Phenyl-isoxazole derivatives and preparation process thereof

摘要

Disclosed are a phenyl-isoxazol derivative compound, which is useful as a treatment material for virus infection, especially, infection of an influenza virus, or its pharmaceutically acceptable derivative, a preparation method thereof, and an illness treatment pharmaceutical composition including the compound as an active ingredient.

主权项

1. A compound or a pharmaceutically acceptable salt, hydrate, solvate, or an acetate, formate or benzoate ester thereof, selected from among: (4-(2-fluorophenyl)-piperazine-1-yl)(5-methyl-3-(2-(trifluoromethyl)-phenyl)isoxazol-4-yl)methanone, (4-(3,4-dichlorophenyl)piperazine-1-yl)(5-methyl-3-(2-(trifluoromethyl)-phenyl)isoxazol-4-yl)methanone, (4-(3-methoxyphenyl)piperazine-1-yl)(5-methyl-3-(2-(trifluoromethyl)-phenyl)isoxazol-4-yl)methanone, (4-(2-methoxyphenyl)-piperazine-1-yl)(5-methyl-3-(2-trifluoromethyl)phenyl)isoxazol-4-yl)methanone, (5-methyl-3-(2-(trifluoromethyl)-phenyl)isoxazol-4-yl)(4-(3-(trifluoromethyl)phenyl)piperazine-1-yl)-methanone, (4-(4-hydroxyphenyl)piperazine-1-yl)(5-methyl-3-(2-(trifluoromethyl)phenyl)-isoxazol-4-yl)methanone, (4-(2-hydroxyphenyl)piperazine-1-yl)(5-methyl-3-(2-(trifluoro-methyl)-phenyl)isoxazol-4-yl)methanone, (4-(4-fluorophenyl)piperazine-1-yl)(5-methyl-3-(2-trifluoromethyl)phenyl)isoxazol-4-yl)methanone, (3-(2-chlorophenyl)-5-methylisoxazol-4-yl)(4-(3-methoxyphenyl)piperazine-1-yl)methanone, (3-(3-fluorophenyl)-5-methylisoxazol-4-yl)(4-(2-fluorophenyl)piperazine-1-yl)methanone, (4-(3,4-dichlorophenyl)piperazine-1-yl)(3-(3-fluorophenyl)-5-methylisoxazol-4-yl)methanone, (3-(3-fluorophenyl)-5-methylisoxazol-4-yl)(4-(3-methoxyphenyl)piperazine-1-yl)methanone, (3-(3-fluorophenyl)-5-methylisoxazol-4-yl)(4-(2-methoxyphenyl)piperazine-1-yl)methanone, (3-(3-fluorophenyl)-5-methylisoxazol-4-yl)(4-(3-(trifluoromethyl)phenyl)piperazine-1-yl)methanone, (3-(3-fluorophenyl)-5-methyl-isoxazol-4-yl)(4-(4-hydroxyphenyl)piperazine-1-yl)methanone, (3-(3-fluorophenyl)-5-methylisoxazol-4-yl)(4-(2-hydroxyphenyl)piperazine-1-yl)methanone, (3-(3-fluorophenyl)-5-methylisoxazol-4-yl)(4-(4-fluorophenyl)piperazine-1-yl)methanone, (3-(2-fluorophenyl)-5-methylisoxazol-4-yl)(4-(2-fluorophenyl)piperazine-1-yl)methanone, (4-(3,4-dichlorophenyl)-piperazine-1-yl)(3-(2-fluorophenyl)-5-methylisoxazol-4-yl)methanone, (3-(2-fluorophenyl)-5-methylisoxazol-4-yl)(4-(3-methoxyphenyl)piperazine-1-yl)methanone, (3-(2-fluorophenyl)-5-methylisoxazol-4-yl)(4-(2-methoxyphenyl)piperazine-1-yl)methanone, (3-(2-fluorophenyl)-5-methylisoxazol-4-yl)(4-(3-(trifluoromethyl)phenyl)piperazine-1-yl)methanone, (3-(2-fluoro-phenyl)-5-methylisoxazol-4-yl)(4-(4-hydroxyphenyl)piperazine-1-yl)methanone, (3-(2-fluoro-phenyl)-5-methylisoxazol-4-yl)(4-(2-hydroxyphenyl)piperazine-1-yl)methanone, (3-(2-fluoro-phenyl)-5-methylisoxazol-4-yl)(4-