KR950026875A - Triazole derivatives and preparation method thereof - Google Patents

Abstract

The present invention relates to a novel triazole derivative represented by the following general formula (I), and more particularly to a triazole derivative having an antifungal activity or a pharmaceutically acceptable salt thereof and a method for preparing the same.

Wherein X and Y represent hydrogen or halogen, Z is nitrogen or carbon, and R may form a ring with lower alkoxy, lower alkoxymethyl, lower alkylthio, lower alkylthiomethyl, amino, or nitrogen (N) Good lower alkylamino or lower alkyl, styryl, phenyl, or heteroaryl, with or without substituents. Lower alkyl herein means straight or branched C ₁ -C ₄ alkyl.

Description

Triazole derivatives and preparation method thereof

Since this is an open matter, no full text was included.

Claims (5)

Triazole derivative represented by the following general formula (I) or a pharmaceutically acceptable salt thereof. Wherein X and Y represent hydrogen or halogen, Z is nitrogen or carbon, and R may form a ring with lower alkoxy, lower alkoxymethyl, lower alkylthio, lower alkylthiomethyl, amino, or nitrogen (N) Good lower alkylamino or lower alkyl, styryl, phenyl, or heteroaryl, with or without substituents. Lower alkyl herein means straight or branched C ₁ -C ₄ alkyl. The compound of claim 1, wherein (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- (3-t-butyl-1,2,4-riadiazol-5-yl) thio -1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- (3-methyl Thio-1,2,4-thiadiazol-5-yl) thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* ) -2 -(2,4-difluorophenyl) -3- (3-cyclopropyl-1,2,4-thiadiazol-5-yl) thio-1- (1H-1,2,4-triazole-1 -Yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- (3-isopropyl-1,2,4-thiadiazol-5-yl) Thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- (3- Methoxy-1,2,4-thiadiazol-5-yl) thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )- 2- (2,4-difluorophenyl-3- (3-chloromethyl-1,2,4-thiadiazol-5-yl) thio-1- (1H-1,2,4-triazole-1 -Yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- (3-dimethylamino-1,2,4-thiadiazol-5-yl) Thio-1- (1H-1,2,4-tree -1-yl) ^{-2-butanol, (2R *, 3R *)} -2- (2,4- difluorophenyl 3- [3- (pyrrolidin Dunn-yl) -1,2,4 -Thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-di Fluorophenyl) -3- (3-amino-1, 2,4-thiadiazol-5-yl) thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- (3-ethoxy-1,2,4-thiadiazol-5-yl) thio-1- (1H-1 , 2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- (3-methacryl-1,2,4 -Thiadiazol-5-yl) thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-di Fluorophenyl) -3- (3-methylthiomethyl-1,2,4-thiadiazol-5-yl) thio-1- (1H-1,2,4-triazol-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- (3-ethyl-1,2,4-thiadiazol-5-yl) thio-1- (1H-1, 2,4-triazol-1-yl) -2-ethanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- (3- (1-chloroethyl) -1, 2,4-thiadiazol-5-yl) thio-1- (1H-1,2,4-tri ^{1-yl-2-ethanol, (2R *, 3R *)} -2- (2,4- difluorophenyl) -3- (3-methoxymethyl-1,2,4-thiadiazol-5 -Yl) thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (4-methoxystyryl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol , (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (3,5-dimethylpyrazol-1-yl) -1,2,4-thiadiazole- 5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3 -(3-crotyl-1,2,4-thiadiazol-5-yl) thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (4-fluorostyryl) -1,2,4-thiadiazol5-yl] thio-1- (1H-1 , 2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (4- (2,2, 3,3, -tetrafluoropropoxy) styryl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2 ^{-butanol, (2R *, 3R *)} -2- (2,4- difluoro Yl) -3- (3-fluoromethyl-1,2,4-thiadiazol-5-yl) thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- (3-phenoxymethyl-1,2,4-thiadiazol-5-yl) thio-1- (1H- 1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (2-fluorophenyl)- 1,2,4-diadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* ) -2- ( 2,4-difluorophenyl) -3- [3- (2,6-difluorophenyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4 -Triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (4-fluorophenyl) -1,2,4 -Thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-di Fluorophenyl) -3- [3- (2-pyridyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) 