of the paw edema inhibitory action of the compounds of the present invention was performed, the paw edema inhibition rate was calculated, and the anti-arthritic effect of each of the compounds of the present invention using the rate obtained as an index.

25 (Preparation of the test compound suspension)

A 1% aqueous solution of methylcellulose was added to each test compound to suspend it, thus preparing a 2 mg / ml suspension of test compound.

30 (Preparation of adjuvant)

Liquid paraffin was added to Mycobacteriun butyricum to suspend it, thus preparing adjuvant 6 mg / ml.

(Experiment procedure)

1) The adjuvant (0.1 ml) was injected subcutaneously in the plant of the left hind leg of each rat (Lewis rat, male, 9 weeks old) to induce arthritis.

2) From the day of injection of the adjuvant (ie day 0) to day 20, the suspension of test compound (10 mg / kg / day) was administered orally once a day consecutively.

3) On the day of the adjuvant injection, day 1, day 4, day 7, day 11, day 14, day 18 and day 21, each leg volume of both hind legs was measured with a plethysmometer

4) A test was performed in the same manner as in 1) to 3) except that the 1% aqueous solution of methylcellulose was used instead of the test compound suspension, and the result was used as a control.

(Evaluation procedure)

Each rate of edema inhibition of the leg of edema of the leg in an untreated leg was calculated with adjuvant

10 (leg with secondary inflammation) in each test compound administration group with respect to edema of the leg in a leg with secondary inflammation in a control group, and the antiarthritic effect of each of the compounds of the present invention was evaluated using the rate obtained as an index.

(Calculation of paw edema inhibition rate)

15 The edema rate of the leg was calculated according to the following calculation equation 1, and then the inhibition rate of the edema of the leg (the average of 8 rats per group) was calculated, which was used as an index of the antiarthritic effect, according to the calculation equation 2.

20 (Calculation equation 1)

Leg edema rate (%) = (leg volume after adjuvant treatment / leg volume before adjuvant treatment) x 100

25 (Calculation equation 2)

Leg edema inhibition rate (%) = 100 - {(Sx - 100) / (So-100)} x 100

So: Edema rate of the control group's leg

30 Sx: Leg edema rate of the test compound suspension administration group

(Test results and discussion)

35 As an example of the test results, Table 3 shows the rates of inhibition of leg edema (%) on day 21 of the test compounds (compound 3-1, compound 3-6, compound 3-8, compound 3-10, compound 4-1, compound 4-10, compound 4-11, compound 9-1, compound 10-1, compound 10-2, compound 12-1 and compound 12-2).

40 Table 3

Compound

Leg edema inhibition rate (%)  Compound Leg edema inhibition rate (%)

3-1

48 4-11 65

3-6

33 9-1 55

3-8

30 10-1 59

3-10

35 10-2 57

4-1

90 12-1 48

4-10

71 12-2 44

As shown in Table 3, the compounds of the present invention showed excellent inhibitory action on leg edema. Therefore, the compounds of the present invention have an excellent antiarthritic effect.

4. Evaluation test of the choroidal neovascularization inhibitory effect

As one of the most widely used procedures for evaluating the inhibitory effects of choroidal neovascularization of drugs, a neovascularization incidence test using models of choroidal neovascularization in rats was reported in Graefe’s Arch. Cli. Exp. Ophthalmol., 235, 313-319 (1997). According to the procedure described in the aforementioned document, a neovascularization incidence test of the compounds of the present invention was performed, the ratio of the neovascularization incidence rate of each of the compound administration groups of the present was calculated invention with respect to a neovascularization incidence rate of the vehicle administration group (control group), and

The choroidal neovascularization inhibitory effect of each of the compounds of the present invention was evaluated using the ratio obtained as an index.

(Preparation of the test compound solution)

A 1% aqueous solution of methylcellulose was added to each test compound to suspend it, thus preparing a 6 mg / 10 ml suspension of test compound.

(Preparation of the laser-induced choroidal neovascularization model in rats)

1) A mixed 7: 1 solution (1 ml / kg) of an injection of 5% ketamine hydrochloride and an injection of 2% xylazine hydrochloride to rats (male rat Brown Norway, 8 weeks of age) was administered intramuscularly. age, weight: 200 to 250 g) to anesthetize them systemically.

