JP2006096739A - New cyclocompound having 4-pyridylalkylthio group to which sustituted or unsubstituted amino group is introduced - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new cyclocompound having a 4-pyridylalkylthio group with substituted or unsubstituted amino group is introduced or its salt which is useful as a remedy. <P>SOLUTION: The compound or its salt of formula [I] is useful as a therapeutic agent for diseases in which angiogenesis takes part. In the formula, ring A shows a benzene ring, or a heteroaromatic five- or six-membered ring optionally condensable with a cycloalkane ring; B shows an alkylene group; R<SP>1</SP>and R<SP>2</SP>show each H, a (substituted) aryl group, or a (sustituted) heterocyclic group; R<SP>3</SP>and R<SP>4</SP>show each H, a (substituted) alkyl group, a (substituted) cycloalkyl group, -Z-R<SP>5</SP>, or the like; R<SP>5</SP>shows a (substituted) alkyl group, a (substituted) aryl group, a (substituted) heterocyclic group, or the like; X and Y each show H, or the like; Z shows -CO-, -COO-, a -CONR<SP>6</SP>-, -SO<SB>2</SB>-, or the like; R<SP>6</SP>shows H, or the like; p shows 0, 1 or 2; and q shows 0 or 1. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a novel cyclic compound having a 4-pyridylalkylthio group having a substituted or unsubstituted amino group, which is useful as a pharmaceutical, or a salt thereof. These compounds are therapeutic agents for diseases involving angiogenesis and increased vascular permeability, especially cancer, rheumatoid arthritis, age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, polypoidal choroidal vessels It is useful as a therapeutic agent for diabetes, macular edema, psoriasis vulgaris, atherosclerosis, etc.

  Angiogenesis is a phenomenon in which a new blood vessel network is formed from existing blood vessels, and is mainly observed in small blood vessels. Angiogenesis is inherently a physiological phenomenon and is essential for embryonic angiogenesis, but in adults it is usually only at limited times, such as in the endometrium, follicles, and in the wound healing process. Not observed. However, in diseases such as cancer, rheumatoid arthritis, age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, polypoidal choroidal vasculopathy, diabetic macular edema, psoriasis vulgaris, atherosclerosis Angiogenesis is observed and is closely related to the pathological progression of these diseases. Angiogenesis and enhancement of vascular permeability are regulated by the balance of the promoter and inhibitory factor, and it is considered that angiogenesis and enhancement of vascular permeability are promoted by disrupting the balance (Non-Patent Documents). 1, refer to Non-Patent Document 2).

  Vascular endothelial cell growth factor (hereinafter referred to as “VEGF”) specifically acts on receptors (Flt-1, KDR / Flk-1, etc.) present on the surface of vascular endothelial cells to proliferate vascular endothelial cells. It is a factor that promotes the construction of capillary networks by migration and tube formation, and plays a very important role in the development of angiogenesis and the enhancement of vascular permeability. Therefore, many attempts have been reported to treat diseases associated with angiogenesis and increased vascular permeability by inhibiting the VEGF and controlling the occurrence of angiogenesis and increased vascular permeability. Examples of drugs used for such treatment include indoline-2-one derivatives (see Patent Document 1), phthalazine derivatives (see Patent Document 2), quinazoline derivatives (see Patent Document 3), anthranilic acid amide derivatives (Patent Document 4). And 2-aminonicotinic acid derivatives (see Patent Document 5).

  However, these patent documents do not describe a cyclic compound having a 4-pyridylalkylthio group, and further describe a compound in which a substituted or unsubstituted amino group is introduced into the pyridine ring of the 4-pyridylalkylthio group. Is not done at all.

On the other hand, compounds having a chemical structure relatively close to a cyclic compound having a 4-pyridylalkylthio group into which a substituted or unsubstituted amino group is introduced have been reported in Non-Patent Document 3 and Patent Document 6. The compound disclosed in Non-Patent Document 3 relates to a benzoamide derivative having a 3-pyridylalkylthio group, and an antibacterial action is mentioned as its use. Patent Document 6 relates to a substituted alkylamine derivative and its pharmaceutical use, and discloses a compound having an enormous combination of chemical structures. For example, a derivative having a 4-pyridylalkylamino group is disclosed. However, there is no description regarding a cyclic compound having a 4-pyridylalkylthio group into which a substituted or unsubstituted amino group is introduced.
Molecular Medicine vol. 35 Special Issue “Molecular Mechanisms of Symptoms and Diseases”, Nakayama Shoten, 73-74 (1998) Protein Nucleic acid Enzyme Extra number “Cutting-edge drug discovery”, Kyoritsu Shuppan, 1182-1187 (2000) II Farmaco-Ed. Sc. , 18, 288 (1963) International Publication WO98 / 50356 Pamphlet International Publication WO98 / 35958 Pamphlet International Publication WO97 / 30035 pamphlet International Publication WO00 / 27819 Pamphlet International Publication WO01 / 55114 Pamphlet International Publication WO02 / 066470 Pamphlet

  Synthetic studies of novel cyclic compounds having a 4-pyridylalkylthio group having a substituted or unsubstituted amino group introduced therein and finding out the pharmacological action of these compounds are very interesting subjects.

  The inventors of the present invention have conducted a synthetic study of a novel cyclic compound having a 4-pyridylalkylthio group into which a substituted or unsubstituted amino group has been introduced, and have succeeded in creating many new compounds.

  Furthermore, when various pharmacological actions of these compounds have been studied, these compounds have cell growth inhibitory action, tumor growth inhibitory action, foot edema inhibitory action and / or choroidal neovascularization inhibitory effect, and angiogenesis and / or blood vessel Remedies for diseases involving increased permeability, especially cancer, rheumatoid arthritis, age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, polypoidal choroidal vasculopathy, diabetic macular edema, vulgaris It was found useful as a therapeutic agent for psoriasis, atherosclerosis and the like, and the present invention was completed.

  The present invention provides a novel cyclic compound or a salt thereof having a 4-pyridylalkylthio group having a substituted or unsubstituted amino group, which is useful as a pharmaceutical. The novel cyclic compound according to the present invention has an excellent cell growth inhibitory effect, tumor growth inhibitory effect, foot edema inhibitory effect and / or choroidal neovascularization inhibitory effect, and involves angiogenesis and / or increased vascular permeability. Diseases such as cancer, rheumatoid arthritis, age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, polypoidal choroidal vasculopathy, diabetic macular edema, psoriasis vulgaris, atherosclerosis, etc. It is useful as a therapeutic agent.

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 otherwise specified) and a pharmaceutical composition containing the compound of the present invention. The compound of the present invention has a chemical structural feature in that a substituted or unsubstituted amino group is introduced into the pyridine ring portion of the 4-pyridylalkylthio group.
Further, the pharmaceutical use of the compound of the present invention will be described in more detail. It relates to a therapeutic agent for diseases involving angiogenesis and / or increased vascular permeability comprising the compound of the present invention as an active ingredient, such as cancer, rheumatoid arthritis. Further, the present invention relates to therapeutic agents for age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, polypoidal choroidal vasculopathy, diabetic macular edema, psoriasis vulgaris, atherosclerosis and the like.

[In the formula, ring A represents a benzene ring or an aromatic hetero 5-membered ring or an aromatic hetero 6-membered ring optionally condensed with a cycloalkane ring;
R ¹ and R ² are the same or different and each represents a hydrogen atom, a hydroxy group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, substituted or unsubstituted A substituted 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 together may form a substituted or unsubstituted heterocycle;
R ³ and R ⁴ are the same or different and each represents 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, substituted or unsubstituted Represents a substituted alkylcarbonyl group, a substituted or unsubstituted arylcarbonyl group or Z—R ⁵ ;
R ³ and R ⁴ together may form a substituted or unsubstituted heterocycle;
Z represents CO, CS, COB ² O, CSB ² O, CONB ² R ⁶ , CSB ² NR ⁶ , CONB ² R ⁶ SO ₂ , CSB ² NR ⁶ SO ₂ or SO ₂ ;
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 substituted or unsubstituted heterocycle, carboxy A 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 together may form a substituted or unsubstituted heterocycle;
R ⁶ represents a hydrogen atom, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted aryl group;
X and Y are the same or different and each represents a hydrogen atom, halogen atom, hydroxy group, substituted or unsubstituted alkoxy group, substituted or unsubstituted aryloxy group, substituted or unsubstituted alkyl group, substituted or unsubstituted cycloalkyl group, substituted or Unsubstituted aryl group, substituted or unsubstituted alkylamino group, substituted or unsubstituted arylamino group, mercapto group, substituted or unsubstituted alkylthio group, substituted or unsubstituted arylthio group, carboxy group or ester or amide thereof, cyano group, And one or more groups selected from nitro groups;
B ¹ represents an alkylene group;
B ² represents a single bond or an alkylene group;
p represents 0, 1 or 2;
q represents 0 or 1; same as below. ]

  Each atom, ring or group as defined above shall have the following meaning throughout the specification.

  The “cycloalkane ring” refers to a cycloalkane ring having 3 to 8 carbon atoms. Specific examples include a cyclopropane ring, a cyclobutane ring, a cyclopentane ring, a cyclohexane ring, a cycloheptane ring, and a cyclooctane ring.

  “Aromatic hetero five-membered ring” refers to a monocyclic aromatic hetero five-membered ring having one or more hetero atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom in the ring. As specific examples, a pyrrole ring, pyrazole ring, imidazole ring or [1,2,3] triazole ring having a nitrogen atom in the ring, a furan ring having an oxygen atom in the ring, and a thiophene having a sulfur atom in the ring The ring is an oxazole ring or isoxazole ring having a nitrogen atom and an oxygen atom in the ring, and a thiazole ring or an isothiazole ring having a nitrogen atom and a sulfur atom in the ring, preferably a pyrazole ring, a furan ring or a thiophene. The ring is particularly preferably a thiophene ring.

  “Aromatic hetero five-membered ring condensed with cycloalkane ring” refers to a two-membered ring in which a cycloalkane ring and an aromatic hetero five-membered ring are condensed.

  “Aromatic hetero 6-membered ring” refers to a monocyclic aromatic hetero 6-membered ring having one or more nitrogen atoms in the ring. Specific examples include a pyridine ring, pyridazine ring, pyrimidine ring, pyrazine ring, [1,2,3] triazine ring, [1,2,4] triazine ring or [1,2,3,4] tetrazine ring. A pyridine ring or a pyrazine ring is preferable, and a pyridine ring is particularly preferable.

  “Aromatic hetero 6-membered ring condensed with cycloalkane ring” refers to a 2-membered ring in which a cycloalkane ring and an aromatic hetero 6-membered ring are condensed.

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

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

  “Alkyl” refers to straight-chain or branched alkyl having 1 to 6 carbon atoms. Specific examples 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, saturated polycyclic hydrocarbons formed by condensation of 2 or 3 cycloalkane rings are also included in the “cycloalkyl” of the present invention. Specific examples of cycloalkyl include adamantyl and the like as specific examples of saturated polycyclic hydrocarbons such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like.

  “Aryl” refers to a monocyclic aromatic hydrocarbon or a bicyclic or tricyclic condensed polycyclic aromatic hydrocarbon having 6 to 14 carbon atoms. Further, condensed polycyclic hydrocarbons formed by the condensation of these with a cycloalkane ring are also included in the “aryl” of the present invention. Specific examples of monocyclic aromatic hydrocarbons include phenyl, specific examples of condensed polycyclic aromatic hydrocarbons, naphthyl, anthryl, phenanthryl, and the like. Specific examples of condensed polycyclic hydrocarbons include indanyl, tetrahydro Examples include naphthyl and tetrahydroanthranyl.

  “Aryloxy” means a monocyclic aromatic hydrocarbon oxy having 6 to 14 carbon atoms, a condensed polycyclic aromatic hydrocarbon oxy, or a condensed polycyclic carbon formed by the condensation of a cycloalkane ring with them. Indicates hydrogen oxy. Specific examples of the monocyclic aromatic hydrocarbon oxy include phenoxy, and specific examples of the condensed polycyclic aromatic hydrocarbon include naphthyloxy, anthryloxy, phenanthryloxy and the like of the condensed polycyclic hydrocarbon. Specific examples include indanyloxy, tetrahydronaphthyloxy, tetrahydroanthranyloxy and the like.

  “Heterocycle” means a saturated or unsaturated monocyclic heterocycle having one or more heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom in the ring, or a bicyclic or tricyclic condensed polycycle. A cyclic heterocycle is shown.

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

  In addition, these saturated monocyclic heterocycles are condensed with a benzene ring or the like to form dihydroindole, dihydroindazole, dihydrobenzimidazole, tetrahydroquinoline, tetrahydroisoquinoline, tetrahydrocinnoline, tetrahydrophthalazine, tetrahydroquinazoline, tetrahydroquinoxaline, dihydroquinone. Benzofuran, dihydroisobenzofuran, chroman, isochroman, dihydrobenzothiophene, dihydroisobenzothiophene, thiochroman, isothiochroman, dihydrobenzoxazole, dihydrobenzoisoxazole, dihydrobenzoxazine, dihydrobenzothiazole, dihydrobenzoisothiazole, dihydrobenzothia Forms condensed polycyclic heterocycles such as gin, xanthene, 4a-carbazole, and perimidine It may be.

Specific examples of the unsaturated monocyclic heterocycle include dihydropyrrole, pyrrole, dihydropyrazole, pyrazole, dihydroimidazole, imidazole, dihydrotriazole, triazole, tetrahydropyridine, dihydropyridine, pyridine, tetrahydropyridazine having a nitrogen atom in the ring, Dihydropyridazine, pyridazine, tetrahydropyrimidine, dihydropyrimidine, pyrimidine, tetrahydropyrazine, dihydropyrazine, pyrazine, etc. are dihydrofurans, furans, dihydropyrans, pyrans, etc. having an oxygen atom in the ring. Thiophene, thiophene, dihydrothiopyran, thiopyran, etc. are dihydrooxazole, oxazole, dihydroisoxazole, Oxazole, dihydro-oxazine, oxazine, and the like, dihydrothiazole having a nitrogen atom and a sulfur atom in the ring, thiazole, dihydro-isothiazole, isothiazole, dihydrothiazine, thiazine and the like.
In addition, these unsaturated monocyclic heterocycles are condensed with a benzene ring or the like to form indole, indazole, benzimidazole, benzotriazole, dihydroquinoline, quinoline, dihydroisoquinoline, isoquinoline, phenanthridine, dihydrocinnoline, cinnoline, Dihydrophthalazine, phthalazine, dihydroquinazoline, quinazoline, dihydroquinoxaline, quinoxaline, benzofuran, isobenzofuran, chromene, isochromene, benzothiophene, isobenzothiophene, thiochromene, isothiochromene, benzoxazole, benzoisoxazole, benzoxazine, benzothiazole, benzo Isothiazole, benzothiazine, phenoxanthine, carbazole, β-carboline, phenanthridine, acridine, phen Ntororin, phenazine, phenothiazine, may form a fused polycyclic heterocyclic ring such as 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.

  “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, dianthrylamino and the like.

  “Acyl” refers to hydrocarbonyl, alkylcarbonyl, cycloalkylcarbonyl, arylcarbonyl or heterocyclic carbonyl. Specific examples of hydrocarbonyl include formyl, specific examples of alkylcarbonyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, monochloroacetyl, trifluoroacetyl, and the like. Specific examples of cycloalkylcarbonyl include cyclopentane. Specific examples of carbonyl, cyclohexanecarbonyl, etc., arylcarbonyl include benzoyl, naphthoyl, toluoyl and the like, and specific examples of heterocyclic carbonyl include furoyl, thenoyl, picolinoyl, nicotinoyl, isonicotinoyl and the like.

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

  “Alkynyl” refers to straight-chain or branched alkynyl having 2 to 8 carbon atoms. Specific examples include ethynyl, 2-propynyl, 2-butynyl, 3-pentynyl, 4-hexynyl, 5-heptynyl, 7-octynyl, 2-methylbutynyl and the like.

“Halogen” refers to fluorine, chlorine, bromine or iodine.
“Ester of carboxy group” refers to an ester with an alkyl alcohol, aryl alcohol or the like. Specific examples of the alkyl alcohol include methanol, ethanol, propanol, butanol, benzyl alcohol, phenethyl alcohol and the like. Specific examples of the aryl alcohol include phenol, naphthol, anthrol, cresol, xylenol and the like.

  “Carboxyamide” refers to an amide with an alkylamine, cycloalkylamine, arylamine, heterocyclic amine or the like. Specific examples of alkylamines include methylamine, ethylamine, ethylmethylamine, dimethylamine, diethylamine, and benzylamine. Specific examples of cycloalkylamine include cyclopentylamine, cyclohexylamine, cyclohexylmethylamine, and the like. Examples include aniline, naphthylamine, diphenylamine, ethylphenylamine, anisidine, toluidine and the like, and specific examples of the heterocyclic amine include benzofuranamine, quinolylamine and the like.

  “Alkylcarbonyl” refers to a straight or branched alkylcarbonyl having 2 to 7 carbon atoms. Specific examples include methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, n-butylcarbonyl, n-pentylcarbonyl, n-hexylcarbonyl, isopropylcarbonyl, isobutylcarbonyl, sec-butylcarbonyl, tert-butylcarbonyl, isopentylcarbonyl and the like. Can be mentioned.

  “Arylcarbonyl” means a monocyclic aromatic hydrocarbon carbonyl having 7 to 15 carbon atoms or a condensed polycyclic aromatic hydrocarbon carbonyl, or a condensed polycyclic ring formed by condensing them with a cycloalkane ring. Indicates hydrocarbon carbonyl. Specific examples of monocyclic aromatic hydrocarbon oxy include phenylcarbonyl, and specific examples of condensed polycyclic aromatic hydrocarbon include naphthylcarbonyl, anthrylcarbonyl, phenanthrylcarbonyl, and the like, condensed polycyclic hydrocarbon. Specific examples of these include indanylcarbonyl, tetrahydronaphthylcarbonyl, tetrahydroanthranylcarbonyl and the like.

  “Heterocyclic carbonyl” means a saturated or unsaturated monocyclic heterocyclic carbonyl having two or more heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom in the ring, or bicyclic or tricyclic Of the fused polycyclic heterocyclic carbonyl.

  “Alkylsulfonyl” refers to a straight or branched alkylsulfonyl having 1 to 6 carbon atoms. Specific examples include methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, n-butylsulfonyl, n-pentylsulfonyl, n-hexylsulfonyl, isopropylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, isopentylsulfonyl and the like. Can be mentioned.

  “Arylsulfonyl” means a monocyclic aromatic hydrocarbon sulfonyl having 6 to 14 carbon atoms or a condensed polycyclic aromatic hydrocarbon sulfonyl, or a condensed polycyclic ring formed by condensing them with a cycloalkane ring. Indicates hydrocarbon sulfonyl. Specific examples of monocyclic aromatic hydrocarbon oxy include phenylsulfonyl, and specific examples of condensed polycyclic aromatic hydrocarbon include naphthylsulfonyl, anthrylsulfonyl, phenanthrylsulfonyl, etc., condensed polycyclic hydrocarbon. Specific examples of these include indanylsulfonyl, tetrahydronaphthylsulfonyl, tetrahydroanthranylsulfonyl and the like.

  “Alkylthio” refers to a linear or branched alkylthio having 1 to 6 carbon atoms. Specific examples include methylthio, ethylthio, n-propylthio, n-butylthio, n-pentylthio, n-hexylthio, isopropylthio, isobutylthio, sec-butylthio, tert-butylthio, isopentylthio and the like.

“Arylthio” refers to monocyclic aromatic hydrocarbon thio or bicyclic or tricyclic fused polycyclic aromatic hydrocarbon thio having 6 to 14 carbon atoms. In addition, bicyclic to tetracyclic fused polycyclic hydrocarbon thios formed by condensation of them with a cycloalkane ring are shown. Specific examples of monocyclic aromatic hydrocarbon thios include phenylthio as specific examples of condensed polycyclic aromatic hydrocarbon thios, naphthylthio, anthrylthio, and phenanthrylthio as specific examples of condensed polycyclic hydrocarbon thios. , Indanthio, tetrahydronaphthylthio, tetrahydroanthrylthio and the like.

  “Halogenoalkoxy” is the same or different and represents an alkoxy group having one or more halogen atoms as substituents.

  “Hydroxyalkoxy” refers to an alkoxy group having one or more hydroxy groups as substituents.

  “Alkoxyalkoxy” is the same or different and represents an alkoxy group having one or more alkoxy groups as a substituent.

  “Aryloxyalkoxy” is the same or different and represents an alkoxy group having one or more aryl groups as a substituent.

  “Halogenoalkyl” is the same or different and represents an alkyl group having one or more halogen atoms as substituents.

  “Hydroxyalkyl” refers to an alkyl group having one or more hydroxy groups as substituents.

  “Alkoxyalkyl” is the same or different and represents an alkyl group having one or more alkoxy groups as a substituent.

  “Aryloxyalkyl” is the same or different and represents an alkyl group having one or more aryl groups as a substituent.

  “Hydroxyaryl” refers to an aryl group having one or more hydroxy groups as substituents.

  “Alkoxyaryl” is the same or different and represents an aryl group having one or more alkoxy groups as a substituent.

  The “substituted alkoxy group” is a halogen atom, a hydroxy group, an alkoxy group, an alkoxy group substituted with an aryl group, an aryloxy group, a cycloalkyl group, an aryl group, an aryl group substituted with an alkoxy group, a heterocyclic group, Alkoxy having one or more groups selected from an amino group, alkylamino group, arylamino group, mercapto group, alkylthio group, arylthio group, carboxy group or ester or amide thereof, cyano group, and nitro group as a substituent Indicates a group.

"Substituted aryloxy group" is a halogen atom, hydroxy group, alkoxy group, aryloxy group, alkyl group, cycloalkyl group, aryl group, heterocyclic group, amino group, alkylamino group, arylamino group, mercapto group, An aryloxy group having one or more groups selected from an alkylthio group, an arylthio group, a carboxy group or an ester or amide thereof, a formyl group, an alkylcarbonyl group, an arylcarbonyl group, a cyano group, and a nitro group as a substituent; Show.

  “Substituted alkyl group” means a halogen atom, a hydroxy 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 One or more groups selected from arylamino group, mercapto group, alkylthio group, arylthio group, carboxy group or ester or amide thereof, formyl group, alkylcarbonyl group, arylcarbonyl group, cyano group, and nitro group The alkyl group which has as a substituent is shown.

The “substituted cycloalkyl group” is a halogen atom, a hydroxy 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, A cycloalkyl group having one or more groups selected from an alkylthio group, an arylthio group, a carboxy group or an ester or amide thereof, a formyl group, an alkylcarbonyl group, an arylcarbonyl group, a cyano group, and a nitro group as a substituent. Show.

  “Substituted aryl group” means a halogen atom, a hydroxy 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 complex From a ring group, amino group, alkylamino group, arylamino group, mercapto group, alkylthio group, arylthio group, carboxy group or ester or amide thereof, formyl group, alkylcarbonyl group, arylcarbonyl group, cyano group, and nitro group An aryl group having one or more selected groups as a substituent, or an aryl group having one or more carbonyl groups or thiocarbonyl groups in the ring is shown.

  “Substituted heterocycle” means a halogen atom, a hydroxy 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 complex From a ring group, amino group, alkylamino group, arylamino group, mercapto group, alkylthio group, arylthio group, carboxy group or ester or amide thereof, formyl group, alkylcarbonyl group, arylcarbonyl group, cyano group, and nitro group A heterocycle having one or more selected groups as a substituent, or a heterocycle having one or more carbonyl groups or thiocarbonyl groups in the ring.

