阅读说明：本技术 新颖的芳基或杂芳基***酮衍生物或其盐、或含有它们的药物组合物 (Novel aryl or heteroaryl triazolone derivatives or salts thereof, or pharmaceutical compositions containing them ) 是由 韩兑东 卓希裁 金恩庆 崔秀份 金东勋 S.朴 丁恩惠 崔铉浩 金台旺 朱美敬 于 2019-03-20 设计创作，主要内容包括：本发明提供芳基或杂芳基三唑酮衍生物或其药学上可接受的盐,其制备方法,含有它们的药物组合物,以及其用途。所述芳基或杂芳基三唑酮衍生物或其药学上可接受的盐对VAP-1具有选择性的抑制活性,因此可以有效地用于诸如非酒精性肝脂肪变性(NASH)的治疗和预防。(The present invention provides aryl or heteroaryl triazolone derivatives or pharmaceutically acceptable salts thereof, processes for their preparation, pharmaceutical compositions containing them and uses thereof. The aryl or heteroaryl triazolone derivatives or pharmaceutically acceptable salts thereof have selective inhibitory activity against VAP-1 and thus can be effectively used for the treatment and prevention of, for example, nonalcoholic liver steatosis (NASH).)

1. A compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein the content of the first and second substances,

a is aryl or heteroaryl, said heteroaryl having 1-5 heteroatom ring members selected from O, N or S, and said aryl or heteroaryl being optionally substituted with one to three substituents selected from: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R; and

r is a substituted or unsubstituted ring optionally containing 1-5 heteroatom ring members selected from O, N or S, and the ring is aromatic or non-aromatic.

2. The compound of claim 1, or an isomer thereof, or a pharmaceutically acceptable salt thereof, wherein a is selected from the group consisting of phenyl, naphthalene, pyridine, pyrimidine, pyrazine, triazine, thiazole, thiophene, pyrrole, pyrazole, imidazole, triazole, tetrazole, furan, oxazole, isoxazole, oxadiazole, and thiadiazole.

3. The compound of claim 1 or 2, or an isomer thereof, or a pharmaceutically acceptable salt thereof, wherein a is selected from the group consisting of phenyl, pyridine, pyrazine and thiazole.

4. A compound of the following formula 1, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein the content of the first and second substances,

a is an aryl or heteroaryl group selected from phenyl, pyridine, pyrazine and thiazole,

wherein said aryl or heteroaryl is optionally substituted with one to three substituents selected from the group consisting of: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ≡ CH-R and-C ≡ C-R,

wherein R is a ring selected from the group consisting of benzene, phenylbenzene, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine, thiophene, thiazole, imidazole, pyrazole, piperazine, morpholine, benzodioxole, benzooxadiazole, benzothiophene, benzothiazole, 2, 3-dihydro-benzodioxine, indazole, indole, 1, 3-indolin-2-one, 1, 2-indolin-3-one, quinoline, isoquinoline, quinolin-2-one, 3, 4-dihydroquinolin-2-one, 3, 4-dihydro-1, 4-benzoxazine, 1, 4-benzoxazin-3-one, 3, 1-benzoxazin-2-one, 2, 3-dihydro-imidazo [ 4], 5-b ] pyridine, oxazolo [4,5-b ] pyridin-2-one, 2, 3-dihydro-pyrido [2,3-b ] [1,4] oxazine, 3, 4-dihydro-pyrido [3,2-b ] [1,4] oxazine, pyrido [2,3-b ] [1,4] oxazin-2-one, pyrido [3,2-b ] [1,4] oxazin-3-one, and dibenzo [ b, d ] furan;

Wherein said ring is optionally substituted with one or two substituents selected from the group consisting of: hydroxy, halogen, C_1-6Alkyl, trifluoromethyl, C_1-6Alkoxy, trifluoromethoxy, amino, mono-or di-C_1-6Alkylamino radical, C_1-6Alkylcarbonylamino, C_1-6Alkylthio, mono-or di-C_1-6Alkylaminosulfonyl radical, C_1-6Alkylsulfonyl radical, C_1-6Alkylcarbonyl, morpholinylcarbonyl, benzodioxolyl, pyrrolidinyl, piperazinyl, acetylpiperazinyl, morpholinyl, tetrahydropyranyl, triazolyl, tetrazolyl, isoxazolyl, oxazolyl, oxadiazolyl, cyclopropyl-oxadiazolyl, C_1-6Alkyl-oxadiazolyl and oxadiazol-5-onyl.

5. The compound of any one of claims 1-4, or an isomer thereof, or a pharmaceutically acceptable salt thereof, wherein A is pyridine.

6. The compound of any one of claims 1-4, or an isomer thereof, or a pharmaceutically acceptable salt thereofA salt wherein the aryl or heteroaryl is substituted with 1 or 2 substituents selected from: c_1-3Alkyl, halogen, -R and-C ≡ C-R.

7. The compound of any one of claims 1-6, or an isomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is a ring selected from the group consisting of benzene, pyridine, and pyrazole.

8. The compound of claim 7, or an isomer thereof, or a pharmaceutically acceptable salt thereof, wherein the ring is unsubstituted or substituted with a substituent selected from the group consisting of: c_1-6Alkyl, trifluoromethyl and oxazolyl.

9. The compound of any one of claims 1-4, or an isomer thereof, or a pharmaceutically acceptable salt thereof, wherein

A is a pyridine, and the compound is represented by the formula,

wherein said pyridine is substituted with one or two substituents selected from the group consisting of: c_1-3Alkyl, halogen, -R and-C.ident.C-R,

wherein R is a ring selected from the group consisting of benzene, pyridine and pyrazole,

wherein said ring is unsubstituted or substituted with a substituent selected from the group consisting of: c_1-6Alkyl, trifluoromethyl and oxazolyl.

10. The compound of any one of claims 1-4, or an isomer thereof, or a pharmaceutically acceptable salt thereof, selected from the following compounds, or an isomer thereof, or a pharmaceutically acceptable salt thereof:

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (benzyloxy) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (benzyloxy) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3, 4-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3, 4-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-2-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-2-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-methylphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-methylphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-methoxyphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-methoxyphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3, 5-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3, 5-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-2, 6-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-2, 6-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-2, 5-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromopyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromopyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromo-5-methylpyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromo-5-methylpyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromo-4-methylpyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromopyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromopyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-3-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-3-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-4-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-4-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-3-fluoropyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-3-fluoropyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromopyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromopyrazin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (1, 3-thiazol-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-1, 3-thiazol-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-1, 3-thiazol-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

4- [4- (5-acetylthiophen-2-yl) phenyl ] -2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 3-fluoro-4' - (4H-1,2, 4-triazol-3-yl) biphenyl-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 3-fluoro-3' - (4H-1,2, 4-triazol-3-yl) biphenyl-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (1, 3-benzodioxol-5-yl) -2-fluorophenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (2,1, 3-benzoxadiazol-5-yl) -2-fluorophenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 5-bromo-2-methoxy-4- (morpholin-4-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1,2,3, 6-tetrahydropyridin-4-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one dihydrochloride;

4- [3- (5-acetylthiophen-2-yl) phenyl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (trifluoromethoxy) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (dimethylamino) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (prop-2-ylsulfanyl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (methylsulfonyl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (methylsulfonyl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

3' - {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -N, N-dimethylbiphenyl-4-sulfonamide hydrochloride;

n- (3' - {1- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } biphenyl-4-yl) acetamide hydrochloride;

N- (3' - {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } biphenyl-4-yl) acetamide hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (4H-1,2, 4-triazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (4H-1,2, 4-triazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3' - (4H-1,2, 4-triazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (1,2, 4-oxadiazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3' - (1,2, 4-oxadiazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {4' - [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] biphenyl-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {3' - [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] biphenyl-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4 "- (methylsulfonyl) -1,1 ': 4', 1" -terphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4 "- (methylsulfonyl) -1,1 ': 3', 1" -terphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- (3 "- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -1,1 ': 4', 1" -terphenyl-4-yl) acetamide hydrochloride;

n- (3 "- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -1,1 ': 3', 1" -terphenyl-4-yl) acetamide hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (1, 3-benzodioxol-5-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3' - (1, 3-benzodioxol-5-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

4- [4' - (4-acetylpiperazin-1-yl) biphenyl-3-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (tetrahydro-2H-pyran-4-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (morpholin-4-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3 '-fluoro-4' - (morpholin-4-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3 '-chloro-4' - (morpholin-4-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3 '-methyl-4' - (morpholin-4-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (morpholin-4-ylcarbonyl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2-methoxypyridin-4-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

N- [4- (3- {1- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) pyridin-2-yl ] acetamide hydrochloride;

n- [4- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) pyridin-2-yl ] acetamide hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (pyridin-3-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (6-methoxypyridin-3-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {3- [6- (trifluoromethyl) pyridin-3-yl ] phenyl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (6-chloropyridin-3-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {3- [6- (morpholin-4-yl) pyridin-3-yl ] phenyl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {3- [ 6-methoxy-5- (trifluoromethyl) pyridin-3-yl ] phenyl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {3- [ 6-hydroxy-5- (trifluoromethyl) pyridin-3-yl ] phenyl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

5- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) -1, 3-dimethylpyridin-2 (1H) -one hydrochloride;

5- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) -1- (prop-2-yl) pyridin-2 (1H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2-methylpyrimidin-5-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1, 3-benzodioxol-5-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1, 3-benzodioxol-5-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2, 3-dihydro-1, 4-benzodioxine-6-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2, 3-dihydro-1, 4-benzodioxine-6-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2,1, 3-benzoxadiazol-5-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1H-indazol-6-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1H-indol-4-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

4- [3- (2-amino-1, 3-benzothiazol-5-yl) phenyl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1H-indol-3-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1-benzothien-2-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) -8-methyl-3, 4-dihydroquinolin-2 (1H) -one hydrochloride;

6- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) -2H-1, 4-benzoxazin-3 (4H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (isoquinolin-4-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (8-methylquinolin-5-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 2-methyl-4' - (methylsulfonyl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- (3'- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -2' -methylbiphenyl-4-yl) acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 2-methyl-4' - (1, 2-oxazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [4- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -2-methylphenyl) pyridin-2-yl ] acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 2-methyl-3- [6- (morpholin-4-yl) pyridin-3-yl ] phenyl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1, 3-benzodioxol-5-yl) -2-methylphenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2, 3-dihydro-1, 4-benzodioxine-6-yl) -2-methylphenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2,1, 3-benzoxadiazol-5-yl) -2-methylphenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [3- (2-amino-1, 3-benzothiazol-5-yl) -2-methylphenyl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 5-methyl-6- [4- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 5-methyl-6- [3- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (1, 3-benzodioxol-5-yl) -5-methylpyridin-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [6- (2-amino-1, 3-benzothiazol-5-yl) -5-methylpyridin-3-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 4-methyl-6- [4- (methylsulfonyl) phenyl ] pyridin-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

N- [4- (5- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -4-methylpyridin-2-yl) phenyl ] acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 4-methyl-6- [4- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 4-methyl-6- [3- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- (5- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -4-methyl-2, 4 '-bipyridin-2' -yl) acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 4-methyl-6 '- (morpholin-4-yl) -2,3' -bipyridin-5-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (2,1, 3-benzoxadiazol-5-yl) -4-methylpyridin-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (1H-indazol-6-yl) -4-methylpyridin-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [6- (2-amino-1, 3-benzothiazol-5-yl) -4-methylpyridin-3-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

N- [5- (5- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -4-methylpyridin-2-yl) -1, 3-benzothiazol-2-yl ] acetamide;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (methylsulfonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

n- [4- (6- {1- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-3-yl) phenyl ] acetamide hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 3-methyl-5- (piperazin-1-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [5- (5-acetylthiophen-2-yl) -3-methylpyridin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (methylsulfonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

n- [4- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) phenyl ] acetamide hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (4H-1,2, 4-triazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (4H-1,2, 4-triazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [3- (4H-1,2, 4-triazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (1,2, 5-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (1,2, 4-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [3- (1,2, 4-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) phenyl ] -3-methylpyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3-methyl-5- {4- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3-methyl-5- {3- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [3- (1H-tetrazol-5-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (piperazin-1-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (morpholin-4-ylcarbonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) -2H-1, 4-benzoxazin-3 (4H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 5-methyl-6 '- (trifluoromethyl) -3,3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 5-methyl-6 '- (morpholin-4-yl) -3,3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (2H-1, 3-benzodioxol-5-yl) -3-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) -1, 3-dihydro-2H-indol-2-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (2,1, 3-benzoxadiazol-5-yl) -3-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1H-indazol-6-yl) -3-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) -8-methyl-3, 4-dihydroquinolin-2 (1H) -one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) -2H-1, 4-benzoxazin-3 (4H) -one hydrochloride;

7- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) -1, 4-dihydro-2H-3, 1-benzoxazin-2-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 4-methyl-5- [4- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 4-methyl-5- [3- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1, 3-benzodioxol-5-yl) -4-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1H-indazol-6-yl) -4-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [5- (2-amino-1, 3-benzothiazol-5-yl) -4-methylpyridin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1, 3-benzodioxol-5-yl) -3-fluoropyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-fluoropyridin-3-yl) -1, 2-dihydro-3H-indol-3-one;

4- [5- (2-amino-1, 3-benzothiazol-5-yl) -3-fluoropyridin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {4- [4- (methylsulfonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [4- (2- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-4-yl) phenyl ] acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {4- [4- (1, 2-oxazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- (2'- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -4,4' -bipyridin-2-yl) acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (morpholin-4-yl) -3,4 '-bipyridin-2' -yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (1, 3-benzodioxol-5-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (2, 3-dihydro-1, 4-benzodioxine-6-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (2,1, 3-benzoxadiazol-5-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [4- (2-amino-1, 3-benzothiazol-5-yl) pyridin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [3- (dimethylamino) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

n- [4- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) phenyl ] acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (1, 2-oxazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (1,2, 5-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [3- (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6- {4- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6- {3- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

3- [4- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) phenyl ] -1,2, 4-oxadiazol-5 (4H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (pyrrolidin-1-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (piperazin-1-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [3- (piperazin-1-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (morpholin-4-ylcarbonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6'- (trifluoromethyl) -2,3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6'- (dimethylamino) -2,3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6'- (morpholin-4-yl) -2,3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6' -fluoro-5 ' -methyl-2, 3' -bipyridin-6-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6' - (dimethylamino) -5' -fluoro-2, 3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [ 1-methyl-3- (trifluoromethyl) -1H-pyrazol-5-yl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (1, 3-benzodioxol-5-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (2, 3-dihydro-1, 4-benzodioxine-6-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (2,1, 3-benzoxadiazol-5-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [6- (2-amino-1, 3-benzothiazol-5-yl) pyridin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) -8-methyl-3, 4-dihydroquinolin-2 (1H) -one hydrochloride;

6- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridyl ] -1-methyl-3, 4-dihydroquinolin-2-one hydrochloride;

6- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) -2H-1, 4-benzoxazin-3 (4H) -one hydrochloride;

7- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) -1, 4-dihydro-2H-3, 1-benzoxazin-2-one hydrochloride;

5- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) quinolin-2 (1H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (4-methyl-3, 4-dihydro-2H-1, 4-benzoxazin-7-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (dibenzo [ b, d ] furan-4-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (2- {4- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-4-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (2- {3- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-4-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {2- [4- (morpholin-4-yl) phenyl ] pyridin-4-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {2- [4- (morpholin-4-ylcarbonyl) phenyl ] pyridin-4-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [2- (1, 3-benzodioxol-5-yl) pyridin-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [3- (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) phenyl ] -3-methylpyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-6- [4- (morpholin-4-ylcarbonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6 '-methoxy-5-methyl-2, 3' -bipyridin-6-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (1, 3-benzodioxol-5-yl) -3-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (1H-indazol-6-yl) -3-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-2-yl) -8-methyl-3, 4-dihydroquinolin-2 (1H) -one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-2-yl) -2H-1, 4-benzoxazin-3 (4H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (methylsulfonyl) phenyl ] pyrazin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (1H-1,2, 4-triazol-3-yl) phenyl ] pyrazin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [3- (1H-1,2, 4-triazol-3-yl) phenyl ] pyrazin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [4- (5- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyrazin-2-yl) pyridin-2-yl ] acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [6- (morpholin-4-yl) pyridin-3-yl ] pyrazin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (2,1, 3-benzoxadiazol-5-yl) pyrazin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1H-indazol-6-yl) pyrazin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [5- (2-amino-1, 3-benzothiazol-5-yl) pyrazin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [5- (5- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyrazin-2-yl) -1, 3-benzothiazol-2-yl ] acetamide;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (methylsulfonyl) phenyl ] -1, 3-thiazol-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (4H-1,2, 4-triazol-3-yl) phenyl ] -1, 3-thiazol-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [3- (4H-1,2, 4-triazol-3-yl) phenyl ] -1, 3-thiazol-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (4H-1,2, 4-oxadiazol-3-yl) phenyl ] -1, 3-thiazol-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [3- (1H-tetrazol-5-yl) phenyl ] -1, 3-thiazol-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [4- (2- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -1, 3-thiazol-5-yl) pyridin-2-yl ] acetamide;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1, 3-benzodioxol-5-yl) -1, 3-thiazol-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (2- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -1, 3-thiazol-5-yl) -1, 3-dihydro-2H-indol-2-one;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (2,1, 3-benzoxadiazol-5-yl) -1, 3-thiazol-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

n- [5- (4- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } benzyl) -1, 3-thiazol-2-yl ] acetamide hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {4- [ (E) -2-phenylethenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [ (E) -2- (thiophen-3-yl) vinyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6- { (E) -2- [4- (trifluoromethyl) phenyl ] vinyl } pyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [ (E) -2- [4- (dimethylamino) phenyl ] vinyl ] -2-pyridinyl ] -1,2, 4-triazol-3-one hydrochloride;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [ (E) -2- (3-methyl-1, 2-dihydroimidazo [4,5-b ] pyridin-6-yl) vinyl ] -2-pyridinyl ] -1,2, 4-triazol-3-one hydrochloride;

7- [ (E) -2- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridinyl ] vinyl ] -1H-pyrido [2,3-b ] [1,4] oxazin-2-one hydrochloride;

6- [ (E) -2- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridinyl ] vinyl ] -3H-oxazolo [4,5-b ] pyridin-2-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (pyridin-3-ylethynyl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (pyridin-2-ylethynyl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (pyridin-3-ylethynyl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (pyridin-4-ylethynyl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [ (6-methoxypyridin-3-yl) ethynyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- [6- (dimethylamino) -3-pyridinyl ] ethynyl ] -2-pyridinyl ] -1,2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (6-morpholino-3-pyridyl) ethynyl ] -2-pyridyl ] -1,2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (3, 4-dihydro-2H-1, 4-benzoxazin-6-yl) ethynyl ] -2-pyridinyl ] -1,2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (2, 3-dihydro-1H-pyrido [2,3-b ] [1,4] oxazin-7-yl) ethynyl ] -2-pyridyl ] -1,2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (3, 4-dihydro-2H-pyrido [3,2-b ] [1,4] oxazin-7-yl) ethynyl ] -2-pyridyl ] -1,2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (2, 3-dihydro-1H-pyrido [2,3-b ] [1,4] oxazin-6-yl) ethynyl ] -2-pyridyl ] -1,2, 4-triazol-3-one;

6- [2- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridinyl ] ethynyl ] -3, 4-dihydro-1H-quinolin-2-one;

7- [2- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridinyl ] ethynyl ] -4H-pyrido [3,2-b ] [1,4] oxazin-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (3-methylimidazol-4-yl) ethynyl ] -2-pyridyl ] -1,2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [ (1-methyl-1H-pyrazol-4-yl) ethynyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

7- [2- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridinyl ] ethynyl ] -1H-pyrido [2,3-b ] [1,4] oxazin-2-one; and

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [ 3-methyl-5- (6-piperazin-1-yl-3-pyridinyl) -2-pyridinyl ] -1,2, 4-triazol-3-one.

11. A compound of formula 10, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein

R is a substituted or unsubstituted ring, optionally containing at least one heteroatom, and the ring is aromatic or non-aromatic; and

R^ais hydrogen, C_1-3Alkyl radical, C_1-3Alkoxy, or halogen.

12. The compound of claim 11, which is formula 10a, or an isomer thereof, or a pharmaceutically acceptable salt thereof

13. The compound of claim 11, which is formula 10b, or an isomer thereof, or a pharmaceutically acceptable salt thereof

14. A compound of formula 11, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein

R is a substituted or unsubstituted ring, optionally comprising at least one heteroatom, and the ring is aromatic or non-aromatic; and

R^ais hydrogen, C_1-3Alkyl radical, C_1-3Alkoxy or halogen.

15. The compound of claim 14, which is formula 11a, or an isomer thereof, or a pharmaceutically acceptable salt thereof

16. The compound of claim 14, which is formula 11b, or an isomer thereof, or a pharmaceutically acceptable salt thereof

17. The compound of claim 14, which is formula 11c, or an isomer thereof, or a pharmaceutically acceptable salt thereof

18. The compound of claim 14, which is formula 11d, or an isomer thereof, or a pharmaceutically acceptable salt thereof

19. The compound of claim 14, which is formula 11e, or an isomer thereof, or a pharmaceutically acceptable salt thereof

20. A compound of formula 12, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein

A' is pyridine; and

r is a substituted or unsubstituted ring, optionally comprising at least one heteroatom, and the ring is aromatic or non-aromatic.

21. The compound of any one of claims 1-3 or 11-20, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein R is selected from the group consisting of benzene, phenylbenzene, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine, thiophene, thiazole, imidazole, pyrazole, piperazine, morpholine, benzodioxole, benzooxadiazole, benzothiophene, benzothiazole, 2, 3-dihydro-benzodioxine, indazole, indole, 1, 3-indolin-2-one, 1, 2-indolin-3-one, quinoline, isoquinoline, quinolin-2-one, 3, 4-dihydroquinolin-2-one, 3, 4-dihydro-1, 4-benzoxazine, 1, 4-benzoxazin-3-one, 3, 1-benzoxazin-2-one, 2, 3-dihydro-imidazo [4,5-b ] pyridine, and mixtures thereof, Oxazolo [4,5-b ] pyridin-2-one, 2, 3-dihydro-pyrido [2,3-b ] [1,4] oxazine, 3, 4-dihydro-pyrido [3,2-b ] [1,4] oxazine, pyrido [2,3-b ] [1,4] oxazin-2-one, pyrido [3,2-b ] [1,4] oxazin-3-one, and dibenzo [ b, d ] furan; and is

R is optionally substituted with one or two substituents selected from: hydroxy, halogen, C_1-6Alkyl, trifluoromethyl, C_1-6Alkoxy, trifluoromethoxy, amino, mono-or di-C_1-6Alkylamino radical, C_1-6Alkylcarbonylamino, C_1-6Alkylthio, mono-or di-C_1-6Alkylaminosulfonyl radical, C_1-6Alkylsulfonyl radical, C_1-6Alkylcarbonyl, morpholinylcarbonyl, benzodioxolylPyrrolidinyl, piperazinyl, acetylpiperazinyl, morpholinyl, tetrahydropyranyl, triazolyl, tetrazolyl, isoxazolyl, oxazolyl, oxadiazolyl, cyclopropyl-oxadiazolyl, C_1-6Alkyl-oxadiazolyl and oxadiazol-5-onyl.

22. A pharmaceutical composition comprising a compound according to any one of claims 1-21, or an isomer thereof or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

23. A method of selectively inhibiting vascular adhesion protein (VAP-1) comprising administering to a mammal a therapeutically effective amount of a compound according to any one of claims 1 to 21, or an isomer thereof or a pharmaceutically acceptable salt thereof.

24. A method of treating NASH in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound according to any one of claims 1-21, or an isomer thereof, or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition of claim 22.

25. Use of a compound according to any one of claims 1-21, or an isomer thereof, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment of NASH.

26. A compound according to any one of claims 1-21, or an isomer thereof, or a pharmaceutically acceptable salt thereof, for use in the treatment of NASH.

27. The composition according to claim 22 for use in the treatment of NASH.

28. A compound according to any one of claims 1 to 21, or an isomer thereof, or a pharmaceutically acceptable salt thereof, for use in the selective inhibition of VAP-1.

29. The composition according to claim 22 for the selective inhibition of VAP-1.

30. A method of treating a VAP-1 mediated disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1-21, or an isomer thereof, or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition according to claim 22.