2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (2-chlorophenyl) -1,2,4-thiadiazol-5-yl ] Thio-1- (1H-1,2,4-triazol-1-yl) -2- ^{Butanol, (2R *, 3R *)} -2- (2,4- difluorophenyl) -3- (3-phenyl-1,2,4-thiadiazole-5-yl) thio -1- (1H- 1,2,4-triazol-1-yl) -2butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (3-pyridyl) -1 , 2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* ) -2- (2 , 4-difluorophenyl) -3- [3- (4-pyridal) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazole- 1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [4- (1- (N-hydroxyimino) ethyl) phenyl) -1 , 2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -20butanol, (2R ^* , 3R ^* )-2- (4- Chlorophenyl) -3- [3- (3,5-difluorophenyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazole-1 -Yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-dichlorophenyl) -3- [3- (4-pyridyl) -1,2,4-thiadiazole-5 -Yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (4-chlorophenyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H -1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (3-fluorophenyl ) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-yl) -2-methanol, (2R ^* , 3R ^* ) -2- ( 2,4-difluorophenyl) -3- (3,4-difluorophenyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazole -1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (2,6-dichlorophenyl) -1,2,4- Thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluoro Phenyl) -3- [3- (3-trifluoromethylphenyl) -1,2,4-thiadiazol-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2 Butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl-3- [3- (3-colophenyl) -1,2,4-thiadiazol-5-yl] thio- 1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (4 -1H-imidazol-1-yl) phenyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2- ^{butanol, (2R *, 3R *)} -2- (2,4- di-flu Lephenyl) -3- [3- (2-pyrazinyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) 2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (2-chloro-6-fluorophenyl) -1,2,4-thiadiazole -Yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (4-bromophenyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (4- (1H-1,2,4-triazol-1-yl) phenyl) -1,2 , 4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* ) -2- (2,4 -Difluorophenyl) -3- [3- (4-azidophenyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazole-1 -Yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (3,5-bistrifluoromethylphenyl) -1,2,4- Thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- (3-styryl-1,2,4-thiadiazol-5-yl ] Thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* ) -2- (2,4-difluorophenyl) -3- [3 -(4- (morpholin-1-yl) phenyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl)- 2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (3-trifluoromethyl-4-acetylamino) phenyl-1,2,4-thia Diazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl ) -3- [3- (4- (1,3,4-oxadiazol-2-yl) phenyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1 , 2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (4- (1,3- Dioxolan-2-yl) phenyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, ( 2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (4-cyanophenyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (thiophene- 2-yl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-tria Zol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (4-nitrophenyl) -1,2,4-ria Diazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl ) -3- [3- (pyridinin-5-yl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) 2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (4-biphenyl) -1,2,4-thiadiazol-5-yl -Thio- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- ( 4- (2,2,3,3-tetrafluoropropoxy) phenyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazole- 1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (4- (4-pyridone-1-yl) phenyl)- 1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* ) -2- ( 2,4-difluorophenyl) -3- [3- (4-methylthyrimidin-2-yl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1, 2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluoro ) -3- [3- (pyridine-N-oxo-4-yl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazole-1 -Yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (4-methylthiophenyl) -1,2,4-thiadiazole -5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl)- 3- [3- (4-methanesulfonylphenyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-5-yl) -2 -Butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (3-nitrophenyl) -1,2,4-thiadiazol-5-yl] thio -1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- ( 2,5-difluorophenyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (4-dimethylaminophenyl) -1,2,4-thiadiazol-5-yl] thio-1- ( 1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (1H-1, 2,4-triazol-1-yl) methyl-1,2,4-thiadiazol-5-yl] O -1- (1H-1,2,4- triazol-1-yl) ^{-2-butanol, (2R *, 3R *)} -2- (2,4- difluorophenyl) -3- [4- (4-methoxysphenyl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (3-pyrrol-1-yl) phenyl-1,2,4-thiadiazol-5-yl] thio-1 -(1H-1,2,4-triazol] -yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3- (pyridazine- 3-yl) -1,2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* ) -2- (2,4-difluorophenyl) -3- [3- (1-chloro-2-methoxy ethyl) -1,2,4-thiadiazol-5-yl] thio-1- ( 1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [3-methoxymethyl-1 , 2,4-thiadiazol-5-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R, 3R) -2- (2,4 -Difluorophenyl) -3- (3-styryl-1,2,4-thiadiazol-5-yl) thio-1- (1H-1,2,4-triazol-1-yl) -2 -Butanol, (2R, 3R) -2- (2,4-difluorophenyl) -3- (3-methoxy-1,2, 4-thiadiazol-5-yl) thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (4-chlorophenyl ) -3- (3-methoxy-1,2,4-thiadiazol-5-yl) thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, ( 2R ^* , 3R ^* )-2- (4-fluorophenyl) -3- (3-methoxy-1,2,4-thiadiazol-5-yl) thio-1- (1H-1,2,4 -Triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (4-fluorophenyl) -3- (3-styryl-1,2,4-thiadiazole-5- Yl) thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [ 4- (2,6-difluorophenyl) -thiazol-2-yl] thio-1- (1H-1,2,4-triazol] -yl) -2-butanol, (2R ^* , 3R ^* ) -2- (2,4-difluorophenyl) -3- [4- (2,4-dichlorophenyl) -thiazol-2-yl] thio-1- (1H-1,2,4-triazole- 1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [4- (4-chlorophenyl) -thiazol-2-yl) thio- 1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- (4-ethyl- Thiazol-2-yl) thio-1- (1H-1,2,4-tria -1-yl) -2-butanol ^{-, (2R *, 3R *} ) -2- (2,4- difluorophenyl) -3- [4- (1-hydroxy-1-methylethyl) -2-thiazol- -Yl] thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- (4-styrylthiazol-2-yl) thio-1- (1H-1,2,4-triazol-1-yl) -2-butanol, (2R ^* , 3R ^* )-2- (2, 4-difluorophenyl) -3- [4- (4-methoxystyryl) thiazol-2-yl] thio-1- (1H-1,2,4-triazol-1-yl) -2- Butanol, or (2R ^* , 3R ^* )-2- (2,4-difluorophenyl) -3- [4- (2,3-dichlorostyryl) thiazol-2-yl] thio-1- (1H Triazole derivatives or pharmaceutically acceptable salts thereof, characterized in that selected from the group consisting of -1,2,4-triazol-1-yl) -2-butanol. Triazole derivative of formula (I) characterized by reacting a compound of formula (II) with a compound of formula (III) or an alkali metal salt of formula (III) in the presence of lithium percholate (LiClO ₄ ) Manufacturing method. Wherein X and Y represent hydrogen or halogen, Z is nitrogen or carbon, and R may form a ring with lower alkoxy, lower alkoxymethyl, lower alkylthio, lower alkylthiomethyl, amino, or nitrogen (N) Good lower alkylamino or lower alkyl, styryl, phenyl, or heteroaryl, with or without substituents. Lower alkyl herein means straight or branched C ₁ -C ₄ alkyl. A method for producing a triazole derivative of formula (I), wherein the compound of formula (IV) and the compound of formula (V) are reacted in the presence of a base. Wherein X and Y represent hydrogen or halogen, Z is nitrogen or carbon, L is halogen, and R is lower alkoxy, lower alkoxymethyl, lower alkylthio, lower alkylthiomethyl, amino, or nitrogen (N) Or lower alkylamino which may form a ring, or lower alkyl, styryl, phenyl, or heteroaryl, with or without substituents. Lower alkyl herein means straight or branched C ₁ -C ₄ alkyl. An antifungal composition comprising the triazole derivative represented by the following general formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. Wherein X and Y represent hydrogen or halogen, Z is nitrogen or carbon, and R may form a ring with lower alkoxy, lower alkoxymethyl, lower alkylthio, lower alkylthiomethyl, amino, or nitrogen (N) Good lower alkylamino or lower alkyl, styryl, phenyl, or heteroaryl, with or without substituents. Lower alkyl herein means straight or branched C ₁ -C ₄ alkyl. ※ Note: The disclosure is based on the initial application.