2) An ophthalmic solution of tropicamide-phenylephrine hydrochloride (trade name: Mydrin-P) was instilled in the eyes to produce mydriasis, and then photocoagulation was performed on the Bruch membrane of each rat using a laser photocoagulation apparatus of Krypton

Laser photocoagulation was performed at 8 points per eye in a scattered manner avoiding thick retinal vessels in a posterior section of the fundus and focusing on the deep layer of the retina. Photocoagulation conditions were adjusted to 100 µm point size, 100 mW intensity and a duration of 0.1 s.

3) After photocoagulation, the fundus was photographed to confirm the photocoagulation sites (laser irradiation).

(Test procedure and measurement procedure)

1) From the day of laser photocoagulation (ie day 0) to day 6, the test compound suspension (30 mg / kg / day) was administered orally once daily for 7 consecutive days.

2) As a vehicle administration group (control group), a test was performed in the same manner as in 1) except that the 1% aqueous solution of methylcellulose was used instead of the test compound suspension, and was used The result as a control.

(Evaluation procedure)

1) On day 7 after photocoagulation, 0.1 ml of a 10% aqueous solution of fluorescein was injected into a vein in the rat's tail, and the fundus photograph was taken with fluorescein.

2) Next, in the fundus photography with fluorescein, a point was evaluated at which a fluorescence leak was not observed as negative, and a point at which a fluorescence leak was observed as positive was evaluated. Photocoagulation sites were evaluated in which a small fluorescence leak was observed as positive when two such sites are present.

3) The neovascularization incidence rate was calculated according to the calculation equation 1. The ratio of the neovascularization incidence rate of the test compound administration group to that of the vehicle administration group was calculated according to the equation of Calculation 2 using the incidence rate of neovascularization of the respective administration groups.

(Calculation equation 1)

Neovascularization incidence rate (%) = (number of positive photocoagulation sites / number of total photocoagulation sites) x 100

(Calculation equation 2)

Reason for the incidence of neovascularization of the test compound administration group with respect to that of the vehicle administration group (control group) (% of control) = Ax / Ao x 100

Ao: Neovascularization incidence rate of the vehicle administration group (control group)

Ax: Neovascularization incidence rate of the test compound administration group

(Test results and discussion) As an example of the test results, Table 4 shows the reasons (% of the control) of the neovascularization incidence rates of the test compound administration groups (compound 1-6, compound 3 -1, compound 3-8, compound 3-10, compound 4-1, compound 4-10, compound 4-11, compound 4-20, compound 91, compound 10-1, compound 10-2, compound 11-2 , compound 12-1, compound 12-2, compound 12-5, compound 12-10 and compound 17-5) with respect to those of the vehicle administration group (control group).

Table 4

Compound

Reason for the incidence of neovascularization (% of control)  Compound Reason for the incidence of neovascularization (% of control)

1-6

38 10-1 eleven

3-1

12 10-2 0

3-8

6 11-2 16

3-10

7 12-1 6

4-1

3 12-2 0

4-10

9 12-5 5

4-11

0 12-10 37

4-20

22 17-5 8

9-1

8

(Values are the average of 3 to 4 rats and 6 to 8 eyes.)

As shown in Table 4, the compounds of the present invention showed a lower incidence rate of neovascularization than that of the vehicle and have a choroidal neovascularization inhibitory effect.

Industrial applicability

The new cyclic compound according to the present invention has an excellent proliferation inhibitory effect.

Cellular, a tumor growth inhibitory effect, a leg edema inhibitory effect and / or a choroidal neovascularization inhibitory effect, and is useful as a therapeutic agent for a disease in which the disease is involved. angiogenesis and / or vascular hyperpermeability, for example, cancer, rheumatoid arthritis, age-related macular degeneration, diabetic retinopathy, prematurity retinopathy, retinal venous occlusion, polypoid choroidal angiopathy, diabetic macular edema, vulgar psoriasis, atherosclerosis or the like.