31. The method according to claim 30, wherein the disease mediated by VAP-1 is selected from the group consisting of lipid and lipoprotein disorders, disorders and diseases caused by chronic fat and fibrosis of the organs due to lipid accumulation, in particular the accumulation of triglycerides and the subsequent activation of the pro-fibrotic pathway, diabetes type I or II and clinical complications thereof, chronic extrahepatic or certain forms of extrahepatic cholestatic diseases, liver fibrosis, acute intrahepatic cholestatic disorders, obstructive or chronic inflammatory disorders caused by inappropriate bile constituents, gastrointestinal disorders accompanied by a reduced intake of dietary fat and fat-soluble dietary vitamins, inflammatory bowel diseases, obesity and metabolic syndrome (dyslipidaemia, diabetes and combined disorders of abnormally high body mass index), persistent infection by intracellular bacteria or by a biological protozoa, persistent infection by bacteria or by a biological protozoa, disorders of the gastrointestinal tract, and diseases caused by lipid accumulation, and the subsequent activation of the pro-fibrotic pathway, Non-malignant hyperproliferative disorders, in particular colon adenocarcinoma and hepatocellular carcinoma, hepatic steatosis and related syndromes, hepatitis b infection, hepatitis c infection and/or cholestasis and fibrosis associated with alcohol-induced cirrhosis or virus-transmitted forms of hepatitis, liver failure or liver dysfunction due to chronic liver disease or surgical liver resection, acute myocardial infarction, acute stroke, thrombosis occurring as an end-point of chronic obstructive atherosclerosis, osteoarthritis, rheumatoid arthritis, psoriasis and cerebral infarction, or any combination thereof.

32. A process for preparing a compound of formula 1a, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

the method comprises the following steps

(a) Reacting a compound of formula 2 with a compound of formula 3a or a compound of formula 3b to obtain a compound of formula 1aa,

Z₂-B-R' (formula 3a)

HC ≡ CR' (formula 3b)

Wherein

Boc is an amine protecting group;

a' is an aryl or heteroaryl group selected from phenyl, pyridine, pyrazine and thiazole;

z is hydroxy or C_1-3Alkoxy, or two Z together with the boron to which they are attached form

R' is one to three groups independently selected from: -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R; and

r is a substituted or unsubstituted ring, optionally comprising at least one heteroatom, and the ring is aromatic or non-aromatic; and

(b) removing the Boc from the compound of formula 1aa under reaction conditions to obtain the compound of formula 1a or its isomer or a pharmaceutically acceptable salt thereof.

33. The method of claim 32, wherein the ring is selected from the group consisting of benzene, phenylbenzene, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine, thiophene, thiazole, imidazole, pyrazole, piperazine, morpholine, benzodioxole, benzoxadiazole, benzothiophene, benzothiazole, 2, 3-dihydro-benzodioxine, indazole, indole, 1, 3-dihydroindol-2-one, 1, 2-dihydroindol-3-one, quinoline, isoquinoline, quinolin-2-one, 3, 4-dihydroquinolin-2-one, 3, 4-dihydro-1, 4-benzoxazine, 1, 4-benzoxazin-3-one, 3, 1-benzoxazin-2-one, 2, 3-dihydro-imidazo [4,5-b ] pyridine, oxazolo [4,5-b ] pyridin-2-one, 2, 3-dihydro-pyrido [2,3-b ] [1,4] oxazine, 3, 4-dihydro-pyrido [3,2-b ] [1,4] oxazine, pyrido [2,3-b ] [1,4] oxazin-2-one, pyrido [3,2-b ] [1,4] oxazin-3-one, and dibenzo [ b, d ] furan;

Wherein said ring is optionally substituted with one or two substituents selected from the group consisting of: hydroxy, halogen, C_1-6Alkyl, trifluoromethyl, C_1-6Alkoxy, trifluoromethoxy, amino, mono-or di-C_1-6Alkylamino radical, C_1-6Alkylcarbonylamino, C_1-6Alkylthio, mono-or di-C_1-6Alkylaminosulfonyl radical, C_1-6Alkylsulfonyl radical, C_1-6Alkylcarbonyl, morpholinylcarbonyl, benzodioxolyl, pyrrolidinyl, piperazinyl, acetylpiperazinyl, morpholinyl, tetrahydropyranyl, triazolyl, tetrazolyl, isoxazolyl, oxazolyl, oxadiazolyl, cyclopropyl-oxadiazolyl, C_1-6Alkyl-oxadiazolyl and oxadiazol-5-onyl.

Technical Field

The present invention relates to aryl or heteroaryl triazolone derivatives or pharmaceutically acceptable salts thereof having inhibitory activity against vascular adhesion protein (VAP-1), processes for their preparation, pharmaceutical compositions containing them and their use.

Background

Vascular adhesion protein 1(VAP-1) is a semicarbazide-sensitive amine oxidase (SSAO) that is abundant in human plasma. VAP-1 is an extracellular enzyme comprising a short cytoplasmic tail, a transmembrane domain, and an extracellular domain comprising an active center with large and high degrees of glycosylation. In addition, VAP-1 can be present not only in membrane-bound form but also in serum in soluble form (soluble VAP-1, sVAP-1). This form appears to be the product of cleavage from membrane-bound VAP-1 and appears to have similar properties to the tissue-bound form. VAP-1 has also been reported to be generally stored in intracellular granules of endothelial cells, but when an inflammatory response is induced in response to inflammatory stimuli, it is translocated to the cell membrane and is up-regulated in expression, and thus, its expression is stronger in inflamed tissues than in normal tissues.

Substrates for VAP-1 include endogenous methylamine, aminoacetone and some exogenous amines, such as tyramine and benzylamine

VAP-1 has two physiological functions: the first is the amine oxidase activity mentioned earlier in this section and the second is cell adhesion activity. Because of these two activities, VAP-1 has been shown to play a key role in the leakage of inflammatory cells, as it acts as an adhesion protein for leukocytes at sites of inflammation [ Trends Immunol. (2001) 22: 211]. VAP-1 deficient transgenic mice are healthy, normally developing, fertile and phenotypically normal, but show a significant reduction in inflammatory response to various inflammatory stimuli. [ Immunity (2005) 22: 105].

Furthermore, the inhibitory activity of VAP-1 by using antibodies or small molecules in a variety of animal models of human disease (e.g., carrageenan-induced paw inflammation, oxazolone-induced colitis, lipopolysaccharide-induced lung inflammation, collagen-induced arthritis, endotoxin-induced uveitis) has been shown to prevent leukocyte rolling, adhesion and leakage, and reduce the levels of inflammatory cytokines and chemokines, thereby reducing the severity of the disease [ Eur J Immunol. (2005) 35: 3119; j Pharmacol Exp Ther (2005) 315: 553; AnnuRep Med chem. (2007) 42: 229; faebj. (2008) 22: 1094]. Inflammation is the first response of the immune system to infection or irritation, during which the entry of leukocytes into tissues through the circulation is an important step. Leukocytes first bind to adsorbed proteins and then adhere to the endothelium before they begin to cross the vessel wall. VAP-1 is highly expressed in endothelial venules (HEVs), such as high endothelial venules in lymphoid organs, as well as Hepatic Sinus Endothelial Cells (HSECs), smooth muscle cells and adipocytes. VAP-1 expression on the cell surface of endothelial cells is tightly regulated and increases during inflammation. VAP-1 activates NF-. kappa.B when present in the substrate, NF-. kappa.B is activated in HSEC, and other adhesion molecules E-selectin and chemokine IL-8 are upregulated ex vivo. This suggests that VAP-1 may be a key factor in the regulation of inflammatory responses, and thus it appears that VAP-1 inhibitors may be potent anti-inflammatory agents in a wide range of human diseases.

Histologically, nonalcoholic fatty liver disease (NAFLD) includes simple steatosis, nonalcoholic liver steatosis (NASH), and cirrhosis of the liver. Among them, NASH may progress to cirrhosis and liver cancer (hepatocellular carcinoma), unlike simple steatosis (nonalcoholic fatty liver, NAFL). In NASH, insulin resistance is known to play an important role in disease progression along with oxidative stress, inflammatory cascades, and fibrosis. In patients with NAFLD, sVAP-1 levels were found to be elevated, whereas in VAP-1 knockout (K/O) mice carbon tetrachloride-induced liver fibrosis was reduced compared to wild-type animals. In addition, improvement in liver fibrosis due to VAP-1 inhibition after administration of VAP-1 antibody was detected by histological changes [ J Clin Invest (2015) 125: 501]. Thus, VAP-1 was found to be associated with NASH in clinical studies and animal disease models. The inhibitory activity of VAP-1 in carbon tetrachloride-induced animal models appears to be due to the reduced leukocyte (e.g., T-cell, B-cell, NKT-cell, and NK-cell) infiltration observed in liver fibrosis, while VAP-1 inhibitors have potential for the treatment of fibrotic diseases.

Therefore, VAP-1 inhibiting substances can be used for the prevention and treatment of various inflammatory diseases and fibrotic diseases.

Disclosure of Invention

The present inventors have found that certain aryl or heteroaryl triazolone derivatives having fluoroallylamine groups, or pharmaceutically acceptable salts thereof, exhibit selective inhibitory activity against VAP-1. Accordingly, the aryl or heteroaryl triazolone derivatives, and salts thereof can be effectively used for the treatment and prevention of various VAP-1 mediated diseases, such as nonalcoholic steatohepatitis (NASH).

Accordingly, the present invention provides aryl or heteroaryl triazolone derivatives or pharmaceutically acceptable salts thereof, processes for their preparation, pharmaceutical compositions containing them and uses thereof.

According to one aspect of the present invention, there is provided an aryl or heteroaryl triazolone derivative or a pharmaceutically acceptable salt thereof.

According to another aspect of the present invention, there is provided a method for preparing an aryl or heteroaryl triazolone derivative.

According to another aspect of the present invention, there is provided a pharmaceutical composition comprising an aryl or heteroaryl triazolone derivative as an active ingredient.

According to another aspect of the invention, there is provided a method of treatment comprising administering an aryl or heteroaryl triazolone derivative.

According to another aspect of the present invention there is provided the use of an aryl or heteroaryl triazolone derivative or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the selective inhibition of vascular adhesion protein-1.

The present inventors have found that certain aryl or heteroaryl triazolone derivatives having fluoroallylamine groups, or pharmaceutically acceptable salts thereof, exhibit selective inhibitory activity against VAP-1. Therefore, the compound according to the present invention, or a pharmaceutically acceptable salt thereof, can be effectively used for the treatment and prevention of VAP-1 mediated various diseases, such as nonalcoholic steatohepatitis (NASH).

In another aspect, the present invention provides a compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein a is aryl or heteroaryl, said heteroaryl having 1-5 heteroatom ring members selected from O, N or S, and said aryl or heteroaryl is optionally substituted with one to three substituents selected from: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R; and R is a substituted or unsubstituted ring optionally containing 1-5 heteroatom ring members selected from O, N or S, and the ring is aromatic or non-aromatic. In some embodiments, a is selected from the group consisting of phenyl, naphthalene, pyridine, pyrimidine, pyrazine, triazine, thiazole, thiophene, pyrrole, pyrazole, imidazole, triazole, tetrazole, furan, oxazole, isoxazole, oxadiazole, and thiadiazole. In some embodiments, a is selected from phenyl, pyridine, pyrazine and thiazole.

In another aspect, the present invention provides a compound of the following formula 1, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein A is an aryl or heteroaryl group selected from the group consisting of: phenyl, pyridine, pyrazine and thiazole, wherein the aryl or heteroaryl group is optionally substituted with one to three substituents selected from the group consisting of: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R, wherein said R is a ring selected from: benzene, phenylbenzene, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine, thiophene, thiazole, imidazole, pyrazole, piperazine, morpholine, benzodioxole, benzoxadiazole, benzothiophene, benzothiazole, 2, 3-dihydro-benzodioxine, indazole, indole, 1, 3-indolin-2-one, 1, 2-indolin-3-one, quinoline, isoquinoline, quinolin-2-one, 3, 4-dihydroquinolin-2-one, 3, 4-dihydro-1, 4-benzoxazine, 1, 4-benzoxazin-3-one, 3, 1-benzoxazin-2-one, 2, 3-dihydro-imidazo [4,5-b ] o]Pyridine, oxazolo [4,5-b ]]Pyridin-2-ones, 2, 3-dihydro-pyrido [2,3-b ]][1,4]Oxazines, 3, 4-dihydro-pyrido [3,2-b][1,4]Oxazine, pyrido [2,3-b ]][1,4]Oxazin-2-ones, pyrido [3,2-b ][1,4]Oxazin-3-ones and dibenzo [ b, d]Furan, wherein said ring is optionally substituted with one or two substituents selected from: hydroxy, halogen, C_1-6Alkyl, trifluoromethyl, C_1-6Alkoxy, trifluoromethoxy, amino, mono-or di-C_1-6Alkylamino radical, C_1-6Alkylcarbonylamino, C_1-6Alkylthio, mono-or di-C_1-6Alkylaminosulfonyl radical, C_1-6Alkylsulfonyl radical, C_1-6Alkylcarbonyl, morpholinylcarbonyl, benzodioxolyl, pyrrolidinyl, piperazinyl, acetylpiperazinyl, morpholinyl, tetrahydropyranyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, cyclopropyl-oxadiazolyl, C_1-6Alkyl-oxadiazolyl and oxadiazol-5-onyl. In some embodiments, a is pyridine. In some embodiments, the aryl or heteroaryl is substituted with one or two substituents selected from the group consisting of: c_1-3Alkyl, halogen, -R and-C ≡ C-R. In some embodiments, the R is a ring selected from: benzene, pyridine and pyrazole. In some embodiments, the ring is unsubstituted; or substituted with a substituent selected from: c_1-6Alkyl, trifluoromethyl and oxazolyl. In some embodiments, a is pyridine, wherein the pyridine is substituted with one or two substituents selected from the group consisting of: c _1-3Alkyl, halo, -R and-C ≡ C-R, wherein R is a ring selected from: benzene, pyridine and pyrazole, wherein the ring is unsubstituted; or substituted with a substituent selected from: c_1-6Alkyl, trifluoromethyl and oxazolyl. In some embodiments, the compound is selected from table 1, or an isomer thereof, or a pharmaceutically acceptable salt thereof.

In another aspect, the present invention provides a compound of formula 10, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein R is a substituted or unsubstituted ring, optionally containing at least one heteroatom,and the ring is aromatic or non-aromatic; r^aIs hydrogen, C_1-3Alkyl radical, C_1-3Alkoxy or halogen. In some embodiments, the compound is of formula 10a, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

in some embodiments, the compound is formula 10b, or an isomer thereof, or a pharmaceutically acceptable salt thereof.

In another aspect, the present invention provides a compound of formula 11, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein R is a substituted or unsubstituted ring, optionally containing at least one heteroatom, and the ring is aromatic or non-aromatic; r^aIs hydrogen, C _1-3Alkyl radical, C_1-3Alkoxy or halogen. In some embodiments, the compound is formula 11a, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

in some embodiments, the compound is formula 11b, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

in some embodiments, the compound is formula 11c, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

in some embodiments, the compound is formula 11d, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

in some embodiments, the compound is formula 11e, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

in another aspect, the present invention provides a compound of formula 12, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein A' is pyridine; r is a substituted or unsubstituted ring, optionally containing at least one heteroatom, and the ring is aromatic or non-aromatic.

In some embodiments of the compounds of formulas X, 10a, 10b, 11a, 11b, 11c, 11d, 11e, and 12, R is selected from the group consisting of benzene, phenylbenzene, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine, thiophene, thiazole, imidazole, pyrazole, piperazine, morpholine, benzodioxole, benzoxadiazole, benzothiophene, benzothiazole, 2, 3-dihydro-benzodioxadiene, indazole, indole, 1, 3-indolin-2-one, 1, 2-indolin-3-one, quinoline, isoquinoline, quinolin-2-one, 3, 4-dihydroquinolin-2-one, 3, 4-dihydro-1, 4-benzoxazine, 1, 4-benzoxazin-3-one, 3, 1-benzoxazin-2-one, 2, 3-dihydro-imidazo [4,5-b ]Pyridine, oxazolo [4,5-b ]]Pyridin-2-ones, 2, 3-dihydro-pyrido [2,3-b ]][1,4]Oxazines, 3, 4-dihydro-pyrido [3,2-b][1,4]Oxazine, pyrido [2,3-b ]][1,4]Oxazin-2-ones, pyrido [3,2-b][1,4]Oxazin-3-ones and dibenzo [ b, d]Furan; r is optionally substituted with one or two substituents selected from: hydroxy, halogen, C_1-6Alkyl, trifluoromethyl, C_1-6Alkoxy, trifluoromethoxy, amino, mono-or di-C_1-6Alkylamino radical, C_1-6Alkylcarbonylamino, C_1-6Alkylthio, mono-or di-C_1-6Alkylaminosulfonyl radical, C_1-6Alkylsulfonyl radical, C_1-6Alkylcarbonyl, morpholinylcarbonyl, benzodioxolyl, pyrrolidinyl, piperazinyl, acetylpiperazinyl, morpholinyl, tetrahydropyranyl, triazolyl, tetrazolyl, isoxazolyl, oxazolyl, oxadiazolyl, cyclopropyl-oxadiazolyl, C_1-6Alkyl-oxadiazolyl and oxadiazol-5-onyl.

In another aspect, the invention provides a pharmaceutical composition comprising a compound disclosed herein and at least one pharmaceutically acceptable excipient.

In another aspect, the present invention provides a method of selectively inhibiting vascular adhesion protein (VAP-1) comprising administering to a mammal a therapeutically effective amount of a compound disclosed herein.

In another aspect, the invention provides a method of treating NASH in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound disclosed herein or a therapeutically effective amount of a pharmaceutical composition.

In another aspect, the invention provides the use of a compound disclosed herein for the manufacture of a medicament for the treatment of NASH.

In another aspect, the invention provides the use of the disclosed compounds for treating NASH.

In another aspect, the invention provides a composition disclosed herein for use in the treatment of NASH.

In another aspect, the invention provides compounds disclosed herein for the selective inhibition of VAP-1.

In another aspect, the invention provides compositions disclosed herein for the selective inhibition of VAP-1.

In another aspect, the invention provides a method of treating a VAP-1 mediated disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound disclosed herein or a therapeutically effective amount of a disclosed pharmaceutical composition. In some embodiments, the disease mediated by VAP-1 is selected from lipid and lipoprotein disorders, conditions and diseases due to accumulation of chronic fat and fibrosis of the organ, especially triglycerides, and subsequent activation of the profibrotic pathway caused by lipid accumulation, diabetes type I or II and clinical complications thereof, chronic intrahepatic or some forms of extrahepatic cholestatic diseases, liver fibrosis, acute intrahepatic cholestatic conditions, obstructive or chronic inflammatory disorders caused by inappropriate bile constituents, gastrointestinal disorders accompanied by decreased intake of dietary fat and fat-soluble dietary vitamins, inflammatory bowel disease, obesity and metabolic syndrome (combined conditions of dyslipidemia, diabetes and abnormally high body mass index), persistent infection of intracellular bacteria or parasitic protozoa, non-malignant hyperproliferative disorders, diseases with decreased intake of dietary fat and fat-soluble dietary vitamins, inflammatory bowel disease, obesity and metabolic syndrome, persistent infections of intracellular bacteria or parasitic protozoa, and the like, Malignant hyperproliferative disorders, in particular colon adenocarcinoma and hepatocellular carcinoma, hepatic steatosis and related syndromes, hepatitis b infection, hepatitis c infection and/or cholestasis and fibrosis associated with alcohol-induced cirrhosis or with viral transmitted forms of hepatitis, liver failure or liver dysfunction due to chronic liver disease or surgical removal of the liver, acute myocardial infarction, acute stroke, thrombosis occurring as an end point of chronic obstructive atherosclerosis, osteoarthritis, rheumatoid arthritis, psoriasis and cerebral infarction, or any combination thereof.

In another aspect, the present invention provides a process for preparing a compound of formula 1a, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

the method comprises the following steps

(a) Reacting a compound of formula 2 with a compound of formula 3a or a compound of formula 3b to obtain a compound of formula 1 aa;

Z₂-B-R' (formula 3a)

HC ≡ CR' (formula 3b)

Wherein Boc is an amine protecting group; a' is an aryl or heteroaryl group selected from the group consisting of: phenyl, pyridine, pyrazine and thiazole; z is hydroxy or C_1-3Alkoxy groups or two Z together with the boron to which they are attached form

R' is one to three groups independently selected from the following groups: -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R; and R is a substituted or unsubstituted ring, optionally containing at least one heteroatom, and said ring is aromatic or non-aromatic; and

(b) removing Boc from the compound of formula 1aa under reaction conditions to obtain the compound of formula 1a or its isomer or pharmaceutically acceptable salt thereof.

In some embodiments, the ring is selected from: benzene, phenylbenzene, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine, thiophene, thiazole, imidazole, pyrazole, piperazine, morpholine, benzodioxole, benzoxadiazole, benzothiophene, benzothiazole, 2, 3-dihydro-benzodioxine, indazole, indole, 1, 3-indolin-2-one, 1, 2-indolin-3-one, quinoline, isoquinoline, quinolin-2-one, 3, 4-dihydroquinolin-2-one, 3, 4-dihydro-1, 4-benzoxazine, 1, 4-benzoxazin-3-one, 3, 1-benzoxazin-2-one, 2, 3-dihydro-imidazo [4,5-b ] o ]Pyridine, oxazolo [4,5-b ]]Pyridin-2-ones, 2, 3-dihydro-pyrido [2,3-b ]][1,4]Oxazines, 3, 4-dihydro-pyrido [3,2-b][1,4]Oxazine, pyrido [2,3-b ]][1,4]Oxazin-2-ones, pyrido [3,2-b][1,4]Oxazin-3-ones and dibenzo [ b, d]Furan; wherein the cyclic group is optionally substituted with one or two substituents selected from: hydroxy, halogen, C_1-6Alkyl, trifluoromethyl, C_1-6Alkoxy, trifluoromethoxyRadical, amino, mono-or di-C_1-6Alkylamino radical, C_1-6Alkylcarbonylamino, C_1-6Alkylthio, mono-or di-C_1-6Alkylaminosulfonyl radical, C_1-6Alkylsulfonyl radical, C_1-6Alkylcarbonyl, morpholinylcarbonyl, benzodioxolyl, pyrrolidinyl, piperazinyl, acetylpiperazinyl, morpholinyl, tetrahydropyranyl, triazolyl, tetrazolyl, isoxazolyl, oxazolyl, oxadiazolyl, cyclopropyl-oxadiazolyl, C_1-6Alkyl-oxadiazolyl and oxadiazol-5-onyl.

Detailed Description

It is noted that, as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. It should also be noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as "solely," "only," and the like in connection with the recitation of claim elements, or use of a "negative" limitation.

As used herein, the term "comprising" is intended to mean that the compositions and methods include the recited elements, but not excluding others. A composition or method that "consists essentially of" an element as defined herein shall not exclude other materials or steps that do not materially affect the basic and novel characteristics of the claimed technology. "consisting of" means excluding other ingredients and elements in substantial process steps that are not trace amounts. Embodiments defined by each of these transition terms are within the scope of the present technology. When an embodiment is defined by one of these terms (e.g., "comprising"), it is to be understood that the present disclosure also includes alternative embodiments, e.g., "consisting essentially of and" consisting of, for the embodiment.

"substantially" means almost entirely or completely, e.g., 95%, 96%, 97%, 98%, 99% or more of some given amount.

As used herein, the term "about" will be understood by those of ordinary skill in the art and will vary to some extent depending on the context in which it is used. If the term given the context of use is not clear to one of ordinary skill in the art, "about" means plus or minus 10% of the particular term.

Certain ranges are provided herein, with values preceded by the term "about". The term "about" is used herein to provide literal support for the exact number following it, as well as numbers that are near or similar to the number following the term. In determining whether a number is near or approximate to a specifically enumerated number, the near or approximate noneenumerated number can be such that: in the context of giving a number, the number provides a substantial equivalent to the specifically recited number.

Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the technology. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and are also encompassed within the technology, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the present technology.