  "Substituted alkylamino group" means that the alkyl moiety is a halogen atom, hydroxy group, alkoxy group, aryloxy group, cycloalkyl group, aryl group, heterocyclic group, amino group, alkylamino group, arylamino group, mercapto Amino group having one or more groups selected from a group, alkylthio group, arylthio group, carboxy group or ester or amide thereof, formyl group, alkylcarbonyl group, arylcarbonyl group, cyano group, and nitro group as a substituent Indicates.

  "Substituted arylamino group" means that the aryl moiety is a halogen atom, hydroxy group, alkoxy group, aryloxy group, alkyl group, cycloalkyl group, aryl group, heterocyclic group, amino group, alkylamino group, arylamino 1 or more groups selected from a group, mercapto group, alkylthio group, arylthio group, carboxy group or ester or amide thereof, formyl group, alkylcarbonyl group, arylcarbonyl group, cyano group, and nitro group Or an arylamino group having one or more carbonyl groups or thiocarbonyl groups in the ring.

  “Substituted acyl group” means halogen atom, hydroxy group, alkoxy group, aryloxy group, cycloalkyl group, aryl group, heterocyclic group, amino group, alkylamino group, arylamino group, mercapto group, alkylthio group, arylthio group An acyl group having one or more groups selected from a group, a carboxy 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 as a substituent.

  “Substituted alkenyl group” means a halogen atom, a hydroxy 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 carboxy group, or an ester thereof. An alkenyl group having one or more groups selected from amide, formyl group, alkylcarbonyl group, arylcarbonyl group, cyano group, and nitro group as a substituent.

  “Substituted alkynyl group” means a halogen atom, hydroxy group, alkoxy group, aryloxy group, cycloalkyl group, aryl group, heterocyclic group, amino group, alkylamino group, arylamino group, carboxy group, ester thereof or the like An alkynyl group having one or more groups selected from amide, formyl group, alkylcarbonyl group, arylcarbonyl group, cyano group, and nitro group as a substituent.

  “Substituted alkylcarbonyl group” means halogen atom, hydroxy group, alkoxy group, aryloxy group, cycloalkyl group, alkenyl group, aryl group, aryl group substituted by halogen atom, heterocyclic group, amino group, alkylamino One or more groups selected from a group, an arylamino group, a mercapto group, an alkylthio group, an arylthio group, a carboxy group or an ester or amide thereof, a formyl group, an alkylcarbonyl group, an arylcarbonyl group, a cyano group, and a nitro group Represents an alkylcarbonyl group having as a substituent.

  The “substituted arylcarbonyl group” is a halogen atom, a hydroxy 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, Heterocyclic group, amino group, alkylamino group, arylamino group, mercapto group, alkylthio group, arylthio group, carboxy group or ester or amide thereof, formyl group, alkylcarbonyl group, arylcarbonyl group, cyano group, and nitro group An arylcarbonyl group having one or more groups selected from the above as a substituent, or an arylcarbonyl group having one or more carbonyl groups or thiocarbonyl groups in the ring

  “Substituted heterocyclic carbonyl group” means a halogen atom, a hydroxy 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 , Heterocyclic group, amino group, alkylamino group, arylamino group, mercapto group, alkylthio group, arylthio group, carboxy group or ester or amide thereof, formyl group, alkylcarbonyl group, arylcarbonyl group, cyano group, and nitro A heterocyclic carbonyl group having one or more groups selected from the group as a substituent, or a heterocyclic carbonyl group having one or more carbonyl groups or thiocarbonyl groups in the ring;

  The “substituted alkylthio group” is a halogen atom, a hydroxy group, an alkoxy group, an alkoxy group substituted with an aryl group, an aryloxy group, a cycloalkyl group, an aryl group, an aryl group substituted with an alkoxy group, a heterocyclic group, One or more groups selected from an amino group, alkylamino group, arylamino group, carboxy group or ester or amide thereof, formyl group, alkylcarbonyl group, arylcarbonyl group, cyano group, and nitro group as substituents The alkylthio group which has.

  “Substituted arylthio group” means a halogen atom, hydroxy group, alkoxy group, aryloxy group, alkyl group, cycloalkyl group, aryl group, heterocyclic group, amino group, alkylamino group, arylamino group, carboxy group or its An arylthio group having one or more groups selected from an ester or its amide, formyl group, alkylcarbonyl group, arylcarbonyl group, cyano group, and nitro group as a substituent, or one or more carbonyl groups in the ring An arylthio group having a group or a thiocarbonyl group

  When the compound of the present invention has a free hydroxy group, a free amino group, a free alkylamino group, a free arylamino group or a free mercapto group as a substituent, these substituents may be protected with a protecting group. Good. In addition, when the heterocyclic group has a free nitrogen atom, the nitrogen atom may be protected with a protecting group.

  The “protecting group for a free hydroxy group” is a substituted or unsubstituted alkyl group such as a methyl group, a methoxymethyl group, a benzyl group, a 4-methoxyphenylmethyl group, an allyl group or an unsubstituted alkenyl group; Substituted, unsubstituted heterocyclic group such as thiol group, tetrahydropyranyl group, tetrahydrofuranyl group; substituted or unsubstituted alkylcarbonyl group such as acetyl group, trifluoroacetyl group, benzoyl group, 4-chlorobenzoyl group, substituted or unsubstituted Substituted arylcarbonyl group; methoxycarbonyl group, ethoxycarbonyl group, isobutoxycarbonyl group, tert-butoxycarbonyl group, benzyloxycarbonyl group, p-methoxybenzyloxycarbonyl group, 9-fluorenylmethoxycarbonyl group, vinyloxycarbo A substituted or unsubstituted alkyloxycarbonyl group, an unsubstituted alkenyloxycarbonyl group, or a substituted or unsubstituted aryloxycarbonyl group such as an alkyl group, an allyloxycarbonyl group, a phenyloxycarbonyl group, a p-nitrophenyloxycarbonyl group; a trimethylsilyl group; Examples of those commonly used as protective groups such as substituted silyl groups such as triethylsilyl group, triisopropylsilyl group, tert-butyldimethylsilyl group, and tert-butyldiphenylsilyl group;

  “A free amino group, a free alkylamino group, a free arylamino group or a heterocyclic group having a nitrogen atom in the ring” means an unsubstituted alkenyl group such as an allyl group. A hydrocarbonyl group such as formyl group; a substituted or unsubstituted alkylcarbonyl group such as acetyl group, trichloroacetyl group, trifluoroacetyl group, benzoyl group, 4-chlorobenzoyl group, picolinoyl group, substituted or unsubstituted arylcarbonyl group; Unsubstituted heterocyclic carbonyl group; methoxycarbonyl group, isobutoxycarbonyl group, tert-butoxycarbonyl group, 2,2,2-trichloroethoxycarbonyl group, benzyloxycarbonyl group, diphenylmethoxycarbonyl group, phenoxycarbonyl group, m-nitro Phenoxy Carboni Substituted or unsubstituted alkyloxycarbonyl or substituted or unsubstituted aryloxycarbonyl group such as a group; methylsulfonyl group, benzylsulfonyl group, phenylsulfonyl group, 4-chlorophenylsulfonyl group, tolylsulfonyl group, 2,4,6-trimethylphenyl A commonly used protecting group such as a substituted or unsubstituted alkylsulfonyl group or a substituted or unsubstituted arylsulfonyl group such as a sulfonyl group;

  The “protecting group for a free mercapto group” is a substituted or unsubstituted alkyl group such as a methyl group, a methoxymethyl group, a benzyl group, a 4-methoxyphenylmethyl group, an allyl group, or an unsubstituted alkenyl group; 3-bromotetrahydropyrani Substituted, unsubstituted heterocyclic group such as thiol group, tetrahydropyranyl group, tetrahydrofuranyl group; substituted or unsubstituted alkylcarbonyl group such as acetyl group, trifluoroacetyl group, benzoyl group, 4-chlorobenzoyl group, substituted or unsubstituted Substituted arylcarbonyl group; methoxycarbonyl group, ethoxycarbonyl group, isobutoxycarbonyl group, tert-butoxycarbonyl group, benzyloxycarbonyl group, p-methoxybenzyloxycarbonyl group, 9-fluorenylmethoxycarbonyl group, vinyloxycarbo Protection of substituted or unsubstituted alkyloxycarbonyl groups, unsubstituted alkenyloxycarbonyl groups, substituted or unsubstituted aryloxycarbonyl groups, such as thiol groups, allyloxycarbonyl groups, phenyloxycarbonyl groups, p-nitrophenyloxycarbonyl groups, etc. It shows what is widely used as a group.

  In the “multiple groups” in the present invention, each group may be the same or different.

  Further, the “group” in the present invention includes each atom and each ring.

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

  When geometrical isomers or optical isomers exist in the compound of the present invention, these isomers are also included in the scope of the present invention.

  The compound of the present invention may take the form of a hydrate or a solvate.

  Furthermore, when proton tautomerism exists in this invention compound, those tautomers are also included in the scope of the present invention.

(A) Preferred examples of the compound of the present invention include compounds that satisfy the following rules or salts thereof.

In general formula (1),
(A1) ring A represents a benzene ring, thiophene ring or pyridine ring; and / or (a2) R ¹ represents an alkyl group, cycloalkyl group, aryl group or heterocyclic ring; and / or (a3) R ¹ represents In the case of an alkyl group, the alkyl group may have one or more substituents selected from an aryl group, a hydroxyaryl group and an alkoxyaryl group; and / or (a4) when R ¹ is an aryl group, The aryl group is one or more substituents selected from a halogen atom, hydroxy group, alkoxy group, halogenoalkoxy group, hydrocarbonyloxy group, alkylcarbonyloxy group, arylcarbonyloxy group, alkyl group, halogenoalkyl group and aryl group And / or (a5) R ² represents a hydrogen atom, an alkyl group or an aryl group; And / or (a6) when R ² is an alkyl group, the alkyl group may have one or more substituents selected from a carboxy group, an alkoxycarbonyl group, and an aryloxycarbonyl group; and / or ( a7) R ³ represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic ring or Z—R ⁵ ; and / or (a8) when R ³ is an alkyl group, the alkyl group is a hydroxy group, an alkoxy group One or more substituents selected from a group, an aryloxy group, an amino group, an alkylamino group and an arylamino group; and / or (a9) when R ³ is a heterocycle, the heterocycle May have one or more cyano groups as substituents; and / or (a10) R ³ and R ⁴ may together form a heterocycle; and / or (a11) R ³ and ^{R 4} When combined to form a heterocyclic ring, the heterocyclic ring is a hydroxy group, an alkoxy 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. , Arylamino group, carboxy group, alkoxycarbonyl group, aryloxycarbonyl group, hydrocarbonyl group, alkylcarbonyl group, arylcarbonyl group, aminocarbonyl group, alkylaminocarbonyl group and arylaminocarbonyl group The heterocyclic ring may have a substituent, and the heterocyclic ring may have a carbonyl group in the ring; and / or (a12) R ⁴ is a hydrogen atom, an alkyl group, an aryl group, a hydrocarbonyl group, an alkyl Represents a carbonyl group or an arylcarbonyl group And / or (a13) if ^{R 4} is an alkylcarbonyl group, the alkylcarbonyl group may have one or more alkyl carbonyloxy group as a substituent; and / or (a14) Z is CO, CS, ^{CO-B 2 -O, CS-} B 2 -O, CO-B 2 -NR 6, CS-B 2 -NR 6, CO-B 2 -NR 6 SO 2, CS-B 2 -NR 6 SO 2 or shows the SO _2; and / or (a15) R ⁵ represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group, a heterocyclic, a carboxy group, an alkoxycarbonyl group, an aryloxycarbonyl group, hydrocarbonyl Group, alkylcarbonyl group, arylcarbonyl group, heterocyclic carbonyl group, aminocarbonyl group, alkylaminocarbonyl group or arylamino And / or (a16) when R ⁵ is an alkyl group, the alkyl group is a halogen atom, hydroxy group, alkoxy group, hydroxyalkoxy group, alkoxyalkoxy group, aryloxyalkoxy group, cycloalkyl group, aryl Group, heterocyclic ring, carboxy group, alkoxycarbonyl group, aryloxycarbonyl group, hydrocarbonyl group, alkylcarbonyl group, arylcarbonyl group, amino group, alkylamino group, arylamino group, alkoxycarbonylamino group, aryloxycarbonylamino group May have one or more substituents selected from a hydrocarbonylamino group, an alkylcarbonylamino group, an arylcarbonylamino group, a mercapto group, an alkylthio group, an arylthio group and a cyano group; and / Or (a17) when R ⁵ is an aryl group, the aryl group may have one or more halogen atoms as substituents; and / or (a18) when R ⁵ is a heterocycle, the heterocycle is ^May have one or more substituents selected from an alkyl group and an aryl group; and / or (a19) when R ⁵ is an alkylcarbonyl group, the alkylcarbonyl group may be a carboxy group, a hydrocarbonyloxy group, ^May have one or more substituents selected from an alkylcarbonyloxy group, an arylcarbonyloxy group, an amino group, an alkylamino group or an arylamino group; and / or (a20) R ⁵ and R ⁶ together And / or (a21) when R ⁵ and R ⁶ together form a heterocycle, the heterocycle is a hydroxy group, alkoxy Group, aryloxy group, alkyl group, hydroxyalkyl group, alkoxyalkyl group, aryloxyalkyl group, carboxy group, alkoxycarbonyl group, aryloxycarbonyl group, carbonyl group, hydrocarbonyl group, alkylcarbonyl group and arylcarbonyl group And / or the heterocyclic ring may have a carbonyl group in the ring; and / or (a22) R ⁶ is a hydrogen atom, an alkyl group or an aryl group And / or (a23) X and Y are the same or different and each represents one or more groups selected from a hydrogen atom, a halogen atom and an alkyl group; and / or (a24) B ¹ represents an alkylene group ; and / or (a25) ^{B 2} represents a single bond or an alkylene group; and / (a26) p is 0, 1 Represents a 2; and / or (a27) q represents 0 or 1.

  That is, in the compound represented by the general formula (1), 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). A compound or a salt thereof comprising one or more combinations selected from (a27).

(B) As a more preferable example in this invention compound, the compound or its salt which satisfy | fills the following prescription | regulation is mentioned.

In general formula (1),
(B1) Ring A represents a benzene ring, thiophene ring or pyridine ring; and / or (b2) R ¹ represents an alkyl group, cycloalkyl group, aryl group or heterocyclic ring; and / or (b3) R ¹ represents In the case of an alkyl group, the alkyl group may have one or more alkoxyaryl groups as substituents; and / or (b4) when R ¹ is an aryl group, the aryl group is a halogen atom, a hydroxy group, May have one or more substituents selected from an alkoxy group, a halogenoalkoxy group, an alkylcarbonyloxy group, an alkyl group and a halogenoalkyl group; and / or (b5) R ² represents a hydrogen atom or an alkyl group. It is shown; and / or (b6) when R ² is an alkyl group, one or more location the alkyl groups are selected from carboxy groups and alkoxycarbonyl groups May have a group; and / or (b7) ^{R 3} is a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic ring or ^{Z-R 5;} and / or (b8) ^{R 3} is alkyl In the case of a group, the alkyl group may have one or more substituents selected from a hydroxy group and an alkylamino group; and / or (b9) when R ³ is a heterocycle, the heterocycle is 1 Or a plurality of cyano groups as substituents; and / or (b10) R ³ and R ⁴ may form a heterocycle together; and / or (b11) R ³ and R ^{If 4} is to form a heterocyclic ring together, heterocycle hydroxy group, an alkyl group, hydroxyalkyl group, an alkylamino group, one or more selected from an alkoxycarbonyl group, an alkylcarbonyl group and an alkylaminocarbonyl group It may have a substituent, and the heterocyclic ring may have a carbonyl group in the ring; and / or (b12) R ⁴ represents a hydrogen atom, an alkyl group or an alkylcarbonyl group; and / Or (b13) when R ⁴ is an alkylcarbonyl group, the alkylcarbonyl group may have one or more alkylcarbonyloxy groups as substituents; and / or (b14) Z is CO, CO-B ^{2 -O, CO-B 2 -NR 6} , CS-B 2 -NR 6, CO-B 2 -NR 6 SO 2 or indicates SO _2; and / or (b15) ^{R 5} is a hydrogen atom, an alkyl group, an alkenyl Group, alkynyl group, cycloalkyl group, aryl group, heterocyclic ring, alkoxycarbonyl group, alkylcarbonyl group, heterocyclic carbonyl group or alkylaminocarbonyl group; and / or (b 6) When R ⁵ is an alkyl group, the alkyl group is a halogen atom, hydroxy group, alkoxy group, hydroxyalkoxy group, alkoxyalkoxy group, a cycloalkyl group, a heterocyclic, a carboxy group, an alkoxycarbonyl group, an amino group, an alkylamino ^May have one or more substituents selected from a group, an alkoxycarbonylamino group, an alkylcarbonylamino group, an alkylthio group, and a cyano group; and / or (b17) when R ⁵ is an aryl group, the aryl The group may have one or more halogen atoms as substituents; and / or (b18) when R ⁵ is a heterocycle, the heterocycle may have one or more alkyl groups as substituents. well; and / or (b19) when R ⁵ is an alkylcarbonyl group, the alkylcarbonyl group is a carboxy group, Al It may have one or more substituents selected from ylcarbonyl group and alkylamino groups; and / or (b20) R ⁵ and R ⁶ together may form a heterocyclic ring; And / or (b21) when R ⁵ and R ⁶ together form a heterocycle, the heterocycle is selected from a hydroxy group, an alkyl group, a hydroxyalkyl group, an alkoxycarbonyl group, or an alkylcarbonyl group The heterocyclic ring may have a plurality of substituents, and the heterocyclic ring may have a carbonyl group in the ring; and / or (b22) R ⁶ represents a hydrogen atom or an alkyl group; and / or ( b23) X and Y represents a hydrogen atom; and / or (b24) ^{B 1} represents an alkylene group; indicates and / or (b25) ^{B 2} is a single bond or an alkylene group; and / or (b26) p is 0 or 1 Shown; and / or (b27) q represents 0.

  That is, in the compound represented by the general formula (1), 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 (a27), or a compound or a salt thereof comprising one or more combinations.

(C) As a further preferred example of the compound of the present invention, a compound satisfying the following provisions or a salt thereof may be mentioned.

In general formula (1),
(C1) ring A represents a benzene ring, thiophene ring or pyridine ring; and / or (c2) R ¹ represents an aryl group or a heterocycle; and / or (c3) when R ¹ is an aryl group, the aryl The group may have one or more substituents selected from halogen atoms, halogenoalkoxy groups, alkyl groups and halogenoalkyl groups; and / or (c4) R ² represents a hydrogen atom; and / or ( c5) R ³ represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic ring or Z—R ⁵ ; and / or (c6) when R ³ is an alkyl group, the alkyl group contains one or more And / or (c7) when R ³ is a heterocycle, the heterocycle may have one or more cyano groups as substituents; and / or (c8) ^{R 3} and R There may form a heterocyclic ring together; if and / or (c9) R ³ and R ⁴ to form a heterocyclic ring together, said heterocyclic is selected from alkyl and alkylcarbonyl groups And / or (c10) R ⁴ represents a hydrogen atom or an alkyl group; and / or (c11) Z is CO, CO—B ² —O, CO—. B ² —NR ⁶ , CO—B ² —NR ⁶ SO ₂ or SO ₂ ; and / or (c12) R ⁵ represents a hydrogen atom, an alkyl group, an aryl group, an alkylcarbonyl group or an alkylaminocarbonyl group. And / or (c13) when R ⁵ is an alkyl group, the alkyl group has one or more substituents selected from a halogen atom, a hydroxy group, a heterocyclic ring, an alkylamino group, and an alkylcarbonylamino group; And / or (c14) when R ⁵ is an aryl group, the aryl group may have one or more halogen atoms as substituents; and / or (c15) R ⁵ is alkylcarbonyl. In the case of a group, the alkylcarbonyl group may have one or more carboxy groups as substituents; and / or (c16) R ⁵ and R ⁶ may together form a heterocycle; And / or (c17) when R ⁵ and R ⁶ together form a heterocycle, the heterocycle may have one or more hydroxyalkyl groups as substituents; and / or (c18) R ⁶ represents a hydrogen atom or an alkyl group; and / or (c19) X and Y represent a hydrogen atom; and / or (c20) B ¹ represents an alkylene group; and / or (c21) B ² represents a single atom Represents a bond or an alkylene group; Beauty / or (c22) p represents 0; and / or (c23) q represents 0.

  That is, in the compound represented by the general formula (1), the above (c1), (c2), (c3), (c4), (c5), (c6), (c7), (c8), (c9), (C10), (c11), (c12), (c13), (c14), (c15), (c16), (c17), (c18), (c19), (c20), (c21), (c22) ) And (c23), or a compound or a salt thereof comprising one or more combinations.

(D) As a pharmacologically preferable example of the compound of the present invention, the provision of any one of the above (a) to (c) is satisfied, and in the general formula (1), ring A is a pyridine ring or thiophene. The compound which is a ring, or its salt is mentioned, The compound or its salt whose ring A is a pyridine ring is especially preferable.

と部分構造（Ｄ）

が環Ａ上の隣接する炭素原子に結合した化合物又はその塩が挙げられる。(E) As a pharmacologically more preferable example of the compound of the present invention, the provision of any one of the above (a) to (d) is satisfied, and the partial structure (C) in the general formula (1)

And partial structure (D)

Is a compound in which is bonded to an adjacent carbon atom on ring A or a salt thereof.

(F) As a further preferred example of the pharmacological activity in the compound of the present invention, the definition of (d) and the definition of (e) are satisfied, and the partial structure (C) or (D) is on ring A. The compound couple | bonded with the carbon atom located in the alpha position of a hetero atom, or its salt is mentioned.

(G) As a particularly preferred example of the compound of the present invention, a compound or a salt thereof satisfying the definition of any one of the above (a) to (f) and satisfying the following definition.

In general formula (1),
(G1) R ³ represents Z—R ⁵ ; and / or (g2) Z represents CO, CO—B ² —O, CO—B ² —NR ⁶ , CO—B ² —NR ⁶ SO ₂ ; And / or (g3) R ⁵ represents a hydrogen atom, an alkyl group, an aryl group, an alkylcarbonyl group or an alkylaminocarbonyl group; and / or (g4) when R ⁵ is an alkyl group, the alkyl group is a halogen atom, ^May have one or more substituents selected from a hydroxy group, a heterocyclic ring, an alkylamino group and an alkylcarbonylamino group; and / or (g5) when R ⁵ is an aryl group, the aryl group is 1 or more halogen atoms may have a substituent; and / or (g6) when R ⁵ is an alkylcarbonyl group, the alkylcarbonyl group may have one or more carboxyl group as a substituent If and / or (g8) R ⁵ and R ⁶ together form a heterocyclic ring; also good; and / or (g7) R ⁵ and R ⁶ together may form a heterocyclic ring The heterocyclic ring may have one or more hydroxyalkyl groups as substituents; and / or (g9) R ⁶ represents a hydrogen atom or an alkyl group; and / or (g10) B ² is a single bond Or an alkylene group is shown.

  That is, the compound described in any one of (a) to (f) is satisfied, and the compound represented by the general formula (1) is the above (g1), (g2), (g3), (g4) , (G5), (g6), (g7), (g8), (g9) and a compound comprising a combination of two or more selected from (g10) or a salt thereof.