Claims (12)

1. Compound represented by the following general formula (1): (wherein ring A represents a benzene ring, or an aromatic five-membered heterocyclic ring or an aromatic six-membered heterocyclic ring that can be fused to a cycloalkane ring; R1 and R2, which are the same or different, represent a hydrogen atom, a hydroxyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted alkyl group, a substituted cycloalkyl group or unsubstituted, a substituted or unsubstituted aryl group, a substituted heterocyclic ring or unsubstituted, an amino group, a substituted or unsubstituted alkylamino group, a substituted or unsubstituted arylamino group or a substituted or unsubstituted acyl group; R1 and R2 can be linked together to form a substituted or unsubstituted heterocyclic ring; R3 and R4, which are the same or different, represent a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted aryl group, a heterocyclic ring Substituted or unsubstituted, a hydrocarbonyl group, a substituted or unsubstituted alkylcarbonyl group, a substituted or unsubstituted arylcarbonyl group or Z-R5; R3 and R4 can be linked together to form a substituted or unsubstituted heterocyclic ring; Z represents CO, CS, COB2O, CSB2O, CONB2R6, CSB2NR6, CONB2R6SO2, CSB2NR6SO2 or SO2; R5 represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted aryl group, a heterocyclic ring substituted or unsubstituted, a carboxyl group or an ester thereof or An amide thereof, a hydrocarbonyl group, a substituted or unsubstituted alkylcarbonyl group, a substituted or unsubstituted arylcarbonyl group or a substituted or unsubstituted heterocyclic carbonyl group; R5 and R6 can be linked together to form a substituted or unsubstituted heterocyclic ring; R6 represents a hydrogen atom, a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group; X and Y, which are the same or different, represent one or more groups selected from a hydrogen atom, a halogen atom, a hydroxyl group, a substituted or unsubstituted alkoxy group, a substituted aryloxy group or 40 unsubstituted, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted alkylamino group, a substituted or unsubstituted arylamino group, a mercapto group, a group substituted or unsubstituted alkylthio, a substituted or unsubstituted arylthio group, a carboxyl group or an ester thereof or an amide thereof, a cyano group and a nitro group; B1 represents an alkylene group; B2 represents a single bond or an alkylene group; p represents 0, 1 or 2; Y 50 q represents 0 or 1), or a salt thereof. 2. Compound represented by the following general formula (1): (wherein ring A represents a benzene ring, a thiophene ring or a pyridine ring; R1 represents an alkyl group, a cycloalkyl group, an aryl group or a heterocyclic ring; in the case where R1 is an alkyl group, the alkyl group may have one or more substituents selected from an aryl group, a hydroxyaryl group and an alkoxyaryl group; in the case where R 1 is an aryl group, the aryl group may have one or more substituents selected from a halogen atom, a hydroxyl group, an alkoxy group, a halogenoalkoxy group, a hydrocarbonyloxy group, an alkylcarbonyloxy group, a arylcarbonyloxy group, an alkyl group, a halogenoalkyl group and an aryl group; R2 represents a hydrogen atom, an alkyl group or an aryl group; in the case where R2 is an alkyl group, the alkyl group may have one or more substituents selected from a carboxyl group, an alkoxycarbonyl group and an aryloxycarbonyl group; R3 represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic ring or Z-R5; in the case where R3 is an alkyl group, the alkyl group may have one or more substituents selected from a hydroxyl group, an alkoxy group, an aryloxy group, an amino group, an alkylamino group and an arylamino group; in the case where R3 is a heterocyclic ring, the heterocyclic ring may have one or more cyano groups as substituents; R3 and R4 can be linked together to form a heterocyclic ring; in the case where R3 and R4 join together to form a heterocyclic ring, the heterocyclic ring may have one or more substituents selected from a hydroxyl group, an alkoxyl group, an aryloxy group, an alkyl group, a hydroxyalkyl group , an alkoxyalkyl group, an aryloxyalkyl group, an aryl group, an amino group, an alkylamino group, an arylamino group, a carboxyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, a hydrocarbonyl group, an alkylcarbonyl group, an arylcarbonyl group, a aminocarbonyl group, an alkylaminocarbonyl group and an