Generally, "substituted" refers to an organic group (e.g., an alkyl group) in which one or more bonds to a hydrogen atom are replaced with a bond to a non-hydrogen or non-carbon atom. Substituted groups also include groups in which one or more bonds to one or more carbon atoms or one or more hydrogen atoms are replaced by one or more bonds to a heteroatom (including double or triple bonds). The present disclosure is understood to include embodiments in which, for example, "substituted alkyl" optionally comprises one or more alkenes and/or alkynes. Unless otherwise specified, a substituted group will be substituted with one or more substituents. In some embodiments, a substituted group is substituted with 1, 2, 3, 4, 5, or 6 substituents. Examples of the substituent include: halogen (i.e., F, Cl, Br, and I), hydroxyl, alkoxy, alkenyloxy, alkynyloxy, aryloxy, aralkyloxy, heterocyclyloxy, and heterocyclyloxy, aryl, heteroaryl, cycloalkyl, heterocyclyl, carbonyl (oxo), carboxyl, ester, carbamate, polyurethane, urea, oxime, hydroxylamine, alkoxyamine, aralkyloxyamine, mercapto, sulfide, sulfoxide, sulfone, sulfonyl, sulfonamide, amine, N-oxide, hydrazine, hydrazide, hydrazone, azide, amide, urea, amidine, guanidine, enamine; imides, isocyanates, isothiocyanates, cyanates, thiocyanates, imines, nitro groups, nitriles (i.e., CN), and the like.

Substituted cyclic groups such as substituted cyclic, substituted cycloalkyl, substituted aryl, substituted heterocyclyl and substituted heteroaryl groups, and also ring and fused ring systems in which the bond to a hydrogen atom is replaced by a bond to a carbon atom. Thus, substituted cyclic, cycloalkyl, aryl, heterocyclyl and heteroaryl groups may also be substituted with substituted or unsubstituted alkyl, alkenyl and alkynyl groups as defined below.

As used herein, the term "ring" refers to an aromatic or non-aromatic ring, optionally containing one or more heteroatoms. Exemplary heteroatoms include, but are not limited to N, O, S or B. In some embodiments, the ring optionally comprises 1 to 5 heteroatom ring members selected from O, N or S. In some embodiments, the ring optionally comprises 1 to 4 heteroatom ring members selected from O, N or S. In some embodiments, the ring optionally comprises 1 to 3 heteroatom ring members selected from O, N or S. Rings include aryl, cycloalkyl and heterocyclyl.

As used herein, "aryl" refers to a cyclic aromatic hydrocarbon that does not contain heteroatoms. Aryl groups include monocyclic, bicyclic, and polycyclic ring systems. Thus, aryl groups include, but are not limited to, phenyl, azulenyl, heptenylene, biphenylene, indacenyl, fluorenyl, phenanthrenyl, triphenylene, pyrenyl, tetracenyl, perylene, Phenyl, biphenyl, anthracenyl, indenyl, indanyl, pentalenyl and naphthyl. In some embodiments, aryl groups contain 6 to 14 carbons, othersWherein the cyclic portion of the group is from 6 to 12 or even from 6 to 10 carbon atoms. Although the phrase "aryl" includes groups containing fused rings, such as fused aromatic-aliphatic ring systems (e.g., indanyl, tetrahydronaphthyl, and the like), it does not include aryl groups having other groups, such as alkyl or halogen groups bonded to one of the ring members. In contrast, groups such as tolyl are referred to as substituted aryl groups. Representative substituted aryl groups may be monosubstituted or substituted more than once. For example, monosubstituted aryl groups include, but are not limited to, 2-, 3-, 4-, 5-, or 6-substituted phenyl or naphthyl groups, which may be substituted with substituents such as those described above.

As used herein, the term "cycloalkyl" refers to cyclic alkyl groups such as, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. In some embodiments, cycloalkyl groups have from 3 to 8 carbon ring members, while in other embodiments the number of ring carbon atoms is from 3 to 5, 3 to 6, or 3 to 7. Cycloalkyl also includes monocyclic, bicyclic, and polycyclic ring systems such as bridged cycloalkyl groups as described below, and fused rings such as, but not limited to, decalinyl and the like. In some embodiments, the polycyclic cycloalkyl has three rings. Substituted cycloalkyl groups may be substituted one or more times by non-hydrogen and non-carbon groups as defined above. However, substituted cycloalkyl also includes rings substituted with straight or branched chain alkyl groups as defined above. Representative substituted cycloalkyl groups may be mono-substituted or substituted more than once, such as, but not limited to, 2-, 2,3-, 2,4-, 2, 5-or 2, 6-disubstituted cyclohexyl groups, which may be substituted with substituents such as those listed above. In some embodiments, cycloalkyl groups have one or more olefinic bonds, but are not aromatic.

As used herein, the term "heterocyclyl" includes aromatic (also referred to as heteroaryl) and non-aromatic ring compounds containing 3 or more ring members, one or more of which is a heteroatom, such as but not limited to N, O, S or B. In some embodiments, heterocyclyl includes 3 to 20 ring members, while other such groups have 3 to 6, 3 to 10, 3 to 12, or 3 to 15 ring members. Heterocyclic groups include unsaturated, partially saturated and saturated ring systems, such as imidazolyl, imidazolinyl and imidazolidinyl. The phrase "heterocyclic group" includes fused rings, which include those containing fused aromatic and non-aromatic groups, such as benzotriazolyl, 2, 3-dihydro-benzo [1,4] dioxadienyl, and benzo [1,3] dioxolyl. The phrase also includes bridged polycyclic ring systems containing heteroatoms such as, but not limited to, quinuclidinyl. However, the phrase does not include heterocyclyl groups having other groups, such as alkyl, oxo, or halogen groups, bonded to one ring member. Instead, these are referred to as "substituted heterocyclyl". Heterocyclyl groups include, but are not limited to, aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, thiazolidinyl, tetrahydrothienyl, tetrahydrofuranyl, dioxolyl, furanyl, thienyl, pyrrolyl, pyrrolinyl, imidazolyl, imidazolinyl, pyrazolyl, pyrazolinyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiazolinyl, isothiazolyl, thiadiazolyl, oxadiazolyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl, tetrahydrothiopyranyl, oxathianyl, dioxyl, dithianyl, pyranyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, dihydropyridinyl, dihydrodithiacyclohexadienyl, dihydrodithiafuranyl, homopiperazinyl, quinuclidinyl, indolyl, indolinyl, isoindolyl, azaindolyl (pyrrolopyridyl), indazolyl, indolizinyl, benzotriazolyl, benzimidazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzooxadiazolyl, benzoxazinyl, benzodioxodienyl, benzoxazolyl, benzothiadiazolyl, benzo [1,3] dioxolyl, pyrazolopyridyl, imidazopyridinyl (azabenzimidazolyl), triazolopyridyl, isoxazolopyridinyl, purinyl, xanthinyl, adenylyl, guaninyl, quinolyl, isoquinolyl, quinolyl, quinoxalinyl, quinazolinyl, cinnolinyl, phthalazinyl, naphthyridinyl, pteridinyl, thianaphthyl, dihydrobenzothiazinyl, dihydrobenzofuranyl, indolinyl, dihydroindolyl, Dihydrobenzodioxinyl, tetrahydroindolyl, tetrahydroindazolyl, tetrahydrobenzimidazolyl, tetrahydrobenzotriazolyl, pyrrolidinopyridinyl, tetrahydropyrazolopyridinyl, tetrahydroimidazopyridinyl, tetrahydrotriazolopyridinyl, and tetrahydroquinolinyl. Representative substituted heterocyclic groups may be mono-or substituted more than once, such as, but not limited to, pyridyl or piperazinyl, which is 2-, 3-, 4-, 5-or 6-substituted, or disubstituted with various substituents such as those listed above.

As used herein, the term "heteroaryl" refers to an aromatic ring compound comprising 5 or more ring members, one or more of which is a heteroatom, such as, but not limited to N, O, S or B. In some embodiments, 1 or more heteroatoms are selected from N, O or S. In some embodiments, 1 to 4 heteroatoms are selected from N, O or S. In some embodiments, 1 to 5 heteroatoms are selected from N, O or S. In some embodiments, heteroaryl includes 5 to 14 ring members, while other such groups have 5 to 6, 5 to 9, 5 to 10, 6 to 9, 6 to 10, or 6 to 14 ring members. For example, a 5-membered heteroaryl has 5 ring members; a 6-membered heteroaryl has 6 ring members; a 9-membered heteroaryl has 9 ring members (such as, but not limited to, benzothiophene). Heteroaryl groups include, but are not limited to, groups such as pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, thienyl, benzothienyl, furyl, benzofuryl, indolyl, azaindolyl (pyrrolopyridyl), indazolyl, benzimidazolyl, imidazopyridinyl (azabenzoimidazolyl), pyrazolopyridinyl, triazolopyridinyl, benzotriazolyl, benzothiazolyl, benzothiadiazolyl, imidazopyridinyl, isoxazolopyridinyl, thianaphthyl, purinyl, xanthine, adenine, guanine, quinolyl, isoquinolyl, tetrahydroquinolyl, quinoxalyl and quinazolinyl. Although the phrase "heteroaryl" includes fused ring compounds such as indolyl and 2, 3-indolinyl, the phrase does not include heteroaryl groups having other groups (e.g., alkyl) bonded to one ring member. In contrast, heteroaryl groups having such substitutions are referred to as "substituted heteroaryl groups". Representative substituted heteroaryl groups may be substituted one or more times with various substituents such as those listed above. An oxazolyl group is a 5-membered heteroaryl group containing as part of the ring a nitrogen atom and at least one other atom selected from nitrogen, sulfur and oxygen. Oxazolyl includes imidazole, pyrazole, 1,2, 3-triazole, 1,2, 4-triazole, tetrazole, pentazole, oxazole, isoxazole, 1,2, 4-oxadiazole, 1,2, 5-oxadiazole, 1,3, 4-oxadiazole, thiazole, isothiazole, 1,2, 3-thiadiazole, 1,2, 4-thiadiazole, 1,2, 5-thiadiazole and 1,3, 4-thiadiazole.

As used herein, the term "alkyl" refers to aliphatic hydrocarbon groups, including straight and branched chain hydrocarbon groups. In some embodiments, the alkyl group has 1 to about 20 carbon atoms, 1 to 12 carbons, 1 to 8 carbons, 1 to 6 carbons, or 1 to 4 carbon atoms. E.g. C_1-6Alkyl refers to an aliphatic hydrocarbon group having 1 to 6 carbons, which includes methyl, ethyl, propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, neopentyl, isopentyl, and the like.

The term "hydroxy" as used herein is defined as-OH.

The term "alkoxy" as used herein, unless otherwise defined herein, refers to a group formed by substituting a hydrogen atom of a hydroxyl group with an alkyl group as defined above. E.g. C_1-6Alkoxy groups include methoxy, ethoxy, propoxy, n-butoxy, n-pentoxy, isopropoxy, sec-butoxy, tert-butoxy, neopentoxy, isopentoxy, and the like.

In addition, the term "halogen" refers to fluorine, bromine, chlorine and iodine.

In addition, the term "amino" is defined as-NH₂The term "alkylamino" refers to a mono-or dialkyl-substituted amino group. E.g. C_1-6Alkylamino includes mono-or di-C_1-6Alkyl-substituted amino groups.

In addition, the term "alkylthio" is defined as-SR (wherein R is alkyl) and the term "cyano" is defined as-CN.

One skilled in the art will appreciate that compounds of the present technology may exhibit tautomerism, conformational isomerism, geometric isomerism and/or optical isomerism. Since structural diagrams in the specification and claims may represent only one of the possible tautomeric, conformational isomeric, enantiomeric or geometric isomeric forms, it is to be understood that the present technology encompasses any of the tautomeric, conformational isomeric, enantiomeric and/or geometric forms of the compound having one or more of the uses described herein, as well as mixtures of these various forms. As used herein, "isomer" refers to a tautomer, conformer, optical isomer, geometric isomer, or any combination thereof, of a compound. As used herein, structural isomers are not included in the meaning of "isomers".

As is readily understood by those skilled in the art, a wide variety of functional groups and other structures may exhibit tautomerism, and all tautomers of the compounds described herein are within the scope of the present technology.

Stereoisomers of compounds, also referred to as "optical isomers", include all chiral, diastereomeric and racemic forms of a structure, unless the specific stereochemistry is explicitly indicated. Thus, as is apparent from the description, compounds useful in the present technology include enriched or resolved optical isomers at any or all of the stereo atoms. In order to be substantially free of their enantiomers or diastereomers, both racemic and diastereomeric mixtures and individual optical isomers may be isolated or synthesized, and these are within the skill of the art.

By "pharmaceutically acceptable" is meant a material that is not biologically or otherwise undesirable, e.g., the material may be incorporated into a pharmaceutical composition for administration to a patient without causing any undesirable biological effects or interacting in a deleterious manner with any of the other components of any of the compositions in which it is contained. When the term "pharmaceutically acceptable" is used to refer to a pharmaceutical carrier or excipient, it is implied that the carrier or excipient has met the required standards of toxicological and manufacturing testing or is included in the inactive ingredient guide written by the U.S. food and drug administration.

In general, reference to certain moieties that can be protected (e.g., hydroxy, amine, carbonyl, etc.) includes protecting groups in some embodiments of the disclosure. For example, in some embodiments, an-OH moiety included herein further includes-OP, wherein P is a protecting group. As referred to herein, protecting groups may be selected by one of ordinary skill in the art and include those set forth in the art such as those described in r.larock, Comprehensive Organic Transformations, VCH Publishers (1989); t.w.greene and p.g.m.wuts, Greene' protective groups in organic synthesis, john wiley & Sons (2006); l.fieser and m.fieser, Fieser and Fieser's reagent for organic Synthesis, John Wiley and Sons (1994); and L.Patquette, ed., encyclopedia of Reagentsfor Organic Synthesis, John Wiley and Sons (1995) and its successors.

"subject" refers to an animal, such as a mammal (including a human), that has been or will become the subject of treatment, observation or experiment. Unless otherwise indicated, "subject" and "patient" may be used interchangeably. The methods described herein can be used for human therapy and/or veterinary applications. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human.

The terms "therapeutically effective amount" and "effective amount" are used interchangeably and refer to an amount of a compound that, when administered in one or more doses to a patient (e.g., human) in need of such treatment, is sufficient to effect effective treatment as defined below. A therapeutically effective amount will depend upon the patient, the disease being treated, the weight and/or age of the patient, the severity of the disease, or the mode of administration determined by a qualified prescriber or caregiver.

The term "treatment" refers to the administration of a compound disclosed herein for the following purposes: (i) delaying the onset of the disease, i.e., causing the clinical symptoms of the disease to not develop or delay its development; (ii) inhibiting disease, i.e., arresting the development of clinical symptoms; and/or (iii) alleviating a disease that is causing worsening of clinical symptoms or its severity.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this technology belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present technology, representative exemplary methods and materials are described herein.

In one aspect, the present invention provides a compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein

A is aryl or heteroaryl, said heteroaryl having 1-5 heteroatom ring members selected from O, N or S, and said aryl or heteroaryl being optionally substituted with one to three substituents selected from: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R; and

r is a substituted or unsubstituted ring optionally containing 1-5 heteroatom ring members selected from O, N or S, and the ring is aromatic or non-aromatic.

In some embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, a is aryl substituted with one to three substituents selected from the group consisting of: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH ₂-R, -CH ═ CH-R and-C ≡ C-R. In some embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, a is C_6-10Aryl radical, said C_6-10Aryl is substituted with one to three substituents selected from the group consisting of: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R. In some embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, a is phenyl substituted with one to three substituents selected from the group consisting of: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R. Some embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereofIn embodiments, a is naphthyl, which is substituted with one to three substituents selected from the group consisting of: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R.

In some embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, a is heteroaryl having 1-5 heteroatom ring members selected from O, N or S, and the heteroaryl is substituted with one to three substituents selected from the group consisting of: c _1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R. In some embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, a is a 5 to 10 membered heteroaryl substituted with one to three substituents selected from the group consisting of: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R. In some embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, a is a 5-9 membered heteroaryl substituted with one to three substituents selected from the group consisting of: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R. In some embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, a is a 5 or 6 membered heteroaryl substituted with one to three substituents selected from the group consisting of: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R.

In some embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, a is a 5-membered heteroaryl having 1-4 heteroatom ring members selected from O, N or S, and the heteroaryl is substituted with one to three substituents selected from: c _1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R. In some embodiments, the 5-membered heteroaryl is selected from the group consisting of thiazole, thiophene, pyrrole, pyrazole, imidazole, triazole, tetrazole, furan, oxazole, triazole, and triazole,Isoxazoles, oxadiazoles and thiadiazoles. In some embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, a is pyrrolyl, and the pyrrolyl is substituted with one to three substituents selected from the group consisting of: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R.

In some embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, a is a 6 membered heteroaryl having 1-3 heteroatom ring members selected from O, N or S, and the heteroaryl is substituted with one to three substituents selected from the group consisting of: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R. In some embodiments, the 6-membered heteroaryl is selected from pyridine, pyrimidine, pyrazine and triazine. In some embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, a is pyridine, which is substituted with one to three substituents selected from the group consisting of: c _1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R. In some embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, a is a pyrimidine substituted with one to three substituents selected from the group consisting of: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R. In some embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, a is pyrazine, which is substituted with one to three substituents selected from the group consisting of: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R. In some embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, a is a triazine substituted with one to three substituents selected from the group consisting of: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R.

In another aspect, the present invention provides a compound having activity as a selective VAP-1 inhibitor or a salt thereof, which is a compound of formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein

A is an aryl or heteroaryl group selected from: phenyl, pyridine, pyrazine and thiazole,

Wherein said aryl or heteroaryl is optionally substituted with one to three substituents selected from the group consisting of: alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ≡ CH-R and-C ≡ C-R,

wherein R is a ring selected from the group consisting of: benzene, phenylbenzene, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine, thiophene, thiazole, imidazole, pyrazole, piperazine, morpholine, benzodioxole, benzoxadiazole, benzothiophene, benzothiazole, 2, 3-dihydro-benzodioxine, indazole, indole, 1, 3-indolin-2-one, 1, 2-indolin-3-one, quinoline, isoquinoline, quinolin-2-one, 3, 4-dihydroquinolin-2-one, 3, 4-dihydro-1, 4-benzoxazine, 1, 4-benzoxazin-3-one, 3, 1-benzoxazin-2-one, 2, 3-dihydro-imidazo [4,5-b ] pyridine, piperazine, morpholine, benzodioxole, benz-oxadiazole, benzpyrole, benzothiazole, Oxazolo [4,5-b ] pyridin-2-one, 2, 3-dihydro-pyrido [2,3-b ] [1,4] oxazine, 3, 4-dihydro-pyrido [3,2-b ] [1,4] oxazine, pyrido [2,3-b ] [1,4] oxazin-2-one, pyrido [3,2-b ] [1,4] oxazin-3-one, and dibenzo [ b, d ] furan,

wherein said ring is optionally substituted with one or two substituents selected from the group consisting of: hydroxy, halogen, C_1-6Alkyl, trifluoromethyl, C_1-6Alkoxy, trifluoromethoxy, amino, mono-or di-C _1-6Alkylamino radical, C_1-6Alkylcarbonylamino, C_1-6Alkylthio, mono-or di-C_1-6Alkylaminosulfonyl radical, C_1-6Alkylsulfonyl radical, C_1-6Alkylcarbonyl, morpholinylcarbonyl, benzodioxolyl, pyrrolidinyl, piperazinyl, acetylpiperazinyl, morpholinyl, tetrahydropyranyl, triazolyl, tetrazolyl, oxazolyl, pyrrolidinyl, piperazinyl, morpholinyl, tetrahydrofuranyl, triazolyl, tetrazolyl, morpholinyl, tetrazolyl, and tetrazolyl,Oxadiazolyl, cyclopropyl-oxadiazolyl, C_1-6Alkyl-oxadiazolyl and oxadiazol-5-onyl.

In another aspect, the present invention provides a compound of formula 10, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein

R is a substituted or unsubstituted ring, optionally containing at least one heteroatom, and the ring is aromatic or non-aromatic; and

R^ais hydrogen, C_1-3Alkyl radical, C_1-3Alkoxy or halogen.

In some embodiments, the compound of formula 10 is a compound of formula 10a, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein R and R^aIs as defined in formula 10.

In some embodiments, the compound of formula 10 is a compound of formula 10b, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein R and R^aAs defined in equation 10.

In another aspect, the present invention provides a compound of formula 11, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

Wherein

R is a substituted or unsubstituted ring, optionally containing at least one heteroatom, and the ring is aromatic or non-aromatic; and

R^ais hydrogen, C_1-3Alkyl radical, C_1-3Alkoxy or halogen.

In some embodiments, the compound of formula 11 is a compound of formula 11a, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein R and R^aIs as defined in formula 11.

In some embodiments, the compound of formula 11 is a compound of formula 11b,

or an isomer thereof, or a pharmaceutically acceptable salt thereof, wherein R and R^aIs as defined in formula 11.

In some embodiments, the compound of formula 11 is a compound of formula 11c,

or an isomer thereof, or a pharmaceutically acceptable salt thereof, wherein R and R^aIs as defined in formula 11.

In some embodiments, the compound of formula 11 is a compound of formula 11d, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein R and R^aIs as defined in formula 11.

In some embodiments, the compound of formula 11 is a compound of formula 11e, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein R and R^aIs as defined in11。

In another aspect, the present invention provides a compound of formula 12, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

wherein

A' is pyridine; and

R is a substituted or unsubstituted ring, optionally containing at least one heteroatom, and the ring is aromatic or non-aromatic.

In some embodiments, a' is

In some embodiments, A' is

In some embodiments of the compound of formula X, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12 or an isomer thereof, or a pharmaceutically acceptable salt thereof, R is selected from the group consisting of benzene, phenylbenzene, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine, thiophene, thiazole, imidazole, pyrazole, piperazine, morpholine, benzodioxole, benzoxadiazole, benzothiophene, benzothiazole, 2, 3-dihydro-benzodioxadiene, indazole, indole, 1, 3-indolin-2-one, 1, 2-indolin-3-one, quinoline, isoquinoline, quinolin-2-one, 3, 4-dihydroquinolin-2-one, 3, 4-dihydro-1, 4-benzoxazine, 1, 4-benzoxazin-3-one, 3, 1-benzoxazin-2-one, 2, 3-dihydro-imidazo [4,5-b ] pyridine, oxazolo [4,5-b ] pyridin-2-one, 2, 3-dihydro-pyrido [2,3-b ] [1,4] oxazine, 3, 4-dihydro-pyrido [3,2-b ] [1,4] oxazine, pyrido [2,3-b ] [1,4] oxazin-2-one, pyrido [3,2-b ] [1,4] oxazin-3-one, and dibenzo [ b, d ] furan.

A compound of the formula X, 10a, 10b, 11a, 11b, 11c, 11d, 11e or 12 or a salt thereofIn some embodiments of the isomer, or a pharmaceutically acceptable salt thereof, R is selected from the group consisting of benzene, phenylbenzene, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine, thiophene, thiazole, imidazole, pyrazole, piperazine, morpholine, benzodioxole, benzoxadiazole, benzothiophene, benzothiazole, 2, 3-dihydro-benzodioxine, indazole, indole, 1, 3-indolin-2-one, 1, 2-indolin-3-one, quinoline, isoquinoline, quinolin-2-one, 3, 4-dihydroquinolin-2-one, 3, 4-dihydro-1, 4-benzoxazine, 1, 4-benzoxazin-3-one, 3, 1-benzoxazin-2-one, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine, thiophene, thiazole, imidazole, pyrazole, piperazine, morpholine, benzodioxole, 3, 4-dihydroquinolin-2-, 2, 3-dihydro-imidazo [4,5-b ]]Pyridine, oxazolo [4,5-b ]]Pyridin-2-ones, 2, 3-dihydro-pyrido [2,3-b ]][1,4]Oxazines, 3, 4-dihydro-pyrido [3,2-b][1,4]Oxazine, pyrido [2,3-b ]][1,4]Oxazin-2-ones, pyrido [3,2-b][1,4]Oxazin-3-ones and dibenzo [ b, d]Furan; and R is optionally substituted with one or two substituents selected from the group consisting of: hydroxy, halogen, C_1-6Alkyl, trifluoromethyl, C_1-6Alkoxy, trifluoromethoxy, amino, mono-or di-C_1-6Alkylamino radical, C_1-6Alkylcarbonylamino, C _1-6Alkylthio, mono-or di-C_1-6Alkylaminosulfonyl radical, C_1-6Alkylsulfonyl radical, C_1-6Alkylcarbonyl, morpholinylcarbonyl, benzodioxolyl, pyrrolidinyl, piperazinyl, acetylpiperazinyl, morpholinyl, tetrahydropyranyl, triazolyl, tetrazolyl, isoxazolyl, oxazolyl, oxadiazolyl, cyclopropyl-oxadiazolyl, C_1-6Alkyl-oxadiazolyl and oxadiazol-5-onyl.