Examples of particularly preferred specific compounds in the compounds of the present invention are shown below.
N- (3,5-dimethylphenyl) -2- [2- (4-methylpiperazin-1-yl) pyridin-4-ylmethylthio] pyridine-3-carboxamide,
2- (2-cyclopropylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
2- [2- (N- (2-dimethylaminoethyl) -N-methylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-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] pyridine-3-carboxamide,
2- [2- (4-acetylpiperazin-1-yl) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
N- (indan-5-yl) -2- (2-morpholinopyridin-4-ylmethylthio) pyridine-3-carboxamide,
2- [2- (4-acetylpiperazin-1-yl) pyridin-4-ylmethylthio] -N- (indan-5-yl) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-n-pentylaminopyridin-4-ylmethylthio) pyridine-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) pyridine-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) pyridine-3-carboxamide,
2- [2- (N-tert-butoxycarbonyl-N-methylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
2- [2- (5-cyanothiazol-2-ylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
2- (2-aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
2- (2-aminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridine-3-carboxamide,
2- (2-aminopyridin-4-ylmethylthio) -N- (indan-5-yl) pyridine-3-carboxamide,
2- (2-aminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) pyridine-3-carboxamide,
2- (2-aminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (indan-5-yl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
2- (2-methylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,
2- (2-aminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridine-3-carboxamide,
2- (2-aminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,
2- (2-aminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) pyridine-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) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-propionylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-trifluoroacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-isobutyrylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-pivaloylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-trifluoromethanesulfonylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
2- (2-acetylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridine-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) pyridine-3-carboxamide,
2- (2-acetylaminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) pyridine-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-4-ylmethylthio) -N- (4-chlorophenyl) thiophene-2-carboxamide,
N- (3,5-dimethylphenyl) -2- [2- (N′-n-propylureido) pyridin-4-ylmethylthio] pyridine-3-carboxamide,
2- [2- (N′-tert-butylureido) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
2- [2- (N′-4-chlorophenylureido) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-formylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-phenylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- [2- (N′-methylureido) pyridin-4-ylmethylthio] pyridine-3-carboxamide,
2- [2- (N′-methylureido) pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,
N- (4-chlorophenyl) -2- [2- (N′-methylureido) pyridin-4-ylmethylthio] pyridine-3-carboxamide,
N- (4-difluoromethoxyphenyl) -2- [2- (N′-methylureido) pyridin-4-ylmethylthio] pyridine-3-carboxamide,
2- (2-acetoxyacetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
2- (2-acetoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,
2- (2-aminoacetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (4-chlorophenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (3,5-dimethyl-4-hydroxyphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) -N- (3-methylphenyl) pyridine-3-carboxamide,
2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethylphenyl) pyridine-3-carboxamide,
2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) pyridine-3-carboxamide,
N- (3-chlorophenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) -N- (indan-5-yl) pyridine-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-dimethylphenyl) pyridine-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-3-carboxamide,
2- [2- (2-hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,
2- [2- (piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-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] pyridine-3-carboxamide,
2- [2- (2-hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3-methylphenyl) pyridine-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- (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) 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) pyridine-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) pyridine-3-carboxamide,
2- (3-aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
2- (3-acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-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) pyridine-3-carboxamide,
2- [2- (2-dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3-methylphenyl) pyridine-3-carboxamide,
N- (3-methylphenyl) -2- [2- (piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] pyridine-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 compound of the present invention can be produced by the following method. In addition, each specific manufacturing method is demonstrated in detail by the below-mentioned Example [section of a manufacturing example]. Further, Hal used in the following synthesis route represents a halogen atom, Boc represents a tert-butoxycarbonyl group, and TBS represents a tert-butyldimethylsilyl group. In the following formula, when R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ contain an oxygen atom, a nitrogen atom, a sulfur atom, etc., they can be protected and deprotected by a widely used method. .

  The manufacturing method of this invention compound can be divided roughly into the method shown below, and the method can be suitably selected according to the kind of substituent.

1) The compound (Ia) of the present invention (R ³ and R ⁴ are alkyl, aryl, hydrogen atom, etc.) can be produced according to Synthesis Route 1. That is, the compound (Ia) of the present invention is obtained by reacting the compound (IIa) and the amine (III) at 100 ° C. to 200 ° C. for 1 hour to 12 hours in a solventless or organic solvent such as tributylamine. Can do.
Synthesis route 1

Compound (II) (Hal is F, Cl, Br) including Compound (IIa) can be produced according to Synthesis Route 1-1. That is, the compound (II) is obtained by converting the compound (IV) and the amine (V) into N, N′-dicyclohexylcarbodiimide in an organic solvent such as methylene chloride and N, N-dimethylformamide (hereinafter referred to as “DMF”). (Hereinafter referred to as “DCC”), O- (7-azabenzotriazol-1-yl) -1,1,3,3-tetramethyluronium hexafluorophosphate (hereinafter referred to as “HATU”), It can be obtained by reacting at room temperature to 50 ° C. for 1 to 24 hours in the presence of a condensing agent such as N-benzyl-N′-cyclohexylcarbodiimide polymer bound and a base such as N, N-diisopropylethylamine.
Synthesis route 1-1

Compound (IV) can be manufactured according to the synthetic pathway 1-2. That is, compound (IV) is obtained by reacting compound (VI) and compound (VII) in an organic solvent such as DMF in the presence of a base such as triethylamine at 0 ° C. to room temperature for 1 to 12 hours. Can do.
Synthesis route 1-2

Compound (VII) can be manufactured according to the synthetic pathway 1-3. That is, compound (VII) is obtained by heating compound (VIII) in an organic solvent such as acetonitrile in the presence of a radical initiator such as benzoyl peroxide and a halogenating agent such as N-chlorosuccinimide and N-bromosuccinimide. It can be obtained by reacting for 1 to 12 hours under reflux. R ⁷ and R ⁸ used in the following synthesis route represent a hydrogen atom, an alkyl group or the like.
Synthesis route 1-3

2) The present compound (Ib) (R ³ is alkyl, aryl, hydrogen atom, R ⁴ is alkyl, aryl, hydrogen atom, COR ⁵ , CONR ⁵ R ^6, etc.) can be produced according to Synthesis route 2. That is, the compound (IIb) obtained by the synthesis route 1-1 is converted into a transition metal catalyst such as palladium acetate or tris (dibenzylideneacetone) dipalladium (0) and a base such as cesium carbonate, or 4,5-bis (diphenylphosphino). In the presence of a catalytic ligand such as -9,9-dimethylxanthene, in an organic solvent such as amine, amide or urea (III) and 1,4-dioxane at 80 to 150 ° C for 1 hour to 12 It can be obtained by reacting for a time.
Synthesis route 2

3) The compound (Ic) of the present invention (Z is CO, SO ₂ etc.) can be produced according to the synthesis route 3. That is, the compound (Ic) of the present invention comprises the compound (Id) of the present invention and an acid anhydride (IX) such as acetic anhydride or an acid halide (X) such as pivaloyl chloride in an organic solvent such as pyridine. It can be obtained by reacting at a temperature of from 80 to 80 ° C. for 1 to 12 hours.
Synthesis route 3

4) This invention compound (Ie) (Z is CO, CS, etc.) can be manufactured according to the synthetic pathway 4. That is, the compound (Ie) of the present invention comprises the compound (Id) of the present invention, an isocyanate (XI) such as n-propyl isocyanate, an isothiocyanate (XII) such as methyl isothiocyanate, and an organic solvent such as DMF. It can be obtained by reacting at room temperature to 100 ° C. for 1 hour to 12 hours.
Synthesis route 4

5) The present compound (Ib) (R ³ is alkyl, aryl, hydrogen atom, R ⁴ is alkyl, aryl, hydrogen atom, COR ⁵ , CONR ⁵ R ^6, etc.) can be produced according to Synthesis route 5. That is, the compound (Ib) of the present invention comprises a compound (XIII) and an amine (V) in a condensing agent such as DCC, HATU, N-benzyl-N′-cyclohexylcarbodiimide polymer bound in an organic solvent such as methylene chloride and DMF. And in the presence of a base such as N, N-diisopropylethylamine, the reaction can be carried out at room temperature to 500 ° C. for 1 to 12 hours.
Synthesis route 5

Compound (XIII) can be manufactured according to the synthetic pathway 5-1. That is, compound (XIII) is compound (VI) and compound (XIV) (W is a leaving group such as a halogen atom, methanesulfonyloxy group, toluenesulfonyloxy group) in an organic solvent such as DMF. It can be obtained by reacting at 0 ° C. to room temperature for 1 to 12 hours in the presence of a base.
Synthesis route 5-1

Compound (XIVa) can be produced according to synthetic route 5-2. That is, compound (XIVa) is obtained by reacting compound (XV) with a halogenating agent such as carbon tetrabromide-triphenylphosphine in an organic solvent such as methylene chloride at 0 ° C. to room temperature for 1 to 4 hours. Can be obtained.
Synthesis route 5-2

Compound (XIVb) can be manufactured according to the synthetic pathway 5-3. That is, compound (XIVb) is a reaction between compound (XV) and methanesulfonyl chloride in an organic solvent such as methylene chloride in the presence of a base such as N, N-diisopropylethylamine at 0 ° C. to room temperature for 30 minutes to 3 hours. Can be obtained.
Synthesis route 5-3

6) This invention compound (If) can be manufactured according to the synthetic pathway 6. That is, the compound (If) of the present invention is obtained by reacting the compound (Id) of the present invention with a formylating agent such as N-formylbenzotriazole in an organic solvent such as tetrahydrofuran under heating and refluxing for 3 to 24 hours. Obtainable.
Synthesis route 6

7) Compound of the present invention (Ig) ^{(R 2} is alkyl, etc.) can be synthesized according to synthetic route 7. That is, the compound (Ig) of the present invention comprises the compound (Ih) of the present invention and R ² -halide (XVI) (where R ² is alkyl, etc.) in an organic solvent such as tetrahydrofuran and DMF in the presence of a base such as sodium hydride. It can be obtained by reacting at 0 ° C. to room temperature for 30 minutes to 3 hours.
Synthesis route 7

8) This invention compound (Ii) can be manufactured according to the synthetic pathway 8. That is, the compound (Ii) of the present invention is obtained by combining the compound (Id) of the present invention with R ³ -halide (XVII) (wherein R ³ is substituted or unsubstituted aryl, etc.) in an organic solvent such as tetrahydrofuran and 1,4-dioxane. Transition metal catalysts such as palladium and tris (dibenzylideneacetone) dipalladium (0) and triphenylphosphine, 1,4-bis (diphenylphosphino) butane, 4,5-bis (diphenylphosphino) -9,9- It can be obtained by reacting at 50 to 120 ° C. for 3 to 24 hours in the presence of a catalyst ligand such as dimethylxanthene and a base such as potassium carbonate or cesium carbonate.
Synthesis route 8

9) The compound (Ij) of the present invention (p = 0, 1 or 2, q = 0 or 1) can be produced according to the synthesis route 9. That is, the present invention wherein the sulfur atom or nitrogen atom in the compound (Ib) of the present invention (R ³ is alkyl, aryl, hydrogen atom, R ⁴ is alkyl, aryl, hydrogen atom, COR ⁵ , CONR ⁵ R ⁶ etc.) is oxidized. Inventive compound (Ij) is obtained by reacting inventive compound (Ib) in an organic solvent such as chloroform in the presence of an oxidizing agent such as m-chloroperbenzoic acid or hydrogen peroxide at 0 ° C. to room temperature for 1 to 12 hours. Can be obtained.
Synthesis route 9

10) The compound (Ik) of the present invention (B ² is alkylene, R ⁷ and R ⁸ are alkyl, hydrogen atom, etc.) can be produced according to Synthesis route 10. That is, the present invention compound (Ik), the present invention compound (Il) ^{(B 2} is alkylene, etc., W is a halogen atom) with an amine (XVIII), without solvent or in DMF, an organic solvent such as methanol, at room temperature It can be obtained by reacting at 100 ° C. for 10 minutes to 12 hours.
Synthesis route 10

11) The compound (Il) of the present invention (B ² is alkylene or the like) can be produced according to synthetic route 11. That is, the compound (Il) of the present invention is obtained by reacting the compound (Im) of the present invention with a halogenating agent such as thionyl chloride at 0 ° C. to 50 ° C. for 10 minutes to 12 hours in an organic solvent such as methylene chloride. Obtainable.
Synthesis route 11

12) The compound (In) of the present invention (R ³ is alkyl, aryl, hydrogen atom, etc., R ⁴ is alkyl, aryl, hydrogen atom, COR ⁵ , CONR ⁵ R ⁶ etc.) can be produced according to synthetic route 12. . That is, the compound (In) of the present invention comprises compound (XIX) and compound (XIV) (W is a leaving group such as bromine atom and methanesulfonyloxy group) in an organic solvent such as DMF in the presence of a base such as triethylamine. It can be obtained by reacting at 0 to 50 ° C. for 30 minutes to 24 hours.
Synthesis route 12

Compound (XIX) can be produced according to synthetic route 12-1. That is, compound (XIX) is prepared by mixing amine (V) and compound (VIa) in an organic solvent such as DMF in the presence of a condensing agent such as DCC, HATU, carbonyldiimidazole, and a base such as N, N-diisopropylethylamine. It can be obtained by reacting at 0 to 50 ° C. for 1 to 12 hours.
Synthesis route 12-1

Compound (XIVc) can be manufactured according to the synthetic pathway 12-2. That is, compound (XIVc) is obtained by reacting compound (XV) with a halogenating agent such as aqueous hydrobromic acid solution in water or an organic solvent such as methylene chloride or DMF at 0 to 100 ° C. for 3 to 12 hours. Can be obtained.
Synthesis route 12-2

13) Compound of the present invention (Io) ^{(B 2} is alkylene, etc.) can be synthesized according to synthetic route 13. That is, the compound (Io) of the present invention is used at room temperature to 100 ° C. in an organic solvent such as methanol and 1,4-dioxane in the presence of the compound (Ip) of the present invention and a base such as hydrazine monohydrate or aqueous sodium hydroxide. And can be obtained by reacting for 1 to 24 hours.
Synthesis route 13

  In order to find out the usefulness of the compound of the present invention, the following 1-4. The pharmacological effect of the compound of the present invention was evaluated. The details thereof will be described in the following [Example of pharmacological test]. In the pharmacological test (in vitro), an excellent cell growth inhibitory action was demonstrated, an angiogenesis inhibitory effect was found, and an increase in vascular permeability was suggested. Furthermore, the compound of the present invention used a specific disease model animal. In an in vivo pharmacological test (in vivo), it exhibits excellent tumor growth inhibitory effect, foot edema inhibitory effect and choroidal neovascularization inhibitory effect, and is useful as a therapeutic agent for specific diseases involving angiogenesis and / or increased vascular permeability. I found out.

1. Evaluation test of angiogenesis inhibitory effect VEGF-induced HUVEC proliferative reaction evaluation system (HUVEC is a normal human umbilical vein-derived vascular endothelial cell). The cell growth inhibitory action test of the compound of the present invention was carried out.

2. Evaluation Test of Anticancer Effect A tumor growth inhibitory effect test of the compound of the present invention was carried out using a mouse tumor-bearing model which is one of the widely used methods for evaluating the anticancer effect of a drug in vivo.

3. Evaluation test of anti-arthritic effect The rat edema inhibitory effect test of the compound of the present invention was carried out using a rat adjuvant arthritis model which is one of the widely used methods for evaluating the anti-arthritic effect of drugs in vivo.

4). Evaluation test of choroidal neovascularization inhibitory effect The neovascularization test of the compound of the present invention was performed using a rat choroidal neovascularization model, which is one of the widely used methods for evaluating the in vivo choroidal neovascularization inhibitory effect of drugs. .
As described above, 1-4. Thus, the compound of the present invention is useful as a therapeutic agent for diseases involving angiogenesis and / or increased vascular permeability, specifically, cancer, rheumatoid arthritis, age-related macular degeneration, diabetic It is very useful as a therapeutic agent for retinopathy, retinopathy of prematurity, retinal vein occlusion, polypoidal choroidal angiopathy, diabetic macular edema, psoriasis vulgaris, and atherosclerosis.

  The compound of the present invention can be administered orally or parenterally. Examples of the dosage form include tablets, capsules, granules, powders, injections, eye drops and the like, and they can be formulated using a widely used technique.

  For example, oral preparations such as tablets, capsules, granules, powders are lactose, mannitol, starch, crystalline cellulose, light anhydrous silicic acid, calcium carbonate, calcium hydrogen phosphate and other excipients, stearic acid, magnesium stearate , Lubricants such as talc, binders such as starch, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, disintegrants such as carboxymethylcellulose, low-substituted hydroxypropylmethylcellulose, calcium citrate, hydroxypropylmethylcellulose, macrogol, A coating agent such as a silicone resin, a stabilizer such as ethyl paraoxybenzoate and benzyl alcohol, a flavoring agent such as a sweetener, an acidulant, and a fragrance can be used as necessary.

  In addition, parenterals such as injections and eye drops are made of isotonic agents such as sodium chloride, concentrated glycerin, propylene glycol, polyethylene glycol, potassium chloride, sorbitol, mannitol, sodium phosphate, sodium hydrogen phosphate, sodium acetate. , Buffers such as citric acid, glacial acetic acid, trometamol, surfactants such as polyoxyethylene sorbitan monooleate, polyoxy 40 stearate, polyoxyethylene hydrogenated castor oil, stabilizers such as sodium citrate and sodium edetate , Benzalkonium chloride, paraben, benzotonium chloride, paraoxybenzoate, sodium benzoate, preservatives such as chlorobutanol, hydrochloric acid, citric acid, phosphoric acid, glacial acetic acid, sodium hydroxide, sodium carbonate, sodium bicarbonate PH adjusting agents such as Use in accordance with emissions benzyl alcohol soothing agent such as such as required, it may be prepared.

  The dose of the compound of the present invention can be appropriately selected and used depending on symptoms, age, dosage form and the like. For example, an oral preparation can be administered usually in an amount of 0.01 to 1000 mg, preferably 1 to 100 mg per day, once or in several divided doses. In addition, the eye drops are usually administered in a concentration of 0.0001% to 10% (w / v), preferably 0.01% to 5% (w / v) in one or several divided doses. it can.

  The production examples, formulation examples, and pharmacological test results of the compounds of the present invention are shown below. In addition, these illustrations are for understanding this invention better, and do not limit the scope of the present invention.

[Production example]
Reference example 1
4-Chloromethyl-2-fluoropyridine (Reference compound 1-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＤＭＳＯ−ｄ_６）
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）At room temperature, 2-fluoro-4-picoline (5.0 g, 45 mmol) in acetonitrile (25 mL) was added to N-chlorosuccinimide (8.8 g, 66 mmol), acetic acid (0.15 mL) and benzoyl peroxide (220 mg, 0.91 mmol) was added and heated to reflux for 2 hours. The reaction solution was cooled to room temperature, water (200 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (300 mL). The organic layer was washed with saturated brine (200 mL) and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure, hexane / ethyl acetate (1: 1) was added to the resulting residue, and the insoluble material was removed by filtration. The filtrate was concentrated under reduced pressure to obtain 6.5 g of the title reference compound as a crude product.

¹ H-NMR (500 MHz, DMSO-d ₆ )
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)

  Hereinafter, using a compound selected from commercially available compounds and known compounds, Reference Compound 1-2 was obtained according to the production method of Reference Compound 1-1.

2-Bromo-4-chloromethylpyridine (Reference compound 1-2)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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)

Reference example 2
2- (2-Fluoropyridin-4-ylmethylthio) pyridine-3-carboxylic acid (Reference compound 2-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＤＭＳＯ−ｄ_６）
δ ４．４３（ｓ，２Ｈ），７．２０（ｓ，１Ｈ），７．２３（ｄｄ，Ｊ ＝ ７．９，４．９ Ｈｚ，１Ｈ），７．３９（ｄ，Ｊ ＝ ５．２ Ｈｚ，１Ｈ），８．１３（ｄ，Ｊ ＝ ５．２ Ｈｚ，１Ｈ），８．２４（ｄｄ，Ｊ ＝ ７．９，１．８ Ｈｚ，１Ｈ），８．６４（ｄｄ，Ｊ ＝ ４．９，１．８ Ｈｚ，１Ｈ），１４．６０（ｂｒ ｓ，１Ｈ）Under ice cooling, a solution of 4-chloromethyl-2-fluoropyridine (reference compound 1-1, 5.5 g, 38 mmol) and 2-mercaptonicotinic acid (6.2 g, 40 mmol) in N, N-dimethylformamide (40 mL). Was added a solution of triethylamine (7.0 mL, 50 mmol) in N, N-dimethylformamide (20 mL), and the mixture was stirred at room temperature for 12 hours. Ethyl acetate (50 mL) was added to the reaction solution, and the mixture was extracted with 0.1N aqueous sodium hydroxide solution (100 mL). The aqueous layer was adjusted to pH 5 with 1N hydrochloric acid, and the precipitated crystals were collected by filtration. The crystals were dried at 80 ° C. under reduced pressure to obtain 5.3 g of the title reference compound as a brown solid (yield 53%).

¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 4.43 (s, 2H), 7.20 (s, 1H), 7.23 (dd, J = 7.9, 4.9 Hz, 1H), 7.39 (d, J = 5.2) Hz, 1H), 8.13 (d, J = 5.2 Hz, 1H), 8.24 (dd, J = 7.9, 1.8 Hz, 1H), 8.64 (dd, J = 4) .9, 1.8 Hz, 1H), 14.60 (br s, 1H)

  Hereinafter, using a compound selected from Reference Compound 1-2, a commercially available compound and a known compound, Reference Compound 2-2 was obtained according to the production method of Reference Compound 2-1.

2- (2-Bromopyridin-4-ylmethylthio) pyridine-3-carboxylic acid (Reference compound 2-2)

¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 4.37 (s, 2H), 7.28 (dd, J = 7.8, 4.7 Hz, 1H), 7.48 (dd, J = 4.9, 1.4 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) pyridine-3-carboxamide (Reference compound 3-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＤＭＳＯ−ｄ_６）
δ ２．２６（ｓ，６Ｈ），４．４６（ｓ，２Ｈ），６．７６（ｓ，１Ｈ），７．１８（ｓ，１Ｈ），７．２９（ｄｄ，Ｊ ＝ ７．３，４．６ Ｈｚ，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）At room temperature, 2- (2-fluoropyridin-4-ylmethylthio) pyridine-3-carboxylic acid (reference compound 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) were added O- (7-azabenzotriazol-1-yl) -N, N, N ′, N '-Tetrauronium hexafluorophosphate (3.0 g, 7.9 mmol) was added and stirred for 12 hours. Ethyl acetate (30 mL) was added to the reaction solution, washed with saturated brine (50 mL), and the organic layer was dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to obtain 0.91 g of the title reference compound as a colorless solid (yield 44%).

¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 2.26 (s, 6H), 4.46 (s, 2H), 6.76 (s, 1H), 7.18 (s, 1H), 7.29 (dd, J = 7.3, 4 .6 Hz, 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)

  Hereinafter, reference compounds 2-1 and 2-2, compounds selected from commercially available compounds and known compounds were used, and reference compounds 3-2 to 7 were obtained according to the production method of reference compound 3-1.

2- (2-Fluoropyridin-4-ylmethylthio) -N- (indan-5-yl) pyridine-3-carboxamide (Reference compound 3-2)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Reference compound 3-3)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Reference compound 3-4)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 (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) pyridine-3-carboxamide (Reference compound 3-5)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Reference compound 3-6)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 4.41 (s, 2H), 7.31 (dd, J = 7.6, 4.9 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) pyridine-3-carboxamide (Reference compound 3-7)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 Hz, 1H), 10.56 (s, 1H)

Reference example 4
(2-tert-Butoxycarbonylaminopyridin-4-yl) methanol (Reference compound 4-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＣＤＣｌ_３）
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（ｂｒ ｓ，１Ｈ），７．９２（ｓ，１Ｈ），８．２１（ｄ，Ｊ ＝ ５．２ Ｈｚ，１Ｈ）At room temperature, 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) and stirred for 12 hours. did. The reaction solution was concentrated under reduced pressure, ethyl acetate (20 mL) was added to the resulting residue, and the insoluble material was removed by filtration. After the filtrate was concentrated under reduced pressure, the resulting residue was purified by silica gel column chromatography to obtain 3.6 g of the title reference compound as colorless crystals (yield 60%).