(4-fluorophenyl)piperazine-1-yl)methanone, (4-(2-fluoro-phenyl)piperazine-1-yl)(5-methyl-3-(4-(trifluoromethoxy)phenyl)isoxazol-4-yl)-methanone, (4-(3,4-dichlorophenyl)piperazine-1-yl)(5-methyl-3-(4-(trifluoromethoxy)-phenyl)isoxazol-4-yl)methanone, (4-(3-methoxyphenyl)piperazine-1-yl)(5-methyl-3-(4-(trifluoromethoxy)-phenyl)isoxazol-4-yl)methanone, (4-(2-methoxyphenyl)piperazine-1-yl)(5-methyl-3-(4-(trifluoromethoxy)phenyl)isoxazol-4-yl)methanone, (5-methyl-3-(4-(trifluoromethoxy)-phenyl)isoxazol-4-yl)(4-(3-(trifluoromethyl)phenyl)piperazine-1-yl)methanone, (4-(4-hydroxyphenyl)piperazine-1-yl)(5-methyl-3-(4-(trifluoromethoxy)phenyl)isoxazol-4-yl)-methanone, (4-(2-hydroxyphenyl)piperazine-1-yl)(5-methyl-3-(4-(trifluoromethoxy)-phenyl)isoxazol-4-yl)methanone, (4-(4-fluorophenyl)piperazine-1-yl)(5-methyl-3-(4-trifluoromethoxy)phenyl)isoxazol-4-yl)methanone, (4-(2-fluorophenyl)piperazine-1-yl)(5-methyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methanone, (4-(3,4-dichlorophenyl)-piperazine-1-yl)(5-methyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methanone, (4-(3-methoxyphenyl)piperazine-1-yl)(5-methyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)-methanone, (4-(2-methoxyphenyl)piperazine-1-yl)(5-methyl-3-(2-trifluoromethoxy)-phenyl)isoxazol-4-yl)methanone, (5-methyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(3-(trifluoromethyl)phenyl)piperazine-1-yl)methanone, (4-(4-hydroxyphenyl)piperazine-1-yl)(5-methyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methanone, (4-(2-hydroxyphenyl)-piperazine-1-yl)(5-methyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methanone, (4-(4-fluorophenyl)piperazine-1-yl)(5-methyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)-methanone, (4-(2-fluorophenyl)piperazine-1-yl)(5-methyl-3-(3-(trifluoromethyl)phenyl)-isoxazol-4-yl)methanone, (4-(3,4-dichlorophenyl)piperazine-1-yl)(5-methyl-3-(3-(trifluoro-methyl)phenyl)isoxazol-4-yl)methanone, (4-(3-methoxyphenyl)piperazine-1-yl)(5-methyl-3-(3-(trifluoromethyl)phenyl)isoxazol-4-yl)methanone, (4-(2-methoxyphenyl)piperazine-1-yl)-(5-methyl-3-(3-(trifluoromethyl)phenyl)isoxazol-4-yl)methanone, (5-methyl-3-(3-trifluoro-methyl)phenyl)isoxazol-4-yl)(4-(3-(trifluoromethyl)phenyl)piperazine-1-yl)-methanone, (4-(4-hydroxyphenyl)piperazine-1-yl)(5-methyl-3-(3-(trifluoromethyl)phenyl)-isoxazol-4-yl)methanone, (4-(2-hydroxyphenyl)piperazine-1-yl)(5-methyl-3-(3-(trifluoromethyl)-phenyl)isoxazol-4-yl)methanone, (4-(4-fluorophenyl)piperazine-1-yl)(5-methyl-3-(3-(trifluoromethyl)phenyl)isoxazol-4-yl)methanone, (4-(2-fluorophenyl)piperazine-1-yl)(5-methyl-3-(3-(trifluoromethoxy)phenyl)isoxazol-4-yl)methanone, (4-(3,4-dichlorophenyl)-piperazine-1-yl)(5-methyl-3-(3-(trifluoromethoxy)phenyl)isoxazol-4-yl)methanone, (4-(3-methoxyphenyl)piperazine-1-yl)(5-methyl-3-(3-(trifluoromethoxy)phenyl)isoxazol-4-yl)-methanone, (4-