The compounds provided in the specification are inhibitors of VAP-1. VAP-1 inhibition can be determined, for example, by determining half the maximum Inhibitory Concentration (IC)₅₀) To measure. An IC for determining VAP-1 is provided herein₅₀The method of (1).

In one embodiment, the compounds are selective inhibitors of VAP-1. Selectivity can be determined, for example, by comparing the inhibition of VAP-1 with other amino oxidases such as MAO-A (monoamine oxidase-A), MAO-B (monoamine oxidase-B) and DAO (diamine oxidase). In one embodiment, the "significantly high inhibitory activity" refers to the inhibition by in vitroEnzymatic assay (in vitro enzymatic assay) IC testing of VAP-1 obtained₅₀IC for MAO-A₅₀Up to 3000 times lower, IC being MAO-B₅₀Up to 100 times lower, or DAO₅₀Up to 100 times lower. In an alternative embodiment, "significantly high inhibitory activity" refers to the IC of VAP-1 obtained from in vitro enzyme assay (in vitro enzyme assay) testing ₅₀IC for MAO-A₅₀Up to 3000 times lower, IC being MAO-B₅₀Up to 100 times smaller, and an IC that is DAO₅₀Up to 100 times lower.

In the compound of formula 1 according to the present invention or a pharmaceutically acceptable salt thereof, a may preferably be pyridine. In some embodiments of the compound of formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof, a is phenyl. In some embodiments of the compound of formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof, a is pyrazine. In some embodiments of the compound of formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof, a is thiazole.

In some embodiments of formula X or formula 1, isomers thereof, or pharmaceutically acceptable salts thereof, a is

In some embodiments of formula X or formula 1, isomers thereof, or pharmaceutically acceptable salts thereof, a isIn some embodiments of formula X or formula 1, isomers thereof, or pharmaceutically acceptable salts thereof, a isIn some embodiments of formula X or formula 1, isomers thereof, or pharmaceutically acceptable salts thereof, a isIn some embodiments of formula X or formula 1, isomers thereof, or pharmaceutically acceptable salts thereof, a is

In some embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, the aryl or heteroaryl is substituted with one or two substituents selected from the group consisting of: c _1-3Alkyl, halogen, -R and-C ≡ C-R. In other embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring selected from the group consisting of: benzene, pyridine and pyrazole. In other embodiments of the compound of formula X, or an isomer thereof, or a pharmaceutically acceptable salt thereof, the ring is unsubstituted; or substituted with a substituent selected from: c_1-6Alkyl, trifluoromethyl and oxazolyl.

Further, in the compound of formula 1 according to the present invention or a pharmaceutically acceptable salt thereof, the aryl or heteroaryl group may be optionally substituted with one or two substituents selected from the group consisting of: c_1-3Alkyl, halogen, -R and-C ≡ C-R. Preferably, said R may be a ring selected from: benzene, pyridine and pyrazole. More preferably, the ring may be unsubstituted; or substituted with a substituent selected from: c_1-6Alkyl, trifluoromethyl and oxazolyl.

In some embodiments of the compound of formula X or formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof, the aryl or heteroaryl is substituted with: c_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R or-C ≡ C-R. In some embodiments of the compound of formula X or formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof, the aryl or heteroaryl is substituted with: c _1-3An alkyl group. In the formula X or the formula 1In some embodiments of the compound, or an isomer thereof, or a pharmaceutically acceptable salt thereof, the aryl or heteroaryl is substituted with: c_1-3An alkoxy group. In some embodiments of the compound of formula X or formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof, the aryl or heteroaryl is substituted with: a halogen. In some embodiments of the compound of formula X or formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof, the aryl or heteroaryl is substituted with: a benzyloxy group. In some embodiments of the compound of formula X or formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof, the aryl or heteroaryl is substituted with: -R. In some embodiments of the compound of formula X or formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof, the aryl or heteroaryl is substituted with: -CH₂-R. In some embodiments of the compound of formula X or formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof, the aryl or heteroaryl is substituted with: -CH ═ CH-R. In some embodiments of the compound of formula X or formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof, the aryl or heteroaryl is substituted with: -C ≡ C-R.

In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted benzene. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted phenyl benzene. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted pyridine. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted tetrahydropyridine. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted pyridin-2-one. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, said R is substituted or unsubstituted pyrimidine. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted thiophene. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted thiazole. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted imidazole. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, said R is substituted or unsubstituted pyrazole. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted piperazine. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted morpholine. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted benzodioxole. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted benzoxadiazole. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted benzothiophene. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted benzothiazole. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted 2, 3-dihydro-benzodioxadiene. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is a substituted or unsubstituted indazole. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is a substituted or unsubstituted indole. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, said R is a substituted or unsubstituted 1, 3-indolin-2-one. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, said R is a substituted or unsubstituted 1, 2-indolin-3-one. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, said R is substituted or unsubstituted quinoline. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, said R is substituted or unsubstituted isoquinoline. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, said R is a substituted or unsubstituted quinolin-2-one. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, said R is a substituted or unsubstituted 3, 4-dihydroquinolin-2-one. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted 3, 4-dihydro-1, 4-benzoxazine. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, said R is a substituted or unsubstituted 1, 4-benzoxazin-3-one. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, said R is a substituted or unsubstituted 3, 1-benzoxazin-2-one. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, said R is substituted or unsubstituted 2, 3-dihydro-imidazo [4,5-b ] pyridine. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, said R is a substituted or unsubstituted oxazolo [4,5-b ] pyridin-2-one. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is a substituted or unsubstituted 2, 3-dihydro-pyrido [2,3-b ] [1,4] oxazine. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted 3, 4-dihydro-pyrido [3,2-b ] [1,4] oxazine. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is a substituted or unsubstituted pyrido [2,3-b ] [1,4] oxazin-2-one. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is a substituted or unsubstituted pyrido [3,2-b ] [1,4] oxazin-3-one. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, the R is substituted or unsubstituted dibenzo [ b, d ] furan.

In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is unsubstituted. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: hydroxy, halogen, C_1-6Alkyl, trifluoromethyl, C_1-6Alkoxy, trifluoromethoxy, amino, mono-or di-C_1-6Alkylamino radical, C_1-6Alkylcarbonylamino, C_1-6Alkylthio, mono-or di-C_1-6Alkylaminosulfonyl radical, C_1-6Alkylsulfonyl radical, C_1-6Alkylcarbonyl, morpholinylcarbonyl, benzodioxolyl, pyrrolidinyl, piperazinyl, acetylpiperazinyl, morpholinyl, tetrahydropyranyl, triazolyl, tetrazolyl, isoxazolyl, oxazolyl, oxadiazolyl, cyclopropyl-oxadiazolyl, C_1-6Alkyl-oxadiazolyl or oxadiazol-5-onyl. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: a hydroxyl group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: a halogen. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: c _1-6An alkyl group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with the following groupsThe following steps: a trifluoromethyl group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: c_1-6An alkoxy group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: a trifluoromethoxy group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: an amino group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: mono-or di-C _1-6An alkylamino group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: mono-C_1-6An alkylamino group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: di-C_1-6An alkylamino group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: c_1-6An alkylcarbonylamino group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: c_1-6An alkylthio group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is taken from the group consisting of Generation: mono-or di-C_1-6An alkylaminosulfonyl group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: mono-C_1-6An alkylaminosulfonyl group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: di-C_1-6An alkylaminosulfonyl group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: c_1-6An alkylsulfonyl group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: c_1-6An alkylcarbonyl group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: morpholinylcarbonyl. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: benzodioxolyl. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: a pyrrolidinyl group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: a piperazinyl group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring And said ring is substituted with: acetyl piperazinyl. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: a morpholino group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: a tetrahydropyranyl group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: a triazolyl group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: a tetrazolyl group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: an oxazolyl group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: an isoxazolyl group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: an oxadiazolyl group. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: cyclopropyl-oxadiazolyl. In some embodiments of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, an isomer thereof, or a pharmaceutically acceptable salt thereof, R is a ring and the ring is substituted with: c _1-6An alkyl-oxadiazolyl group. In the formulae X, 1, 10,In some embodiments of the compounds of 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, isomers thereof, or pharmaceutically acceptable salts thereof, R is a ring and the ring is substituted with: oxadiazol-5-onyl.

In one embodiment of the present invention, there is provided a compound, wherein a is pyridine; said pyridine is substituted with one or two substituents selected from the group consisting of: c_1-3Alkyl, halogen, -R and-C ≡ C-R; said R is a ring selected from the group consisting of: benzene, pyridine and pyrazole; and said ring is unsubstituted or substituted with a substituent selected from the group consisting of: c_1-6Alkyl, trifluoromethyl and oxazolyl; or a pharmaceutically acceptable salt thereof.

In another aspect, the compound of formula X or formula 1, or an isomer thereof, or a pharmaceutically acceptable salt thereof, is selected from the group consisting of the following compounds, or an isomer thereof, or a pharmaceutically acceptable salt thereof,

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (benzyloxy) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (benzyloxy) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3, 4-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3, 4-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-2-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-2-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-methylphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-methylphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-methoxyphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-methoxyphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3, 5-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3, 5-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-2, 6-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-2, 6-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-2, 5-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromopyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromopyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromo-5-methylpyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromo-5-methylpyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromo-4-methylpyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromopyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromopyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-3-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-3-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-4-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-4-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-3-fluoropyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-3-fluoropyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromopyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromopyrazin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (1, 3-thiazol-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-1, 3-thiazol-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-1, 3-thiazol-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

4- [4- (5-acetylthiophen-2-yl) phenyl ] -2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 3-fluoro-4' - (4H-1,2, 4-triazol-3-yl) biphenyl-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 3-fluoro-3' - (4H-1,2, 4-triazol-3-yl) biphenyl-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (1, 3-benzodioxol-5-yl) -2-fluorophenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (2,1, 3-benzoxadiazol-5-yl) -2-fluorophenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 5-bromo-2-methoxy-4- (morpholin-4-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1,2,3, 6-tetrahydropyridin-4-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one dihydrochloride;

4- [3- (5-acetylthiophen-2-yl) phenyl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (trifluoromethoxy) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (dimethylamino) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (prop-2-ylsulfanyl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (methylsulfonyl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (methylsulfonyl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

3' - {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -N, N-dimethylbiphenyl-4-sulfonamide hydrochloride;

n- (3' - {1- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } biphenyl-4-yl) acetamide hydrochloride;

N- (3' - {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } biphenyl-4-yl) acetamide hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (4H-1,2, 4-triazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (4H-1,2, 4-triazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3' - (4H-1,2, 4-triazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (1,2, 4-oxadiazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3' - (1,2, 4-oxadiazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {4' - [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] biphenyl-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {3' - [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] biphenyl-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4 "- (methylsulfonyl) -1,1':4', 1" -terphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4 "- (methylsulfonyl) -1,1':3', 1" -terphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- (3 "- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -1,1':4', 1" -terphenyl-4-yl) acetamide hydrochloride;

n- (3 "- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -1,1':3', 1" -terphenyl-4-yl) acetamide hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (1, 3-benzodioxol-5-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3' - (1, 3-benzodioxol-5-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

4- [4' - (4-acetylpiperazin-1-yl) biphenyl-3-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (tetrahydro-2H-pyran-4-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (morpholin-4-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3 '-fluoro-4' - (morpholin-4-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3 '-chloro-4' - (morpholin-4-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3 '-methyl-4' - (morpholin-4-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (morpholin-4-ylcarbonyl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2-methoxypyridin-4-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

N- [4- (3- {1- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) pyridin-2-yl ] acetamide hydrochloride;

n- [4- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) pyridin-2-yl ] acetamide hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (pyridin-3-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (6-methoxypyridin-3-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {3- [6- (trifluoromethyl) pyridin-3-yl ] phenyl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (6-chloropyridin-3-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {3- [6- (morpholin-4-yl) pyridin-3-yl ] phenyl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {3- [ 6-methoxy-5- (trifluoromethyl) pyridin-3-yl ] phenyl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {3- [ 6-hydroxy-5- (trifluoromethyl) pyridin-3-yl ] phenyl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

5- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) -1, 3-dimethylpyridin-2 (1H) -one hydrochloride;

5- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) -1- (prop-2-yl) pyridin-2 (1H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2-methylpyrimidin-5-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1, 3-benzodioxol-5-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1, 3-benzodioxol-5-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2, 3-dihydro-1, 4-benzodioxine-6-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2, 3-dihydro-1, 4-benzodioxine-6-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2,1, 3-benzoxadiazol-5-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1H-indazol-6-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1H-indol-4-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

4- [3- (2-amino-1, 3-benzothiazol-5-yl) phenyl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1H-indol-3-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1-benzothien-2-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) -8-methyl-3, 4-dihydroquinolin-2 (1H) -one hydrochloride;

6- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) -2H-1, 4-benzoxazin-3 (4H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (isoquinolin-4-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (8-methylquinolin-5-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 2-methyl-4' - (methylsulfonyl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- (3'- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -2' -methylbiphenyl-4-yl) acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 2-methyl-4' - (1, 2-oxazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [4- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -2-methylphenyl) pyridin-2-yl ] acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 2-methyl-3- [6- (morpholin-4-yl) pyridin-3-yl ] phenyl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1, 3-benzodioxol-5-yl) -2-methylphenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2, 3-dihydro-1, 4-benzodioxine-6-yl) -2-methylphenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2,1, 3-benzoxadiazol-5-yl) -2-methylphenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [3- (2-amino-1, 3-benzothiazol-5-yl) -2-methylphenyl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 5-methyl-6- [4- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 5-methyl-6- [3- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (1, 3-benzodioxol-5-yl) -5-methylpyridin-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [6- (2-amino-1, 3-benzothiazol-5-yl) -5-methylpyridin-3-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 4-methyl-6- [4- (methylsulfonyl) phenyl ] pyridin-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

N- [4- (5- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -4-methylpyridin-2-yl) phenyl ] acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 4-methyl-6- [4- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 4-methyl-6- [3- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- (5- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -4-methyl-2, 4 '-bipyridin-2' -yl) acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 4-methyl-6 '- (morpholin-4-yl) -2,3' -bipyridin-5-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (2,1, 3-benzoxadiazol-5-yl) -4-methylpyridin-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (1H-indazol-6-yl) -4-methylpyridin-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [6- (2-amino-1, 3-benzothiazol-5-yl) -4-methylpyridin-3-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

N- [5- (5- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -4-methylpyridin-2-yl) -1, 3-benzothiazol-2-yl ] acetamide;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (methylsulfonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

n- [4- (6- {1- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-3-yl) phenyl ] acetamide hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 3-methyl-5- (piperazin-1-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [5- (5-acetylthiophen-2-yl) -3-methylpyridin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (methylsulfonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

n- [4- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) phenyl ] acetamide hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (4H-1,2, 4-triazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (4H-1,2, 4-triazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [3- (4H-1,2, 4-triazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (1,2, 5-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (1,2, 4-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [3- (1,2, 4-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) phenyl ] -3-methylpyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3-methyl-5- {4- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3-methyl-5- {3- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [3- (1H-tetrazol-5-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (piperazin-1-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (morpholin-4-ylcarbonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) -2H-1, 4-benzoxazin-3 (4H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 5-methyl-6 '- (trifluoromethyl) -3,3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 5-methyl-6 '- (morpholin-4-yl) -3,3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (2H-1, 3-benzodioxol-5-yl) -3-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) -1, 3-dihydro-2H-indol-2-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (2,1, 3-benzoxadiazol-5-yl) -3-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1H-indazol-6-yl) -3-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) -8-methyl-3, 4-dihydroquinolin-2 (1H) -one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) -2H-1, 4-benzoxazin-3 (4H) -one hydrochloride;

7- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) -1, 4-dihydro-2H-3, 1-benzoxazin-2-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 4-methyl-5- [4- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 4-methyl-5- [3- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1, 3-benzodioxol-5-yl) -4-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1H-indazol-6-yl) -4-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [5- (2-amino-1, 3-benzothiazol-5-yl) -4-methylpyridin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1, 3-benzodioxol-5-yl) -3-fluoropyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-fluoropyridin-3-yl) -1, 2-dihydro-3H-indol-3-one;

4- [5- (2-amino-1, 3-benzothiazol-5-yl) -3-fluoropyridin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {4- [4- (methylsulfonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [4- (2- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-4-yl) phenyl ] acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {4- [4- (1, 2-oxazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- (2'- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -4,4' -bipyridin-2-yl) acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (morpholin-4-yl) -3,4 '-bipyridin-2' -yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (1, 3-benzodioxol-5-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (2, 3-dihydro-1, 4-benzodioxine-6-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (2,1, 3-benzoxadiazol-5-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [4- (2-amino-1, 3-benzothiazol-5-yl) pyridin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [3- (dimethylamino) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

n- [4- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) phenyl ] acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (1, 2-oxazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (1,2, 5-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [3- (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6- {4- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6- {3- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

3- [4- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) phenyl ] -1,2, 4-oxadiazol-5 (4H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (pyrrolidin-1-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (piperazin-1-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [3- (piperazin-1-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (morpholin-4-ylcarbonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6'- (trifluoromethyl) -2,3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6'- (dimethylamino) -2,3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6'- (morpholin-4-yl) -2,3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6' -fluoro-5 ' -methyl-2, 3' -bipyridin-6-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6' - (dimethylamino) -5' -fluoro-2, 3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [ 1-methyl-3- (trifluoromethyl) -1H-pyrazol-5-yl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (1, 3-benzodioxol-5-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (2, 3-dihydro-1, 4-benzodioxine-6-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (2,1, 3-benzoxadiazol-5-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [6- (2-amino-1, 3-benzothiazol-5-yl) pyridin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) -8-methyl-3, 4-dihydroquinolin-2 (1H) -one hydrochloride;

6- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridyl ] -1-methyl-3, 4-dihydroquinolin-2-one hydrochloride;

6- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) -2H-1, 4-benzoxazin-3 (4H) -one hydrochloride;

7- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) -1, 4-dihydro-2H-3, 1-benzoxazin-2-one hydrochloride;

5- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) quinolin-2 (1H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (4-methyl-3, 4-dihydro-2H-1, 4-benzoxazin-7-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (dibenzo [ b, d ] furan-4-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (2- {4- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-4-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (2- {3- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-4-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {2- [4- (morpholin-4-yl) phenyl ] pyridin-4-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {2- [4- (morpholin-4-ylcarbonyl) phenyl ] pyridin-4-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [2- (1, 3-benzodioxol-5-yl) pyridin-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [3- (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) phenyl ] -3-methylpyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-6- [4- (morpholin-4-ylcarbonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6 '-methoxy-5-methyl-2, 3' -bipyridin-6-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (1, 3-benzodioxol-5-yl) -3-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (1H-indazol-6-yl) -3-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-2-yl) -8-methyl-3, 4-dihydroquinolin-2 (1H) -one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-2-yl) -2H-1, 4-benzoxazin-3 (4H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (methylsulfonyl) phenyl ] pyrazin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (1H-1,2, 4-triazol-3-yl) phenyl ] pyrazin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [3- (1H-1,2, 4-triazol-3-yl) phenyl ] pyrazin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [4- (5- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyrazin-2-yl) pyridin-2-yl ] acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [6- (morpholin-4-yl) pyridin-3-yl ] pyrazin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (2,1, 3-benzoxadiazol-5-yl) pyrazin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1H-indazol-6-yl) pyrazin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [5- (2-amino-1, 3-benzothiazol-5-yl) pyrazin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [5- (5- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyrazin-2-yl) -1, 3-benzothiazol-2-yl ] acetamide;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (methylsulfonyl) phenyl ] -1, 3-thiazol-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (4H-1,2, 4-triazol-3-yl) phenyl ] -1, 3-thiazol-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [3- (4H-1,2, 4-triazol-3-yl) phenyl ] -1, 3-thiazol-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (4H-1,2, 4-oxadiazol-3-yl) phenyl ] -1, 3-thiazol-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [3- (1H-tetrazol-5-yl) phenyl ] -1, 3-thiazol-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [4- (2- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -1, 3-thiazol-5-yl) pyridin-2-yl ] acetamide;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1, 3-benzodioxol-5-yl) -1, 3-thiazol-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (2- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -1, 3-thiazol-5-yl) -1, 3-dihydro-2H-indol-2-one;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (2,1, 3-benzoxadiazol-5-yl) -1, 3-thiazol-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

n- [5- (4- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } benzyl) -1, 3-thiazol-2-yl ] acetamide hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {4- [ (E) -2-phenylethenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [ (E) -2- (thiophen-3-yl) vinyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6- { (E) -2- [4- (trifluoromethyl) phenyl ] vinyl } pyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [ (E) -2- [4- (dimethylamino) phenyl ] vinyl ] -2-pyridinyl ] -1,2, 4-triazol-3-one hydrochloride;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [ (E) -2- (3-methyl-1, 2-dihydroimidazo [4,5-b ] pyridin-6-yl) vinyl ] -2-pyridinyl ] -1,2, 4-triazol-3-one hydrochloride;

7- [ (E) -2- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridinyl ] vinyl ] -1H-pyrido [2,3-b ] [1,4] oxazin-2-one hydrochloride;

6- [ (E) -2- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridinyl ] vinyl ] -3H-oxazolo [4,5-b ] pyridin-2-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (pyridin-3-ylethynyl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (pyridin-2-ylethynyl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (pyridin-3-ylethynyl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (pyridin-4-ylethynyl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [ (6-methoxypyridin-3-yl) ethynyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- [6- (dimethylamino) -3-pyridinyl ] ethynyl ] -2-pyridinyl ] -1,2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (6-morpholino-3-pyridyl) ethynyl ] -2-pyridyl ] -1,2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (3, 4-dihydro-2H-1, 4-benzoxazin-6-yl) ethynyl ] -2-pyridinyl ] -1,2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (2, 3-dihydro-1H-pyrido [2,3-b ] [1,4] oxazin-7-yl) ethynyl ] -2-pyridyl ] -1,2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (3, 4-dihydro-2H-pyrido [3,2-b ] [1,4] oxazin-7-yl) ethynyl ] -2-pyridyl ] -1,2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (2, 3-dihydro-1H-pyrido [2,3-b ] [1,4] oxazin-6-yl) ethynyl ] -2-pyridyl ] -1,2, 4-triazol-3-one;

6- [2- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridinyl ] ethynyl ] -3, 4-dihydro-1H-quinolin-2-one;

7- [2- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridinyl ] ethynyl ] -4H-pyrido [3,2-b ] [1,4] oxazin-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (3-methylimidazol-4-yl) ethynyl ] -2-pyridyl ] -1,2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [ (1-methyl-1H-pyrazol-4-yl) ethynyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

7- [2- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridinyl ] ethynyl ] -1H-pyrido [2,3-b ] [1,4] oxazin-2-one; and

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [ 3-methyl-5- (6-piperazin-1-yl-3-pyridinyl) -2-pyridinyl ] -1,2, 4-triazol-3-one.