¹ H-NMR (500 MHz, CDCl ₃ )
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 (brs, 1H), 7.92 (s, 1H), 8.21 (d, J = 5.2 Hz, 1H)

Reference Example 5
2-tert-Butoxycarbonylamino-4- (tert-butyldimethylsilyloxymethyl) pyridine (Reference compound 5-1)

^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＤＭＳＯ−ｄ_６）
δ ０．０９（ｓ，６Ｈ），０．９２（ｓ，９Ｈ），１．４６（ｓ，９Ｈ），４．７２（ｓ，２Ｈ），６．９３（ｄｄ，Ｊ ＝ ４．９，０．９ Ｈｚ，１Ｈ），７．７８（ｓ，１Ｈ），８．１６（ｄ，Ｊ ＝ ４．９ Ｈｚ，１Ｈ），９．６７（ｓ，１Ｈ）To a solution of (2-tert-butoxycarbonylaminopyridin-4-yl) methanol (reference compound 4-1, 6.2 g, 28 mmol) in N, N-dimethylformamide (120 mL) at room temperature, imidazole (2.1 g, 31 mmol) and tert-butyldimethylsilyl chloride (4.4 g, 29 mmol) were added and stirred for 2 hours. Ethyl acetate (300 mL) was added to the reaction solution, washed with water (750 mL) and saturated brine (200 mL), and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure to obtain 9.0 g of the title reference compound as a colorless solid (yield 96%).

¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 0.09 (s, 6H), 0.92 (s, 9H), 1.46 (s, 9H), 4.72 (s, 2H), 6.93 (dd, J = 4.9, 0 .9 Hz, 1H), 7.78 (s, 1H), 8.16 (d, J = 4.9 Hz, 1H), 9.67 (s, 1H)

Reference Example 6
2- (N-tert-butoxycarbonyl-N-methylamino) -4- (tert-butyldimethylsilyloxymethyl) pyridine (reference compound 6-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＣＤＣｌ_３）
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 Ｈｚ，１Ｈ）60% sodium hydride (310 mg, 7.6 mmol) was washed with hexane (5.0 mL) and suspended in N, N-dimethylformamide (20 mL). Under ice cooling, 2-tert-butoxycarbonylamino-4- (tert-butyldimethylsilyloxymethyl) pyridine (reference compound 5-1, 1.3 g, 3.7 mmol) was added dropwise to the suspension over 15 minutes. Further, methyl iodide (2.4 mL, 39 mmol) was added, and the mixture was stirred overnight at room temperature. Water (70 mL) was added to the reaction suspension, and the mixture was extracted with ethyl acetate (100 mL). The organic layer was washed with saturated aqueous sodium hydrogen carbonate (50 mL) and saturated brine (100 mL), and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure to obtain 1.4 g of a mixture containing the title reference compound as an orange oil.

¹ H-NMR (500 MHz, CDCl ₃ )
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 Hz, 1H)

Reference Example 7
[2- (N-tert-butoxycarbonyl-N-methylamino) pyridin-4-yl] methanol (Reference compound 7-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＣＤＣｌ_３）
δ １．５３（ｓ，９Ｈ），１．９３（ｔ，Ｊ ＝ ５．６ Ｈｚ，１Ｈ），３．４０（ｓ，３Ｈ），４．７３（ｄ，Ｊ ＝ ５．６ Ｈｚ，２Ｈ），７．０２（ｄ，Ｊ ＝ ５．１ Ｈｚ，１Ｈ），７．７０（ｓ，１Ｈ），８．３４（ｄ，Ｊ ＝ ５．１ Ｈｚ，１Ｈ）At room temperature, 2- (N-tert-butoxycarbonyl-N-methylamino) -4- (tert-butyldimethylsilyloxymethyl) pyridine (reference compound 6-1, 1.4 g, 3.7 mmol) in tetrahydrofuran (20 mL) ) A solution of tetra-n-butylammonium fluoride trihydrate (1.3 g, 4.2 mmol) in tetrahydrofuran (20 mL) was added over 5 minutes, and the mixture was further stirred for 15 minutes. Ethyl acetate (50 mL) and water (100 mL) were added to the reaction solution for partitioning, and the aqueous layer was extracted with ethyl acetate (50 mL). The organic layers were combined, washed with saturated brine (100 mL), and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to obtain 450 mg of the title reference compound as a reddish brown oil (yield 50%).

¹ H-NMR (500 MHz, CDCl ₃ )
δ 1.53 (s, 9H), 1.93 (t, J = 5.6 Hz, 1H), 3.40 (s, 3H), 4.73 (d, J = 5.6 Hz, 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 8-1)

^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）
δ １．５４（ｓ，９Ｈ），４．３８（ｓ，２Ｈ），６．９９（ｄ，Ｊ ＝５．１ Ｈｚ，１Ｈ），７．６１（ｂｒ ｓ，１Ｈ），７．９８（ｓ，１Ｈ），８．２２（ｄ，Ｊ ＝ ５．１ Ｈｚ，１Ｈ）Under ice cooling, triphenylphosphine (970 mg, 3.7 mmol) was added to a solution of (2-tert-butoxycarbonylaminopyridin-4-yl) methanol (reference compound 4-1, 690 mg, 3.1 mmol) in methylene chloride (20 mL). And carbon tetrabromide (1.5 g, 4.6 mmol) were added, and the mixture was stirred at room temperature for 2 hours. Ethyl acetate (30 mL) was added to the reaction solution, washed with saturated aqueous sodium hydrogen carbonate (20 mL) and saturated brine (20 mL), and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure, and the resulting solid was collected by filtration with ethyl acetate to obtain 550 mg of the title reference compound as a colorless solid (yield 62%).

¹ H-NMR (400 MHz, CDCl ₃ )
δ 1.54 (s, 9H), 4.38 (s, 2H), 6.99 (d, J = 5.1 Hz, 1H), 7.61 (brs, 1H), 7.98 (s) , 1H), 8.22 (d, J = 5.1 Hz, 1H)

  Hereinafter, using a compound selected from Reference Compound 7-1, a commercially available compound and a known compound, Reference Compounds 8-2 to 3 were obtained according to the production method of Reference Compound 8-1.

4-Bromomethyl-2- (N-tert-butoxycarbonyl-N-methylamino) pyridine (Reference compound 8-2)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.48 (s, 9H), 3.29 (s, 3H), 4.67 (s, 2H), 7.17 (d, J = 5.1 Hz, 1H), 7.70 (s, 1H), 8.35 (d, J = 5.1 Hz, 1H)

4-Bromomethyl-2-phthaloylaminopyridine (Reference compound 8-3)
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)

Reference Example 9
2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) pyridine-3-carboxylic acid (Reference compound 9-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＤＭＳＯ−ｄ_６）
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（ｂｒ ｓ，１Ｈ）Under ice-cooling, N, N-dimethylformamide of 4-bromomethyl-2-tert-butoxycarbonylaminopyridine (reference compound 8-1,500 mg, 1.7 mmol) and 2-mercaptonicotinic acid (270 mg, 1.7 mmol) ( (3.0 mL) was added a solution of triethylamine (0.75 mL, 5.4 mmol) in N, N-dimethylformamide (2.0 mL), and the mixture was stirred at room temperature for 12 hours. Ethyl acetate (20 mL) was added to the reaction solution, and the mixture was extracted with 0.1N aqueous sodium hydroxide solution (50 mL). The aqueous layer was adjusted to pH 5 with 1N hydrochloric acid, and the precipitated crystals were collected by filtration. The crystals were dried at 60 ° C. under reduced pressure to obtain 560 mg of the title reference compound as colorless crystals (yield 88%).

¹ H-NMR (500 MHz, DMSO-d ₆ )
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 (brs, 1H)

  Hereinafter, reference compounds 9-2 to 6 were obtained using reference compounds 8-2 and 8-3, a compound selected from commercially available compounds and known compounds, according to the production method of reference compound 9-1.

2- [2- (N-tert-butoxycarbonyl-N-methylamino) pyridin-4-ylmethylthio] pyridine-3-carboxylic acid (reference compound 9-2)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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), 8.21-8.26 (m, 2H), 8.63 (dd, J = 4. 9, 1.8 Hz, 1H), 13.49 (brs, 1H)

2- (2-phthaloylaminopyridin-4-ylmethylthio) pyridine-3-carboxylic acid (reference compound 9-3)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 (brs, 1H)

2- [2- (5-Cyanothiazol-2-ylamino) pyridin-4-ylmethylthio] pyridine-3-carboxylic acid (Reference compound 9-4)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1.7 Hz, 1H), 12.19 (s, 1H), 13.52 (br s, 1H)

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) benzoic acid (Reference compound 9-5)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 (brs, 1H)

3- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) thiophene-2-carboxylic acid (Reference compound 9-6)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 (br s, 1H)

Reference Example 10
N- (3,5-dimethylphenyl) -2-thioxo-1,2-dihydropyridine-3-carboxamide (Reference compound 10-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＤＭＳＯ−ｄ_６）
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）Under cooling with ice, 2-mercaptonicotinic acid (90 g, 0.58 mol) was suspended in N, N-dimethylformamide (660 mL), carbonyldiimidazole (110 g, 0.70 mol) was added, and the mixture was stirred at room temperature for 2 hours. After adding water (5.4 mL) and stirring for 40 minutes, 3,5-xylidine (76 mL, 0.61 mol) was added, and the mixture was stirred at 60 ° C. for 16 hours. After allowing to cool, water (1.3 L) was added, and the precipitated solid was collected by filtration, heated to 45 ° C. under reduced pressure and dried to obtain 130 g of the title reference compound as a yellow solid (yield 89%).

¹ H-NMR (500 MHz, DMSO-d ₆ )
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)

  Hereinafter, reference compounds 10-2 to 10 were obtained using a compound selected from commercially available compounds and known compounds according to the production method of reference compound 10-1.

2-Thioxo-N- (4-trifluoromethoxyphenyl) -1,2-dihydropyridine-3-carboxamide (Reference compound 10-2) ¹ H-NMR (500 MHz, DMSO-d ₆ )
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-dihydropyridine-3-carboxamide (Reference compound 10-3)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 7.08 (dd, J = 7.6, 6.1 Hz, 1H), 7.43 (d, J = 8.7 Hz, 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-dihydropyridine-3-carboxamide (Reference compound 10-4)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 10-5)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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-dihydropyridine-3-carboxamide (Reference compound 10-6)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.32 (s, 3H), 6.95 (d, J = 7.6 Hz, 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 10-7) ¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 1.8 Hz, 1H), 8.47 (dd, J = 7.6, 1.8 Hz, 1H), 13.04 (s, 1H) ), 14.20 (br s, 1H)

N- (3-Chlorophenyl) -2-thioxo-1,2-dihydropyridine-3-carboxamide (Reference compound 10-8)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 7.08 (dd, J = 7.6, 5.8 Hz, 1H), 719 (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 (brs, 1H)

N- (4-Difluoromethoxyphenyl) -2-thioxo-1,2-dihydropyridine-3-carboxamide (Reference compound 10-9)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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-dihydropyridine-3-carboxamide (Reference compound 10-10)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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
4-Acetoxymethyl-2-acetylaminopyridine (Reference compound 11-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＤＭＳＯ−ｄ_６）
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）Under ice cooling, (2-aminopyridin-4-yl) methanol (5.0 g, 40 mmol) was suspended in pyridine (20 mL), acetic anhydride (11 mL, 120 mmol) was added, and the mixture was stirred at room temperature for 5 hours. Ethyl acetate (150 mL) was added to the reaction mixture, and the mixture was washed successively with water (150 mL), saturated aqueous sodium hydrogen carbonate (150 mL), and saturated brine (150 mL). did. The obtained solid was collected by filtration using hexane, heated to 40 ° C. under reduced pressure, and dried to obtain 6.7 g of the title reference compound as a colorless solid (yield 79%).

¹ H-NMR (500 MHz, DMSO-d ₆ )
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)

Reference Example 12
(2-acetylaminopyridin-4-yl) methanol (reference compound 12-1)

^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＤＭＳＯ−ｄ_６）
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）Under ice cooling, 4-acetoxymethyl-2-acetylaminopyridine (reference compound 11-1, 6.6 g, 32 mmol) was dissolved in tetrahydrofuran (20 mL), and 2N aqueous sodium hydroxide solution (19 mL, 38 mmol) was added dropwise. After stirring at room temperature for 40 minutes, water (100 mL) was added, extracted six times with ethyl acetate (80 mL), and the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting solid was collected by filtration using a mixed solvent of ethyl acetate and hexane, heated to 40 ° C. under reduced pressure and dried to obtain 4.5 g of the title reference compound as a colorless solid. (Yield 86%).

¹ H-NMR (400 MHz, DMSO-d ₆ )
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)

Reference Example 13
2-acetylamino-4-methanesulfonyloxymethylpyridine (reference compound 13-1)

^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ_３）
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）Under ice-cooling, triethylamine (1.7 mL, 12 mmol) and (2-acetylaminopyridin-4-yl) methanol (reference compound 12-1, 1.0 g, 6.0 mmol) in anhydrous tetrahydrofuran solution (9.0 mL) were added. An anhydrous tetrahydrofuran solution (3.0 mL) of methanesulfonyl chloride (0.70 mL, 9.0 mmol) was added and stirred for 20 minutes. Water (30 mL) was added to the reaction solution, followed by extraction three times with ethyl acetate (40 mL), and the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting solid was collected by filtration using hexane and dried at 40 ° C. under reduced pressure to obtain 1.3 g of the title reference compound as a yellowish white solid (yield 87%).

¹ H-NMR (400 MHz, CDCl ₃ )
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 14-1)

^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＤＭＳＯ−ｄ_６）
δ ４．６９（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（ｂｒ ｓ，２Ｈ），１３．２８（ｂｒ ｓ，１Ｈ）(2-Aminopyridin-4-yl) methanol (15 g, 12 mmol) was suspended in a 47% aqueous hydrogen bromide solution (120 mL, 72 mmol) at room temperature, and the mixture was heated and stirred at an external temperature of 120 ° C. for 6 hours. After further stirring at room temperature for 15 hours, the precipitated solid was collected by filtration and washed with ethyl acetate. The solid was dried under reduced pressure to obtain 23 g of the title reference compound as a gray solid (yield 71%).

¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 4.69 (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 (brs, 2H), 13.28 (brs, 1H)

Example 1
N- (3,5-dimethylphenyl) -2- [2- (4-methylpiperazin-1-yl) pyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 1-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＤＭＳＯ−ｄ_６）
δ ２．１９（ｓ，３Ｈ），２．２５（ｓ，６Ｈ），２．３５（ｔ，Ｊ ＝ ５．０ Ｈｚ，４Ｈ），３．４２（ｔ，Ｊ ＝ ５．０ Ｈｚ，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）N-methylpiperazine was added to N- (3,5-dimethylphenyl) -2- (2-fluoropyridin-4-ylmethylthio) pyridine-3-carboxamide (Reference compound 3-1, 100 mg, 0.27 mmol) at room temperature. (2.0 mL) was added, the tube was sealed, and the mixture was stirred at 150 ° C. for 3 hours. The reaction solution was cooled to room temperature, ethyl acetate (20 mL) was added to the reaction solution, washed with saturated brine (20 mL), and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure, and the resulting solid was collected by filtration with ethyl acetate to obtain 39 mg of the target compound as colorless crystals (yield 32%).

¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 2.19 (s, 3H), 2.25 (s, 6H), 2.35 (t, J = 5.0 Hz, 4H), 3.42 (t, J = 5.0 Hz, 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), 7.9 (D, J = 5.2 Hz, 1H), 8.59 (dd, J = 4.9, 1.8 Hz, 1H), 10.30 (s, 1H)

  Hereafter, compounds 1-2 to 21 were obtained according to the production method of compound 1-1 using compounds selected from reference compounds 3-1 to 3 and commercially available compounds and known compounds.

2- (2-Cyclopropylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (Compound 1-2) ¹ H-NMR (500 MHz, CDCl ₃ )
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 (br s, 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 1-3) ¹ H-NMR (500 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 1-4)
¹ H-NMR (500 MHz, CDCl ₃ )
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] pyridine-3-carboxamide (Compound 1-5)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 1-6)
¹ H-NMR (500 MHz, CDCl ₃ )
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) pyridine-3-carboxamide (Compound 1-7) ¹ H— NMR (400 MHz, CDCl ₃ )
δ 1.47 (s, 9H), 2.29 (s, 6H), 3.49 (br s, 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)
¹ H-NMR (500 MHz, CDCl ₃ )
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] pyridine-3-carboxamide (Compound 1-9)
¹ H-NMR (500 MHz, CDCl ₃ )
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), 6.64 (dd, J = 5.1) , 1.1 Hz, 1H), 6.73 (s, 1H), 6.82 (s, 1H), 7.14 (dd, J = 7.6, 4.8 Hz, 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) pyridine-3-carboxamide (Compound 1-10)
¹ H-NMR (500 MHz, CDCl ₃ )
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 = 4.9 Hz, 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) pyridine-3-carboxamide (Compound 1-11)
¹ H-NMR (500 MHz, CDCl ₃ )
δ 2.09 (t, J = 7.3 Hz, 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)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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) .6 Hz, 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) pyridine-3-carboxamide (Compound 1-13)
¹ H-NMR (400 MHz, CDCl ₃ )
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 1-14)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 1-15)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1.7 Hz, 1H), 10.31 (s, 1H)

N- (3,5-dimethylphenyl) -2- [2- (3-hydroxymethylpiperidin-1-yl) pyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 1-16)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 13.1 Hz, 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 1-17)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 13.6 Hz, 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) pyridine-3-carboxamide (Compound 1-18)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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] pyridine-3-carboxamide (Compound 1-19)
¹ H-NMR (400 MHz, CDCl ₃ )
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) pyridine-3-carboxamide (Compound 1-20)
¹ H-NMR (500 MHz, CDCl ₃ )
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) , 1.5 Hz, 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)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.18 (t, J = 7.0 Hz, 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)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＤＭＳＯ−ｄ_６）
δ １．４５（ｓ，９Ｈ），２．２５（ｓ，６Ｈ），４．３８（ｓ，２Ｈ），６．７６（ｓ，１Ｈ），７．０３（ｄ，Ｊ ＝ ５．２ Ｈｚ，１Ｈ），７．２８（ｄｄ，Ｊ ＝ ７．６，４．９ Ｈｚ，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（ｂｒ ｓ，１Ｈ）
以下、参考化合物９−１〜６、市販化合物及び既知化合物から選択される化合物を使用して、化合物２−１の製造方法に準じ、化合物２−２〜３６を得た。Example 2
2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (Compound 2-1)
At room temperature, 2- (2-tert-butoxycarbonylaminopyridin-4-ylmethylthio) pyridine-3-carboxylic acid (Reference compound 9-1, 500 mg, 1.4 mmol) and 3,5-xylidine (180 mg, 1.. 5 mmol) and N, N-diisopropylethylamine (0.72 mL, 4.1 mmol) in N, N-dimethylformamide (7 mL) was added O- (7-azabenzotriazol-1-yl) -N, N, N ′. , N′-Tetrauronium hexafluorophosphate (630 mg, 1.7 mmol) was added and stirred for 12 hours. Ethyl acetate (30 mL) was added to the reaction solution, washed with saturated brine (50 mL), and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to quantitatively obtain 670 mg of the target compound as a colorless solid.

¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.45 (s, 9H), 2.25 (s, 6H), 4.38 (s, 2H), 6.76 (s, 1H), 7.03 (d, J = 5.2 Hz, 1H), 7.28 (dd, J = 7.6, 4.9 Hz, 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 (br s, 1H)
Hereinafter, compounds 2-2 to 36 were obtained according to the production method of compound 2-1, using compounds selected from reference compounds 9-1 to 6, commercially available compounds, and known compounds.

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridine-3-carboxamide (Compound 2-2)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 1.5 Hz, 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) pyridine-3-carboxamide (Compound 2-3)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.45 (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, 4.9 Hz, 1H) 7.38 (d, J = 8.2 Hz, 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)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.45 (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, 1H)

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) pyridine-3-carboxamide (Compound 2-5)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 8.8 Hz, 2H), 7.87 ( s, 1H), 7.94 (dd, J = 7.6, 1.5 Hz, 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) pyridine-3-carboxamide (Compound 2-6)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 4.9 Hz, 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 2-7)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 4.9 Hz, 1H), 7.31 (s, 2H), 7.64 (s, 1H), 7.93 (dd, J = 7.6, 1.5 Hz, 1H), 8.25 (d, J = 5.2 Hz, 1H), 8.58 (dd, J = 4.9, 1.H). 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)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 9.2 Hz, 2H), 7.9 (dd, J = 7.6, 1.8 Hz, 1H), 8.23 (d, J = 5.2 Hz, 1H), 8.60 (dd , J = 4.9, 1.8 Hz, 1H), 10.65 (s, 1H)

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridine-3-carboxamide (Compound 2-10)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 8.9 Hz, 2H), 7.72 (d, J = 8.9 Hz, 2H), 7.87 (s, 1H), 7.98 ( dd, J = 7.6, 1.5 Hz, 1H), 8.10 (d, J = 5.2 Hz, 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 2-11)
¹ H-NMR (400 MHz, CDCl ₃ )
δ 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, 1.4 Hz, 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, 1.8 Hz, 1H), 7.97. (S, 1H), 8.25 (d, J = 5.1 Hz, 1H), 8.55 (dd, J = 4.9, 1.8 Hz, 1H)

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3-chlorophenyl) pyridine-3-carboxamide (Compound 2-12)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.45 (s, 9H), 4.39 (s, 2H), 7.03 (d, J = 5.2 Hz, 1H), 7.19 (d, J = 8.2 Hz, 1H) , 7.30 (dd, J = 7.6, 4.9 Hz, 1H), 7.38 (t, J = 8.1 Hz, 1H), 7.59 (d, J = 8.2 Hz, 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) pyridine-3-carboxamide (Compound 2-13)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 0.0 Hz, 1H), 7.88 (br s, 1H), 7.98 (d, J = 7.1 Hz, 1H), 8.06 (dd, J = 7.6, 1.7 Hz, 1H), 8.08 (brs, 1H), 8.11 (d, J = 5.2 Hz, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 8 .59 (d, J = 1.0 Hz, 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 2-14)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 8.9 Hz, 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) pyridine-3-carboxamide (Compound 2-15)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 2-16)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 2-17)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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), 8.59-8.60 (m, 2H), 9.19 (s, 1H), 11.15 (s, 1H)

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- [2- (4-methoxyphenyl) ethyl] pyridine-3-carboxamide (Compound 2-18)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 (br s, 1H), 8.11 (d, J = 4.9 Hz, 1H), 8.52 (dd, J = 4.9, 1.7 Hz, 1H), 8.58 (t , J = 5.4 Hz, 1H), 9.68 (s, 1H)

N- (adamantan-1-yl) -2- (2-tert-butoxycarbonylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 2-19)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 1.47 (s, 9H), 1.64 (br s, 6H), 2.03 (br s, 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 )
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 2-21)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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] pyridine-3-carboxamide (Compound 2-22)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 8.8 Hz, 2H), 7.99 (dd, J = 7.6, 1 .7 Hz, 1H), 8.25 (s, 1H), 8.28 (d, J = 5.1 Hz, 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) pyridine-3-carboxamide (Compound 2-23)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 4.43 (s, 2H), 7.11 (d, J = 5.1 Hz, 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 .7 Hz, 1H), 8.25 (s, 1H), 8.28 (d, J = 5.1 Hz, 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) pyridine-3-carboxamide (Compound 2-24)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 4.9 Hz, 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 2-25)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 1H), 10.48 (s, 1H)

2- (2-tert-Butoxycarbonylaminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) benzamide (Compound 2-26)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 7.6 Hz, 1H), 7.49 (d, J = 7.6 Hz, 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 2-27)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 2-28)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 (br s, 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-4-ylmethylthio) -N- (3-isopropylphenyl) benzamide (Compound 2-29)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 (br s, 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)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 7.3 Hz, 1H) 7.54 (d, J = 8.6 Hz, 1H), 7.72-7.80 (m, 2H), 7.84 (brs, 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)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 7.3 Hz, 1H), 7.68 (d, J = 8.6 Hz, 1H), 7.84 (s, 1H), 7.99 (brs, 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 2-32)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.45 (s, 9H), 2.25 (s, 6H), 4.22 (s, 2H), 6.74 (s, 1H), 7.00 (dd, J = 4.9). 2 Hz, 1H), 7.28 (t, J = 7.3 Hz, 1H), 7.35 (s, 2H), 7.41 (m, 1H), 7.45 (s, 1H), 7 .48 (t, J = 7.3 Hz, 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 2-33)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 2-34)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 1.46 (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 2-35)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 2.4 Hz, 1H), 8.10 (d, J = 5.2 Hz, 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 2-36)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 7.9 Hz, 1H), 7.60 (t, J = 7.9 Hz, 1H), 7.88 (s, 1H), 7.91 ( d, J = 7.9 Hz, 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)

もしくは以下の方法によって化合物３−１の遊離塩基を合成することができる。1 of 2- (2-tert-butoxycarbonylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (Compound 2-1, 420 mg, 0.90 mmol) at room temperature 4,4-Dioxane (5.0 mL) solution was added 4N hydrogen chloride 1,4-dioxane solution (5.0 mL), and the mixture was stirred for 12 hours. Ethanol (6.0 mL) was added to the reaction solution, and the precipitated solid was collected by filtration. The solid was dried at 60 ° C. under reduced pressure to obtain 320 mg of the target compound as colorless crystals (yield 88%).