arylaminocarbonyl group, in addition, the heterocyclic ring may have a carbonyl group in the ring; R4 represents a hydrogen atom, an alkyl group, an aryl group, a hydrocarbonyl group, an alkylcarbonyl group or an arylcarbonyl group; in the case where R4 is an alkylcarbonyl group, the alkylcarbonyl group may have one or more alkylcarbonyloxy groups as substituents; Z represents CO, CS, CO-B2-O, CS-B2-O, CO-B2-NR6, CS-B2-NR6, CO-B2-NR6SO2, CS-B2-NR6SO2 or SO2; R5 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group, a heterocyclic ring, a carboxyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, a hydrocarbonyl group, an alkylcarbonyl group , an arylcarbonyl group, a heterocyclic carbonyl group, an aminocarbonyl group, an alkylaminocarbonyl group or an arylaminocarbonyl group; in the case where R5 is an alkyl group, the alkyl group may have one or more substituents selected from a halogen atom, a hydroxyl group, an alkoxyl group, a hydroxyalkoxy group, alkoxyalkoxy group, an aryloxyalkoxy group, a group cycloalkyl, an aryl group, a heterocyclic ring, a carboxyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, a hydrocarbonyl group, an alkylcarbonyl group, an arylcarbonyl group, an amino group, an alkylamino group, an arylamino group, an alkoxycarbonylamino group, an aryloxycarbonylamino group, a hydrocarbonylamino group, an alkylcarbonylamino group, an arylcarbonylamino group, a mercapto group, an alkylthio group, an arylthio group and a cyano group; in the case where R5 is an aryl group, the aryl group may have one or more halogen atoms as substituents; in the case where R5 is a heterocyclic ring, the heterocyclic ring may have one or more substituents selected from an alkyl group and an aryl group; in the case where R5 is an alkylcarbonyl group, the alkylcarbonyl group may have one or more substituents selected from a carboxyl group, a hydrocarbonyloxy group, an alkylcarbonyloxy group, an arylcarbonyloxy group, an amino group, an alkylamino group and a group arylamino; R5 and R6 can be linked together to form a heterocyclic ring; in the case where R5 and R6 join together to form a heterocyclic ring, the heterocyclic ring may have one or more substituents selected from a hydroxyl group, an alkoxyl group, an aryloxy group, an alkyl group, a hydroxyalkyl group, an alkoxyalkyl group, an aryloxyalkyl group, a carboxyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, a carbonyl group, a hydrocarbonyl group, an alkylcarbonyl group and an arylcarbonyl group, furthermore, the heterocyclic ring may have a carbonyl group in the ring; R6 represents a hydrogen atom, an alkyl group or an aryl group; X and Y, which are the same or different, represent one or more groups selected from a hydrogen atom, a halogen atom and an alkyl group; B1 represents an alkylene group; B2 represents a single bond or an alkylene group; p represents 0, 1 or 2; Y q represents 0 or 1), or a salt thereof. 3. Compound according to claim 2, wherein in the general formula (1), Ring A represents a benzene ring, a thiophene ring or a pyridine ring; R1 represents an alkyl group, a cycloalkyl group, an aryl group or a heterocyclic ring; in the case where R1 is an alkyl group, the alkyl group may have one or more alkoxyaryl groups as substituents; in the case where R1 is an aryl group, the aryl group may have one or more substituents selected from between a halogen atom, a hydroxyl group, an alkoxy group, a halogenoalkoxy group, a group alkylcarbonyloxy, an alkyl group and a halogenoalkyl group; R2 represents a hydrogen atom or an alkyl group; in the case where R2 is an alkyl group, the alkyl group may have one or more substituents selected from a carboxyl group and an alkoxycarbonyl group; R3 represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic ring or Z-R5; in the case where R3 is an alkyl group, the alkyl group may have one or more substituents selected from a hydroxyl group and an alkylamino group; in the case where R3 is a heterocyclic ring, the heterocyclic ring can have one or several cyano groups as substituents; R3 and R4 can be linked together to form a heterocyclic ring; in the case where R3 and R4 join together to form a heterocyclic ring, the heterocyclic ring may have one or more substituents selected from a hydroxyl group, an alkyl group, a hydroxyalkyl group, an alkylamino group, an alkoxycarbonyl group , an alkylcarbonyl group and an alkylaminocarbonyl group, in addition, the heterocyclic ring may have a carbonyl group in the ring; R4 represents