As for the compound of formula 1 or its isomer, or a pharmaceutically acceptable salt thereof, a preferred compound may be a compound selected from the group consisting of the following compounds, or its isomer, or a pharmaceutically acceptable salt thereof,

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (benzyloxy) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (benzyloxy) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3, 4-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3, 4-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-2-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-2-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-methylphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-methylphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-methoxyphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3-methoxyphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3, 5-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-3, 5-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-2, 6-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-2, 6-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (4-bromo-2, 5-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromopyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromopyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromo-5-methylpyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromo-5-methylpyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromo-4-methylpyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromopyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromopyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-3-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-3-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-4-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-4-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-3-fluoropyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-3-fluoropyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6-bromopyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromopyrazin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (1, 3-thiazol-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-1, 3-thiazol-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-1, 3-thiazol-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

4- [4- (5-acetylthiophen-2-yl) phenyl ] -2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 3-fluoro-4' - (4H-1,2, 4-triazol-3-yl) biphenyl-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 3-fluoro-3' - (4H-1,2, 4-triazol-3-yl) biphenyl-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (1, 3-benzodioxol-5-yl) -2-fluorophenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (2,1, 3-benzoxadiazol-5-yl) -2-fluorophenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 5-bromo-2-methoxy-4- (morpholin-4-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1,2,3, 6-tetrahydropyridin-4-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one dihydrochloride;

4- [3- (5-acetylthiophen-2-yl) phenyl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (trifluoromethoxy) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (dimethylamino) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (prop-2-ylsulfanyl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (methylsulfonyl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (methylsulfonyl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

3' - {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -N, N-dimethylbiphenyl-4-sulfonamide hydrochloride;

n- (3' - {1- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } biphenyl-4-yl) acetamide hydrochloride;

n- (3' - {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } biphenyl-4-yl) acetamide hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (4H-1,2, 4-triazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (4H-1,2, 4-triazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3' - (4H-1,2, 4-triazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (1,2, 4-oxadiazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3' - (1,2, 4-oxadiazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {4' - [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] biphenyl-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {3' - [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] biphenyl-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4 "- (methylsulfonyl) -1,1 ': 4', 1" -terphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4 "- (methylsulfonyl) -1,1 ': 3', 1" -terphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

N- (3 "- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -1,1 ': 4', 1" -terphenyl-4-yl) acetamide hydrochloride;

n- (3 "- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -1,1 ': 3', 1" -terphenyl-4-yl) acetamide hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (1, 3-benzodioxol-5-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3' - (1, 3-benzodioxol-5-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

4- [4' - (4-acetylpiperazin-1-yl) biphenyl-3-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (tetrahydro-2H-pyran-4-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (morpholin-4-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3 '-fluoro-4' - (morpholin-4-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3 '-chloro-4' - (morpholin-4-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3 '-methyl-4' - (morpholin-4-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (morpholin-4-ylcarbonyl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2-methoxypyridin-4-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

n- [4- (3- {1- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) pyridin-2-yl ] acetamide hydrochloride;

n- [4- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) pyridin-2-yl ] acetamide hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (pyridin-3-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (6-methoxypyridin-3-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {3- [6- (trifluoromethyl) pyridin-3-yl ] phenyl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (6-chloropyridin-3-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {3- [6- (morpholin-4-yl) pyridin-3-yl ] phenyl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {3- [ 6-methoxy-5- (trifluoromethyl) pyridin-3-yl ] phenyl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {3- [ 6-hydroxy-5- (trifluoromethyl) pyridin-3-yl ] phenyl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

5- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) -1, 3-dimethylpyridin-2 (1H) -one hydrochloride;

5- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) -1- (prop-2-yl) pyridin-2 (1H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2-methylpyrimidin-5-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1, 3-benzodioxol-5-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1, 3-benzodioxol-5-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2, 3-dihydro-1, 4-benzodioxine-6-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2, 3-dihydro-1, 4-benzodioxine-6-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2,1, 3-benzoxadiazol-5-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1H-indazol-6-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1H-indol-4-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

4- [3- (2-amino-1, 3-benzothiazol-5-yl) phenyl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1H-indol-3-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1-benzothien-2-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) -8-methyl-3, 4-dihydroquinolin-2 (1H) -one hydrochloride;

6- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } phenyl) -2H-1, 4-benzoxazin-3 (4H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (isoquinolin-4-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (8-methylquinolin-5-yl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 2-methyl-4' - (methylsulfonyl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- (3'- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -2' -methylbiphenyl-4-yl) acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 2-methyl-4' - (1, 2-oxazol-3-yl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [4- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -2-methylphenyl) pyridin-2-yl ] acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 2-methyl-3- [6- (morpholin-4-yl) pyridin-3-yl ] phenyl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (1, 3-benzodioxol-5-yl) -2-methylphenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2, 3-dihydro-1, 4-benzodioxine-6-yl) -2-methylphenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (2,1, 3-benzoxadiazol-5-yl) -2-methylphenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [3- (2-amino-1, 3-benzothiazol-5-yl) -2-methylphenyl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 5-methyl-6- [4- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 5-methyl-6- [3- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (1, 3-benzodioxol-5-yl) -5-methylpyridin-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [6- (2-amino-1, 3-benzothiazol-5-yl) -5-methylpyridin-3-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 4-methyl-6- [4- (methylsulfonyl) phenyl ] pyridin-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [4- (5- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -4-methylpyridin-2-yl) phenyl ] acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 4-methyl-6- [4- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 4-methyl-6- [3- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-3-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- (5- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -4-methyl-2, 4 '-bipyridin-2' -yl) acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 4-methyl-6 '- (morpholin-4-yl) -2,3' -bipyridin-5-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (2,1, 3-benzoxadiazol-5-yl) -4-methylpyridin-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (1H-indazol-6-yl) -4-methylpyridin-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [6- (2-amino-1, 3-benzothiazol-5-yl) -4-methylpyridin-3-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [5- (5- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -4-methylpyridin-2-yl) -1, 3-benzothiazol-2-yl ] acetamide;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (methylsulfonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

n- [4- (6- {1- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-3-yl) phenyl ] acetamide hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 3-methyl-5- (piperazin-1-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [5- (5-acetylthiophen-2-yl) -3-methylpyridin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (methylsulfonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

n- [4- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) phenyl ] acetamide hydrochloride;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (4H-1,2, 4-triazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (4H-1,2, 4-triazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [3- (4H-1,2, 4-triazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (1,2, 5-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (1,2, 4-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [3- (1,2, 4-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) phenyl ] -3-methylpyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3-methyl-5- {4- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (3-methyl-5- {3- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [3- (1H-tetrazol-5-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (piperazin-1-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-5- [4- (morpholin-4-ylcarbonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) -2H-1, 4-benzoxazin-3 (4H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 5-methyl-6 '- (trifluoromethyl) -3,3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [ 5-methyl-6 '- (morpholin-4-yl) -3,3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (2H-1, 3-benzodioxol-5-yl) -3-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) -1, 3-dihydro-2H-indol-2-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (2,1, 3-benzoxadiazol-5-yl) -3-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1H-indazol-6-yl) -3-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) -8-methyl-3, 4-dihydroquinolin-2 (1H) -one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) -2H-1, 4-benzoxazin-3 (4H) -one hydrochloride;

7- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-3-yl) -1, 4-dihydro-2H-3, 1-benzoxazin-2-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 4-methyl-5- [4- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 4-methyl-5- [3- (1H-1,2, 4-triazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1, 3-benzodioxol-5-yl) -4-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1H-indazol-6-yl) -4-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [5- (2-amino-1, 3-benzothiazol-5-yl) -4-methylpyridin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1, 3-benzodioxol-5-yl) -3-fluoropyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-fluoropyridin-3-yl) -1, 2-dihydro-3H-indol-3-one;

4- [5- (2-amino-1, 3-benzothiazol-5-yl) -3-fluoropyridin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {4- [4- (methylsulfonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [4- (2- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-4-yl) phenyl ] acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {4- [4- (1, 2-oxazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

N- (2'- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -4,4' -bipyridin-2-yl) acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (morpholin-4-yl) -3,4 '-bipyridin-2' -yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (1, 3-benzodioxol-5-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (2, 3-dihydro-1, 4-benzodioxine-6-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (2,1, 3-benzoxadiazol-5-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [4- (2-amino-1, 3-benzothiazol-5-yl) pyridin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [3- (dimethylamino) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

n- [4- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) phenyl ] acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (1, 2-oxazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (1,2, 5-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [3- (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6- {4- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6- {3- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

3- [4- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) phenyl ] -1,2, 4-oxadiazol-5 (4H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (pyrrolidin-1-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (piperazin-1-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [3- (piperazin-1-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (morpholin-4-ylcarbonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6'- (trifluoromethyl) -2,3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6'- (dimethylamino) -2,3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6'- (morpholin-4-yl) -2,3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6' -fluoro-5 ' -methyl-2, 3' -bipyridin-6-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6' - (dimethylamino) -5' -fluoro-2, 3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [ 1-methyl-3- (trifluoromethyl) -1H-pyrazol-5-yl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (1, 3-benzodioxol-5-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (2, 3-dihydro-1, 4-benzodioxine-6-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (2,1, 3-benzoxadiazol-5-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [6- (2-amino-1, 3-benzothiazol-5-yl) pyridin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) -8-methyl-3, 4-dihydroquinolin-2 (1H) -one hydrochloride;

6- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridyl ] -1-methyl-3, 4-dihydroquinolin-2-one hydrochloride;

6- (3- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) -2H-1, 4-benzoxazin-3 (4H) -one hydrochloride;

7- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) -1, 4-dihydro-2H-3, 1-benzoxazin-2-one hydrochloride;

5- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyridin-2-yl) quinolin-2 (1H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (4-methyl-3, 4-dihydro-2H-1, 4-benzoxazin-7-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (dibenzo [ b, d ] furan-4-yl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [4- (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (2- {4- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-4-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (2- {3- [5- (prop-2-yl) -1,2, 4-oxadiazol-3-yl ] phenyl } pyridin-4-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {2- [4- (morpholin-4-yl) phenyl ] pyridin-4-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {2- [4- (morpholin-4-ylcarbonyl) phenyl ] pyridin-4-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [2- (1, 3-benzodioxol-5-yl) pyridin-4-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [3- (5-cyclopropyl-1, 2, 4-oxadiazol-3-yl) phenyl ] -3-methylpyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- { 3-methyl-6- [4- (morpholin-4-ylcarbonyl) phenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6 '-methoxy-5-methyl-2, 3' -bipyridin-6-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (1, 3-benzodioxol-5-yl) -3-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6- (1H-indazol-6-yl) -3-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-2-yl) -8-methyl-3, 4-dihydroquinolin-2 (1H) -one hydrochloride;

6- (6- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -5-methylpyridin-2-yl) -2H-1, 4-benzoxazin-3 (4H) -one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (methylsulfonyl) phenyl ] pyrazin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (1H-1,2, 4-triazol-3-yl) phenyl ] pyrazin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [3- (1H-1,2, 4-triazol-3-yl) phenyl ] pyrazin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [4- (5- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyrazin-2-yl) pyridin-2-yl ] acetamide;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [6- (morpholin-4-yl) pyridin-3-yl ] pyrazin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (2,1, 3-benzoxadiazol-5-yl) pyrazin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1H-indazol-6-yl) pyrazin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

4- [5- (2-amino-1, 3-benzothiazol-5-yl) pyrazin-2-yl ] -2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [5- (5- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } pyrazin-2-yl) -1, 3-benzothiazol-2-yl ] acetamide;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (methylsulfonyl) phenyl ] -1, 3-thiazol-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (4H-1,2, 4-triazol-3-yl) phenyl ] -1, 3-thiazol-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [3- (4H-1,2, 4-triazol-3-yl) phenyl ] -1, 3-thiazol-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [4- (4H-1,2, 4-oxadiazol-3-yl) phenyl ] -1, 3-thiazol-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {5- [3- (1H-tetrazol-5-yl) phenyl ] -1, 3-thiazol-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

n- [4- (2- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -1, 3-thiazol-5-yl) pyridin-2-yl ] acetamide;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (1, 3-benzodioxol-5-yl) -1, 3-thiazol-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

6- (2- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } -1, 3-thiazol-5-yl) -1, 3-dihydro-2H-indol-2-one;

2- [ (2Z) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (2,1, 3-benzoxadiazol-5-yl) -1, 3-thiazol-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

n- [5- (4- {1- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -5-oxo-1, 5-dihydro-4H-1, 2, 4-triazol-4-yl } benzyl) -1, 3-thiazol-2-yl ] acetamide hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {4- [ (E) -2-phenylethenyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [ (E) -2- (thiophen-3-yl) vinyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (6- { (E) -2- [4- (trifluoromethyl) phenyl ] vinyl } pyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [ (E) -2- [4- (dimethylamino) phenyl ] vinyl ] -2-pyridinyl ] -1,2, 4-triazol-3-one hydrochloride;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [ (E) -2- (3-methyl-1, 2-dihydroimidazo [4,5-b ] pyridin-6-yl) vinyl ] -2-pyridinyl ] -1,2, 4-triazol-3-one hydrochloride;

7- [ (E) -2- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridinyl ] vinyl ] -1H-pyrido [2,3-b ] [1,4] oxazin-2-one hydrochloride;

6- [ (E) -2- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridinyl ] vinyl ] -3H-oxazolo [4,5-b ] pyridin-2-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [3- (pyridin-3-ylethynyl) phenyl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (pyridin-2-ylethynyl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (pyridin-3-ylethynyl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4- (pyridin-4-ylethynyl) pyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [ (6-methoxypyridin-3-yl) ethynyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- [6- (dimethylamino) -3-pyridinyl ] ethynyl ] -2-pyridinyl ] -1,2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (6-morpholino-3-pyridyl) ethynyl ] -2-pyridyl ] -1,2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (3, 4-dihydro-2H-1, 4-benzoxazin-6-yl) ethynyl ] -2-pyridinyl ] -1,2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (2, 3-dihydro-1H-pyrido [2,3-b ] [1,4] oxazin-7-yl) ethynyl ] -2-pyridyl ] -1,2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (3, 4-dihydro-2H-pyrido [3,2-b ] [1,4] oxazin-7-yl) ethynyl ] -2-pyridyl ] -1,2, 4-triazol-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (2, 3-dihydro-1H-pyrido [2,3-b ] [1,4] oxazin-6-yl) ethynyl ] -2-pyridyl ] -1,2, 4-triazol-3-one;

6- [2- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridinyl ] ethynyl ] -3, 4-dihydro-1H-quinolin-2-one;

7- [2- [6- [1- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -5-oxo-1, 2, 4-triazol-4-yl ] -2-pyridinyl ] ethynyl ] -4H-pyrido [3,2-b ] [1,4] oxazin-3-one;

2- [ (E) -2- (aminomethyl) -3-fluoro-allyl ] -4- [6- [2- (3-methylimidazol-4-yl) ethynyl ] -2-pyridyl ] -1,2, 4-triazol-3-one; and

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- {6- [ (1-methyl-1H-pyrazol-4-yl) ethynyl ] pyridin-2-yl } -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride.

With respect to compound 1 of formula (la), or an isomer or a pharmaceutically acceptable salt thereof, more preferred compounds may be selected from the following compounds, or an isomer or a pharmaceutically acceptable salt thereof,

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- (5-bromo-3-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [4' - (methylsulfanyl) biphenyl-3-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [5- (2H-1, 3-benzodioxol-5-yl) -3-methylpyridin-2-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4-6- [4- (1, 2-oxazol-3-yl) phenyl ] pyridin-2-yl-2, 4-dihydro-3H-1, 2, 4-triazol-3-one;

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4- [6'- (trifluoromethyl) -2,3' -bipyridin-6-yl ] -2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride; and

2- [ (2E) -2- (aminomethyl) -3-fluoroprop-2-en-1-yl ] -4-6- [ (1-methyl-1H-pyrazol-4-yl) ethynyl ] pyridin-2-yl-2, 4-dihydro-3H-1, 2, 4-triazol-3-one hydrochloride.

The compounds of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e or 12 or salts thereof may exist in geometric isomeric forms having cis-trans structures. Thus, unless otherwise indicated, the compounds of formula 1 or salts thereof include both cis and trans geometric isomers.

The compounds of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e or 12 of the present invention may be in the form of pharmaceutically acceptable salts. As used herein, the term "pharmaceutically acceptable salt" refers to a salt or zwitterionic form of a compound of the present technology, which is water or oil soluble or dispersible; it is suitable for the treatment of diseases without excessive toxicity, irritation and allergic reaction; which corresponds to a reasonable benefit/risk ratio; and, it is effective for the intended use. The salts may be prepared during the final isolation and purification of the compounds or separately, for example, by reaction of a suitable acid with the free base form of the appropriate compound. Such salts include conventional acid addition salts, for example derived from inorganic acids (e.g. hydrochloric, bromic, sulphuric, sulphamic, phosphoric or nitric acids) and from organic acids (e.g. acetic, propionic, succinic, glycolic, stearic, citric, maleic, malonic, methanesulphonic, tartaric, malic, phenylacetic, glutamic, benzoic, salicylic, 2-acetoxybenzoic, fumaric, p-toluenesulphonic, oxalic or trifluoroacetic acids). Furthermore, the salts include conventional metal salt types, for example, salts derived from, for example, metallic lithium, sodium, potassium, magnesium or calcium. The acid addition salts or metal salts can be prepared according to conventional methods.

According to the invention, the compounds of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e or 12 or salts thereof can be prepared by a variety of methods. For example, compounds of formula 1a, or isomers or salts thereof, wherein A is a substituted aryl or heteroaryl group (i.e., compounds of formula 1a wherein A is an aryl or heteroaryl group selected from the group consisting of phenyl, pyridine, pyrazine and thiazole; and wherein the aryl or heteroaryl group is optionally substituted with one to three substituents selected from the group consisting of C_1-3Alkyl radical, C_1-3Alkoxy, halogen, benzyloxy, -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R), which may be prepared by a preparation method comprising the step of reacting the compound of formula 2 with the compound of formula 3a or the compound of formula 3b to obtain the compound of formula 1 aa; and deprotecting the compound of formula 1 aa.

Z₂-B-R' (formula 3a)

HC ≡ CR' (formula 3b)

In said formulae 1a, 1aa, 2, 3a and 3b, Boc is an amine protecting group (e.g., t-butyloxycarbonyl, 9-Fluorenylmethyloxycarbonyl (FMOC), benzyloxycarbonyl (CBZ), trityl (trityl), etc.), A' is an aryl or heteroaryl group selected from the group consisting of: phenyl, pyridine, pyrazine and thiazole; z is hydroxy or C_1-3Alkoxy groups or two Z together with the boron to which they are attached form R' is one to three groups independently selected from the following groups: -R, -CH₂-R, -CH ═ CH-R and-C ≡ C-R; and R is as defined above. In some embodiments, R is a substituted or unsubstituted ring, optionally comprising at least one heteroatom, and the ring is aromatic or non-aromatic. In some embodiments, R is a ring selected from:benzene, phenylbenzene, pyridine, tetrahydropyridine, pyridin-2-one, pyrimidine, thiophene, thiazole, imidazole, pyrazole, piperazine, morpholine, benzodioxole, benzoxadiazole, benzothiophene, benzothiazole, 2, 3-dihydro-benzodioxine, indazole, indole, 1, 3-indolin-2-one, 1, 2-indolin-3-one, quinoline, isoquinoline, quinolin-2-one, 3, 4-dihydroquinolin-2-one, 3, 4-dihydro-1, 4-benzoxazine, 1, 4-benzoxazin-3-one, 3, 1-benzoxazin-2-one, 2, 3-dihydro-imidazo [4,5-b ] o]Pyridine, oxazolo [4,5-b ]]Pyridin-2-ones, 2, 3-dihydro-pyrido [2,3-b ]][1,4]Oxazines, 3, 4-dihydro-pyrido [3,2-b][1,4]Oxazine, pyrido [2,3-b ]][1,4]Oxazin-2-ones, pyrido [3,2-b][1,4]Oxazin-3-ones and dibenzo [ b, d]Furan; wherein said ring is optionally substituted with one or two substituents selected from the group consisting of: hydroxy, halogen, C _1-6Alkyl, trifluoromethyl, C_1-6Alkoxy, trifluoromethoxy, amino, mono-or di-C_1-6Alkylamino radical, C_1-6Alkylcarbonylamino, C_1-6Alkylthio, mono-or di-C_1-6Alkylaminosulfonyl radical, C_1-6Alkylsulfonyl radical, C_1-6Alkylcarbonyl, morpholinylcarbonyl, benzodioxolyl, pyrrolidinyl, piperazinyl, acetylpiperazinyl, morpholinyl, tetrahydropyranyl, triazolyl, tetrazolyl, isoxazolyl, oxazolyl, oxadiazolyl, cyclopropyl-oxadiazolyl, C_1-6Alkyl-oxadiazolyl and oxadiazol-5-onyl.

The reaction of the compound of formula 2 above with a commercially available compound of formula 3a can be carried out by a Suzuki reaction. The reaction may be carried out by using a palladium catalyst. The palladium catalyst comprises palladium diacetate (Pd (OAc)₂) Tris (dibenzylideneacetone) dipalladium (Pd)₂(dba)₃) Tetrakis (triphenylphosphine) palladium (Pd (PPh)₃)₄) Or [1,1' -bis (diphenylphosphino) ferrocene]Palladium dichloride (PdCl)₂(dppf)₂) And the like. In the reaction carried out under a palladium catalyst, a ligand and a base may be added in addition to the palladium catalyst. The ligand includes (S) -2, 2-bis (diphenylphosphino) -1, 1-Binaphthyl (BINAP), 1,1' -bis (diphenylphosphino) ferrocene (dppf) or (tri-O-tolyl) phosphine (P (O-To) l)₃) Etc., including inorganic bases such as cesium carbonate (Cs)₂CO₃) Sodium carbonate (Na)₂CO₃) Potassium carbonate (K)₂CO₃) Potassium fluoride (KF), cesium fluoride (CsF), sodium hydroxide (NaOH), potassium phosphate (K3PO4), sodium tert-butoxide (tert-BuONa), potassium tert-butoxide (tert-BuOK), and the like. The reaction may be carried out in a non-polar organic solvent such as benzene or toluene, or in a polar solvent such as dioxane, tetrahydrofuran, acetonitrile, 1, 2-dimethoxyethane, N-dimethylformamide and the like, at a temperature in the range of 50 ℃ to 150 ℃, preferably 80 ℃ to 110 ℃. Other reaction conditions, including, for example, the reaction time can be determined from the reaction conditions of conventional Suzuki reaction (barbarara Czako and Laszlo Kurti, STRATEGIC APPLICATIONS ofNAMED REACTIONS in ORGANIC SYNTHESIS, 2005.) furthermore, the reaction of the compound of formula 2 with a commercially available compound of formula 3b (i.e., an acetylene derivative) can be carried out by Sonogashira coupling reaction using a palladium reagent such as bis (triphenylphosphine) palladium (II) dichloride, tetrakis (triphenylphosphine) palladium (0), etc., and copper iodide. The coupling reaction may be carried out at room temperature or at an elevated temperature, for example, a temperature of 20 ℃ to 60 ℃. In addition, in order to improve the reaction rate and reaction yield, the coupling reaction may be carried out in the presence of a base such as diisopropylamine, triethylamine, etc., and a ligand such as triphenylphosphine, etc.

Deprotection of the compound of formula 1aa may be carried out by conventional methods for removing amine protecting groups. For example, the amine protecting group in an organic solvent (e.g., dichloromethane, etc.) may be removed as a free amine by using an acid (e.g., trifluoroacetic acid), or may be removed as a hydrochloride by using hydrogen chloride dissolved in an organic solvent (e.g., diethyl ether, 1, 4-dioxane, etc.).

The compound of formula 2 can be prepared according to the following reaction scheme 1.

Reaction scheme 1.

In reaction scheme 1, a' and Boc are as defined above.

The compounds of formula 4 are commercially available. The compound of formula 4 may be converted to the compound of formula 5 by a nucleophilic acyl substitution reaction. The nucleophilic acyl group substitution reaction can be performed by using pyridine or triethylamine or the like in a solvent such as ethyl acetate, tetrahydrofuran or the like at 0 ℃ to room temperature. (Chunqan Sheng; Xiaoaying Chen; Wenyawang; Shengzheng Wang; Yongbin Cao; Zhenyuan Miao; Jianzhong Yang Yao; Wannian Zhang, European journal of medical Chemistry,46,5276-5282,2011).

The compound of formula 5 may be converted to the compound of formula 6 by a hydrazinolysis reaction. The hydrazinolysis reaction can be carried out according to known methods (e.g., WO2005/014583, etc.).

The compound of formula 6 may be converted to the compound of formula 7 by a cyclization reaction. The cyclization reaction can be carried out by using acetic acid in N, N-dimethylformamide at room temperature to 80 ℃ (Chunqan Sheng; Xiaoying Chen; Wenyawang; Shengzheng Wang; Yongbingg Cao; Zhenyuan Miao; Jianzhong Yao; Wannian Zhang, European Journal of Medicinal Chemistry,46,5276-5282, 2011).

The coupling reaction of the compound of formula 7 with the compound of formula 9 may be carried out in the presence of a base and a solvent. The base may be cesium carbonate, potassium carbonate, sodium carbonate, etc., and the solvent may be an organic solvent, such as N, N-dimethylformamide, dioxane, tetrahydrofuran, etc. In addition, the reaction may be performed at room temperature to 100 ℃.

The compound of formula 9 can be obtained from a commercially available chlorination reaction of the compound of formula 8. The chlorination reaction may be carried out in the presence of a conventional inorganic base and an organic solvent.

The aryl or heteroaryl triazolone derivatives according to the present technology, i.e., the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e or 12, or an isomer thereof, or a pharmaceutically acceptable salt thereof, has selective inhibitory effect on VAP-1, and thus, it can be effectively used for the prevention or treatment of diseases mediated by VAP-1. Preferably, a compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e or 12 or an isomer thereof, or a pharmaceutically acceptable salt thereof according to the present technology may be used, for example, for the prevention or treatment of nonalcoholic steatohepatitis (NASH).