Alternatively, the free base of compound 3-1 can be synthesized by the following method.

Under ice cooling, N- (3,5-dimethylphenyl) -2-thioxo-1,2-dihydropyridine-3-carboxamide (Reference compound 10-1, 100 g, 0.39 mol) and 2-amino-4-bromomethyl Pyridine hydrobromide (Reference compound 14-1, 110 g, 0.40 mol) was dissolved in N, N-dimethylformamide (840 mL), and then triethylamine (160 mL, 1.2 mol) was added dropwise at room temperature for 6 hours. Stir. The reaction solution was poured into water (2.5 L), and the precipitated solid was collected by filtration, heated to 45 ° C. under reduced pressure and dried to quantitatively obtain 140 g of the free base of the target compound as a pale yellow solid. .
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 4.9 Hz, 1H), 7.34 (s, 2H), 7.84 (d, J = 6.7 Hz, 1H), 7. 97 (br s, 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 (br s, 1H)

  Hereafter, compounds 2-2 to 36, compounds selected from commercially available compounds and known compounds were used, and compounds 3 to 37 were obtained according to the production method of compound 3-1.

2- (2-Aminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridine-3-carboxamide monohydrochloride (Compound 3-2)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.21 (d, J = 6.7 Hz, 6H), 2.87 (m, 1H), 4.41 (s, 2H), 6.89 (d, J = 6.7 Hz, 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 (brs, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (indan-5-yl) pyridine-3-carboxamide monohydrochloride (Compound 3-3)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 4.9 Hz, 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 (brs, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) pyridine-3-carboxamide monohydrochloride (Compound 3-4)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 4.9 Hz, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.62 (d, J = 8.8 Hz, 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 (brs, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) pyridine-3-carboxamide monohydrochloride (Compound 3-5)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 4.42 (s, 2H), 6.39 (br s, 1H), 6.89 (d, J = 6.4 Hz, 1H), 7.06 (s, 1H), 7.29-7 .36 (m, 2H), 7.70 (d, J = 8.5 Hz, 1H), 7.85 (d, J = 6.4 Hz, 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 (br s, 1H)

N- (3,5-dimethylphenyl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide monohydrochloride (Compound 3-6)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 2.26 (s, 6H), 2.91 (d, J = 4.9 Hz, 3H), 4.41 (s, 2H), 5.98 (brs, 1H), 6.77 (s , 1H), 6.87 (dd, J = 7.7, 1.5 Hz, 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, 1.5 Hz, 1H), 10.39 (s, 1H), 13.48 (brs, 1H)

N- (Indan-5-yl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide monohydrochloride (Compound 3-7)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 8.3 Hz, 1H), 7.31 (Dd, J = 7.6, 4.9 Hz, 1H), 7.42 (d, J = 8.8 Hz, 1H), 7.63 (s, 1H), 7.80 (d, J = 6.6 Hz, 1H), 8.01 (dd, J = 7.6, 1.7 Hz, 1H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 8. 97 (br s, 1H), 10.44 (s, 1H), 13.43 (br s, 1H)

2- (2-Methylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide monohydrochloride (Compound 3-8)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 2.91 (d, J = 4.9 Hz, 3H), 4.42 (s, 2H), 6.87 (dd, J = 6.7, 1.5 Hz, 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 (br s , 1H), 10.77 (s, 1H), 13.32 (br s, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridine-3-carboxamide monohydrochloride (Compound 3-9)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 8.6 Hz, 2H), 7.75 (d, J = 8.6 Hz, 2H), 7.84 (d, J = 6.4 Hz, 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 (brs, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 3-10)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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.H). 8 Hz, 1H), 10.67 (s, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (3-chlorophenyl) pyridine-3-carboxamide monohydrochloride (Compound 3-11)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 8.1 Hz, 1H), 7.64 (d, J = 8.1 Hz, 1H), 7.85 (d, J = 6.6 Hz, 1H), 7.93 (s, 1H), 8.04 (brs, 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 (brs, 1H)

N- (3,5-dimethylphenyl) -2- (2-ethylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 3-12)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1.5 Hz, 1H) , 8.57 (dd, J = 4.8, 1.5 Hz, 1H), 10.30 (s, 1H)

2- (2-aminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) pyridine-3-carboxamide (Compound 3-13) ¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 1.2 Hz, 1H), 7.78 (d, J = 5.2 Hz, 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 (brs, 1H), 9.19 (brs, 1H), 11.15 (s, 1H)

N- (4-Chlorophenyl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 3-14)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 3-15)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 4.9 Hz, 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) pyridine-3-carboxamide (Compound 3-16)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 8.8 Hz, 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.H). 7 Hz, 1H), 10.39 (s, 1H)

N- (isoquinolin-3-yl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 3-17)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 8.1 Hz, 1H), 8.04 (dd, J = 7.6, 1.7 Hz, 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)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 1.65 (br s, 6H), 2.04 (br s, 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 (brs, 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] pyridine-3-carboxamide dihydrochloride (Compound 3-19)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 3-20)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 (br s, 2H), 10.21 (s, 1H), 13.43 (br s, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) benzamide monohydrochloride (Compound 3-21)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 4.25 (s, 2H), 6.81 (dd, J = 6.7, 1.5 Hz, 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 (brs, 2H), 10.51 (s, 1H), 13.33 (brs, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) benzamide monohydrochloride (Compound 3-22)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 8.8 Hz, 2H), 7.40-7.47 (m, 2H), 7.53 (d, J = 6.6). Hz, 1H), 7.63 (d, J = 8.8 Hz, 2H), 7.83 (d, J = 6.6 Hz, 1H), 7.90 (brs, 2H), 10.29 (S, 1H), 13.36 (br s, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) benzamide monohydrochloride (Compound 3-23)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 8.9 Hz, 2H), 7.43-7.49 (m, 2H), 7.57 (d, J = 6.7 Hz, 1H), 7.83 (s, 1H), 7. 83 (d, J = 8.9 Hz, 2H), 7.88 (br s, 2H), 10.57 (s, 1H), 13.41 (br s, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) benzamide monohydrochloride (Compound 3-24)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 (br s, 2H), 8.09 (D, J = 8.2 Hz, 1H), 8.59 (s, 1H), 9.20 (s, 1H), 10.99 (s, 1H), 13.51 (brs, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) benzamide (Compound 3-25)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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), 7.24 (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 = 7.6 Hz, 1H), 7 , 51 (d, J = 7.6 Hz, 1H), 7.54 (d, J = 8.2 Hz, 1H), 7.64 (br s, 1H), 7.79 (d, J = 5 .2 Hz, 1H), 10.28 (s, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (4-chloro-3-methylphenyl) benzamide (Compound 3-26)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 (br s, 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 3-27)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 (brs, 1H), 8.26 (brs, 1H), 10.50 (s, 1H), 12.93 (s, 1H)

3- (2-Aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) thiophene-2-carboxamide (Compound 3-28)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 3-29)
¹ H-NMR (500 MHz, CDCl ₃ )
δ 2.30 (s, 6H), 4.15-4.60 (br s, 2H), 4.38 (s, 2H), 6.81 (s, 1H), 7.09 (d, J = 4.9 Hz, 1H), 7.13 (dd, J = 7.6, 4.9 Hz, 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, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (3,5-dimethyl-4-hydroxyphenyl) pyridine-3-carboxamide (Compound 3-30)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 3-31)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 3-32)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 3-33)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 7.8 Hz, 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) pyridine-3-carboxamide (Compound 3-34)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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.H). 7 Hz, 1H), 10.83 (s, 1H)

2- (2-Aminopyridin-4-ylmethylthio) -N- (3-chloro-4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 3-35)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 2.4 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) pyridine-3-carboxamide (Compound 3-36)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 7.1 Hz, 1H), 7.77 (d, J = 5.1 Hz, 1H), 7.91 (d, J = 8.1 Hz, 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) pyridine-3-carboxamide (Compound 3-37)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.20 (d, J = 7.0 Hz, 6H), 2.87 (m, 1H), 4.24 (s, 2H), 5.83 (s, 2H), 6.45 (br 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) pyridine-3-carboxamide (Compound 4-1)

もしくは以下の方法によっても合成できる。At room temperature, 2- (2-aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide monohydrochloride (Compound 3-1, 1.0 g, 2.5 mmol) Acetic anhydride (1.0 mL, 10 mmol) was added to a pyridine (10 mL) solution and stirred for 4 hours. Ethyl acetate (30 mL) was added to the reaction solution, washed with water (20 mL) and saturated brine (20 mL), and the organic layer was dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure, and the resulting solid was collected by filtration with a hexane / ethyl acetate (1: 1) solution to obtain 770 mg of the target compound as colorless crystals (yield 76%).

Alternatively, it can be synthesized by the following method.

N- (3,5-dimethylphenyl) -2-thioxo-1,2-dihydropyridine-3-carboxamide (Reference compound 10-1, 200 mg, 0.77 mmol) and 2-acetylamino under ice-cooling and nitrogen atmosphere -4-Methanesulfonyloxymethylpyridine (reference compound 13-1, 190 mg, 0.77 mmol) was suspended in N, N-dimethylformamide (2.0 mL), triethylamine (022 mL, 1.5 mmol) was added, and room temperature was added. For 2 hours. Ethyl acetate (40 mL) was added to the reaction mixture, and the mixture was washed with water (30 mL) and saturated brine (20 mL). The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained solid was collected by filtration using a mixed solvent of diisopropyl ether and ethyl acetate, and dried at 40 ° C. under reduced pressure to obtain 250 mg of the target compound as a pale yellow solid (yield 81%).
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 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)

  Hereinafter, compounds 4-2 to 68 were obtained according to the production method of compound 4-1, using compounds selected from compounds 3-1 to 37, commercially available compounds, and known compounds.

N- (3,5-dimethylphenyl) -2- (2-propionylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 4-2)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.05 (t, J = 7.3 Hz, 3H), 2.25 (s, 6H), 2.36 (q, J = 7.3 Hz, 2H), 4.39 (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 4-3)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 4.9 Hz, 1H), 8.58 (dd, J = 4.9, 1.H). 7 Hz, 1H), 10.30 (s, 1H), 11.97 (brs, 1H)

N- (3,5-dimethylphenyl) -2- (2-isobutyrylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 4-4)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 1.8 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), 8.17-8.19 (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) pyridine-3-carboxamide (Compound 4-5)
¹ H-NMR (400 MHz, CDCl ₃ )
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 (brs, 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 4-6)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 (br s, 1H)

N- (3,5-dimethylphenyl) -2- (2-methanesulfonylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 4-7)
¹ H-NMR (500 MHz, CDl ₃ )
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 (brs, 1H)

2- (2-acetylaminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridine-3-carboxamide (Compound 4-8)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 4-9)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 4-10)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 5.2 Hz, 1H), 8.59 (dd, J = 4.9, 1.8 Hz, 1H) ), 10.40 (s, 1H), 10.59 (s, 1H)

2- (2-acetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 4-11)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 4-12)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 1H)

2- (2-acetylaminopyridin-4-ylmethylthio) -N- (quinolin-6-yl) pyridine-3-carboxamide (Compound 4-13)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.06 (s, 3H), 4.42 (s, 2H), 7.11 (d, J = 5.2 Hz, 1H), 7.33 (dd, J = 7.6, 4.9) Hz, 1H), 7.51 (dd, J = 8.2, 4.3 Hz, 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 = 7.6 Hz, 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 4-14)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 4-15)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 4-16)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 4-17)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 1.27 (s, 9H), 2.06 (s, 3H), 4.39 (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, 1.8 Hz, 1H), 10 .39 (s, 1H), 10.41 (s, 1H)

2- (2-acetylaminopyridin-4-ylmethylthio) -N- (4-fluoro-3-methylphenyl) pyridine-3-carboxamide (Compound 4-18)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 4-19)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 4-20)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.06 (s, 3H), 2.30 (s, 3H), 4.40 (s, 2H), 6.93 (d, J = 8.1 Hz, 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, 4.9 Hz, 1H), 7.45 (d, J = 8.1 Hz, 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) pyridine-3-carboxamide (Compound 4-21)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1H)

2- (2-acetylaminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) pyridine-3-carboxamide (Compound 4-22)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 4-23)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 4-24)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 4-25)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 4-26)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 8.4 Hz, 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), 10.40 (s, 1H)

2- [2- (N-acetyl-N-methylamino) pyridin-4-ylmethylthio] -N- (4-chlorophenyl) pyridine-3-carboxamide (Compound 4-27)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 2.1 Hz, 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) pyridine-3-carboxamide (Compound 4-28)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 4-29)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 4-30)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 4-31)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 8.9). Hz, 2H), 8.00 (dd, J = 7.6, 1.8 Hz, 1H), 8.35 (d, J = 4.9 Hz, 1H), 8.60 (dd, J = 4). .7, 1.8 Hz, 1H), 10.66 (s, 1H)

N- (3-chlorophenyl) -2- [2- (N-methyl-N-propionylamino) pyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 4-32)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 0.9 Hz, 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 0.00 (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) pyridine-3-carboxamide (Compound 4-33)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 (br s, 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] pyridine-3-carboxamide (Compound 4-34)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 1.8 Hz, 1H), 8 .15 (br s, 1H), 8.17 (d, J = 5.2 Hz, 1H), 8.52 (dd, J = 4.9, 1.8 Hz, 1H), 8.57 (t , J = 5.5 Hz, 1H), 10.41 (s, 1H)

2- (2-acetylaminopyridin-4-ylmethylthio) -N- (2-chlorophenyl) pyridine-3-carboxamide (Compound 4-35)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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-dimethoxyphenyl) pyridine-3-carboxamide (Compound 4-36)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 4-37)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1H)

N- (3,5-dimethylphenyl) -2- [2- (2,5-dioxopyrrolidin-1-yl) pyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 4-38)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 2.26 (s, 6H), 2.80 (s, 4H), 4.48 (s, 2H), 6.76 (s, 1H), 7.28 (dd, J = 7.6, 4 .9 Hz, 1H), 7.32 (s, 2H), 7.40 (s, 1H), 7.52 (d, J = 4.9 Hz, 1H), 7.94 (dd, J = 7) .6, 1.5 Hz, 1H), 8.47 (d, J = 4.9 Hz, 1H), 8.57 (dd, J = 4.9, 1.5 Hz, 1H), 10.31 (S, 1H)

N- (3,5-dimethylphenyl) -2- (2-methoxycarbonylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 4-39)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 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) pyridine-3-carboxamide (Compound 4-40)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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] pyridine-3-carboxamide (Compound 4-41)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 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 4-42)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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), 10.48 (s, 1H)

2- (2-acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) benzamide (Compound 4-43)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 4-44)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 7.3 Hz, 1H), 7.50 (d, J = 7.3 Hz, 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 4-45)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 4-46)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 4-47)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 7.6 Hz, 1H), 7.41 (t, J = 7.6 Hz, 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, 1H)

2- (2-acetylaminopyridin-4-ylmethylthio) -N- (4-chloro-3-methylphenyl) benzamide (Compound 4-48)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 4-49)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 4-50)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 (br s, 1H), 8.18 (d, J = 5.2 Hz, 1H), 8.25 (t, J = 6.4 Hz, 1H) , 10.43 (s, 1H)

3- (2-acetylaminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) thiophene-2-carboxamide (Compound 4-51)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 4-52)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 (br s, 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 4-53)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 4-54)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 (br s, 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 4-55)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 5.2 Hz, 1H), 8.06 (t, J = 5) .5 Hz, 1 H), 8.08 (br s, 1 H), 8.18 (d, J = 4.9 Hz, 1 H), 10.46 (s, 1 H)

3- (2-acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) thiophene-2-carboxamide (Compound 4-56)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1 H), 7.22-7.27 (m, 3 H), 7.83 (d, J = 5.1 Hz, 1 H), 8.11 (s, 1 H), 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 4-57)
¹ H-NMR (500 MHz, CDCl ₃ )
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 4-58)
¹ H-NMR (400 MHz, CDCl ₃ )
δ 2.10 (s, 3H), 3.98 (s, 2H), 6.48 (dd, J = 5.1, 1.7 Hz, 1H), 7.15 (d, J = 0.7 Hz, 1H), 7.17 (d, J = 5.1 Hz, 2H), 7.54 (dd, J = 7.8, 2.2 Hz, 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) pyridine-3-carboxamide (Compound 4-59)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 Hz, 1H), 9.89 (s, 1H), 10.30 (s, 1H)

2- (2-methoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 4-60)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 8.6 Hz, 2H), 7.9 (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) pyridine-3-carboxamide (Compound 4-61)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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-chlorophenyl) pyridine-3-carboxamide (Compound 4-62)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 (brs, 1H), 8.20 (d, J = 5.2 Hz, 1H), 8.58 (dd, J = 4.9, 1.5 Hz, 1H), 10.59 (s, 1H), 10.60 (s, 1H)

N- (3,5-dimethylphenyl) -2- (3-methanesulfonylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 4-63)
¹ H-NMR (500 MHz, CDCl ₃ )
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) pyridine-3-carboxamide (Compound 4-64)
¹ H-NMR (400 MHz, CDCl ₃ )
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 4-65)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 4-66)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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)

2- [2- (4-Hydroxycarbonylbutyryl) aminopyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (Compound 4-67)
¹ H-NMR (400 MHz, DMSO-d ₆ )
[delta] 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 (br s, 1H)

2- [2- (3,5-Dioxomorpholin-4-yl) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (Compound 4-68)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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)

Example 5
N- (3,5-dimethylphenyl) -2- [2- (N′-n-propylureido) pyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 5-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＤＭＳＯ−ｄ_６）
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（ｂｒ ｓ，１Ｈ），８．５７（ｄｄ，Ｊ ＝ ４．９，１．５ Ｈｚ，１Ｈ），９．１３（ｓ，１Ｈ），１０．２９（ｓ，１Ｈ）At room temperature, 2- (2-aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (Compound 3-1 free base, 28 mg, 0.077 mmol) in N, To a solution of N-dimethylformamide (0.60 mL) was added n-propyl isocyanate (20 mg, 0.23 mmol), and the mixture was stirred at 80 ° C. for 4 hours. Ethyl acetate (10 mL) was added to the reaction solution, washed with water (15 mL) and saturated brine (15 mL), and the organic layer was dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to obtain 12 mg of the target compound as a colorless solid (yield 33%).

¹ H-NMR (500 MHz, DMSO-d ₆ )
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 (br s, 1H), 8.57 (dd, J = 4.9, 1.5 Hz, 1H), 9.13 (s, 1H), 10.29 (s, 1H)

  Hereinafter, compounds 5-2 to 6 were obtained according to the production method of compound 5-1, using compounds selected from compounds 3-1 to 37, commercially available compounds, and known compounds.

2- [2- (N′-tert-butylureido) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (Compound 5-2)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.30 (s, 9H), 2.25 (s, 6H), 4.33 (s, 2H), 6.76 (s, 1H), 6.91 (d, J = 5.2 Hz, 1H), 7.28 (dd, J = 7.6, 4.9 Hz, 1H), 7.32 (s, 2H), 7.42 (s, 1H), 7.93 (dd, J = 7) .6, 1.5 Hz, 1H), 8.03 (d, J = 5.2 Hz, 1H), 8.06 (brs, 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) pyridine-3-carboxamide (Compound 5-3)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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)

N- (3,5-dimethylphenyl) -2- [2- (N′-methylthioureido) pyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 5-4)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 1.5 Hz, 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] pyridine-3-carboxamide (Compound 5-5)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 5.4 Hz, 1H), 8.24 (br s, 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) pyridine-3-carboxamide (Compound 5-6)

¹ H-NMR (500 MHz, DMSO-d ₆ )
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 (brs, 1H), 8.60 (dd, J = 4.9, 1.5 Hz, 1H), 9.13 (s, 1H), 10.65 (s) , 1H)

Example 6
N- (3,5-dimethylphenyl) -2- (2-formylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 6-1)

^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＤＭＳＯ−ｄ_６）
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）2- (2-aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (free base of compound 3-1, 50 mg, 0.14 mmol) was added to 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 the mixture was heated to reflux for 16 hours. The mixture was diluted with dichloromethane (15 mL), washed twice with 2N aqueous sodium hydroxide solution (4.0 mL), and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to quantitatively obtain 60 mg of the target compound as a colorless solid.

¹ H-NMR (400 MHz, DMSO-d ₆ )
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 7-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＤＭＳＯ−ｄ_６）
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）To a suspension of 60% sodium hydride (13 mg, 0.30 mmol) in anhydrous N, N-dimethylformamide (1.0 mL) under ice-cooling, 2- (2-aminopyridin-4-ylmethylthio) -N- (3 , 5-dimethylphenyl) pyridine-3-carboxamide (free base of compound 3-1, 50 mg, 0.14 mmol) in anhydrous N, N-dimethylformamide (2 mL) was added dropwise and stirred for 5 minutes. Bromoacetic acid tert-butyl ester (22 μL, 0.15 mmol) was added to the reaction solution, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into ice water (15 mL) and extracted with ethyl acetate (15 mL). The organic layer was washed with saturated aqueous sodium hydrogen carbonate (30 mL) and saturated brine (30 mL), and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 45 mg of the target compound as a colorless amorphous (yield 69%).