a hydrogen atom, an alkyl group or an alkylcarbonyl group; in the case where R4 is an alkylcarbonyl group, the alkylcarbonyl group may have one or more alkylcarbonyloxy groups as substituents; Z represents CO, CO-B2-O, CO-B2-NR6, CS-B2-NR6, CO-B2-NR6SO2 or SO2; R5 represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group, a heterocyclic ring, an alkoxycarbonyl group, an alkylcarbonyl group, a heterocyclic carbonyl group or an alkylaminocarbonyl group; in the case where R5 is an alkyl group, the alkyl group may have one or more substituents selected from a halogen atom, a hydroxyl group, an alkoxyl group, a hydroxyalkoxy group, an alkoxyalkoxy group, a cycloalkyl group, a heterocyclic ring, a carboxyl group, an alkoxycarbonyl group, an amino group, an alkylamino group, an alkoxycarbonylamino group, an alkylcarbonylamino group, an alkylthio group and a cyano group; in the case where R5 is an aryl group, the aryl group may have one or more halogen atoms as substituents; in the case where R5 is a heterocyclic ring, the heterocyclic ring may have one or more alkyl groups as substituents; in the case where R5 is an alkylcarbonyl group, the alkylcarbonyl group may have one or more substituents selected from a carboxyl group, an alkylcarbonyloxy group and an alkylamino group; R5 and R6 can be linked together to form a heterocyclic ring; in the case where R5 and R6 join together to form a heterocyclic ring, the heterocyclic ring may have one or more substituents selected from a hydroxyl group, an alkyl group, a hydroxyalkyl group, an alkoxycarbonyl group and an alkylcarbonyl group, furthermore, the heterocyclic ring may have a carbonyl group in the ring; R6 represents a hydrogen atom or an alkyl group; X and Y represent a hydrogen atom; B1 represents an alkylene group; B2 represents a single bond or an alkylene group; p represents 0 or 1; Y q represents 0, or a salt thereof. 4. Compound according to claim 2 or 3, wherein in the general formula (1), Ring A represents a benzene ring, a thiophene ring or a pyridine ring; R1 represents an aryl group or a heterocyclic ring; in the case where R1 is an aryl group, the aryl group may have one or more substituents selected from between a halogen atom, a halogenoalkoxy group, an alkyl group and a halogenoalkyl group; R2 represents a hydrogen atom; R3 represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic ring or Z-R5; in the case where R3 is an alkyl group, the alkyl group may have one or more alkylamino groups as substituents; in the case where R3 is a heterocyclic ring, the heterocyclic ring may have one or more cyano groups as substituents; R3 and R4 can be linked together to form a heterocyclic ring; in the case where R3 and R4 join together to form a heterocyclic ring, the heterocyclic ring may have one or more substituents selected from an alkyl group and an alkylcarbonyl group; R4 represents a hydrogen atom or an alkyl group; Z represents CO, CO-B2-O, CO-B2-NR6, CO-B2-NR6SO2 or SO2; R5 represents a hydrogen atom, an alkyl group, an aryl group, an alkylcarbonyl group or a group Alkylaminocarbonyl; in the case where R5 is an alkyl group, the alkyl group may have one or more substituents selected from a halogen atom, a hydroxyl group, a heterocyclic ring, an alkylamino group and an alkylcarbonylamino group; twenty in the case where R5 is an aryl group, the aryl group may have one or more halogen atoms as substituents; in the case where R5 is an alkylcarbonyl group, the alkylcarbonyl group may have one or more groups Carboxyl as substituents; R5 and R6 can be linked together to form a heterocyclic ring; in the case where R5 and R6 join together to form a heterocyclic ring, the heterocyclic ring can 30 presenting one or more hydroxyalkyl groups as substituents; R6 represents a hydrogen atom or an alkyl group; X and Y represent a hydrogen atom; B1 represents an alkylene group; B2 represents a single bond or an alkylene group; 40 p represents 0; and q represents 0, or a salt thereof. 5. A compound according to any one of claims 1 to 4, wherein in the general formula (1), ring A 45 represents a pyridine ring or a thiophene ring, or a salt thereof. 6. A compound according to claim 5, wherein in the general formula (1), ring A represents a pyridine ring, or a salt thereof. A compound according to any one of claims 1 to 6, wherein in the general formula (1), a partial structure (C): 55 and a partial structure (D): they are attached to adjacent carbon atoms in ring A, or a salt thereof.