In some embodiments, provided herein is the use of an aryl or heteroaryl triazolone derivative according to the present technology, i.e. a compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e or 12, or an isomer thereof, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the prevention and/or treatment of: lipid and lipoprotein disorders (such as, but not limited to, hypercholesterolemia, hypertriglyceridemia and atherosclerosis), conditions and diseases due to chronic fat and fibrosis of the organs caused by lipid accumulation (especially accumulation of triglycerides and subsequent activation of the profibrotic pathway) (such as, but not limited to, NASH and chronic cholestatic disease of the liver, glomerulosclerosis and diabetic nephropathy of the kidney, macular and diabetic retinopathy of the eye and neurodegenerative diseases such as alzheimer's disease of the brain or diabetic neuropathy of the peripheral nervous system), type I or type II diabetes and clinical complications of type I and type II diabetes (such as, but not limited to, diabetic nephropathy, diabetic retinopathy, diabetic neuropathy or Peripheral Arterial Occlusive Disease (PAOD)), chronic intrahepatic or certain forms of extrahepatic cholestatic disease, chronic intrahepatic or certain forms of biliary juice stasis, Liver fibrosis, acute intrahepatic cholestatic conditions, obstructive or chronic inflammatory disorders caused by inappropriate bile constituents (such as, but not limited to, cholelithiasis, also known as cholesterol gallstones), gastrointestinal disorders with reduced intake of dietary fat and fat-soluble dietary vitamins, inflammatory bowel diseases, obesity and metabolic syndrome (dyslipidemia, diabetes and a combination of abnormally high body mass indices), persistent infection by intracellular bacteria or parasitic protozoa, non-malignant hyperproliferative disorders, malignant hyperproliferative disorders (such as, but not limited to, different forms of cancer, in particular certain forms of breast cancer, liver cancer or colon cancer, or diseases selected from hepatocellular carcinoma, colon adenoma and polyposis), in particular colon adenocarcinoma and hepatocellular carcinoma, hepatic steatosis and related syndromes, hepatitis b infection, hepatitis c infection and/or bile stasis and fibrosis associated with alcohol-induced cirrhosis or viral transmitted forms of hepatitis A vitamin function, chronic liver disease or liver failure or liver insufficiency following surgical removal of the liver, acute myocardial infarction, acute stroke, thrombosis as an end point of chronic obstructive atherosclerosis, osteoarthritis, rheumatoid arthritis, psoriasis, cerebral infarction, alone or in any combination thereof.

The compounds and/or pharmaceutical compositions disclosed herein are useful for the prevention and/or treatment of chronic intrahepatic diseases, such as Primary Biliary Cirrhosis (PBC), Primary Sclerosing Cholangitis (PSC), progressive familiar cholestasis (PFIC), alcohol-induced cirrhosis and associated cholestasis, certain forms of extrahepatic cholestasis or liver fibrosis.

In some embodiments, provided herein is a method of treating chronic intrahepatic disease and/or certain forms of extrahepatic cholestatic disease in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein. In some embodiments, the chronic intrahepatic disease is selected from PBC, PSC, PFIC, and alcohol-induced cirrhosis and associated cholestasis.

In some embodiments, provided herein is a method of treating liver fibrosis in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein are methods of treating lipid and lipoprotein disorders in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein. In some embodiments, the lipid and lipoprotein disorders are selected from hypercholesterolemia, hypertriglyceridemia and atherosclerosis.

In some embodiments, provided herein are methods of treating conditions and diseases caused by accumulation of lipid-induced chronic adipose and fibrosis of an organ, particularly accumulation of triglycerides and subsequent activation of pro-fibrotic pathways, in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein. In some embodiments, the conditions and diseases caused by chronic adipose and fibrosis of organs due to lipid accumulation, in particular accumulation of triglycerides and subsequent activation of pro-fibrotic pathways are selected from NASH and chronic cholestatic disease of the liver, glomerulosclerosis and diabetic nephropathy of the kidney, macular degeneration and diabetic retinopathy of the eye and neurodegenerative diseases. In some other embodiments, the neurodegenerative disease is selected from alzheimer's disease of the brain or diabetic neuropathy of the peripheral nervous system.

In some embodiments, provided herein is a method of treating type I or type II diabetes and clinical complications of type I and type II diabetes in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein. In some embodiments, provided herein is a method of treating type I diabetes in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein. In some embodiments, provided herein is a method of treating type II diabetes in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein. In some embodiments, provided herein is a method of treating one or more clinical complications of type I and type II diabetes in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein. In some embodiments, the clinical complication of type I and type II diabetes is selected from diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, and Peripheral Arterial Occlusive Disease (PAOD), or any combination thereof.

In some embodiments, provided herein is a method of treating an acute intrahepatic cholestatic disorder in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating an obstructive or chronic inflammatory disorder caused by bile component inappropriateness in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein. In some embodiments, the obstructive or chronic inflammatory disorder caused by biliary component insufficiency is cholelithiasis, also known as cholesterol gallstone.

In some embodiments, provided herein is a method of treating a gastrointestinal disease with reduced intake of dietary fat and fat-soluble dietary vitamins in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating an inflammatory bowel disease in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein are methods of treating obesity and metabolic syndrome in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating a persistent infection by an intracellular bacterium or a parasitic protozoan in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating a non-malignant hyperproliferative disorder in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating a malignant hyperproliferative disorder in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein. In some embodiments, the malignant hyperproliferative disorder is selected from different forms of cancer, in particular certain forms of breast, liver or colon cancer, or a disease selected from hepatocellular carcinoma, colon adenoma and polyposis.

In some embodiments, provided herein is a method of treating colon adenocarcinoma in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating hepatocellular carcinoma in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein are methods of treating hepatic steatosis and associated syndromes in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating a hepatitis b infection in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating a hepatitis c infection in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating bile stasis and fibrosis associated with alcohol-induced cirrhosis or a virally transmitted form of hepatitis in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating chronic liver disease or liver failure or liver insufficiency resulting from surgical removal of the liver in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating acute myocardial infarction in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating acute stroke in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating thrombosis occurring as an endpoint of chronic obstructive atherosclerosis in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating osteoarthritis in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating rheumatoid arthritis in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating psoriasis in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

In some embodiments, provided herein is a method of treating cerebral infarction in a patient in need thereof, the method comprising (or consisting essentially of or consisting of): administering to the subject a therapeutically effective amount of a compound or composition disclosed herein.

The present technology includes a pharmaceutical composition for selectively inhibiting vascular adhesion protein-1 (VAP-1), comprising a therapeutically effective amount of a compound of X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, or an isomer thereof, or a pharmaceutically acceptable salt thereof, as an active ingredient. In one embodiment, the present technology provides a pharmaceutical composition for preventing or treating nonalcoholic steatohepatitis (NASH), comprising a therapeutically effective amount of a compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, or a pharmaceutically acceptable salt thereof, as an effective ingredient. In some embodiments provided herein are pharmaceutical compositions for the prevention or treatment of NASH comprising (consisting essentially of or consisting of): a therapeutically effective amount of a compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12 or an isomer thereof, or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier or excipient.

In another aspect, the present technology provides a pharmaceutical composition for preventing or treating diabetic nephropathy, comprising (consisting essentially of or consisting of): a therapeutically effective amount of a compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12 or an isomer thereof, or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier or excipient.

In another aspect, the present technology provides a pharmaceutical composition for preventing or treating primary sclerosing cholangitis, comprising (consisting essentially of or consisting of): a therapeutically effective amount of a compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12 or an isomer thereof, or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier or excipient.

In some embodiments, the compounds disclosed herein may be used in combination with one or more additional therapies for the prevention or treatment of a disease or disorder amenable to treatment by inhibition of VAP-1.

In some embodiments, the compositions disclosed herein comprise at least one additional active agent.

Exemplary such additional active agents include, but are not limited to, one or more of the following: ACE inhibitors, acetyl CoA carboxylase inhibitors, adenosine A3 receptor agonists, adiponectin receptor agonists, AKT protein kinase inhibitors, AMP-activated protein kinase (AMPK), dextrin receptor agonists, angiotensin IIAT-1 receptor antagonists, apoptosis signal kinase 1 inhibitors, Autotaxin inhibitors, bioactive lipids, calcitonin agonists, caspase inhibitors, caspase-3 stimulators, cathepsin inhibitors, caveolin 1 inhibitors, CCR2 chemokine antagonists, CCR3 chemokine antagonists, CCR5 chemokine antagonists, chloride channel stimulators, CNR1 inhibitors, cyclin D1 inhibitors, cytochrome P4507A1 inhibitors, DGAT1/2 inhibitors, dipeptidyl peptidase IV inhibitors, endosialin modulators, eotaxin ligand inhibitors, Extracellular matrix protein modulators, farnesoid X receptor agonists, fatty acid synthase inhibitors, FGF1 receptor agonists, fibroblast growth factor (FGF-15, FGF-19, FGF-21) ligands, galectin-3 inhibitors, glucagon receptor agonists, glucagon-like peptide 1 agonists, G-protein coupled bile acid receptor 1 agonists, Hedgehog (Hh) modulators, hepatitis c virus NS3 protease inhibitors, hepatocyte nuclear factor 4 alpha modulators (HNF4A), hepatocyte growth factor modulators, HMG CoA reductase inhibitors, IL-10 agonists, IL-17 antagonists, ileal sodium bile acid cotransporter inhibitors, insulin sensitizers, integrin modulators, interleukin-1 receptor-related kinase 4 (irjaak 4) inhibitors, tyrosine kinase inhibitors of k2, Ketohexokinase inhibitors, Klotho beta stimulators, 5-lipoxygenase inhibitors, lipoprotein lipase inhibitors, liver X receptors, LPL gene stimulators, lysophosphatidic acid-1 receptor antagonists, lysyl oxidase homolog 2 inhibitors, Matrix Metalloproteinase (MMPs) inhibitors, MEKK-5 protein kinase inhibitors, membrane copper amine oxidase (VAP-1) inhibitors, methionine aminopeptidase-2 inhibitors, methyl CpG binding protein 2 modulators, MicroRNA-21(miR-21) inhibitors, mitochondrial uncouplers, myelin basic protein stimulators, NACHT LRRPYD domain protein 3(NLRP3) inhibitors, NAD-dependent deacetylase sirtuin stimulators, NADPH oxidase inhibitors (NOX), nicotinic acid receptor 1 agonists, P2Y13 purine receptor stimulators, PDE 3 inhibitors, PDE 4 inhibitors, PDE 5 inhibitors, PDGF receptor beta modulators, phospholipase C inhibitors, PPAR alpha agonists, PPAR gamma modulators, protease-activated receptor-2 antagonists, protein kinase modulators, Rho-associated protein kinase inhibitors, sodium glucose transporter-2 inhibitors, SREBP transcription factor inhibitors, STAT-1 inhibitors, stearoyl CoA desaturase-1 inhibitors, inhibitors of cytokine signaling-1 stimulators, inhibitors of cytokine signaling-3 stimulators, transforming growth factor beta (TGF-beta), transforming growth factor beta activated kinase 1(TAK1), thyroid hormone receptor beta agonists, TLR-4 antagonists, transglutaminase inhibitors, tyrosine kinase receptor modulators, GPCR modulators, nuclear hormone receptor modulators, beta-agonists, inhibitors, WNT modulators and YAP/TAZ modulators. Examples of JAK inhibitors include, but are not limited to, filgotonib and tofacitinib. A non-limiting example of an apoptosis-signaling kinase inhibitor is selonsertib.

The compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e or 12, or an isomer thereof, or a pharmaceutically acceptable salt thereof, and the at least one additional active agent may be administered in any order or even simultaneously. The multiple active agents may be provided in a single, unified form or in multiple forms (as a single pill or as two separate pills, by way of example only). One of the active agents may be administered in multiple doses, or both may be administered in multiple doses. If not administered simultaneously, the time interval between multiple doses may vary from greater than zero weeks to less than four weeks. In addition, the combination methods, compositions, and formulations are not limited to the use of only two agents.

The pharmaceutical compositions of the present technology may comprise a pharmaceutically acceptable carrier, such as a diluent, disintegrant, sweetener, glidant, or flavoring agent, and may be formulated into an oral dosage form, such as a tablet, capsule, powder, microgranule, suspension, emulsion, or syrup; or parenteral dosage forms such as liquid for external use, suspension for external use, emulsion for external use, gel (ointment etc.), inhalant, spray, injection, etc. The dosage form may be formulated in various forms, for example, single administration or multiple administration.

Pharmaceutical compositions of the present technology may include excipients such as lactose, corn starch, and the like, glidants such as magnesium stearate, and the like, emulsifiers, suspending agents, stabilizers, isotonic agents, and the like. If desired, sweeteners and/or flavoring agents may be added. Exemplary excipients include, but are not limited to, polyethylene glycol (PEG), Hydrogenated Castor Oil (HCO), cremophor, carbohydrates, starches (e.g., corn starch), inorganic salts, antimicrobials, antioxidants, binders/fillers, surfactants, lubricants (e.g., calcium stearate or magnesium stearate), glidants, e.g., talc, disintegrants, diluents, buffering agents, acids, bases, film coatings, combinations thereof, and the like.

Specific carbohydrate excipients include, for example: monosaccharides such as fructose, maltose, galactose, glucose, D-mannose, sorbose and the like; disaccharides such as lactose, sucrose, trehalose, cellobiose, and the like; polysaccharides such as raffinose, melezitose, maltodextrin, dextran, starch, and the like; alditols, such as mannitol, xylitol, maltitol, lactitol, xylitol, sorbitol (glucitol), pyranosyl sorbitol, inositol, and the like.

Inorganic salts or buffers include, but are not limited to: citric acid, sodium chloride, potassium chloride, sodium sulfate, potassium nitrate, sodium dihydrogen phosphate, disodium hydrogen phosphate, and combinations thereof.

Suitable antioxidants for use in the present disclosure include, for example, ascorbyl palmitate, butyl hydroxyanisole, butyl hydroxytoluene, hypophosphorous acid, monothioglycerol, propyl gallate, sodium bisulfite, sodium formaldehyde sulfoxylate, sodium metabisulfite, and combinations thereof.

Additional exemplary excipients include surfactants, e.g., polysorbates, e.g., "Tween 20" and "Tween 80", and pluronic such as F68 and F88 (both available from BASF, mount olive, NJ), sorbitan esters, lipids (e.g., phospholipids (e.g., lecithin and other phosphatidylcholines and phosphatidylethanolamines), fatty acids and fatty esters, steroids (e.g., cholesterol) and chelators (e.g., EDTA), zinc and other such suitable cations.

In addition, the compositions disclosed herein may optionally include one or more acids or bases. Non-limiting examples of acids that may be used include those selected from the group consisting of: hydrochloric acid, acetic acid, phosphoric acid, citric acid, malic acid, lactic acid, formic acid, trichloroacetic acid, nitric acid, perchloric acid, phosphoric acid, sulfuric acid, fumaric acid, and combinations thereof. Non-limiting examples of suitable bases include bases selected from the group consisting of: sodium hydroxide, sodium acetate, ammonium hydroxide, potassium hydroxide, ammonium acetate, potassium acetate, sodium phosphate, potassium phosphate, sodium citrate, sodium formate, sodium sulfate, potassium fumarate, and combinations thereof.

The amount of any individual excipient in the composition will vary depending on the effect of the excipient, the dosage requirements of the active agent component, and the particular needs of the composition.

Typically, however, the excipient is present in the composition in an amount of about 1% to about 99% by weight, preferably about 5% to about 98% by weight, more preferably about 15% to about 95% by weight. Typically, the amount of excipient present in the compositions of the present disclosure is selected from the following: at least about 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or even 95% by weight thereof.

The compositions of the present technology may be administered orally or parenterally, including inhalation, intravenous, intraperitoneal, subcutaneous, rectal and topical routes of administration. Thus, the compositions of the present technology may be formulated in various forms, such as tablets, capsules, aqueous solutions, suspensions, and the like. For oral tablets, carriers such as lactose, corn starch and lubricants, for example magnesium stearate, may be added conventionally thereto. For oral capsules, lactose and/or dried corn starch may be used as diluents. When aqueous suspensions for oral administration are desired, the active ingredient may be combined with emulsifying and/or suspending agents. If desired, certain sweetening and/or flavoring agents may be added thereto. For intramuscular, intraperitoneal, subcutaneous and intravenous administration, sterile solutions of the active ingredient are generally prepared, and the pH of the solutions should be appropriately adjusted and buffered. For intravenous administration, the total concentration of solutes should be controlled to render the formulation isotonic. The compositions of the present technology may be in the form of an aqueous solution containing a pharmaceutically acceptable carrier, such as saline at a pH of 7.4. The solution may be introduced into the intramuscular blood flow of a patient by a topical bolus injection.

The aryl or heteroaryl triazolone derivative, i.e., the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e or 12, or an isomer thereof, or a pharmaceutically acceptable salt thereof, can be administered to a subject in an effective amount of about 0.001mg/kg to about 100mg/kg per day. Which includes 0.001, 0.0025, 0.005, 0.0075, 0.01, 0.025, 0.05, 0.075, 0.1, 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 mg/kg.

Generally, a therapeutically effective amount of a compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e or 12, or an isomer thereof, or a pharmaceutically acceptable salt thereof, ranges from a total daily dose of about 0.1 mg/day to 1000 mg/day, about 30-720 mg/day, about 60-600 mg/day or about 100-480 mg/day, or more. In some embodiments, a therapeutically effective amount of a compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, or an isomer thereof, or a pharmaceutically acceptable salt thereof, ranges from about 1 to 240 mg/day, about 30 to 200 mg/day, about 30 to 120 mg/day, about 1 to 120 mg/day, about 50 to 150 mg/day, about 60 to 120 mg/day, or about 60 to 100 mg/day, administered as a single dose or as multiple doses. In some embodiments, the multiple doses include two, three, or four doses per day.

In some embodiments, the therapeutically effective amount of the compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, or an isomer thereof, or a pharmaceutically acceptable salt thereof, is at least 0.1 mg/day, at least 0.5 mg/day, at least 1 mg/day, at least 5 mg/day, at least 10 mg/day, at least 20 mg/day, at least 30 mg/day, at least 40 mg/day, at least 50 mg/day, at least 60 mg/day, at least 70 mg/day, at least 80 mg/day, at least 90 mg/day, at least 100 mg/day, at least 110 mg/day, at least 120 mg/day, at least 130 mg/day, at least 140 mg/day, at least 150 mg/day, at least 160 mg/day, at least 170 mg/day, or a pharmaceutically acceptable salt thereof, At least 180 mg/day, at least 190 mg/day, at least 200 mg/day, at least 225 mg/day, at least 250 mg/day, at least 275 mg/day, at least 300 mg/day, at least 325 mg/day, at least 350 mg/day, at least 375 mg/day, at least 400 mg/day, at least 425 mg/day, at least 450 mg/day, at least 475 mg/day, at least 500 mg/day, at least 525 mg/day, at least 550 mg/day, at least 575 mg/day, at least 600 mg/day, at least 625 mg/day, at least 650 mg/day, at least 675 mg/day, at least 700 mg/day, at least 725 mg/day, at least 750 mg/day, at least 775 mg/day, at least 800 mg/day, at least 825 mg/day, at least 850 mg/day, At least 875 mg/day, at least 900 mg/day, at least 925 mg/day, at least 950 mg/day, at least 975 mg/day, or at least 1000 mg/day.

Of course, the dosage may vary depending on the age, weight, susceptibility, symptoms, or efficacy of the compound of the patient.

In one embodiment, the present technology provides a method of selectively inhibiting Vascular Adhesion Protein (VAP) -1 in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, or an isomer thereof, or a pharmaceutically acceptable salt thereof. In one embodiment, the present technology provides a method for treating nonalcoholic liver steatosis (NASH) comprising administering to a mammal a therapeutically effective amount of a compound of formula 1, or a pharmaceutically acceptable salt thereof. In some embodiments, provided herein is a method of treating NASH in a subject in need thereof, the method comprising administering to the subject (consisting essentially of or consisting of) a therapeutically effective amount of a compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, or an isomer thereof, or a pharmaceutically acceptable salt thereof. Mammals include, but are not limited to, mice, rodents, rats, simians, humans, farm animals, dogs, cats, sport animals, and pets.

The present technology provides the use of a compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, or an isomer thereof, or a pharmaceutically acceptable salt thereof, as described above, in the manufacture of a medicament for selectively inhibiting vascular adhesion protein-1 (VAP-1) in a mammal. In one embodiment, the present technology provides the use of a compound of formula X, 1, 10a, 10b, 11a, 11b, 11c, 11d, 11e, or 12, or an isomer thereof, or a pharmaceutically acceptable salt thereof, as described above, in the manufacture of a medicament for the treatment or prevention of nonalcoholic liver steatosis (NASH).

The following examples and experimental examples are provided for illustrative purposes only and are not intended to limit the scope of the present technology.

It will be apparent to those skilled in the art upon reading this disclosure that each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope of the present invention. Any recited method may be performed in the recited order of events or any other order that is logically possible.

All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference herein as though fully set forth, and methods and/or materials were specifically and individually indicated to be incorporated by reference herein as though fully set forth. Any publication cited is prior to the filing date and is not to be construed as an admission that the present technology is not entitled to antedate such publication by virtue of prior art. Further, the release date provided may be different from the actual release date, which may require independent confirmation.

Examples

The analysis of the compounds prepared in the following examples was carried out as follows: nuclear Magnetic Resonance (NMR) spectroscopy was performed using a Bruker400 MHz spectrometer and an Agilent 600MHz spectrometer and chemical shifts were analyzed in ppm. In addition, the molecular weights shown were measured by using an Agilent 1260 Infinity series liquid chromatography/mass spectrometry selective detector (MSD) equipped with an electrostatic spray interface (by using Single quadrupolode, which represents the M/z value in ESI + (ESI-MS (cation)), consisting of [ M + H +]⁺Peak representation). Column chromatography was performed on silica gel (Merck, 70-230 mesh). (w.c. still, j.org.chem.,43, 2923, 1978). Abbreviations used in the following examples are as follows: "methyl" is abbreviated "Me"; "ethyl" is abbreviated "Et"; "phenyl" is abbreviated "Ph" and "t-butyloxycarbonyl" is abbreviated "BOC". In addition, the starting materials in each example were known compounds, synthesized according to the publication or obtained from Sigma-Aldrich.

Reference example 1 (Z) - (2- (chloromethyl) -3-fluoroallyl) carbamic acid tert-butyl ester

290.0mg of tert-butyl (Z) - (3-fluoro-2- (hydroxymethyl) allyl) carbamate, 350.2mg of 4-methylbenzenesulfonyl chloride and 0.26mL of triethylamine were dissolved in 5.0mL of dichloromethane, and the solution was stirred at room temperature overnight. Dichloromethane was added to the reaction mixture. The obtained reaction mixture was washed with distilled water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate 2/1) to obtain 312.0mg of the title compound (yield: 98.9%) as a white solid. ¹H-NMR(CDCl₃，400MHz)6.63(d，1H)，4.73(bs，1H)，4.07(s，2H)，3.79(bs，2H)，1.47(s，9H)

Reference example 2 (E) - (2- (chloromethyl) -3-fluoroallyl) carbamic acid tert-butyl ester

440.0mg of (E) - (3-fluoro-2- (hydroxymethyl) allyl) aminoTert-butyl formate, 531.3mg of 4-methylbenzenesulfonyl chloride and 0.39mL of triethylamine were dissolved in 5.0mL of dichloromethane, and the solution was stirred at room temperature overnight. Dichloromethane was added to the obtained reaction mixture. The reaction mixture was washed with distilled water, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate 2/1) to obtain 400.0mg of the title compound present as a white solid (yield: 83.6%).¹H-NMR(CDCl₃，400MHz)6.72(d，1H)，4.74(bs，1H)，4.05(s，2H)，3.98(s，2H)，1.44(s，9H)

Reference example 3.4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

Step 1: (4-bromophenyl) carbamic acid phenyl ester

1.0g of 4-bromoaniline and 0.98mL of pyridine were dissolved in 10mL of ethyl acetate. 0.77mL of phenyl chloroformate was slowly added to the obtained solution at 0 ℃ and the solution was stirred at room temperature for 3 hours. Ethyl acetate was added to the solution, and the obtained reaction mixture was washed with a 1N hydrochloric acid solution and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 1.4g of the title compound present as a yellow solid (yield: 80%).

Step 2: n- (4-bromophenyl) hydrazinecarboxamide

1.4g of phenyl (4-bromophenyl) carbamate prepared in step 1 and 480.0mg of hydrazine hydrate were dissolved in 4.0mL of tetrahydrofuran and 4.0mL of ethanol, and the resulting solution was stirred at room temperature overnight. The obtained reaction mixture was concentrated and then washed with ethyl acetate to obtain 890.0mg of the title compound present as a white solid (yield: 80.0%).