¹ H-NMR (500 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 8-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＤＭＳＯ−ｄ_６）
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）To the 1,4-dioxane (2.0 mL) while bubbling nitrogen, 2- (2-aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (Compound 3- 1 free base, 63 mg, 0.18 mmol), cesium carbonate (130 mg, 0.38 mmol), iodobenzene (37 μL, 0.33 mmol), 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene ( 8.1 mg, 0.014 mmol) and tris (dibenzylideneacetone) dipalladium (0) (4.3 mg, 0.0047 mmol) were added. The mixture was stirred in a sealed tube at 90 ° C. for 20 hours, diluted with ethyl acetate (30 mL), and washed with saturated aqueous sodium hydrogen carbonate (30 mL). The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The product was purified by silica gel column chromatography, and the resulting solid was collected by filtration using diethyl ether. It dried under reduced pressure and obtained 31 mg of target compounds as a colorless solid (yield 31%).

¹ H-NMR (500 MHz, DMSO-d ₆ )
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
N- (3,5-dimethylphenyl) -2- [2- (N′-methylureido) pyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 9-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＤＭＳＯ−ｄ_６）
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）While bubbling nitrogen, 1,4-dioxane (2.0 mL) was added to 2- (2-bromopyridin-4-ylmethylthio) -N- (3.5-dimethylphenyl) pyridine-3-carboxamide (Reference Compound 3). -4,100 mg, 0.23 mmol), cesium carbonate (91 mg, 0.28 mmol), N-methylurea (52 mg, 0.70 mmol), 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene ( 8.1 mg, 0.014 mmol) and tris (dibenzylideneacetone) dipalladium (0) (4.3 mg, 0.0047 mmol) were added. The mixture was stirred at 100 ° C. for 5 hours in a sealed tube, diluted with ethyl acetate (30 mL), and washed twice with saturated aqueous sodium hydrogen carbonate (30 mL). The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The product was purified by silica gel column chromatography, and the resulting solid was collected by filtration using ethyl acetate. It dried under reduced pressure and obtained 21 mg of target compounds as a colorless solid (yield 22%).

¹ H-NMR (500 MHz, DMSO-d ₆ )
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)

Hereinafter, compounds 9-2 to 4 were obtained according to the production method of compound 9-1 using compounds selected from reference compounds 3-4 to 7, commercially available compounds, and known compounds.

2- [2- (N′-methylureido) pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 9-2)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 8.9 Hz, 2H), 7.80 (d, J = 8 .9 Hz, 2H), 7.9 (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)

N- (4-chlorophenyl) -2- [2- (N′-methylureido) pyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 9-3)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.71 (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 (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.H). 7 Hz, 1H), 9.21 (s, 1H), 10.60 (s, 1H)

N- (4-difluoromethoxyphenyl) -2- [2- (N′-methylureido) pyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 9-4)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.70 (d, J = 4.6 Hz, 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 = 8.9 Hz, 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) pyridine-3-carboxamide (Compound 10-1)

もしくは以下のようにしても合成できる。While bubbling nitrogen, 1,4-dioxane (20 mL) was added to 2- (2-bromopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (Reference compound 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-dimethyl Xanthene (810 mg, 1.4 mmol) and tris (dibenzylideneacetone) dipalladium (0) (430 mg, 0.47 mmol) were added. The mixture was stirred at 100 ° C. for 3 hours in a sealed tube, diluted with ethyl acetate (300 mL), and washed with saturated aqueous sodium hydrogen carbonate (300 mL). The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Purification by silica gel column chromatography gave 1.0 g of the target compound as a yellowish white solid (yield 47%).

Alternatively, it can be synthesized as follows.

At room temperature, acetoxyacetic acid (1.2 g, 10 mmol) was dissolved in pyridine (12 ml), acetoxyacetic acid chloride (1.1 mL, 10 mmol) was added, and the mixture was stirred at room temperature for 4 hours. Further, 2- (2-aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (Compound 3-1 free base, 1.0 g, 2.5 mmol) was added. Stir for hours. Ethyl acetate (100 mL) was added to the reaction mixture, and the mixture was washed 3 times with 1N hydrochloric acid (150 mL), twice with saturated aqueous sodium hydrogen carbonate (150 mL), and saturated brine (150 mL), and then the organic layer was dried over anhydrous sodium sulfate. . The residue obtained by distilling off the solvent under reduced pressure was purified by silica gel column chromatography. The obtained solid was collected by filtration using ethyl acetate and dried under reduced pressure to obtain 0.97 g of the target compound as a brown solid (yield 77%).
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 Hz, 1H), 8.57 (dd, J = 4. 8, 1.8 Hz, 1H), 10.30 (s, 1H), 10.60 (s, 1H)

  Hereinafter, using compounds selected from Reference Compounds 3-4 and 3-5, Compounds 3-1 to 37 Commercially Available Compounds and Known Compounds, Compounds 10-2 to 21 are converted according to the production method of Compound 10-1. Obtained.

2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 10-2)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.09 (s, 3H), 4.41 (s, 2H), 4.68 (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 = 8.3 Hz, 2H), 7.98 (dd, J = 7.6, 1.8 Hz, 1H), 8.10 (s, 1H), 8.20 (d, J = 5.2 Hz, 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 10-3)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 10-4)
¹ H-NMR (400 MHz, CDCl ₃ )
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] pyridine-3-carboxamide (Compound 10-5)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 4.9, 1.7 Hz, 1H), 10.31 (s, 1H), 10.42 (s, 1H)

2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (indan-5-yl) pyridine-3-carboxamide (Compound 10-6)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 10-7)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.10 (s, 3H), 2.30 (s, 3H), 4.41 (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, 1H)

2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethylphenyl) pyridine-3-carboxamide (Compound 10-8)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1.7 Hz, 1H), 8.11 (s, 1H), 8.20 (d, J = 5.1 Hz, 1H), 8.60 (dd , J = 4.9, 1.7 Hz, 1H), 10.60 (s, 1H), 10.82 (s, 1H)

N- (4-chlorophenyl) -2- (2-methoxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 10-9)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1.7 Hz, 1H), 8.17 (s, 1H), 8.19 (d, J = 5.1 Hz, 1H), 8.60 (dd , J = 4.9, 1.7 Hz, 1H), 9.90 (s, 1H), 10.60 (s, 1H)

2- (2-Acetoxyacetylaminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) pyridine-3-carboxamide (Compound 10-10)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 4.9 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), 8.10 (brs, 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 10-11)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) .7 Hz, 2H), 7.81 (d, J = 8.7 Hz, 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 10-12)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 Hz, 1H), 8.10 (brs, 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) pyridine-3-carboxamide (Compound 10-13)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 (brs, 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 10-14)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 (brs, 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 10-15)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 10-16)
¹ H-NMR (500 MHz, CDCl ₃ )
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, 1.5 Hz, 1H), 7.16 (dd, J = 7.6, 4.8 Hz, 1H), 7.22. (D, J = 8.9 Hz, 2H), 7.70 (d, J = 8.9 Hz, 2H), 7.90 (dd, J = 7.6, 1.8 Hz, 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) -tert-butoxycarbonylamino-5-hydroxypentanoyl) aminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 10- 17)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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)

2- [2- (2-oxopyrrolidin-1-yl) pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 10-18)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 10-19)
¹ H-NMR (500 MHz, CDCl ₃ )
δ 3.66 (s, 2H), 4.55 (s, 2H), 7.16 (dd, J = 7.6, 4.9 Hz, 1H), 7.23 (d, J = 8.6) Hz, 2H), 7.24-7.29 (m, 2H), 7.75 (d, J = 8.6 Hz, 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 10-20)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1.7 Hz, 1H), 8.16-8.17 (m, 2H), 8 .59 (dd, J = 4.9, 1.7 Hz, 1H), 10.41 (s, 1H), 10.55 (s, 1H)

2- (2-tert-Butoxycarbonylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-difluoromethoxyphenyl) pyridine-3-carboxamide (Compound 10-21)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 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 11-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＤＭＳＯ−ｄ_６）
δ ２．０４（ｓ，６Ｈ），４．４４（ｂｒ ｓ，４Ｈ），５．３５（ｂｒ ｓ，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）2- (2-aminopyridin-4-ylmethylthio) -N- (tert-butoxycarbonylmethyl) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (Compound 7-1, 40 mg, 0.084 mmol) ) Was dissolved in ethyl acetate (1.0 mL), 4N hydrogen chloride ethyl acetate solution (1.0 mL) was added, and the mixture was stirred at room temperature for 18 hr. The precipitated solid was collected by filtration with diethyl ether and dried under reduced pressure to obtain 30 mg of the target compound as a colorless solid (yield 86%).

¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 2.04 (s, 6H), 4.44 (br s, 4H), 5.35 (br s, 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)

  Hereinafter, using compounds selected from Compounds 10-3 and 17, commercially available compounds, and known compounds, Compounds 11-2 to 3-3 were obtained according to the production method of Compound 11-1.

2- (2-Aminoacetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide monohydrochloride (Compound 11-2)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 2.25 (s, 6H), 3.81 (s, 2H), 4.46 (s, 2H), 6.76 (s, 1H), 7.10 (brs, 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 = 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-3-carboxamide monohydrochloride (compound 11-3 )
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.78-1.86 (m, 2H), 2.6-2.29 (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), 10.68 (s, 1H)

Example 12
2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 12-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＤＭＳＯ−ｄ_６）
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 ＝ ８．３ Ｈｚ，２Ｈ），７．８０（ｄ，Ｊ ＝ ８．３ Ｈｚ，２Ｈ），７．９８（ｄｄ，Ｊ ＝ ７．６，１．８ Ｈｚ，１Ｈ），８．１９（ｓ，１Ｈ），），８．２０（ｓ，１Ｈ），８．６０（ｄｄ，Ｊ ＝ ４．９，１．８ Ｈｚ，１Ｈ），９．５８（ｓ，１Ｈ），１０．６５（ｓ，１Ｈ）2- (2-acetoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 10-2, 25 mg, 0.048 mmol) in methanol (2.0 mL) And tetrahydrofuran (1.0 mL) was dissolved, and 4N aqueous sodium hydroxide solution (60 μL) was added under ice cooling. The mixture was stirred at room temperature for 15 minutes, diluted with ethyl acetate (30 mL), and washed with saturated aqueous sodium hydrogen carbonate (30 mL) and saturated brine (30 mL). The organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and 23 mg of the target compound was quantitatively obtained as a pale yellow solid.

¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 8.3 Hz, 2H), 7.80 (d, J = 8.3 Hz, 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, 1.8 Hz, 1H), 9.58 (s, 1H), 10.65 (s, 1H)

  Hereinafter, compounds 12-2 to 16 were obtained according to the production method of compound 12-1, using compounds selected from compounds 10-1 to 21, commercially available compounds, and known compounds.

N- (3,5-dimethylphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 12-2)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 12-3)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1.7 Hz, 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] pyridine-3-carboxamide (Compound 12-4)
¹ H-NMR (400 MHz, CDCl ₃ )
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), 7.09-7.13 (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 12-5)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 2.15 (s, 6H), 4.01-4.05 (m, 2H), 4.41 (s, 2H), 5.75 (br s, 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) pyridine-3-carboxamide (Compound 12-6)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (compound 12-7)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 12-8)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 1.27 (s, 9H), 4.01 (d, J = 5.5 Hz, 2H), 4.42 (s, 2H), 5.74 (t, J = 5.5 Hz, 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 (br s, 1H), 10.40 (s, 1H)

2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) pyridine-3-carboxamide (Compound 12-9)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 12-10)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 12-11)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 4.9 Hz, 1H), 7.38 (d, J = 6.9 Hz, 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 12-12)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 12-13)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 (br s, 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 12-14)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 12-15)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 12-16)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 13-1)

^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＤＭＳＯ−ｄ_６）
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）2- (2-aminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 3-11, 800 mg, 1.9 mmol) was dissolved in pyridine (10 mL), Acetoxyacetic chloride (0.66 mL, 6.1 mmol) was added under ice cooling, and the mixture was stirred at room temperature for 18 hours. The mixture was diluted with ethyl acetate (100 mL), washed with saturated aqueous sodium hydrogen carbonate (100 mL), and then washed twice with 1N hydrochloric acid (50 mL). After washing again with saturated aqueous sodium hydrogen carbonate (100 mL) and drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. The obtained solid was recrystallized from ethyl acetate-hexane to obtain 300 mg of the target compound as a colorless solid (yield 30%).

¹ H-NMR (400 MHz, DMSO-d ₆ )
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)

  Hereinafter, compounds 13-2 to 14 were obtained according to the production method of compound 13-1, using compounds 3-1 to 37, a compound selected from commercially available compounds and known compounds.

2- [2-Bis (acetoxyacetyl) aminopyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (Compound 13-2)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 4.9 Hz, 1H), 7.33 (s, 2H), 7.58 (s, 1H), 7.59 (d, J = 5.6 Hz, 1H), 7.95 (dd, J = 7.6, 1.7 Hz, 1H), 8.49 (d, J = 5.6 Hz, 1H), 8.54 (dd, J = 4.9, 1.H). 7 Hz, 1H), 10.31 (s, 1H)

N- (3,5-dimethylphenyl) -2- (2-ethoxycarbonyloxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 13-3)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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- (3-Hydroxycarbonylpropionyloxy) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 13-4)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 (brs, 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 (br s, 1H)

N- (3,5-dimethylphenyl) -2- (2-methanesulfonylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 13-5)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 (s, 2H), 7.47 (s, 1H), 7.92 (d, J = 7.6 Hz, 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 13-6)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 13-7)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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), 7.9 (dd, J = 7.6, 1.7 Hz, 1H), 8.12 (s, 1H), 8.19 (d, J = 5.1 Hz) , 1H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 10.52 (s, 1H), 10.67 (s, 1H)

2- (2-morpholinocarbonyloxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 13-8)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 8.8 Hz) , 2H), 7.80 (d, J = 8.8 Hz, 2H), 7.99 (dd, J = 7.6, 1.7 Hz, 1H), 8.12 (s, 1H), 8 .19 (d, J = 5.1 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 13-9)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 1H)

2- [2- (4-Hydroxycarbonylbutyryl) oxyacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 13-10)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 4.9 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 (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 (br s, 1H)

2- (2-acetoxyacetoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 13-11)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 13-12)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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), 8.18-8.20 (m, 2H), 8.60 (dd, J = 4.9, 1.7 Hz, 1H), 9.78 (s, 1H), 10.66. (S, 1H)

2- (2-Dimethylaminoacetylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 13-13)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1.6 Hz, 1H), 10.45 (s, 1H), 10.66 (s, 1H)

N- (4-Difluoromethoxyphenyl) -2- (2-dimethylaminocarbonyloxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 13-14)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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)

Example 14
N- (4-tert-butylphenyl) -2- (2-dimethylaminopyridin-4-ylmethylthio) benzamide (Compound 14-1)

^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＤＭＳＯ−ｄ_６）
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 ＝ ８．５ Ｈｚ，２Ｈ），７．９５（ｄｄ，Ｊ ＝ ５．１，０．７ Ｈｚ，１Ｈ），１０．２７（ｓ，１Ｈ）4-Chloromethyl-2-dimethylaminopyridine (36 mg, 0.21 mmol), N- (4-tert-butylphenyl) -2-mercaptobenzamide (36 mg, 0.13 mmol) in N, N-dimethyl at room temperature Triethylamine (61 μL, 0.44 mmol) was added to a formamide (1.0 mL) solution and stirred for 68 hours. The mixture was diluted with ethyl acetate (30 mL), washed successively with saturated aqueous sodium hydrogen carbonate (30 mL) and saturated brine (30 mL), and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 19 mg of the target compound as a pale yellow oil (yield 22%).

¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 8.5 Hz, 2H), 7.95 (dd, J = 5.1, 0.7 Hz, 1H), 10.27 (s, 1H)

  Hereinafter, using a compound selected from Reference Compound 10-1, a commercially available compound, and a known compound, Compound 14-2 was obtained according to the production method of Compound 14-1.

2- (2-Dimethylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (Compound 14-2)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 1H)

Example 15
2- (2-acetylaminopyridin-4-ylmethylsulfinyl) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (Compound 15-1)

^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＤＭＳＯ−ｄ_６）
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）Under ice cooling, 2- (2-acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (Compound 4-1, 60 mg, 0.15 mmol) in methylene chloride ( 3 mL) solution was added m-chloroperbenzoic acid (75%, 60 mg, 0.26 mmol) and stirred for 1 hour. The reaction solution was diluted with ethyl acetate (30 mL), washed twice with saturated aqueous sodium hydrogen carbonate (10 mL) and saturated brine (10 mL), and then dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure, and the precipitated solid was collected by filtration with ethyl acetate to obtain 30 mg of the target compound as a colorless solid (yield 48%).

¹ H-NMR (400 MHz, DMSO-d ₆ )
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 16-1)

^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＤＭＳＯ−ｄ_６）
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）Under ice-cooling, N- (4-tert-butylphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 12-8, 250 mg, 0.55 mmol) was added to anhydrous dichloromethane. (5.0 mL) and thionyl chloride (80 μL, 1.1 mmol) was added. After stirring at room temperature for 6 hours, the solvent was distilled off under reduced pressure. The obtained solid was collected by filtration with ethyl acetate and washed with diethyl ether to quantitatively obtain 270 mg of the target compound as a pale yellow solid.

¹ H-NMR (400 MHz, DMSO-d ₆ )
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)

  Hereinafter, compounds 16-2 to 16-9 were obtained according to the production method of compound 16-1, using compounds selected from compounds 12-1 to 16, commercial compounds, and known compounds.

2- (2-Chloroacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 16-2)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 8.8 Hz, 2H), 7.99 (dd, J = 7 .8, 1.7 Hz, 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) pyridine-3-carboxamide (Compound 16-3)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 8.8 Hz, 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) pyridine-3-carboxamide (Compound 16-4)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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.. 7 Hz, 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 16-5)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 4.32 (s, 2H), 4.43 (s, 2H), 7.17 (t, J = 74.2 Hz, 1H), 7.17-7.19 (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), 10.75 (s, 1H)

2- (2-Chloroacetylaminopyridin-4-ylmethylthio) -N- (3-methylphenyl) pyridine-3-carboxamide (Compound 16-6)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.30 (s, 3H), 4.32 (s, 2H), 4.42 (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, 4.9 Hz, 1H), 7.46 (d, J = 7.8 Hz, 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) pyridine-3-carboxamide (Compound 16-7)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 4.32 (s, 2H), 4.44 (s, 2H), 7.17 (d, J = 5.1, 1.0 Hz, 1H), 7.32 (dd, J = 7.7) , 4.9 Hz, 1H), 7.73 (d, J = 8.5 Hz, 2H), 7.92 (d, J = 8.5 Hz, 2H), 8.02 (dd, J = 7 .7, 1.7 Hz, 1H), 8.15 (s, 1H), 8.22 (d, J = 5.1 Hz, 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) pyridine-3-carboxamide (Compound 16-8)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 4.32 (s, 2H), 4.44 (s, 2H), 7.18 (d, J = 5.1, 1.2 Hz, 1H), 7.33 (dd, J = 7.6) , 4.8 Hz, 1H), 7.48 (d, J = 8.1 Hz, 1H), 7.61 (t, J = 8.1 Hz, 1H), 7.92 (d, J = 8 .1 Hz, 1H), 8.04 (dd, J = 7.6, 1.7 Hz, 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 16-9)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 7.6 Hz, 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
N- (4-tert-butylphenyl) -2- (2-morpholinoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 17-1)

^１Ｈ−ＮＭＲ（５００ＭＨｚ，ＣＤＣｌ_３）
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 ＝ ５．２，１．５ Ｈｚ，１Ｈ），７．１３（ｄｄ，Ｊ ＝ ７．６，４．９ Ｈｚ，１Ｈ），７．３８（ｄ，Ｊ ＝ ８．７ Ｈｚ，２Ｈ），７．５６（ｄ，Ｊ ＝ ８．７ Ｈｚ，２Ｈ），７．８７（ｄ，Ｊ ＝ ７．６ Ｈｚ，１Ｈ），８．１１（ｂｒ ｓ，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）N- (4-tert-butylphenyl) -2- (2-chloroacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 16-1, 50 mg, 0.11 mmol) in morpholine (1.0 mL) And the mixture was heated and stirred for 2 hours at 80 ° C. Ethyl acetate (50 mL) was added to the reaction mixture, washed with water (50 mL) and saturated brine (50 mL), and the organic layer was dried over anhydrous sodium sulfate. The solid obtained by evaporating the solvent under reduced pressure was collected by filtration using diethyl ether, and dried under reduced pressure to obtain 17 mg of the target compound as a pale yellow solid (yield 32%).

¹ H-NMR (500 MHz, CDCl ₃ )
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, 1.5 Hz, 1H), 7.13 (dd, J = 7.6, 4.9 Hz, 1H), 7.38 (d, J = 8.7 Hz, 2H), 7.56 (d, J = 8.7 Hz, 2H), 7.87 (d, J = 7.6 Hz, 1H), 8. 11 (br s, 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)

  Hereinafter, compounds 17-2 to 88 were obtained according to the production method of compound 17-1, using compounds 16-1 to 9, compounds selected from commercially available compounds and known compounds.