8.

Compound according to claim 5 or 6, wherein in the general formula (1), the partial structure (C) and the partial structure (D) are attached to adjacent carbon atoms in ring A, and the positions of the atoms Carbon are an α position and a β position with respect to a heteroatom in ring A, or a salt thereof.

9.

Compound according to any of claims 2 to 8, wherein in the general formula (1), R3 represents Z-R5; Z represents CO, CO-B2-O, CO-B2-NR6 or CO-B2-NR6SO2; R5 represents a hydrogen atom, an alkyl group, an aryl group, an alkylcarbonyl group or a group

alkylaminocarbonyl; in the case where R5 is an alkyl group, the alkyl group may have one or more substituents selected from a halogen atom, a hydroxyl group, a heterocyclic ring, an alkylamino group and an alkylcarbonylamino group; in the case where R5 is an aryl group, the aryl group may have one or more halogen atoms as substituents; in the case where R5 is an alkylcarbonyl group, the alkylcarbonyl group may have one or more groups carboxyl as substituents; R5 and R6 can be linked together to form a heterocyclic ring; in the case where R5 and R6 join together to form a heterocyclic ring, the heterocyclic ring can present one or more hydroxyalkyl groups as substituents; R6 represents a hydrogen atom or an alkyl group; B2 represents a single bond or an alkylene group, or a salt thereof. 10. Compound selected from the group consisting of

•

N- (3,5-Dimethylphenyl) -2- [2- (4-methylpiperazin-1-yl) pyridin-4-ylmethylthio] pyridin-3-carboxamide,

•

2- (2-Cyclopropylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide,

•

2- [2- (N- (2-Dimethylaminoethyl) -N-methylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- (2-morpholinopyridin-4-ylmethylthio) pyridin-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- [2- (piperidin-1-yl) pyridin-4-ylmethylthio] pyridin-3-carboxamide,

•

2- [2- (4-Acetylpiperazin-1-yl) pyridin-4-ylmethylthio] -N- (3,5-dimethyl-phenyl) pyridin-3-carboxamide,

•

N- (Indan-5-yl) -2- (2-morpholinopyridin-4-ylmethylthio) pyridin-3-carboxamide,

•

2- [2- (4-Acetylpiperazin-1-yl) pyridin-4-ylmethylthio] -N- (indan-5-yl) pyridin-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- (2-n-pentylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide,

•

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,

•

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridine-3-carboxamide,

•

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (indan-5-yl) pyridin-3-carboxamide,

•

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) pyridine-3-carboxamide,

•

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) pyridin-3-carboxamide

•

2- [2- (N-tert-Butoxycarbonyl-N-methylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide,

•

2- [2- (5-Cyanothiazol-2-ylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide,

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide,

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridin-3-carboxamide,

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (indan-5-yl) pyridin-3-carboxamide,

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) pyridin-3-carboxamide,

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) pyridin-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide,

•

N- (Indan-5-yl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide,

•

2- (2-Methylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridin-3-carboxamide,

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide,

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) pyridin-3-carboxamide,

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) benzamide,

•

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) benzamide,

•

3- (2-Aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) thiophene-2-carboxamide,

•

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- (2-propionylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- (2-trifluoroacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- (2-isobutyrylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- (2-pivaloylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- (2-trifluoromethanesulfonylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,

•

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridin-3-carboxamide,

•

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (9-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

2- [2- (N-Acetyl-N-methylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide,

•

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) pyridin-3-carboxamide,

•

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethyl-4-hydroxyphenyl) pyridine-3-carboxamide,

•

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) benzamide,

•

2- (2-Acetylaminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) benzamide,

•

3- (2-Acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) thiophene-2-carboxamide,

•

3- (2-Acetylaminopyridin-9-ylmethylthio) -N- (4-chlorophenyl) thiophene-2-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- [2- (N’-n-propylureido) pyridin-4-ylmethylthio] pyridin-3-carboxamide,

•

2- [2- (N’-tert-Butylureido) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide,

•

2- [2- (N’-4-Chlorophenylureido) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- (2-formylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- (2-phenylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- [2- (N’-methylureido) pyridin-4-ylmethylthio] pyridin-3-carboxamide,

•

2- [2- (N’-Methylureido) pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide,

•

N- (9-Chlorophenyl) -2- [2- (N’-methylureido) pyridin-4-ylmethylthio] pyridin-3-carboxamide,

•

N- (4-Difluoromethoxyphenyl) -2- [2- (N’-methylureido) pyridin-4-ylmethylthio] pyridin-3-carboxamide,

•

2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide,

•

2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

2- (2-Aminoacetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide,

•

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide,

•

N- (4-Chlorophenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide,

•

N- (3,5-Dimethyl-4-hydroxyphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,