And step 3: 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

890.0mg of N- (4-bromophenyl) hydrazinecarboxamide prepared in step 2 and 1.6g of formamidine acetate were dissolved in 8.9mL of 1-propanol, and the resulting solution was stirred at room temperature for 30 minutes, followed by addition of 1.3mL of acetic acid and further stirring at 80 ℃ for 8 hours. The reaction mixture was cooled to room temperature, distilled water was added to the cooled reaction mixture, and then the reaction mixture was stirred overnight. The obtained crystals were filtered and dried to obtain 742.8mg of the title compound present as a white solid (yield: 80.2%). MS (ESI) M/z 241.9(M + H) +

Reference example 4.4- (3-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

540.0mg of the title compound (yield: 38.7%) was prepared in the same manner as in reference example 3, except that 1.0g of 3-bromoaniline was used in place of 4-bromoaniline in step 1. MS (ESI) M/z 241.5(M + H) +

Reference example 5.4- (4-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

527.0mg of the title compound (yield: 32.7%) was prepared in the same manner as in reference example 3, except that 1.0g of 4-fluoroaniline was used in place of 4-bromoaniline in step 1. MS (ESI) M/z 180.1(M + H)⁺

Reference example 6.4- (4- (benzyloxy) phenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

487.0mg of the title compound (yield: 36.3%) was prepared in the same manner as in reference example 3, except that 1.0g of 4- (benzyloxy) aniline was used in place of 4-bromoaniline in step 1.¹H-NMR(CDCl₃,400MHz)9.58(bs,1H)，7.62(s,1H)，7.33-7.41(m,6H)，7.21-7.25(m,1H)，7.06(d,2H)，5.10(s,2H)

Reference example 7.4- (3, 4-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

492.0mg of the title compound (yield: 32.2%) was prepared in the same manner as in reference example 3, except that 1.0g of 3, 4-difluoroaniline was used in place of 4-bromoaniline in step 1. MS (ESI) 198.0(M + H) M/z⁺

Reference example 8.4- (4-bromo-2-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

443.5mg of the title compound (yield: 32.7%) was prepared in the same manner as in reference example 3, except that 1.0g of 4-bromo-2-fluoroaniline was used in place of 4-bromoaniline in step 1. MS (ESI) M/z 259.9(M + H)⁺

Reference example 9.4- (4-bromo-3-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

517.3mg of the title compound (yield: 38.1%) was prepared in the same manner as in reference example 3, except that 1.0g of 4-bromo-3-fluoroaniline was used in place of 4-bromoaniline in step 1. MS (ESI) M/z 259.4(M + H)⁺

Reference example 10.4- (4-bromo-3-methylphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

750mg of the title compound (yield: 55.0%) was prepared in the same manner as in reference example 3, except that 1.0g of 4-bromo-3-methylaniline was used in place of 4-bromoaniline in step 1. MS (ESI) 255.2(M + H) M/z⁺

Reference example 11.4- (3-bromo-2-methylphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

5.1g of the title compound (yield: 69.9%) was prepared in the same manner as in reference example 3 except that 5.0g of 3-bromo-2-methylaniline was used in place of 4-bromoaniline in step 1. MS (ESI) 255.2(M + H) M/z⁺

Reference example 12.4- (4-bromo-3-methoxyphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

500.5mg of the title compound (yield: 37.4%) was prepared in the same manner as in reference example 3, except that 1.0g of 4-bromo-3-methoxyaniline was used in place of 4-bromoaniline in step 1. Ms (esi) 271.1(M + H) M/z⁺

Reference example 13.4- (5-bromo-2-methoxyphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

628.5mg of the title compound (yield: 47.1%) was prepared in the same manner as in reference example 3, except that 1.0g of 5-bromo-2-methoxyaniline was used in place of 4-bromoaniline in step 1. MS (ESI) M/z 271.2(M + H) +

Reference example 14.4- (4-bromo-3, 5-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

570.0mg of the title compound (yield: 42.9%) was prepared in the same manner as in reference example 3 except that 1.0g of 4-bromo-3, 5-difluoroaniline was used in place of 4-bromoaniline in step 1. MS (ESI) 277.8(M + H) M/z⁺

Reference example 15.4- (4-bromo-2, 6-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

530.0mg of the title compound (yield: 39.9%) was prepared in the same manner as in reference example 3, except that 1.0g of 4-bromo-2, 6-difluoroaniline was used in place of 4-bromoaniline in step 1. MS (ESI) 277.0(M + H) M/z⁺

Reference example 16.4- (4-bromo-2, 5-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

424.5mg of the title compound (yield: 32.0%) was prepared in the same manner as in reference example 3, except that 1.0g of 4-bromo-2, 5-difluoroaniline was used in place of 4-bromoaniline in step 1. MS (ESI) M/z 277.1(M + H) +

Reference example 17.4- (6-Bromopyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

500.7mg of the title compound (yield: 35.9%) was prepared in the same manner as in reference example 3, except that 1.0g of 3-amino-6-bromopyridine was used in place of 4-bromoaniline in step 1. MS (ESI) 242.1(M + H) M/z⁺

Reference example 18.4- (6-bromo-5-methylpyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

362.1mg of the title compound (yield: 26.5%) was prepared in the same manner as in reference example 3, except that 1.0g of 5-amino-2-bromo-3-methylpyridine was used in place of 4-bromoaniline in step 1. MS (ESI) M/z 256.4(M + H) +

Reference example 19.4- (6-bromo-4-methylpyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

4.5g of the title compound (yield: 66.1%) was prepared in the same manner as in reference example 3 except that 5.0g of 2-bromo-4-methyl-5-aminopyridine was used in place of 4-bromoaniline in step 1. MS (ESI) 256.0(M + H) M/z⁺

Reference example 20.4- (5-Bromopyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

526.5mg of the title compound (yield: 37.8%) was prepared in the same manner as in reference example 3, except that 1.0g of 2-amino-5-bromopyridine was used in place of 4-bromoaniline in step 1. MS (ESI) 252.7(M + H) M/z⁺

Reference example 21.4- (5-bromo-3-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

1.9g of headingsA compound (yield: 69.6%) was prepared in the same manner as in reference example 3, except that 2.0g of 2-amino-5-bromo-3-methylpyridine was used in place of 4-bromoaniline in step 1.¹H-NMR(DMSO-d₆,400MHz)8.55(d,1H)，8.21(s,1H)，8.13(s,1H)，2.27(s,3H)

Reference example 22.4- (5-bromo-4-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

1.1g of the title compound (yield: 80.6%) was prepared in the same manner as in reference example 3 except that 1.0g of 2-amino-5-bromo-4-methylpyridine was used in place of 4-bromoaniline in step 1. MS (ESI) 256.3(M + H) M/z⁺

Reference example 23.4- (5-bromo-3-fluoropyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

715.0mg of the title compound (yield: 52.7%) was prepared in the same manner as in reference example 3, except that 1.0g of 2-amino-5-bromo-3-fluoropyridine was used in step 1 in place of 4-bromoaniline. MS (ESI) M/z 260.2(M + H) +

Reference example 24.4- (6-Bromopyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

6.0g of the title compound (yield: 86.1%) was prepared in the same manner as in reference example 3 except that 5.0g of 2-amino-6-bromopyridine was used in place of 4-bromoaniline in step 1.¹H-NMR(MeOD,400MHz)8.44(s,1H)，8.24(d,1H)，7.83(t,1H)，7.53(d,1H)

Reference example 25.4- (4-Bromopyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

902.2mg of the title compound (yield: 64.8%) was prepared in the same manner as in reference example 3, except that 1.0g of 2-amino-4-bromopyridine was used in place of 4-bromoaniline of step 1. MS (ESI) 252.1(M + H) M/z ⁺

Reference example 26.4- (2-Bromopyridin-4-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

2.0g of the title compound (yield: 28.7%) was prepared in the same manner as in reference example 3, except that 5.0g of 4-amino-2-bromopyridine was used in place of 4-bromoaniline of step 1.¹H-NMR(DMSO-d₆,600MHz)8.65(s,1H)，8.45(d,1H)，8.17(s,1H)，8.12(d,1H)，7.97(dd,1H)

Reference example 27.4- (6-bromo-3-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

1.8g of the title compound (yield: 65.9%) was prepared in the same manner as in reference example 3 except that 2.0g of 2-amino-6-bromo-3-methylpyridine was used in place of 4-bromoaniline of step 1. MS (ESI) 256.7(M + H) M/z⁺

Reference example 28.4- (5-Bromopyrazin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

4.3g of the title compound (yield: 61.9%) was prepared in the same manner as in reference example 3, except that 5.0g of 2-amino-5-bromopyrazine was used in place of 4-bromoaniline of step 1. MS (ESI) M/z 243.4(M + H) +

Reference example 29.4- (5-Bromothiazol-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

475.9mg of the title compound (yield: 34.6%) was prepared in the same manner as in reference example 3, except that 1.0g of 2-amino-5-bromothiazole was used in place of 4-bromoaniline of step 1. MS (ESI) M/z 248.0(M + H) +

Reference example 30.4- (3-bromophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazole-1-carboxylic acid tert-butyl ester

5.0g of 4- (3-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 4 and 2.6g of sodium carbonate were dissolved in 15.0mL of 1, 4-dioxane and 25.0mL of distilled water. To the solution obtained, 5.7mL of di-tert-butyl dicarbonate and 10.0mL of 1, 4-dioxane were added, and then the solution was stirred at room temperature overnight. The obtained reaction mixture was neutralized with 1N aqueous hydrochloric acid solution, and then crystallized using added ethyl acetate. The obtained crystals were filtered, washed with diisopropyl ether and then dried to obtain 5.1g of the title compound present as a white solid (yield: 71.2%). ms (esi) M/z 241.9(M + H)⁺

Reference example 31.3- (4- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) -1- ((2- (trimethylsilyl) ethoxy) methyl) -1H-1,2, 4-triazole

Step 1: (E) -4-bromo-N- ((dimethylamino) methylene) benzamide

A reaction mixture of 2.0g of 4-bromobenzamide and 5.4g of N, N-dimethylformamide dimethyl acetal was stirred at 90 ℃ for 15 minutes. The reaction mixture was cooled to room temperature, and 30.0mL of diethyl ether was added to obtain a crystal. The obtained crystals were filtered and dried to obtain 1.89g of the title compound present as a yellow solid (yield: 100.0%).

Step 2: 3- (4-bromophenyl) -1H-1,2, 4-triazole

1.5g of (E) -4-bromo-N- ((dimethylamino) methylene) benzamide prepared in step 1 and 0.3mL of hydrazine hydrate were dissolved in 15.0mL of acetic acid, and the resulting solution was stirred at 90 ℃ for 2 hours. The reaction mixture was cooled to room temperature, and then 30mL of diethyl ether was added. The obtained reaction mixture was stirred at room temperature for 1 hour, and then further stirred at 0 ℃ for 1 hour to obtain a crystal. The obtained crystals were filtered and dried to obtain 1.57g of the title compound present as a yellow solid (yield: 100.0%).¹H-NMR(DMSO-d₆,400MHz)14.23(s,1H)，8.51(s,1H)，7.96(d,2H)，7.69(d,2H)

And step 3: 3- (4-bromophenyl) -1- ((2- (trimethylsilyl) ethoxy) methyl) -1H-1,2, 4-triazole

1.5g of 3- (4-bromophenyl) -1H-1,2, 4-triazole prepared in step 2 was dissolved in 5.0mL of N, N-dimethylformamide, and the resulting reaction mixture was cooled to 0 ℃. 0.32g of sodium cyanide was added to the reaction mixture, and then the reaction mixture was stirred for 30 minutes. 1.67g of (2- (chloromethoxy) ethyl) trimethylsilane was added and the reaction mixture was subsequently stirred at 0 ℃ for 15 minutes and for a further 2 hours. Distilled water was added, and the reaction mixture was extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain a residue as a yellow liquid. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate-2/1) to obtain 1.1g of the title compound present as a yellow solid (yield: 46.3%). ¹H-NMR(CDCl₃,400MHz)8.25(s,1H)，8.01(d,2H)，7.58(d,2H)，5.52(s,2H)，3.69(t,2H)，0.96(t,2H)，0.00(s,9H)

And 4, step 4: 3- (4- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) -1- ((2- (trimethylsilyl) ethoxy) methyl) -1H-1,2, 4-triazole

500.0mg of 3- (4-bromophenyl) -1- ((2- (trimethylsilyl) ethoxy) methyl) -1H-1,2, 4-triazole, prepared in step 3, 720.0mg of bis (pinacolato) diboron and 420.0mg of potassium acetate were dissolved in 10.0mL of 1, 4-dioxane. 103.0mg of [1, 1' -bis (diphenylphosphino) ferrocene]Palladium dichloride (PdCl)₂(dppf)) and 39.0mg of 1, 1' -bis (diphenylphosphino) ferrocene (dppf) were added to the obtained solution, and the solution was stirred at 95 ℃ overnight. The reaction mixture thus obtained was concentrated, and ethyl acetate was added. The concentrated reaction mixture was washed with distilled water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate 1/1) to obtain 403.0mg of the title compound (yield: 70.6%) as a yellow solid.¹H-NMR(CDCl₃,400MHz)8.27(s,1H)，8.14(d,2H)，7.93(m,2H)，5.54(s,2H)，3.71(t,2H)，1,38(s,12H)，0.96(t,2H)，0.01(s,9H)

Reference example 32.3- (3- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) -1- ((2- (trimethylsilyl) ethoxy) methyl) -1H-1,2, 4-triazole

1.57g of the title compound (yield: 66.0%) present as a yellow solid was prepared in the same manner as in reference example 32 except that 2.0g of 3-bromobenzamide was used in place of 4-bromobenzamide in step 1.¹H-NMR(CDCl₃,400MHz)8.59(s,1H)，8.27(s,1H)，8.21(d,2H)，7.84(d,2H)，7.45(t,2H)，5.53(s,2H)，3.69(t,2H)，1,35(s,12H)，0.96(t,2H)，0.01(s,9H).

Reference example 33 tert-butyl (Z) - (2- ((4- (4-bromophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

20.9mg of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 3 and 23.1mg of potassium carbonate were dissolved in 0.6mL of N, N-dimethylformamide. 30.0mg of tert-butyl (Z) - (2- (chloromethyl) -3-fluoroallyl) carbamate prepared in reference example 1 was added to the obtained solution, and then the solution was stirred at 100 ℃ for 4 hours. The obtained reaction mixture was concentrated, and methylene chloride was added, and the concentrated reaction mixture was washed with distilled water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate 2/1) to give 17.0mg of the title compound (yield: 34.9%) as a colorless liquid ms (esi) M/z 328.2(M + H) +

Reference example 34 tert-butyl (E) - (2- ((4- (4-bromophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

16.3mg of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 3 and 23.1mg of potassium carbonate were dissolved in 0.6mL of N, N-dimethylformamide. 30.0mg of tert-butyl (E) - (2- (chloromethyl) -3-fluoroallyl) carbamate prepared in reference example 2 was added to the obtained solution, and the solution was stirred at 100 ℃ for 4 hours. The obtained reaction mixture was concentrated and dichloromethane was added. The concentrated reaction mixture was washed with distilled water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate 2/1) to give 19.0mg of the title compound (yield: 64.7%) as a colorless liquid ms (esi) M/z 328.2(M + H) +

Reference example 35 tert-butyl (Z) - (2- ((4- (4-bromo-2-fluorophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

31.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 33 (yield: 84.3%) except that 21.5mg of 4- (4-bromo-2-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 8 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 346.1(M + H) +

Reference example 36 tert-butyl (E) - (2- ((4- (4-bromo-2-fluorophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

20.0mg of the title compound present as a white solid was prepared in the same manner as in reference example 34 (yield: 72.6%) except that 16.0mg of 4- (4-bromo-2-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 8 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one.¹H-NMR(MeOD,400MHz)8.11(s,1H)，7.65(d,1H)，7.53-7.59(m,2H)，7.18(d,1H)，4.53(s,2H)，3.73(d,2H)，1.41(s,9H)

Reference example 37 tert-butyl (Z) - (2- ((4- (4-bromo-3-fluoroallyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluorophenyl) carbamate

81.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 33 (yield: 64.3%) except that 71.8mg of 4- (4-bromo-3-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 9 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 346.3(M + H) +

Reference example 38 (E) - (tert-butyl 2- ((4- (4-bromo-3-fluoroallyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluorophenyl) carbamate

26.0mg of the title compound present as a white solid was prepared in the same manner as in reference example 34 (yield: 72.6%) except that 16.0mg of 4- (4-bromo-3-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 9 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. ¹H-NMR(MeOD,400MHz)8.34(s,1H)，7.71-7.80(m,2H)，7.48(dd,1H)，7.18(d,1H)，4.53(d,2H)，3.73(d,2H)，1.42(s,9H)

Reference example 39 (Z) - (tert-butyl 2- ((4- (4-bromo-3-methylphenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

79.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 33 (yield: 63.9%) except that 70.7mg of 4- (4-bromo-3-methylphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 10 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z ═ 342.2(M + H) +

Reference example 40 tert-butyl (E) - (2- ((4- (4-bromo-3-methylphenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

26.0mg of the title compound present as a colorless liquid was prepared in the same manner as in reference example 34 (yield: 95.2%) except that 16.0mg of 4- (4-bromo-3-methylphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 10 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one.¹H-NMR(MeOD,400MHz)8.26(s,1H)，7.68(d,1H)，7.62(s,1H)，7.40(dd,1H)，7.18(d,1H)，4.53(d,2H)，3.73(d,2H)，2.45(s,3H)，1.41(s,9H)

Reference example 41 tert-butyl (Z) - (2- ((4- (4-bromo-3-methoxyphenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

77.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 33 (yield: 60.1%) except that 75.1mg of 4- (4-bromo-3-methoxyphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 12 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 358.3(M + H) +

Reference example 42 tert-butyl (E) - (2- ((4- (4-bromo-3-methoxyphenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

20.0mg of the title compound present as a white solid was prepared in the same manner as in reference example 34 (yield: 71.0%) except that 17.0mg of 4- (4-bromo-3-methoxyphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 12 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one.¹H-NMR(MeOD,400MHz)8.31(s,1H)，7.65(d,1H)，7.40(s,1H)，7.18(d,1H)，7.15(dd,1H)，4.55(d,2H)，3.93(s,3H)，3.75(s,2H)，1.42(s,9H)

Reference example 43 (Z) - (tert-butyl 2- ((4- (4-bromo-3, 5-difluorophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

82.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 33 (yield: 63.2%) except that 76.8mg of 4- (4-bromo-3, 5-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 14 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 364.6(M + H) +

Reference example 44 (E) - (tert-butyl 2- ((4- (4-bromo-3, 5-difluorophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

24.0mg of the title compound present as a colorless liquid was prepared in the same manner as in reference example 34 (yield: 83.9%) except that 17.0mg of 4- (4-bromo-3, 5-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 14 was used in place of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one in step 1.¹H-NMR(MeOD,400MHz)8.39(s,1H)，7.64(dd,2H)，7.18(d,1H)，4.53(d,2H)，3.73(d,2H)，1.42(s,9H)

Reference example 45 (Z) - (tert-butyl 2- ((4- (4-bromo-2, 6-difluorophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

9.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 33 (yield: 23.4%) except that 23.0mg of 4- (4-bromo-2, 6-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 15 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 364.5(M + H) +

Reference example 46 (E) - (tert-butyl 2- ((4- (4-bromo-2, 6-difluorophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

14.0mg of the title compound present as a white solid was prepared in the same manner as in reference example 34 (yield: 48.4%) except that 17.0mg of 4- (4-bromo-2, 6-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 15 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one.¹H-NMR(MeOD,400MHz)8.10(s,1H)，7.57(d,2H)，7.18(d,1H)，4.55(d,2H)，3.73(d,2H)，1.41(s,9H).

Reference example 47 (E) - (tert-butyl 2- ((4- (4-bromo-2, 5-difluorophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

12.0mg of the title compound present as a white solid was prepared in the same manner as in reference example 34 (yield: 41.9%) except that 17.0mg of 4- (4-bromo-2, 5-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 16 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. ¹H-NMR(MeOD,400MHz)8.15(s,1H)，7.79(dd,1H)，7.69(dd,1H)，7.09(d,1H)，7.08(d,1H)，4.54(d,2H)，4.12(d,2H)，1.42(s,9H).

Reference example 48 (E) - (tert-butyl 2- ((4- (5-bromo-2-methoxy-4-morpholinophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

Step 1: (5-bromo-2-methoxy-4-morpholinophenyl) carbamic acid phenyl ester

1.0g of 5-bromo-2-methoxy-4-morpholinoaniline and 0.62mL of pyridine were dissolved in 10.0mL of ethyl acetate. 0.17mL of phenyl chloroformate was slowly added to the obtained solution at 0 ℃ and the solution was stirred at room temperature overnight. Ethyl acetate was added to the solution, and the obtained mixture was washed with a 1N hydrochloric acid solution and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 0.78g of the title compound present as a yellow solid (yield: 55.0%).¹H-NMR(CDCl₃,400MHz)8.35(bs,1H)，7.40(t,3H)，7.18-7.26(m,3H)，6.63(s,1H)，3.92(s,3H)，3.88(d,4H)，3.02(d,4H)

Step 2: n- (5-bromo-2-methoxy-4-morpholinophenyl) hydrazinecarboxamide

780mg of phenyl (5-bromo-2-methoxy-4-morpholinophenyl) carbamate prepared in step 1 and 186uL of hydrazine hydrate were dissolved in 2.0mL of tetrahydrofuran and 2.0mL of ethanol, and the resulting solution was stirred at 80 ℃ overnight. The obtained reaction mixture was concentrated, followed by washing with ethyl acetate to obtain 637mg of the title compound present as a white solid (yield: 96.1%). ¹H-NMR(DMSO-d₆,400MHz)8.37(s,1H)，7.68(s,1H)，6.82(s,1H)，4.55(s,2H)，3.86(s,3H)，3.72(s,4H)，2.92(s,4H)

And step 3: 4- (5-bromo-2-methoxy-4-morpholinophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

637mg of N- (5-bromo-2-methoxy-4-morpholinophenyl) hydrazinecarboxamide prepared in step 2 and 766mg of formamidine acetate were dissolved in 10.0mL of 1-propanol, and the resulting solution was stirred at room temperature for 30 minutes, followed by addition of 632uL of acetic acid and further stirring at 80 ℃ for 8 hours. The reaction mixture was cooled to room temperature, distilled water was added to the cooled reaction mixture, and then the reaction mixture was stirred overnight. The obtained crystals were filtered and dried to obtain 615mg of the title compound present as a white solid (yield: 94.1%).¹H-NMR(CDCl₃,400MHz)9.67(s,1H)，7.67(s,1H)，7.56(s,1H)，6.68(s,1H)，3.90(s,4H)，3.86(s,3H)，3.08(s,4H)

And 4, step 4: (E) - (2- ((4- (5-bromo-2-methoxy-4-morpholinophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamic acid tert-butyl ester

213mg of 4- (5-bromo-2-methoxy-4-morpholinophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in step 3 and 231mg of potassium carbonate were dissolved in 3.0mL of N, N-dimethylformamide. 300mg of tert-butyl (E) - (2- (chloromethyl) -3-fluoroallyl) carbamate prepared in reference example 2 was added to the obtained solution, and the solution was stirred at 100 ℃ for 4 hours. The obtained reaction mixture was concentrated and dichloromethane was added, and the concentrated reaction mixture was washed with distilled water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate) ═ 2/1) to give 221mg of the title compound present as a colorless liquid (yield: 48.8%). ms (esi) M/z ═ 443.3(M + H) +

Reference example 49 tert-butyl (Z) - (2- ((4- (3-bromophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

22.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 33 (yield: 62.0%) except that 20.0mg of 4- (3-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 4 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z ═ 328.2(M + H) +

Reference example 50 tert-butyl (E) - (2- ((4- (3-bromophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

27.0mg of the title compound present as a colorless liquid was prepared in the same manner as in reference example 34 (yield: 100.0%) except that 15.0mg of 4- (3-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 4 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one.¹H-NMR(CDCl₃,400MHz)7.81(s,1H)，7.70(s,1H)，7.50-7.53(m,2H)，7.35(t,1H)，6.76(d,1H)，5.20(bs,1H)，4.39(d,2H)，3.90(d,2H)，1.42(s,9H)