2- (2-Isopropylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 17-2)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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)
¹ H-NMR (400 MHz, CDCl ₃ )
δ 2.32 (s, 6H), 2.60 (t, J = 4.6 Hz, 4H), 3.14 (s, 2H), 3.78 (t, J = 4.6 Hz, 4H) , 4.51 (s, 2H), 6.81 (s, 1H), 7.10 (dd, J = 5.1, 1.5 Hz, 1H), 7.13 (dd, J = 7.6) , 4.9 Hz, 1H), 7.27 (s, 2H), 7.67 (m, 1H), 7.87 (dd, J = 7.6, 1.7 Hz, 1H), 8.19. (D, J = 5.1 Hz, 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) pyridine-3-carboxamide (Compound 17-4)
¹ H-NMR (400 MHz, CDCl ₃ )
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 17-5)
¹ H-NMR (500 MHz, CDCl ₃ )
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, 0.6 Hz, 1H), 8.28 (d, J = 0.0). 6 Hz, 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 17-6)
¹ H-NMR (500 MHz, CDCl ₃ )
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 = 8.3 Hz, 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 17-7)
¹ H-NMR (500 MHz, CDCl ₃ )
δ 0.46-0.49 (m, 4H), 1.32 (s, 9H), 2.15 (br s, 1H), 2.27 (m, 1H), 3.49 (s, 2H) , 4.51 (s, 2H), 7.07 (dd, J = 4.9, 1.4 Hz, 1H), 7.13 (dd, J = 7.3, 4.9 Hz, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz, 2H), 7.88 (d, J = 7.3 Hz, 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)
¹ H-NMR (500 MHz, CDCl ₃ )
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, 0.8 Hz, 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 17-9)
¹ H-NMR (400 MHz, CDCl ₃ )
δ 1.31 (s, 9H), 2.10 (s, 3H), 2.68 (t, J = 6.1 Hz, 2H), 2.86 (t, J = 6.1 Hz, 2H) 3.40 (s, 2H), 4.51 (s, 2H), 7.08 (dd, J = 5.1, 1.5 Hz, 1H), 7.13 (dd, J = 7.6) , 4.9 Hz, 1H), 7.38 (d, J = 8.7 Hz, 2H), 7.56 (d, J = 8.7 Hz, 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 17-10)
¹ H-NMR (400 MHz, CDCl ₃ )
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, 0.7 Hz, 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 17-11)
¹ H-NMR (400 MHz, CDCl ₃ )
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, 0.9 Hz, 1H), 8.29 (d, J = 0.9 Hz, 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-3-carboxamide ( Compound 17-12)
¹ H-NMR (400 MHz, CDCl ₃ )
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 = 8.9 Hz) , 2H), 7.70 (d, J = 8.9 Hz, 2H), 7.88 (dd, J = 7.6, 1.7 Hz, 1H), 8.17 (d, J = 5. 1 Hz, 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 17-13)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 17-14)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.53-1.59 (m, 2H), 2.57 (t, J = 6.9 Hz, 2H), 3.26 (s, 2H), 3.46 (t, J = 6.3) Hz, 2H), 4.41 (br s, 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 17-15)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 5.1 Hz, 1H), 8.20 (s, 1H), 8.60 (dd, J = 4.9). 1.7 Hz, 1H), 10.11 (br s, 1H), 10.66 (s, 1H)

2- [2- (4-Hydroxypiperidin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 17-16)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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), 7.9 (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-hydroxycyclohexane-1-yl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 17 -17)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 4.6 Hz, 1H), 7.14 (d, J = 5.2, 1.5 Hz, 1H), 7 .31 (dd, J = 7.6, 4.9 Hz, 1H), 7.37 (d, J = 8.2 Hz, 2H), 7.81 (d, J = 8.2 Hz, 2H), 7.9 (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)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.17 (t, J = 7.0 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, 4.9 Hz, 1H), 7.37 (d, J = 8.6 Hz, 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 17-19)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1.7 Hz, 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) pyridine-3-carboxamide (Compound 17-20)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.71-1.77 (m, 4H), 2.55 to 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 17-21)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 17-22)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 17-23)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.13 (s, 6H), 2.31 (t, J = 6.1 Hz, 2H), 2.60 (t, J = 6.1 Hz, 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 = 5.1 Hz, 1H), 8.20 (s, 1H), 8.59 (dd, J = 4.9, 1.7 Hz, 1H), 10.25 (br s, 1H), 10.60 (s, 1H)

N- (4-chlorophenyl) -2- [2- (pyridin-2-yl) methylaminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 17-24)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 4.9 Hz, 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 17-25)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1 H), 8.07 (s, 1 H), 8.19-8.27 (m, 3 H), 8.55 (dd, J = 4.9, 1.5 Hz, 1 H), 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) pyridine-3-carboxamide (Compound 17-26)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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), 7.9 (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, 1H)

2- (2-Methylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 17-27)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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), 7.9 (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)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 1H)

2- "2- (N- (2-diethylaminoethyl) -N-ethylamino) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 17-29 )
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 0.91 (t, J = 7.2 Hz, 6H), 0.98 (t, J = 7.1 Hz, 3H), 2.43-2.51 (m, 6H), 2.61 ( q, J = 7.2 Hz, 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 17-30)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 (br s, 1H), 4.42 (s, 2H), 7.13 (d, J = 5.2, 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 = 8.9 Hz, 2H) ), 7.99 (dd, J = 7.6, 1.8 Hz, 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 17-31)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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, 1.5 Hz, 1H), 7.31 (dd, J = 7.6, 4.9 Hz) , 1H), 7.37 (d, J = 8.7 Hz, 2H), 7.81 (d, J = 8.7 Hz, 2H), 7.99 (dd, J = 7.6, 1.. 8 Hz, 1H), 8.18 (d, J = 5.0 Hz, 1H), 8.21 (s, 1H), 8.60 (dd, J = 4.9, 1.8 Hz, 1H) , 10.12 (br s, 1H), 10.66 (s, 1H)

2- [2- (2-Ethoxyethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 17-32)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 8.8 Hz, 2H), 7.81 (d, J = 8.8 Hz, 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 (br s, 1H), 10.66 (s, 1H)

2- [2- (2- (2-hydroxyethoxy) ethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 17-33)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 (brs, 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 = 8.9 Hz, 2H), 7.99 ( dd, J = 7.6, 1.7 Hz, 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 (br s, 1H), 10.66 (s, 1H)

2- [2- (Piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 17-34)
¹ H-NMR (500 MHz, CDCl ₃ )
δ 2.57 (br s, 4H), 2.95-2.98 (m, 4H), 3.11 (s, 2H), 4.53 (s, 2H), 7.08 (d, J = 5.2, 1.8 Hz, 1H), 7.14 (dd, J = 7.6, 4.9 Hz, 1H), 7.22 (d, J = 8.6 Hz, 2H), 7. 70 (d, J = 8.6 Hz, 2H), 7.88 (dd, J = 7.6, 1.7 Hz, 1H), 8.19 (dd, J = 5.2, 0.6 Hz) , 1H), 8.28 (d, J = 0.6 Hz, 1H), 8.41 (brs, 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 17-35)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 17-36)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 17-37)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 17-38)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.54-1.59 (m, 2H), 2.57 (t, J = 6.9 Hz, 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 17-39)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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] pyridine-3-carboxamide (Compound 17-40)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 2.43 (br s, 4H), 2.72 (t, J = 4.9 Hz, 4H), 3.09 (s, 2H), 4.42 (s, 2H), 7.15 (m , 1H), 7.30 (dd, J = 7.5, 4.9 Hz, 1H), 7.41 (d, J = 8.9 Hz, 2H), 7.72 (d, J = 8. 9 Hz, 2H), 7.98 (m, 1H), 8.18-8.19 (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) pyridine-3-carboxamide (Compound 17-41)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.79 (s, 3H), 2.57 (t, J = 6.4 Hz, 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, 1H)

N- (4-chlorophenyl) -2- [2- (3-dimethylaminopropyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 17-42)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.51-1.57 (m, 2H), 2.10 (s, 6H), 2.25 (t, J = 7.0 Hz, 2H), 2.52 to 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 17-43)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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), 7.9 (dd, J = 7.6, 1.6 Hz, 1H), 8.15 (s, 1H), 8.25 (d, J = 5. 4 Hz, 1H), 8.58 (dd, J = 4.9, 1.6 Hz, 1H), 9.97 (s, 1H), 10.43 (s, 1H), 11.15 (s, 1H)

2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3-methylphenyl) pyridine-3-carboxamide (Compound 17-44)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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] pyridine-3-carboxamide (Compound 17-45)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 7.9 Hz, 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) pyridine-3-carboxamide (Compound 17-46)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 5.2 Hz, 1H), 6.93 (d, J = 7.8 Hz, 1H), 7.13 (dd, J = 5.1, 1.5 Hz, 1 H), 7.22 (t, J = 7.8 Hz, 1 H), 7.29 (dd, J = 7.6, 4.9 Hz, 1 H), 7 .45 (d, J = 7.8 Hz, 1H), 7.55 (s, 1H), 7.94 (dd, J = 7.6, 1.6 Hz, 1H), 8.18 (d, J = 5.1 Hz, 1H), 8.20 (s, 1H), 8.58 (dd, J = 4.9, 1.6 Hz, 1H), 10.14 (s, 1H), 10. 38 (s, 1H)

N- (4-difluoromethoxyphenyl) -2- [2- (2-dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 17-47)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 17-48)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 5.2 Hz, 1H), 7.14 (dd, J = 5.1, 1.7 Hz, 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, 1.7 Hz, 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 (Compounds 17-49)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 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, 1.5 Hz, 1H), 7.18 (t, J = 74.2 Hz, 1H), 7.18 (d, J = 9.0 Hz, 2H), 7.30 (dd, J = 7.6, 4.9 Hz, 1H), 7.72 (d, J = 9.0 Hz, 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 17-50) )
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.14 (s, 6H), 2.33 (s, 3H), 2.36 (t, J = 6.4 Hz, 2H), 2.56 (t, J = 6.4 Hz, 2H) 3.17 (s, 2H), 4.41 (s, 2H), 7.13 (dd, J = 5.1, 1.1 Hz, 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, 1.7 Hz, 1H), 10.38 (s, 1H), 10.55 (s, 1H)

2- (2-Dimethylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethylphenyl) pyridine-3-carboxamide (Compound 17-51)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 17-52)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 4.9 Hz, 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. (Br s, 1H), 10.82 (s, 1H)

2- [2- (2-hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethylphenyl) pyridine-3-carboxamide (compound 17-53)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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 = 8.7 Hz, 2H), 8.02 (dd, J = 7.6, 1.. 8 Hz, 1H), 8.18 (d, J = 5.2 Hz, 1H), 8.21 (s, 1H), 8.61 (dd, J = 4.9, 1.8 Hz, 1H) , 10.22 (br s, 1H), 10.82 (s, 1H)

2- [2- (Piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethylphenyl) pyridine-3-carboxamide (Compound 17-54)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.43 (br s, 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 = 8.8 Hz, 2H), 7.91 (d, J = 8.8 Hz, 2H), 8.02 (dd, J = 7.6, 1.7 Hz, 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 (br s, 1H), 10.82 (s, 1H)

2- (2-Dimethylaminoacetylaminopyridin-4-ylmethylthio) -N- (3-trifluoromethylphenyl) pyridine-3-carboxamide (Compound 17-55)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 5.1 Hz, 1H), 8.19 (s, 1H), 8.61 (dd, J = 4.9, 1.7 Hz, 1H), 9.81 (s, 1H), 10 .79 (s, 1H)

2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3-trifluoromethylphenyl) pyridine-3-carboxamide (Compound 17-56)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 4.9 Hz, 1H), 7.48 (d, J = 7.9 Hz, 1H), 7.61 (t, J = 7.9 Hz, 1H), 7.91 (d, J = 7.9 Hz, 1H), 8. 03 (dd, J = 7.7, 1.7 Hz, 1H), 8.18 (s, 1H), 8.18 (d, J = 5.1 Hz, 1H), 8.21 (s, 1H) ), 8.61 (dd, J = 4.9, 1.7 Hz, 1H), 10.26 (br s, 1H), 10.79 (s, 1H)

2- [2- (Piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (3-trifluoromethylphenyl) pyridine-3-carboxamide monohydrochloride (Compound 17-57)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 3.40 (br s, 4H), 3.49 (br s, 4H), 4.14 (br s, 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 (br s , 1H), 8.22 (s, 1H), 8.27 (d, J = 5.0 Hz, 1H), 8.61 (dd, J = 4.9, 1.5 Hz, 1H), 9 .70 (br s, 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 17-58 )
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.38 (t, J = 6.3 Hz, 2H), 2.45 (br s, 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 = 5.1 Hz, 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 17-59)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1.6 Hz, 1H), 9.94 (s, 1H), 10.66 (s, 1H)

2- [2- (2-hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3-isopropylphenyl) pyridine-3-carboxamide (compound 17-60)
¹ H-NMR (500 MHz, DMSO-d ₆ )
δ 1.20 (d, J = 7.1 Hz, 6H), 2.60 (br s, 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 17-61)
¹ H-NMR (400 MHz, CDCl ₃ )
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 17-62)
¹ H-NMR (400 MHz, CDCl ₃ )
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-propyn-1-yl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 17-63)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.80 (br s, 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 17-64)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1H)

N- (4-difluoromethoxyphenyl) -2- [2- (N- (2-hydroxyethyl) -N-methylamino) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 17-65)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1.5 Hz, 1H), 7.17 (d, J = 9.0 Hz, 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 17-66)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.42 (br s, 4H), 2.72 (br s, 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 = 7.6 Hz, 1H), 8.18-8.19 (m, 2H), 8.59 (dd , J = 4.9, 1.7 Hz, 1H), 9.82 (s, 1H), 10.55 (s, 1H)

2- (2-Aminoacetylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridine-3-carboxamide (Compound 17-67)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 8.8 Hz, 2H), 7.73 (d, J = 8.8 Hz, 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) pyridine-3-carboxamide (Compounds 17-68)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1H), 10.60 (s, 1H)

N- (4-difluoromethoxyphenyl) -2- (2-phthaloylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 17-69)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1H)

N- (4-difluoromethoxyphenyl) -2- [2- (4-methylpiperazin-1-yl) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 17-70)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.17 (s, 3H), 2.36 (br s, 4H), 2.51 (br s, 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, 1.7 Hz, 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 17-71)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 0.99 (d, J = 6.1 Hz, 6H), 2.72 (m, 1H), 3.26 (s, 2H), 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 = 9.0 Hz, 2H), 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), 10.10 (s, 1H), 10.54 (s, 1H)

2- [2- (2-Dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide (Compound 17-72)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 17-73)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1.2 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), 8.16-8.20 (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) pyridine-3-carboxamide (Compound 17-74)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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), 7.9 (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 (br s, 1H), 10.66 (s, 1H)

2- [2- (2-Methylaziridin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 17-75)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1.7 Hz, 1H), 8.20 (d, J = 5) .1 Hz, 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) pyridine-3-carboxamide (Compound 17-76)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 4.9 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), 8.19 (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) pyridine-3-carboxamide (Compound 17-77)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 1.99-2.06 (m, 2H), 3.21 (s, 2H), 3.28 (t, J = 7.0 Hz, 4H), 4.42 (s, 2H), 7. 14 (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 17-78)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1.6 Hz, 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, 1H)

N- (4-chlorophenyl) -2- [2- (2- (pyrrolidin-1-yl) ethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 17-79)
¹ H-NMR (500 MHz, DMSO-d ₆ )
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) pyridine-3-carboxamide (Compound 17- 80)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 4.41 (s, 2H), 4.82 (s, 2H), 6.06 (d, J = 7.6 Hz, 2H), 7.16 (d, J = 5.1 Hz, 1H) 7.30 (dd, J = 7.6, 4.9 Hz, 1H), 7.37 (d, J = 8.9 Hz, 2H), 7.58 (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 17-81)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.17 (s, 3H), 2.35 (br s, 6H), 3.14 (s, 2H), 3.32 (s, 2H), 4.42 (s, 2H), 7.15 (D, J = 6.3 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, 1.6 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 17-82)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 8.8 Hz, 2H), 7.98 (dd, J = 7.6, 1.7 Hz, 1H), 8.11 (s, 1H), 8.22 (d, J = 5.1 Hz) , 1H), 8.57 (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] pyridine-3-carboxamide (Compound 17-83)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 17-84)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 (br s, 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 .7 Hz, 1H), 8.17-8.21 (m, 2H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 10.07 (brs, 1H), 10.59 (s, 1H)

N- (3,5-dimethylphenyl) -2- [2- (2-morpholinoethyl) aminoacetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide (Compound 17-85)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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 = 5.1 Hz, 1H), 7. 28 (dd, J = 7.6, 4.9 Hz, 1H), 7.32 (s, 2H), 7.93 (dd, J = 7.6, 1.7 Hz, 1H), 8.17. −8.21 (m, 2H), 8.57 (dd, J = 4.9, 1.7 Hz, 1H), 10.17 (brs, 1H), 10.30 (s, 1H)

2- (2-Ethylaminoacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 17-86)
¹ H-NMR (400 MHz, CDCl ₃ )
δ 1.15 (t, J = 7.1 Hz, 3H), 2.72 (q, J = 7.1 Hz, 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 (brs, 1H)

2- (2-Cyclopropylmethoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide (Compound 17-87)
¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1.5 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 = 5.0 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 17-88)
¹ H-NMR (400 MHz, DMSO-d ₆ )
δ 2.24 (s, 6H), 4.38 (s, 2H), 4.50 (s, 2H), 6.74 (s, 1H), 7.15 (d, J = 5.1 Hz, 1H), 7.25 (dd, J = 7.8, 4.9 Hz, 1H), 7.30 (s, 2H), 7.83 (s, 1H), 7.88-7.94 (m , 4H), 8.06 (br s, 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) pyridine-3-carboxamide (Compound 18-1)

^１Ｈ−ＮＭＲ（４００ＭＨｚ，ＤＭＳＯ−ｄ_６）
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，１Ｈ）N- (4-Difluoromethoxyphenyl) -2- (2-phthaloylaminoacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide (Compound 17-69, 50 mg, 0.085 mmol) and hydrazine 1 at room temperature Hydrate (42 μl, 0.42 mmol) was suspended in a mixed solvent of methanol (2.0 mL) and 1,4-dioxane (2.0 mL), heated to 80 ° C. and stirred for 1 hour. The mixture was diluted with ethyl acetate (30 mL), washed twice with saturated brine (30 mL), and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 11 mg of the target compound as a colorless solid (yield 29%).

¹ H-NMR (400 MHz, DMSO-d ₆ )
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, 1H)

The chemical structure of the compound of the present invention described above is shown below.

[Formulation example]
The typical formulation example of this invention compound is shown below.
1) Compound of the present invention 1 mg in 100 mg tablet
Lactose 66.4mg
Corn starch 20mg
Carboxymethylcellulose calcium 6mg
Hydroxypropylcellulose 4mg
Magnesium stearate 0.6mg

  A tablet having the above formulation is coated with 2 mg of a coating agent (for example, a normal coating agent such as hydroxypropylmethylcellulose, macrogol, silicone resin, etc.) to obtain a target coated tablet. Moreover, a desired tablet can be obtained by changing suitably the kind and / or quantity of this invention compound and / or an additive.

2) Capsule Formulation 2 150 mg of the present compound 5 mg
Lactose 145mg

  A desired capsule can be obtained by appropriately changing the mixing ratio of the compound of the present invention and lactose.

3) Eye drop formulation 3 100 mg of the present compound in 100 mL
Sodium chloride 900mg
Polysorbate 80 200mg
Sodium hydroxide appropriate amount hydrochloric acid appropriate amount sterilized purified water appropriate amount

  Desired eye drops can be obtained by appropriately changing the type and / or amount of the compound and / or additive of the present invention.

[Pharmacological test]
1. Evaluation Test for Angiogenesis Inhibitory Effect As one of the widely used methods for evaluating the angiogenesis inhibitory effect of drugs, a cell growth inhibitory action test using a VEGF-induced HUVEC proliferation reaction evaluation system is disclosed in Cancer Res. 59, 99-106 (1999). Therefore, according to the method described in the above-mentioned literature, the cell growth inhibitory action test of the compound of the present invention was performed, the cell growth inhibition rate was calculated, and the angiogenesis inhibitory effect of the compound of the present invention was evaluated using it as an index.

(Preparation of test compound solution)
The test compound was dissolved in dimethyl sulfoxide (hereinafter referred to as DMSO) and then diluted with a commercially available phosphate buffer solution (hereinafter referred to as PBS) to prepare a 20 μg / mL test compound solution.

(Preparation of HUVEC suspension)
HUVEC was suspended in F12K medium containing 0.5% fetal bovine serum (hereinafter referred to as FBS) to prepare a HUVEC suspension of 2 × 10 ⁴ cells / mL.

(Preparation of VEGF solution)
VEGF was dissolved in PBS containing 0.1% bovine serum albumin and then diluted with F12K medium containing 0.5% FBS to prepare a 400 ng / mL VEGF solution.

(Test method and measurement method)
1) 100 μL of HUVEC suspension was seeded in 96-well plates coated with type I collagen (2 × 10 ³ cells per well).
2) One day after sowing, 5 μL of the test compound solution was added per well.
3) One hour after the addition of the test compound solution, 5 μL of VEGF solution was added per well.
4) Three days after the addition of the VEGF solution, 10 μL of WST-8 assay reagent (Dojin Chemical) was added per well.
5) After 3 hours, the plate was attached to an absorptiometer (multi-label counter ARVO), and the absorbance of each well suspension (hereinafter referred to as test compound suspension) at 450 nm was measured.
6) In place of the test compound solution, 1.0% DMSO was used, and the others were tested in the same manner as in the above 1-5), and the result was used as a control.
All the test steps were incubated in an incubator under conditions of 37 ° C., 5% carbon dioxide, and 95% oxygen.

(Calculation of cell growth inhibition rate)
The cell growth inhibition rate (%), which is an index of the angiogenesis inhibitory effect, was calculated from the formula shown below.

(a formula)
Cell growth inhibition rate (%)
= 100-{(absorbance of test compound suspension-A) / (absorbance of control-A)} × 100
A: Absorbance of only cell suspension (cell + medium)

表２に示されるとおり、本発明化合物は優れた細胞増殖阻害作用を示した。よって、本発明化合物は優れた血管新生阻害効果を有する。(Test results and discussion)
As an example of test results, 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 4-2, 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 12-3, Compound 12-5, Compound 12-6, Compound 12-7 , Compound 12-9, Compound 12-10, Compound 12-11, 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 17-34, 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, Compound 18-1) (%) Is shown in Table 2.

As shown in Table 2, the compound of the present invention exhibited an excellent cell growth inhibitory action. Therefore, the compound of the present invention has an excellent angiogenesis inhibitory effect.

2. Evaluation Test for Anticancer Effect As one of the widely used methods for evaluating the anticancer effect of drugs, a tumor growth inhibition test using a mouse tumor bearing model is Cancer Res. 59, 5209-5218 (1999). Therefore, according to the method described in the above literature, the tumor growth inhibitory action test of the compound of the present invention was performed, the tumor tissue weight suppression rate was calculated, and the anticancer effect of the compound of the present invention was evaluated using this as an index.

(Preparation of test compound suspension)
A 1% aqueous methylcellulose solution was added to the test compound, and this solution was suspended with a sonicator to prepare a 10 mg / mL test compound suspension.

(Preparation of B16 cell suspension)
Saline was added to B16 cells to prepare a B16 cell suspension of 3.3 × 10 ⁷ cells / mL.

(Test method and measurement method)
1) The hair of the back of a mouse (female, 6 weeks old, C57BL / 6N mouse) was removed with a depilatory agent under Nembutal anesthesia.
2) A few days after depilation, B16 cell suspension (300 μL) was transferred into the dorsal skin of mice under Nembutal anesthesia.
3) From the day of B16 cell transfer (day 0) to day 10, the test compound suspension (100 mg / kg / day) was orally administered once daily per day.
4) On day 10 after cell transfer, mice were euthanized with CO ₂ gas.
5) The tumor tissue was extracted from the mouse, and the weight of the tumor tissue was measured using an electronic balance.
6) A 1% methylcellulose aqueous solution was used instead of the test compound suspension, and the others were tested in the same manner as in 1-5), and the results were used as controls.

(Calculation of tumor tissue weight suppression rate)
The tumor tissue weight suppression rate (average value of 9 mice per group), which is an index of the anticancer effect, was calculated from the formula shown below.

(a formula)
Tumor tissue weight inhibition rate (%) = 100− (Mx / Mo) × 100
Mo: Weight of tumor tissue in control group Mx: Weight of tumor tissue in test compound solution administration group

表３に示されるとおり、本発明化合物は優れた腫瘍増殖抑制作用を示した。よって、本発明化合物は優れた抗癌効果を有する。(Test results and discussion)
As an example of test results, 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 4-11, 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, Compound 17-35) Tumor tissue The amount inhibition rate (%) shown in Table 3.

As shown in Table 3, the compound of the present invention showed an excellent tumor growth inhibitory action. Therefore, the compound of the present invention has an excellent anticancer effect.

3. Anti-arthritic effect evaluation test As one of the widely used methods for evaluating the anti-arthritic effect of drugs, a foot edema suppression test using a rat adjuvant arthritis model is known. Therefore, the foot edema inhibitory action test of the compound of the present invention was conducted, the foot edema suppression rate was calculated, and the anti-arthritic effect of the compound of the present invention was evaluated using it as an index.

(Preparation of test compound suspension)
To the test compound, a 1% methylcellulose aqueous solution was added and suspended to prepare a 2 mg / mL test compound suspension.

(Preparation of adjuvant)
Liquid paraffin was added to and suspended in Mycobacterium-butyricum to prepare a 6 mg / mL adjuvant.

(experimental method)
1) Adjuvant (0.1 mL) was injected subcutaneously into the left hind footpad of a rat (male, 9 weeks old, Lewis rat) to induce arthritis.
2) From the day of adjuvant injection (day 0) to day 20, the test compound suspension (10 mg / kg / day) was orally administered once a day for consecutive days.
3) On the day of adjuvant injection, on the 1st day, 4th day, 7th day, 11th day, 14th day, 18th day and 21st day, the foot volume of both hind limbs was measured for each hind limb using a plethysmometer. Measured.
4) A 1% methylcellulose aqueous solution was used instead of the test compound suspension, and the others were tested in the same manner as in 1-3), and the results were used as controls.