•

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (3-methylphenyl) pyridin-3-carboxamide,

•

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethyl-phenyl) pyridin-3-carboxamide,

•

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) pyridin-3-carboxamide,

•

N- (3-Chlorophenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridin-3-carboxamide,

•

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (indan-5-yl) pyridin-3-carboxamide,

•

N- (3-Chloro-4-trifluoromethoxyphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,

•

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridine-3-carboxamide,

•

N- (4-Difluoromethoxyphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,

•

2- (2-Hydroxyacetylaminopyridin-4-ylmethylthio) -N- (3-trifluoromethylphenyl) pyridin-3-carboxamide,

•

2- [2- (3-Hydroxycarbonylpropionyloxy) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- (2-methanesulfonylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,

•

2- (2-Dimethylaminocarbonyloxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

2- (2-Isopropylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

2- (2-Dimethylaminoacetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide,

•

2- (2-Dimethylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

2- (2-Morpholinoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

2- [2- (2-Morpholinoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

2- [2- (3-Hydroxypropyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (9-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

N- (4-Chlorophenyl) -2- [2- (2-dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide,

•

2- (2-Aminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide,

•

2- [2- (N- (2-Dimethylaminoethyl) -N-methylamino) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3carboxamide,

•

2- [2- (2-Hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (9-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

2- [2- (Piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide,

•

N- (4-Difluoromethoxyphenyl) -2- (2-dimethylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,

•

2- [2- (2-Acetylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

N- (4-Chlorophenyl) -2- [2- (piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] pyridin-3-carboxamide,

•

2- [2- (2-Hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3-methylphenyl) pyridin-3-carboxamide,

•

N- (4-Difluoromethoxyphenyl) -2- [2- (2-dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide,

•

N- (4-Difluoromethoxyphenyl) -2- [2- (2-hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide,

•

2- [2- (2-Acetylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-difluoromethoxyphenyl) pyridin-3-carboxamide,

•

N- (4-Difluoromethoxyphenyl) -2- [2- (N- (2-dimethylaminoethyl) -N-methylamino) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide,

•

2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethylphenyl) pyridine-3-carboxamide,

•

2- [2- (4- (2-Hydroxyethyl) piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridin-3-carboxamide,

•

N- (4-Difluoromethoxyphenyl) -2- [2- (piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide,

•

N- (4-Difluoromethoxyphenyl) -2- (2-isopropylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,

•

2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridin-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- (2-isopropylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- [2- (3-hydroxypropyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- [2- (2-morpholinoethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide,

•

2- (2-Ethylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

2- (2-Aminoacetylaminopyridin-4-ylmethylthio) -N- (4-difluoromethoxyphenyl) pyridin-3-carboxamide,

•

2- (3-Aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide,

•

2- (3-Acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridin-3-carboxamide,

•

N- (3,5-Dimethylphenyl) -2- (2-morpholinoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,

•

2- [2- (3-Dimethylaminopropyl) aminoacetylamino] pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,

•

2- (2-Dimethylaminoacetylaminopyridin-4-ylmethylthio) -N- (3-methylphenyl) pyridin-3-carboxamide,

•

2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3-methylphenyl) pyridin-3-carboxamide,

•

N- (3-Methylphenyl) -2- [2- (piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] pyridin-3-carboxamide,

•

2- [2- (Piperazin-1-yl) acetylaminopyridin-9-ylmethylthio] -N- (4-trifluoromethylphenyl) pyridin-3-carboxamide and

•

N- (4-Difluoromethoxyphenyl) -2- [2- (N- (2-hydroxyethyl) -N-methylamino) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide

or a salt thereof.

eleven.

Pharmaceutical composition comprising the compound or a salt thereof according to any of claims 1 to 10 as active ingredient.

12.

Therapeutic agent for a disease in which angiogenesis or vascular hyperpermeability is involved, which comprises the compound or a salt thereof according to any of claims 1 to 10 as active ingredient.

13.

Therapeutic agent according to claim 12, wherein the disease in which angiogenesis is involved

or the increase in vascular permeability, is cancer, rheumatoid arthritis, age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal venous occlusion, polypoid choroidal angiopathy, diabetic macular edema, vulgar psoriasis or atherosclerosis.