Reference example 51 tert-butyl (Z) - (3-fluoro-2- ((4- (4-fluorophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) allyl) carbamate

25.0mg of the title compound present as a colorless liquid was prepared in the same manner as in reference example 33 (yield: 74.2%) except that 16.5mg of 4- (4-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 5 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 267.3(M + H) +

Reference example 52 tert-butyl (E) - (3-fluoro-2- ((4- (4-fluorophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) allyl) carbamate

12.0mg of the title compound present as a colorless liquid was prepared in the same manner as in reference example 34 (yield: 39.0%) except that 15.0mg of 4- (4-fluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 5 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 267.3(M + H) +

Reference example 53 tert-butyl (Z) - (2- ((4- (4- (benzyloxy) phenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

37.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 33 (yield: 98.1%) except that 22.3mg of 4- (4- (benzyloxy) phenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 6 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 355.6(M + H) +

Reference example 54 tert-butyl (E) - (2- ((4- (4- (benzyloxy) phenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

18.0mg of the title compound present as a colorless liquid was prepared in the same manner as in reference example 34 (yield: 47.7%) except that 22.3mg of 4- (4- (benzyloxy) phenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 6 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 355.3(M + H) +

Reference example 55 tert-butyl (Z) - (2- ((4- (3, 4-difluorophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

25.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 33 (yield: 77.4%) except that 16.5mg of 4- (3, 4-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 7 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 285.1(M + H) +

Reference example 56 tert-butyl (E) - (2- ((4- (3, 4-difluorophenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

27.0mg of the title compound present as a colorless liquid was prepared in the same manner as in reference example 34 (yield: 83.6%) except that 16.5mg of 4- (3, 4-difluorophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 7 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 285.2(M + H) +

Reference example 57 tert-butyl (E) - (2- ((4- (3-bromo-2-methylphenyl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

157.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 34 (yield: 45.2%) except that 200.0mg of 4- (3-bromo-2-methylphenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 11 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z ═ 342.3(M + H) +

Reference example 58 tert-butyl (Z) - (2- ((4- (6-bromopyridin-3-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

103.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 33 (yield: 86.5%) except that 67.1mg of 4- (6-bromopyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 17 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 329.2(M + H) +

Reference example 59 tert-butyl (E) - (2- ((4- (6-bromopyridin-3-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

20.0mg of the title compound (yield: 74.2%) as a yellow liquid was prepared in the same manner as in reference example 34 except that 15.0mg of 4- (6-bromopyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 17 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one.¹H-NMR(MeOD,400MHz)8.74(d,1H)，8.36(s,1H)，8.06(dd,1H)，7.76(d,1H)，7.19(d,1H)，4.54(d,2H)，3.74(s,2H)，1.41(s,9H)

Reference example 60 tert-butyl (Z) - (2- ((4- (6-bromo-5-methylpyridin-3-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

14.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 33 (yield: 37.9%) except that 21.3mg of 4- (6-bromo-5-methylpyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 18 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 343.3(M + H) +

Reference example 61 (E) - (tert-butyl 2- ((4- (6-bromo-5-methylpyridin-3-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

14.0mg ofThe title compound was present as a yellow solid (yield: 50.0%) except that 16.0mg of 4- (6-bromo-5-methylpyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 18 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one.¹H-NMR(MeOD,400MHz)8.58(d,1H)，8.35(s,1H)，8.07(d,1H)，7.19(d,1H)，4.55(d,2H)，3.75(s,1H)，2.46(s,3H)，1.41(s,9H)

Reference example 62 (E) - (tert-butyl 2- ((4- (6-bromo-4-methylpyridin-3-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

13.2mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 34 (yield: 47.6%) except that 16.0mg of 4- (6-bromo-4-methylpyridin-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 19 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 343.2(M + H) +

Reference example 63 tert-butyl (Z) - (2- ((4- (5-bromopyridin-2-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

13.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 33 (yield: 34.3%) except that 21.3mg of 4- (5-bromopyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one as prepared in reference example 20 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 329.1(M + H) +

Reference example 64 (E) - (tert-butyl 2- ((4- (5-bromopyridin-2-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

30.0mg of the title compound present as a white solid was prepared in the same manner as in reference example 34 (yield: 90.3%) except that 30.0mg of 4- (5-bromopyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 20 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one.¹H-NMR(MeOD,400MHz)8.65(s,1H)，8.57(d,1H)，8.22(d,1H)，8.15(dd,1H)，7.19(d,1H)，4.53(d,2H)，3.73(d,2H)，1.42(s,9H)

Reference example 65 (Z) - (2- ((4- (5-bromo-3-methylpyridin-2-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamic acid tert-butyl ester

13.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 33 (yield: 35.2%) except that 21.3mg of 4- (5-bromo-3-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 21 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 343.4(M + H) +

Reference example 66 (E) - (tert-butyl 2- ((4- (5-bromo-3-methylpyridin-2-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

27.0mg of the title compound present as a colorless liquid was prepared in the same manner as in reference example 34 (yield: 98.4%) except that 16.0mg of 4- (5-bromo-3-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 21 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. ¹H-NMR(CDCl₃,400MHz)7.98(s,1H)，7.38(s,1H)，6.61(d,1H)，4.40(bs,1H)，3.93-3.97(m,2H)，2.11(s,3H)，1.45(s,9H)

Reference example 67 (Z) - (2- ((4- (5-bromo-4-methylpyridin-2-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamic acid tert-butyl ester

15.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 33 (yield: 43.2%) except that 20.0mg of 4- (5-bromo-4-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 22 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 343.5(M + H) +

Reference example 68 (E) - (tert-butyl 2- ((4- (5-bromo-4-methylpyridin-2-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

26.0mg of the title compound (yield: 95.2%) as a white solid was prepared in the same manner as in reference example 34 except that 16.0mg of 4- (5-bromo-4-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazole prepared in reference example 22 was used-3-one instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one.¹H-NMR(CDCl₃,400MHz)8.42(s,1H)，8.40(s,1H)，8.26(s,1H)，6.76(d,1H)，5.16(bs,1H)，4.38(s,2H)，3.90(bs,2H)，2.47(s,3H)，1.41(s,9H)

Reference example 69 (Z) - (tert-butyl 2- ((4- (5-bromo-3-fluoropyridin-2-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

12.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 33 (yield: 34.8%) except that 20.0mg of 4- (5-bromo-3-fluoropyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 23 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 347.5(M + H) +

Reference example 70 (E) - (tert-butyl 2- ((4- (5-bromo-3-fluoropyridin-2-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

18.0mg of the title compound (yield: 52.2%) present as a yellow solid was prepared in the same manner as in reference example 34 except that 20.0mg of 4- (5-bromo-3-fluoropyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 23 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 347.4(M + H) +

Reference example 71 tert-butyl (E) - (2- ((4- (4-bromopyridin-2-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

17.5mg of the title compound present as a yellow solid (yield: 49.2%) was prepared in the same manner as in reference example 34 except that 20.0mg of 4- (4-bromopyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 25 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one.¹H-NMR(CDCl₃,400MHz)8.60(s,1H)，8.43(s,1H)，8.23(d,1H)，7.41(d,1H)，6.76(d,1H)，5.14(bs,1H)，4.39(s,2H)，3.89(bs,2H)，1.41(s,9H)

Reference example 72 tert-butyl (E) - (2- ((4- (6-bromopyridin-2-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

21.3mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 34 (yield: 59.9%) except that 20.0mg of 4- (6-bromopyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 24 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. ¹H-NMR(CDCl₃,400MHz)8.41(s,1H)，8.32(d,1H)，7.69(t,1H)，7.42(d,1H)，6.75(d,1H)，5.13(bs,1H)，4.38(s,2H)，3.88(bs,1H)，1.41(s,9H)

Reference example 73 tert-butyl (E) - (2- ((4- (2-bromopyridin-4-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

19.1mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 34 (yield: 53.7%) except that 20.0mg of 4- (2-bromopyridin-4-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 26 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 329.5(M + H) +

Reference example 74 (E) - (tert-butyl 2- ((4- (6-bromo-3-methylpyridin-2-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

27.8mg of the title compound present as a yellow solid (yield: 64.1%) was prepared in the same manner as in reference example 34 except that 25.0mg of 4- (6-bromo-3-methylpyridin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 27 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 343.2(M + H) +

Reference example 75 tert-butyl (E) - (2- ((4- (5-bromopyrazin-2-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

20.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 34 (yield: 45.2%) except that 25.0mg of 4- (5-bromopyrazin-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 28 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 330.1(M + H) +

Reference example 76 tert-butyl (Z) - (2- ((4- (5-bromothiazol-2-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

13.0mg of the title compound present as a yellow solid was prepared in the same manner as in reference example 33 (yield: 35.4%) except that 20.9mg of 4- (5-bromothiazol-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 29 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one. MS (ESI) M/z 335.2(M + H) +

Reference example 77 (E) - (tert-butyl 2- ((4- (5-bromothiazol-2-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

14.0mg of the title compound present as a white solid was prepared in the same manner as in reference example 34 (yield: 51.6%) except that 15.0mg of 4- (5-bromothiazol-2-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 29 was used instead of 4- (4-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one.¹H-NMR(MeOD,400MHz)8.56(s,1H)，7.62(s,1H)，7.20(d,1H)，4.55(d,2H)，3.72(d,2H)，1.41(s,9H)

Reference example 78.3- (4- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) -1,2, 4-oxadiazole

Step 1: 4-bromo-N-hydroxybenzamidine (hydroybenzamidamide)

5.0g of 4-bromobenzonitrile, 4.77g of hydroxylamine hydrochloride and 7.28g of sodium carbonate were dissolved in 60.0mL of an 80% ethanol solution, and the resulting solution was refluxed at 80 ℃ for 7 hours. The reaction mixture was cooled to room temperature, then concentrated under reduced pressure, ethyl acetate was added to the concentrated reaction mixture, and the reaction mixture was washed with distilled water. The organic layer thus obtained was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate 3/1) to obtain 5.06g of the title compound as a yellow liquid (yield: 85.4%).

Step 2: 3- (4-bromophenyl) -1,2, 4-oxadiazole

1.0g of 4-bromo-N-hydroxybenzamidine prepared in step 1 was dissolved in 3.0mL of triethyl orthoformate and the resulting solution was stirred at 90 ℃ for 5 hours. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure to give a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate ═ 2/1) to obtain 612.0mg of the title compound present as a yellow solid (yield: 57.9%).

And step 3: 3- (4- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) -1,2, 4-oxadiazole

500.0mg of 3- (4-bromophenyl) -1,2, 4-oxadiazole prepared in step 2, 1.13g of bis (pinacolato) diboron and 650.0mg of potassium acetate were dissolved in 10.0mL of 1, 4-dioxane, and 161.0mg of [1, 1' -bis (diphenylphosphino) ferrocene]Palladium dichloride (PdCl)₂(dppf)) and 61.0mg of 1, 1' -bis (diphenylphosphino) ferrocene](dppf) was added to the obtained solution, and the solution was stirred at 95 ℃ overnight. The reaction mixture was concentrated, and ethyl acetate was added, and the reaction was washed with distilled water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate ═ 1/1) to obtain 397.0mg of the title compound present as a yellow solid (yield: 65.7%). ¹H-NMR(CDCl₃,400MHz)8.77(s,1H)，8,12(d,2H)，7.94(d,2H)，1.37(s,12H)

Reference example 79.3- (3- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) -1,2, 4-oxadiazole

325.0mg of the title compound present as a yellow solid (yield: 53.8%) was prepared in the same manner as in reference example 78 except that 5.0g of 3-bromobenzonitrile was used in place of 4-bromobenzonitrile of step 1.¹H-NMR(CDCl₃,400MHz)8.76(s,1H)，8.56(s,1H)，8.21(d,1H)，7.95(d,1H)，7.51(t,1H)，1.36(s,12H)

Reference example 80.5-cyclopropyl-3- (4- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) -1,2, 4-oxadiazole

Step 1: 4-bromo-N-hydroxybenzenecarboxamides

5.0g of 4-bromobenzonitrile, 4.77g of hydroxylamine hydrochloride and 7.28g of sodium carbonate were dissolved in 60.0mL of an 80% ethanol solution, and the resulting solution was refluxed at 80 ℃ for 7 hours. The obtained reaction mixture was cooled to room temperature, then concentrated under reduced pressure and ethyl acetate was added to the concentrated reaction mixture, and the reaction mixture was washed with distilled water. The organic layer thus obtained was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate 3/1) to obtain 5.06g of the title compound as a yellow liquid (yield: 85.6%).

Step 2: 3- (4-bromophenyl) -5-cyclopropyl-1, 2, 4-oxadiazole

1.0g of 4-bromo-N-hydroxybenzamidine prepared in step 1 was dissolved in 10.0mL of dichloromethane and 1.65mL of triethylamine and 0.71mL of cyclopropylcarbonyl chloride were added to the solution obtained, and the solution was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure and redissolved in toluene, and then concentrated to obtain a residue. The residue was dissolved in 10.0mL of toluene, and the resulting solution was stirred at 110 ℃ for 18 hours. The reaction mixture thus obtained was cooled to room temperature, then concentrated under reduced pressure, dichloromethane was further added and the reaction mixture was washed with distilled water. The organic layer thus obtained was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate) ═ 2/1) to give 818.0mg of the title compound as a yellow liquid (yield: 77.1%). ms (esi) M/z ═ 266.2(M + H) +

And step 3: 5-cyclopropyl-3- (4- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) -1,2, 4-oxadiazole

500.0mg of 3- (4-bromophenyl) -5-cyclopropyl-1, 2, 4-oxadiazole prepared in step 2, 1.13g of bis (pinacolato) diboron, 650.0mg of potassium acetate were dissolved in 10.0mL of 1, 4-dioxane, and 161.0mg of [1, 1' -bis (diphenylphosphino) ferrocene ]Palladium dichloride (PdCl)₂(dppf)) and 61.0mg of 1, 1' -bis (diphenylphosphino) ferrocene](dppf) was added and the resulting solution was stirred at 95 ℃ overnight. The reaction mixtureConcentration was performed, ethyl acetate was added, and then the reaction mixture was washed with distilled water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate 1/1) to obtain 403.0mg of the title compound present as a white solid (yield: 58.1%).¹H-NMR(CDCl₃,400MHz)8.35(d,2H)，7.89(d,2H)，2.25(m,1H)，1.35(m,2H)，1.30(m,2H)，1.26(s,12H)

Reference example 81.5-cyclopropyl-3- (3- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) -1,2, 4-oxadiazole

307.0mg of the title compound present as a yellow solid (yield: 44.3%) was prepared in the same manner as in reference example 80 except that 5.0g of 3-bromobenzonitrile was used in place of 4-bromobenzonitrile of step 1. MS (ESI) M/z 313.2(M + H) +

Reference example 82.5-isopropyl-3- (4- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) -1,2, 4-oxadiazole

486.0mg of the title compound was prepared in the same manner as in reference example 80 (yield: 69.7%) as a white solid except that 0.82mL of isobutyryl chloride was used in place of cyclopropylcarbonyl chloride in step 2.¹H-NMR(CDCl₃,400MHz)8.09(d,2H)，7.91(d,2H)，3.29(m,1H)，1.46(d,6H)，1.26(s,12H)

Reference example 83.5-isopropyl-3- (3- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) -1,2, 4-oxadiazole

325.0mg of the title compound present as a yellow solid (yield: 46.6%) was prepared in the same manner as in reference example 80 except that 5.0g of 3-bromobenzonitrile was used in place of 4-bromobenzonitrile in step 1 and 0.82mL of isobutyryl chloride was used in place of cyclopropylcarbonyl chloride in step 2.¹H-NMR(CDCl₃,400MHz)8.52(s,1H)，8.16(d,1H)，7.92(d,1H)，7.49(t,1H)，3.29(m,1H)，1.46(d,6H)，1.26(s,12H)

Reference example 84 (E) - (tert-butyl 2- ((4- (4 '-bromo- [1,1' -biphenyl ] -3-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

Step 1: 4- (3- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

2.0g of 4- (3-bromophenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in reference example 4, 4.0g of bis (pinacolato) diboron, 3.6g of potassium acetate and 303.0mg of [1,1' -bis (diphenylphosphino) ferrocene]Palladium dichloride (PdCl)₂(dppf)) was dissolved in 20.0mL of 1, 4-dioxane, and the resulting solution was stirred at 95 ℃ overnight. The reaction mixture was concentrated, ethyl acetate was added, and then the reaction mixture was washed with distilled water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate 1/1) to obtain 1.1g of the title compound as a yellow liquid (yield: 46.0%). ¹H-NMR(CDCl₃,400MHz)10.6(s,1H)，7.84(s,1H)，7.81(d,1H)，7.75(dd,2H)，7.51(t,1H)，1.35(s,12H)

Step 2: 4- (4 '-bromo- [1,1' -biphenyl ] -3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one

230.0mg of 4- (3- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one prepared in step 1, 226.0mg of 1-bromo-4-iodobenzene and 20.0mg of [1,1' -bis (diphenylphosphino) ferrocene]Palladium dichloride (PdCl)₂(dppf)) was dissolved in 5.0mL of 1, 4-dioxane, and 4.0mL of 1M aqueous potassium carbonate solution was added thereto, and the resulting solution was stirred at 100 ℃ for 3.5 hours. The reaction mixture was concentrated, ethyl acetate was added, and then the reaction mixture was washed with distilled water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate) ═ 2/1) to give 90.0mg of the title compound (yield: 35.0%) present as a brown solid ms (esi) M/z ═ 318.0(M + H) +

And step 3: (E) - (2- ((4- (4 '-bromo- [1,1' -biphenyl ] -3-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamic acid tert-butyl ester

Will be in step 2Preparation of 90.0mg of 4- (4 '-bromo- [1,1' -biphenyl)]-3-yl) -2, 4-dihydro-3H-1, 2, 4-triazol-3-one and 77.0mg of potassium carbonate were dissolved in 1.0mL of N, N-dimethylformamide, 101.0mg of tert-butyl (E) - (2- (chloromethyl) -3-fluoroallyl) carbamate prepared in reference example 2 was added, and then the obtained solution was stirred at 80 ℃ for 3 hours. The reaction mixture was concentrated, ethyl acetate was added, and then the reaction mixture was washed with distilled water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate 2/1) to obtain 108.0mg of the title compound present as a white solid (yield: 77.0%). ¹H-NMR(CDCl₃,400MHz)7.76(d,2H)，7.55-7.59(m,4H)，7.46-7.50(m,3H)，6.77(d,1H)，5.25(m,4H)，4.41(s,2H)，3.90(bs,2H)，1.41(s,9H)

Reference example 85 (E) - (tert-butyl 2- ((4- (3 '-bromo- [1,1' -biphenyl ] -3-yl) -5-oxo-4, 5-dihydro-1H-1, 2, 4-triazol-1-yl) methyl) -3-fluoroallyl) carbamate

151.0mg of the title compound present as a white solid was prepared in the same manner as in reference example 84 (yield: 73.7%) except that 132.0uL of 1-bromo-3-iodobenzene was used in place of 1-bromo-4-iodobenzene in step 2.¹H-NMR(CDCl₃,400MHz)7.76(s,1H)，7.75(d,2H)，7.51-7.56(m,5H)，7.33(t,1H)，6.77(d,1H)，5.25(bs,1H)，4.41(s,2H)，3.91(bs,2H)，1.42(s,9H)

Reference example 86.5- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) benzo [ d ] thiazol-2-amine

4.0g of 2-amino-5-bromobenzothiazole, 5.7g of bis (pinacolato) diboron and 5.1g of potassium acetate were dissolved in 40.0mL of 1, 4-dioxane, and 426.0mg of [1,1' -bis (diphenylphosphino) ferrocene]Palladium dichloride (PdCl)₂(dppf)) the resulting solution was added and stirred at 95 ℃ overnight. The reaction mixture was concentrated, ethyl acetate was added, and then the reaction mixture was washed with distilled water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexyl)Alkane/ethyl acetate ═ 2/1) to give 1.9g of the title compound present as a yellow solid (yield: 39.4%). ¹H-NMR(CDCl₃,400MHz)7.97(s,1H)，7.58(dd,2H)，5.39(bs,2H)，1.36(s,12H)

Reference example 87N- (5- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) benzo [ d ] thiazol-2-yl) acetamide

Step 1: n- (5-bromobenzo [ d ] thiazol-2-yl) acetamide

2.0g of 2-amino-5-bromobenzothiazole was dissolved in 20.0mL of pyridine, 688uL of chloroacetyl was added, and the resulting solution was stirred at room temperature overnight. The reaction mixture thus obtained was concentrated, then ethyl acetate and a 1N aqueous hydrochloric acid solution were added, and the obtained solution was stirred for about 30 minutes. The solid thus obtained was filtered under reduced pressure while being washed with ethyl acetate to obtain 1.18g of the title compound as a white solid (yield: 49.8%).¹H-NMR(CDCl₃,400MHz)9.71(bs,1H0,7.91(s,1H)，7.68(d,1H)，7.43(d,1H)，2.32(s,3H)

Step 2: n- (5- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) benzo [ d ] thiazol-2-yl) acetamide

500.0mg of N- (5-bromobenzo [ d ] prepared in step 1]Thiazol-2-yl) acetamide, 607.0mg of bis (pinacolato) diboron, 542.0mg of potassium acetate and 45.0mg of [1, 1' -bis (diphenylphosphino) ferrocene]Palladium dichloride (PdCl)₂(dppf)) was dissolved in 5.0mL of 1, 4-dioxane, and the resulting solution was stirred at 95 ℃ overnight. The obtained mixture was concentrated, ethyl acetate was added and the reaction mixture was washed with distilled water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate-1/1) to obtain 492.0mg of the title compound as an orange solid (yield: 84.0%). ¹H-NMR(CDCl₃,400MHz)10.9(bs,1H)，8.22(s,1H)，7.84(d,1H)，7.74(d,1H)，2.32(s,3H)，1.36(s,12H)

Reference example 88.5- (3- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) -1- ((2- (trimethylsilyl) ethoxy) methyl) -1H-tetrazole

Step 1: 5- (3-bromophenyl) -1H-tetrazole

2.00g of 3-bromobenzonitrile was dissolved in 10.0mL of dimethyl sulfoxide, and sodium azide and copper sulfate were added to stir the resulting solution at 120 ℃ for 6 hours. The reaction mixture was cooled to room temperature, and a 1N aqueous hydrochloric acid solution was added, and the obtained reaction mixture was washed with water. The reaction mixture was extracted with ethyl acetate, and the obtained extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 0.97g of the title compound present as a dark yellow liquid (yield: 39.1%).

Step 2: 5- (3-bromophenyl) -1((2- (trimethylsilyl) ethoxy) methyl) -1H-tetrazole

0.97g of 5- (3-bromophenyl) -1H-tetrazole prepared in step 1 was dissolved in 3.0mL of N, N-dimethylformamide, and the reaction mixture was cooled to 0 ℃ followed by addition of 0.21g of sodium hydride and stirring of the reaction mixture for 30 minutes. 1.67g of (2- (chloromethoxy) ethyl) trimethylsilane were added to the reaction mixture, which was stirred at 0 ℃ for 15 minutes and then at room temperature for an additional 2 hours. Distilled water was added to the reaction mixture, which was extracted with dichloromethane and the extract thus obtained was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate: 2/1) to obtain 0.87g of the title compound present as a yellow solid (yield: 57.6%).

And step 3: 5- (3- (4,4,5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenyl) -1- ((2- (trimethylsilyl) ethoxy) methyl) -1H-tetrazole

500.0mg of 5- (3-bromophenyl) -1- ((2- (trimethylsilyl) ethoxy) methyl) -1H-tetrazole prepared in step 2, 710.0mg of bis (pinacolato) diboron and 410.0mg of potassium acetate were dissolved in 10.0mL of 1, 4-dioxane. 103.0mg of [1, 1' -bis (diphenylphosphino) ferrocene]Palladium dichloride (PdCl)₂(dppf)) and 80.0mg of 1, 1' -bis (diphenylphosphino) ferrocene](dppf) was added to the obtained solution, and the solution was stirred at 95 deg.CAnd (4) at night. The reaction mixture thus obtained was concentrated, ethyl acetate was added, and then the reaction mixture was washed with distilled water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate 1/1) to obtain 333.0mg of the title compound (yield: 57.1%) as a yellow solid.¹H-NMR(CDCl₃,400MHz)8.36(s,1H)，8.30(d,1H)，7.62(d,1H)，7.38(t,1H)，5.93(s,2H)，3.75(t,2H)，0.98(t,2H)，0.00(s,9H)