(Evaluation methods)
The anti-arthritic effect of the compound of the present invention was calculated by calculating the foot edema suppression rate of foot edema in the secondary inflammatory foot of each test compound administration group for foot edema in the non-adjuvant treated foot (secondary inflammatory foot) of the control group. Evaluated.

(Calculation of foot edema suppression rate)
From the calculation formula 1 shown below, the foot edema rate was calculated, and then from the calculation formula 2, the foot edema suppression rate (an average value of 8 animals per group) serving as an index of the anti-arthritic effect was calculated.

(Calculation formula 1)
Foot edema rate (%)
= (Foot volume after adjuvant treatment / foot volume before adjuvant treatment) x 100
(Calculation formula 2)
Foot edema suppression rate (%)
= 100-{(Sx-100) / (So-100)} * 100
So: Foot edema rate in the control group Sx: Foot edema rate in the test compound suspension administration group

表４に示されるように、本発明化合物は優れた足浮腫抑制作用を示した。よって、本発明化合物は優れた抗関節炎作用を有する。(Test results and discussion)
As an example of the test results, 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 Table 4 shows the inhibition rate (%) of foot edema on Day 21 of 10-1, Compound 10-2, Compound 12-1, and Compound 12-2).

As shown in Table 4, the compound of the present invention showed an excellent foot edema inhibitory action. Therefore, the compound of the present invention has an excellent anti-arthritic action.

4). Evaluation test of choroidal neovascularization inhibitory effect As one of widely used methods for evaluating the choroidal neovascularization inhibitory effect of drugs, a neovascularization test using a rat choroidal neovascularization model is described in Graefe's Arch. Cli. Exp. Ophthalmol. , 235, 313-319 (1997). Therefore, the neovascular expression test of the compound of the present invention was conducted in accordance with the method described in the above literature, and the ratio of the neovascularization rate of the compound administration group to the neovascular expression rate of the base administration group (control group) was calculated. The choroidal neovascularization inhibitory effect of the compound of the present invention was evaluated using the calculated value as an index.

(Preparation of test compound solution)
A 1% methylcellulose aqueous solution was added to the test compound and suspended therein to prepare a 6 mg / 10 mL test compound suspension.

(Laser-induced rat choroidal neovascularization model)
1) A 7: 1 mixture (1 mL / kg) of 5% ketamine hydrochloride injection and 2% xylazine hydrochloride injection was intramuscularly administered to rats (Brown Norway male rats, 8 weeks old, body weight 200-250 g), and whole body Anesthetized.
2) After tropicamide / phenylephrine hydrochloride ophthalmic solution (trade name: Midrin P) was instilled to make mydriatic, the Bruch membrane of the rat was photocoagulated using a krypton laser photocoagulator.
Laser irradiation was performed in a scattered manner at 8 locations per eye, avoiding thick retinal blood vessels in the back of the fundus and focusing on the deep retina. The photocoagulation conditions were a spot size of 100 μm, an output of 100 mM, and a coagulation time of 0.1 seconds.
3) After photocoagulation, fundus photography was performed to confirm the photocoagulation (laser irradiation) site.

(Test method and measurement method)
1) The test compound suspension (30 mg / kg / day) was orally administered once a day for 7 days once a day from the laser irradiation day (day 0) to the sixth day.
2) As a base administration group (control group), instead of the test compound suspension, a 1% methylcellulose aqueous solution was used, and the others were tested in the same manner as 1), and the result was used as a control.

(Evaluation methods)
1) On the seventh day of photocoagulation, 0.1 mL of 10% fluorescein aqueous solution was injected from the tail vein of the rat, and fluorescence fundus imaging was performed.
2) Next, a spot where no fluorescence leakage was observed in fluorescence fundus angiography was negative, a spot where fluorescence leakage was observed was positive, and there were two photocoagulation sites where some fluorescence leakage was observed. Judgment was positive.
3) The neovascularization rate was calculated according to Formula 1. According to the calculation formula 2, the ratio of the neovascularization rate of the test compound administration group to the base administration group was calculated from the neovascularization rate of each administration group.

(Calculation formula 1)
New blood vessel expression rate (%) = (number of positive photocoagulation sites / total number of photocoagulation sites) × 100

(Calculation formula 2)
Ratio of neovascularization rate of test compound administration group to base administration group (control group) (% of control) = Ax / Ao × 100
Ao: New blood vessel expression rate of base administration group (control group) Ax: New blood vessel expression rate of test compound administration group

表４に示されるように、本発明化合物は基剤に比べて低い新生血管発現率を示し、脈絡膜血管新生阻害効果を有する。(Test results and discussion)
As an example of the test results, test compounds (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 9) -1, compound 10-1, compound 10-2, compound 11-2, compound 12-1, compound 12-2, compound 12-5, compound 12-10, compound 17-5) Table 4 shows the ratio (% of control) of the neovascularization rate in the test compound administration group with respect to the group).

As shown in Table 4, the compound of the present invention exhibits a low neovascularization rate compared to the base and has a choroidal neovascularization inhibitory effect.

Claims (13)

A compound represented by the following general formula (1) or a salt thereof

[In the formula, ring A represents a benzene ring or an aromatic hetero 5-membered ring or an aromatic hetero 6-membered ring optionally condensed with a cycloalkane ring;
R ¹ and R ² are the same or different and each represents a hydrogen atom, a hydroxy group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, substituted or unsubstituted A substituted 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 together may form a substituted or unsubstituted heterocycle;
R ³ and R ⁴ are the same or different and each represents 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, substituted or unsubstituted Represents a substituted alkylcarbonyl group, a substituted or unsubstituted arylcarbonyl group or Z—R ⁵ ;
R ³ and R ⁴ together may form a substituted or unsubstituted heterocycle;
Z represents CO, CS, COB ² O, CSB ² O, CONB ² R ⁶ , CSB ² NR ⁶ , CONB ² R ⁶ SO ₂ , CSB ² NR ⁶ SO ₂ or SO ₂ ;
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 substituted or unsubstituted heterocycle, carboxy A 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 together may form a substituted or unsubstituted heterocycle;
R ⁶ represents a hydrogen atom, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted aryl group;
X and Y are the same or different and each represents a hydrogen atom, halogen atom, hydroxy group, substituted or unsubstituted alkoxy group, substituted or unsubstituted aryloxy group, substituted or unsubstituted alkyl group, substituted or unsubstituted cycloalkyl group, substituted or Unsubstituted aryl group, substituted or unsubstituted alkylamino group, substituted or unsubstituted arylamino group, mercapto group, substituted or unsubstituted alkylthio group, substituted or unsubstituted arylthio group, carboxy group or ester or amide thereof, cyano group, And one or more groups selected from nitro groups;
B ¹ represents an alkylene group;
B ² represents a single bond or an alkylene group;
p represents 0, 1 or 2;
q represents 0 or 1; ] A compound represented by the following general formula (1) or a salt thereof

[Wherein ring A represents a benzene ring, a thiophene ring or a pyridine ring;
R ¹ represents an alkyl group, a cycloalkyl group, an aryl group or a heterocyclic ring;
When R ¹ 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;
When R ¹ is an aryl group, the aryl group is selected from a halogen atom, a hydroxy group, an alkoxy group, a halogenoalkoxy group, a hydrocarbonyloxy group, an alkylcarbonyloxy group, an arylcarbonyloxy group, an alkyl group, a halogenoalkyl group and an aryl group. May have one or more substituents selected;
R ² represents a hydrogen atom, an alkyl group or an aryl group;
When R ² is an alkyl group, the alkyl group may have one or more substituents selected from a carboxy group, an alkoxycarbonyl group, and an aryloxycarbonyl group;
R ³ represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic ring or Z—R ⁵ ;
When R ³ is an alkyl group, the alkyl group may have one or more substituents selected from a hydroxy group, an alkoxy group, an aryloxy group, an amino group, an alkylamino group, and an arylamino group;
When R ³ is a heterocycle, the heterocycle may have one or more cyano groups as substituents;
R ³ and R ⁴ together may form a heterocycle;
When R ³ and R ⁴ together form a heterocyclic ring, the heterocyclic ring is a hydroxy group, an alkoxy group, an aryloxy group, an alkyl group, a hydroxyalkyl group, an alkoxyalkyl group, an aryloxyalkyl group, an aryl group, Selected from amino group, alkylamino group, arylamino group, carboxy group, alkoxycarbonyl group, aryloxycarbonyl group, hydrocarbonyl group, alkylcarbonyl group, arylcarbonyl group, aminocarbonyl group, alkylaminocarbonyl group and arylaminocarbonyl group The heterocyclic ring may have a carbonyl group in the ring;
R ⁴ represents a hydrogen atom, an alkyl group, an aryl group, a hydrocarbonyl group, an alkylcarbonyl group or an arylcarbonyl group;
When R ⁴ is an alkylcarbonyl group, the alkylcarbonyl group may have one or more alkylcarbonyloxy groups as substituents;
Z is ^{CO, CS, CO-B 2} -O, CS-B 2 -O, CO-B 2 -NR 6, CS-B 2 -NR 6, CO-B 2 -NR 6 SO 2, CS-B 2 indicates -NR ⁶ SO ₂ or SO _2;
R ⁵ represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group, a heterocyclic ring, a carboxy group, an alkoxycarbonyl group, an aryloxycarbonyl group, a hydrocarbonyl group, an alkylcarbonyl group, an arylcarbonyl group, a complex A ring carbonyl group, an aminocarbonyl group, an alkylaminocarbonyl group or an arylaminocarbonyl group;
When R ⁵ is an alkyl group, the alkyl group is a halogen atom, hydroxy group, alkoxy group, hydroxyalkoxy group, alkoxyalkoxy group, aryloxyalkoxy group, cycloalkyl group, aryl group, heterocycle, carboxy group, alkoxycarbonyl group. Aryloxycarbonyl group, hydrocarbonyl group, alkylcarbonyl group, arylcarbonyl group, amino group, alkylamino group, arylamino group, alkoxycarbonylamino group, aryloxycarbonylamino group, hydrocarbonylamino group, alkylcarbonylamino group, May have one or more substituents selected from an arylcarbonylamino group, a mercapto group, an alkylthio group, an arylthio group and a cyano group;
When R ⁵ is an aryl group, the aryl group may have one or more halogen atoms as substituents;
When R ⁵ is a heterocycle, the heterocycle may have one or more substituents selected from alkyl and aryl groups;
When R ⁵ is an alkylcarbonyl group, the alkylcarbonyl group is one or more selected from a carboxy group, a hydrocarbonyloxy group, an alkylcarbonyloxy group, an arylcarbonyloxy group, an amino group, an alkylamino group, or an arylamino group. May have a substituent;
R ⁵ and R ⁶ together may form a heterocycle;
When R ⁵ and R ⁶ together form a heterocyclic ring, the heterocyclic ring is a hydroxy group, an alkoxy group, an aryloxy group, an alkyl group, a hydroxyalkyl group, an alkoxyalkyl group, an aryloxyalkyl group, a carboxy group, The heterocyclic ring may have one or more substituents selected from an alkoxycarbonyl group, an aryloxycarbonyl group, a carbonyl group, a hydrocarbonyl group, an alkylcarbonyl group and an arylcarbonyl group, and the heterocyclic ring has a carbonyl group in the ring. May have a group;
R ⁶ represents a hydrogen atom, an alkyl group or an aryl group;
X and Y are the same or different and each represents one or more groups selected from a hydrogen atom, a halogen atom and an alkyl group;
B ¹ represents an alkylene group;
B ² represents a single bond or an alkylene group;
p represents 0, 1 or 2;
q represents 0 or 1; ] In general formula (1),
Ring A represents a benzene ring, a thiophene ring or a pyridine ring;
R ¹ represents an alkyl group, a cycloalkyl group, an aryl group or a heterocyclic ring;
When R ¹ is an alkyl group, the alkyl group may have one or more alkoxyaryl groups as substituents;
When R ¹ is an aryl group, the aryl group has one or more substituents selected from a halogen atom, a hydroxy group, an alkoxy group, a halogenoalkoxy group, an alkylcarbonyloxy group, an alkyl group, and a halogenoalkyl group. Well;
R ² represents a hydrogen atom or an alkyl group;
When R ² is an alkyl group, the alkyl group may have one or more substituents selected from a carboxy group and an alkoxycarbonyl group;
R ³ represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic ring or Z—R ⁵ ;
When R ³ is an alkyl group, the alkyl group may have one or more substituents selected from a hydroxy group and an alkylamino group;
When R ³ is a heterocycle, the heterocycle may have one or more cyano groups as substituents;
R ³ and R ⁴ together may form a heterocycle;
When R ³ and R ⁴ together form a heterocycle, the heterocycle is selected from a hydroxy group, an alkyl group, a hydroxyalkyl group, an alkylamino group, an alkoxycarbonyl group, an alkylcarbonyl group, and an alkylaminocarbonyl group. One or more substituents, and the heterocyclic ring may have a carbonyl group in the ring;
R ⁴ represents a hydrogen atom, an alkyl group or an alkylcarbonyl group;
When R ⁴ is an alkylcarbonyl group, the alkylcarbonyl group may have one or more alkylcarbonyloxy groups as substituents;
Z represents CO, CO—B ² —O, CO—B ² —NR ⁶ , CS—B ² —NR ⁶ , CO—B ² —NR ⁶ SO ₂ or SO ₂ ;
R ⁵ 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;
When R ⁵ is an alkyl group, the alkyl group is a halogen atom, hydroxy group, alkoxy group, hydroxyalkoxy group, alkoxyalkoxy group, cycloalkyl group, heterocyclic ring, carboxy group, alkoxycarbonyl group, amino group, alkylamino group, May have one or more substituents selected from an alkoxycarbonylamino group, an alkylcarbonylamino group, an alkylthio group and a cyano group;
When R ⁵ is an aryl group, the aryl group may have one or more halogen atoms as substituents;
When R ⁵ is a heterocycle, the heterocycle may have one or more alkyl groups as substituents;
When R ⁵ is an alkylcarbonyl group, the alkylcarbonyl group may have one or more substituents selected from a carboxy group, an alkylcarbonyloxy group, and an alkylamino group;
R ⁵ and R ⁶ together may form a heterocycle;
When R ⁵ and R ⁶ together form a heterocycle, the heterocycle has one or more substituents selected from a hydroxy group, an alkyl group, a hydroxyalkyl group, an alkoxycarbonyl group, or an alkylcarbonyl group. And the heterocycle may have a carbonyl group in the ring;
R ⁶ represents a hydrogen atom or an alkyl group;
X and Y represent a hydrogen atom;
B ¹ represents an alkylene group;
B ² represents a single bond or an alkylene group;
p represents 0 or 1;
The compound or a salt thereof according to claim 2, wherein q represents 0. In general formula (1),
Ring A represents a benzene ring, a thiophene ring or a pyridine ring;
R ¹ represents an aryl group or a heterocyclic ring;
When R ¹ 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;
R ² represents a hydrogen atom;
R ³ represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic ring or Z—R ⁵ ;
When R ³ is an alkyl group, the alkyl group may have one or more alkylamino groups as substituents;
When R ³ is a heterocycle, the heterocycle may have one or more cyano groups as substituents;
R ³ and R ⁴ together may form a heterocycle;
When R ³ and R ⁴ together form a heterocycle, the heterocycle may have one or more substituents selected from alkyl and alkylcarbonyl groups;
R ⁴ represents a hydrogen atom or an alkyl group;
Z represents CO, CO—B ² —O, CO—B ² —NR ⁶ , CO—B ² —NR ⁶ SO _{2 or} SO ₂ ;
R ⁵ represents a hydrogen atom, an alkyl group, an aryl group, an alkylcarbonyl group or an alkylaminocarbonyl group;
When R ⁵ is an alkyl group, the alkyl group may have one or more substituents selected from a halogen atom, a hydroxy group, a heterocyclic ring, an alkylamino group and an alkylcarbonylamino group;
When R ⁵ is an aryl group, the aryl group may have one or more halogen atoms as substituents;
When R ⁵ is an alkylcarbonyl group, the alkylcarbonyl group may have one or more carboxy groups as substituents;
R ⁵ and R ⁶ together may form a heterocycle;
When R ⁵ and R ⁶ together form a heterocycle, the heterocycle may have one or more hydroxyalkyl groups as substituents;
R ⁶ represents a hydrogen atom or an alkyl group;
X and Y represent a hydrogen atom;
B ¹ represents an alkylene group;
B ² represents a single bond or an alkylene group;
p represents 0;
The compound or a salt thereof according to claim 2 or 3, wherein q represents 0. The compound according to any one of claims 1 to 4, or a salt thereof, wherein, in the general formula (1), ring A represents a pyridine ring or a thiophene ring. The compound or a salt thereof according to claim 5, wherein, in the general formula (1), ring A represents a pyridine ring. In general formula (1),
Partial structure (C)

And partial structure (D)

Is bonded to an adjacent carbon atom on ring A, or the compound according to any one of claims 1 to 6, or a salt thereof. In the general formula (1), the partial structure (C) and the partial structure (D) are bonded to adjacent carbon atoms on the ring A, and the position of these carbon atoms is relative to the hetero atom on the ring A. And a compound or a salt thereof according to claim 5 or 6, which are α-position and β-position. In general formula (1),
R ³ represents Z—R ⁵ ;
Z represents CO, CO—B ² —O, CO—B ² —NR ⁶ , CO—B ² —NR ⁶ SO ₂ ;
R ⁵ represents a hydrogen atom, an alkyl group, an aryl group, an alkylcarbonyl group or an alkylaminocarbonyl group;
When R ⁵ is an alkyl group, the alkyl group may have one or more substituents selected from a halogen atom, a hydroxy group, a heterocyclic ring, an alkylamino group and an alkylcarbonylamino group;
When R ⁵ is an aryl group, the aryl group may have one or more halogen atoms as substituents;
When R ⁵ is an alkylcarbonyl group, the alkylcarbonyl group may have one or more carboxy groups as substituents;
R ⁵ and R ⁶ together may form a heterocycle;
When R ⁵ and R ⁶ together form a heterocycle, the heterocycle may have one or more hydroxyalkyl groups as substituents;
R ⁶ represents a hydrogen atom or an alkyl group;
Compound or a salt thereof of any one of claims 2-8 B ² represents a single bond or an alkylene group. N- (3,5-dimethylphenyl) -2- [2- (4-methylpiperazin-1-yl) pyridin-4-ylmethylthio] pyridine-3-carboxamide,
2- (2-cyclopropylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
2- [2- (N- (2-dimethylaminoethyl) -N-methylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-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] pyridine-3-carboxamide,
2- [2- (4-acetylpiperazin-1-yl) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
N- (indan-5-yl) -2- (2-morpholinopyridin-4-ylmethylthio) pyridine-3-carboxamide,
2- [2- (4-acetylpiperazin-1-yl) pyridin-4-ylmethylthio] -N- (indan-5-yl) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-n-pentylaminopyridin-4-ylmethylthio) pyridine-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) pyridine-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) pyridine-3-carboxamide,
2- [2- (N-tert-butoxycarbonyl-N-methylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
2- [2- (5-cyanothiazol-2-ylamino) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
2- (2-aminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
2- (2-aminopyridin-4-ylmethylthio) -N- (3-isopropylphenyl) pyridine-3-carboxamide,
2- (2-aminopyridin-4-ylmethylthio) -N- (indan-5-yl) pyridine-3-carboxamide,
2- (2-aminopyridin-4-ylmethylthio) -N- (4-tert-butylphenyl) pyridine-3-carboxamide,
2- (2-aminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (indan-5-yl) -2- (2-methylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
2- (2-methylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,
2- (2-aminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridine-3-carboxamide,
2- (2-aminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,
2- (2-aminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) pyridine-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) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-propionylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-trifluoroacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-isobutyrylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-pivaloylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-trifluoromethanesulfonylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
2- (2-acetylaminopyridin-4-ylmethylthio) -N- (4-chlorophenyl) pyridine-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) pyridine-3-carboxamide,
2- (2-acetylaminopyridin-4-ylmethylthio) -N- (1H-indazol-6-yl) pyridine-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-4-ylmethylthio) -N- (4-chlorophenyl) thiophene-2-carboxamide,
N- (3,5-dimethylphenyl) -2- [2- (N′-n-propylureido) pyridin-4-ylmethylthio] pyridine-3-carboxamide,
2- [2- (N′-tert-butylureido) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
2- [2- (N′-4-chlorophenylureido) pyridin-4-ylmethylthio] -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-formylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-phenylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- [2- (N′-methylureido) pyridin-4-ylmethylthio] pyridine-3-carboxamide,
2- [2- (N′-methylureido) pyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,
N- (4-chlorophenyl) -2- [2- (N′-methylureido) pyridin-4-ylmethylthio] pyridine-3-carboxamide,
N- (4-difluoromethoxyphenyl) -2- [2- (N′-methylureido) pyridin-4-ylmethylthio] pyridine-3-carboxamide,
2- (2-acetoxyacetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
2- (2-acetoxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,
2- (2-aminoacetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-3-carboxamide,
2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,
N- (3,5-dimethylphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (4-chlorophenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
N- (3,5-dimethyl-4-hydroxyphenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) -N- (3-methylphenyl) pyridine-3-carboxamide,
2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) -N- (4-trifluoromethylphenyl) pyridine-3-carboxamide,
2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) -N- (isoquinolin-3-yl) pyridine-3-carboxamide,
N- (3-chlorophenyl) -2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) pyridine-3-carboxamide,
2- (2-hydroxyacetylaminopyridin-4-ylmethylthio) -N- (indan-5-yl) pyridine-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-dimethylphenyl) pyridine-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-3-carboxamide,
2- [2- (2-hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-3-carboxamide,
2- [2- (piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethoxyphenyl) pyridine-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] pyridine-3-carboxamide,
2- [2- (2-hydroxyethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3-methylphenyl) pyridine-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- (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) 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) pyridine-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, and
2- (2-aminoacetylaminopyridin-4-ylmethylthio) -N- (4-difluoromethoxyphenyl) pyridine-3-carboxamide 2- (3-aminopyridin-4-ylmethylthio) -N- (3 , 5-dimethylphenyl) pyridine-3-carboxamide,
2- (3-acetylaminopyridin-4-ylmethylthio) -N- (3,5-dimethylphenyl) pyridine-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) pyridine-3-carboxamide,
2- [2- (2-dimethylaminoethyl) aminoacetylaminopyridin-4-ylmethylthio] -N- (3-methylphenyl) pyridine-3-carboxamide,
N- (3-methylphenyl) -2- [2- (piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide,
2- [2- (piperazin-1-yl) acetylaminopyridin-4-ylmethylthio] -N- (4-trifluoromethylphenyl) pyridine-3-carboxamide,
A compound selected from N- (4-difluoromethoxyphenyl) -2- [2- (N- (2-hydroxyethyl) -N-methylamino) acetylaminopyridin-4-ylmethylthio] pyridine-3-carboxamide Or its salt. The pharmaceutical composition containing the compound or its salt of any one of Claims 1-10. A therapeutic agent for a disease involving angiogenesis and / or enhanced vascular permeability, comprising the compound according to any one of claims 1 to 10 or a salt thereof as an active ingredient. Diseases involving angiogenesis and / or increased vascular permeability are cancer, rheumatoid arthritis, age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, polypoidal choroidal angiopathy, diabetic macular edema The therapeutic agent according to claim 12, which is psoriasis vulgaris or atherosclerosis.