(2-methoxyphenyl)piperazine-1-yl)(5-methyl-3-(3-(trifluoromethoxy)-phenyl)isoxazol-4-yl)methanone, (5-methyl-3-(3-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(3-trifluoromethyl)phenyl)piperazine-1-yl)methanone, (4-(4-hydroxyphenyl)piperazine-1-yl)-(5-methyl-3-(3-(trifluoromethoxy)phenyl)isoxazol-4-yl)methanone, (4-(2-hydroxyphenyl)-piperazine-1-yl)(5-methyl-3-(3-(trifluoromethoxy)phenyl)isoxazol-4-yl)methanone, (4-(4-fluorophenyl)piperazine-1-yl)(5-methyl-3-(3-(trifluoromethoxy)phenyl)isoxazol-4-yl)-methanone, (5-amino-3-(2-chlorophenyl)isoxazol-4-yl)(4-(2-fluorophenyl)piperazine-1-yl)-methanone, (5-amino-3-(2-chlorophenyl)isoxazol-4-yl)(4-(3,4-dichlorophenyl)piperazine-1-yl)methanone, (5-amino-3-(2-chlorophenyl)isoxazol-4-yl)(4-(3-methoxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(2-chlorophenyl)isoxazol-4-yl)(4-(2-methoxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(2-chlorophenyl)isoxazol-4-yl)(4-(3-(trifluoromethyl)phenyl)-piperazine-1-yl)methanone, (5-amino-3-(2-chlorophenyl)isoxazol-4-yl)(4-(4-hydroxyphenyl)-piperazine-1-yl)methanone, (5-amino-3-(2-chlorophenyl)isoxazol-4-yl)(4-(2-hydroxyphenyl)-piperazine-1-yl)methanone, (5-amino-3-(2-chlorophenyl)isoxazol-4-yl)(4-(4-fluorophenyl)-piperazine-1-yl)methanone, (5-amino-3-(3-fluorophenyl)isoxazol-4-yl)(4-(2-fluorophenyl)-piperazine-1-yl)methanone, (5-amino-3-(3-fluorophenyl)isoxazol-4-yl)(4-(3,4-dichloro-phenyl)piperazine-1-yl)methanone, (5-amino-3-(3-fluorophenyl)isoxazol-4-yl)(4-(3-methoxy-phenyl)piperazine-1-yl)methanone, (5-amino-3-(3-fluorophenyl)isoxazol-4-yl)(4-(2-methoxy-phenyl)piperazine-1-yl)methanone, (5-amino-3-(3-fluorophenyl)isoxazol-4-yl)(4-(3-(trifluoro-methyl)phenyl)piperazine-1-yl)methanone, (5-amino-3-(3-fluorophenyl)isoxazol-4-yl)(4-(4-hydroxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(3-fluorophenyl)isoxazol-4-yl)(4-(2-hydroxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(3-fluorophenyl)isoxazol-4-yl)(4-(4-fluorophenyl)piperazine-1-yl)methanone, (5-amino-3-(2-fluorophenyl)isoxazol-4-yl)(4-(2-fluorophenyl)piperazine-1-yl)methanone, (5-amino-3-(2-fluorophenyl)isoxazol-4-yl)(4-(3,4-dichlorophenyl)piperazine-1-yl)methanone, (5-amino-3-(2-fluorophenyl)isoxazol-4-yl)(4-(3-methoxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(2-fluorophenyl)isoxazol-4-yl)(4-(2-methoxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(2-fluorophenyl)isoxazol-4-yl)(4-(3-(trifluoromethyl)phenyl)piperazine-1-yl)methanone, (5-amino-3-(2-fluorophenyl)-isoxazol-4-yl)(4-(4-hydroxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(2-fluorophenyl)-isoxazol-4-yl)(4-(2-hydroxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(2-fluorophenyl)-isoxazol-4-yl)(4-(4-fluorophenyl)piperazine-1-yl)methanone, (5-amino-3-(2-(trifluoro-methoxy)phenyl)-isoxazol-4-yl)(4-(2-fluorophenyl)piperazine-1-yl)methanone, (5-amino-3-(2-(trifluoro-methoxy)phenyl)isoxazol-4-yl)(3,4-dichlorophenyl)piperazine-1-yl)methanone, (5-amino-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(3-methoxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(2-methoxyphenyl)-piperazine-1-yl)methanone, (5-amino-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(3-(trifluoromethyl)phenyl)piperazine-1-yl)methanone, (5-amino-3-(2-(trifluoromethoxy)-phenyl)isoxazol-4-yl)(4-(4-hydroxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(2-hydroxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(4-fluorophenyl)piperazine-1-yl)-methanone, (5-amino-3-(2-(trifluoromethyl)phenyl)isoxazol-4-yl)(4-(2-fluorophenyl)-piperazine-1-yl)methanone, (5-amino-3-(2-(trifluoromethyl)phenyl)isoxazol-4-yl)(4-(3,4-dichlorophenyl)piperazine-1-yl)methanone, (5-amino-3-(2-trifluoromethyl)phenyl)isoxazol-4-yl)(4-(3-methoxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(2-(trifluoromethyl)-phenyl)isoxazol-4-yl)(4-(2-methoxyphenyl)piperazine-1-yl)methanone, 5-amino-3-(2-(trifluoromethyl)phenyl)isoxazol-4-yl)(4-(3-(trifluoromethyl)phenyl)piperazine-1-yl)-methanone, (5-amino-3-(2-(trifluoromethyl)phenyl)isoxazol-4-yl)(4-(4-hydroxyphenyl)-piperazine-1-yl)methanone, (5-amino-3-(2-(trifluoromethyl)phenyl)isoxazol-4-yl)(4-(2-hydroxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(2-(trifluoromethyl)phenyl)isoxazol-4-yl)(4-(4-fluorophenyl)piperazine-1-yl)methanone, (5-amino-3-(4-(trifluoromethoxy)-phenyl)isoxazol-4-yl)(4-(2-fluorophenyl)piperazine-1-yl)methanone, (5-amino-3-(4-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(3,4-dichlorophenyl)piperazine-1-yl)methanone, (5-amino-3-(4-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(3-methoxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(4-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(2-methoxyphenyl)-piperazine-1-yl)methanone, (5-amino-3-(4-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(3-(trifluoromethylphenyl)piperazine-1-yl)methanone, (5-amino-3-(4-(trifluoromethoxy)-phenyl)isoxazol-4-yl)(4-(4-hydroxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(4-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(2-hydroxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(4-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(4-fluorophenyl)piperazine-1-yl)-methanone, (5-amino-3-(3-(trifluoromethyl)phenyl)isoxazol-4-yl)(4-(2-fluorophenyl)-piperazine-1-yl)methanone, (5-amino-3-(3-(trifluoromethyl)phenyl)isoxazol-4-yl)(4-(3,4-dichlorophenyl)piperazine-1-yl)methanone, (5-amino-3-(3-(trifluoromethyl)phenyl)isoxazol-4-yl)(4-(3-methoxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(3-(trifluoromethyl)-phenyl)isoxazol-4-yl)(4-(2-methoxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(3-(trifluoromethyl)phenyl)isoxazol-4-yl)(4-(3-(trifluoromethyl)phenyl)piperazine-1-yl)-methanone, (5-amino-3-(3-(trifluoromethyl)phenyl)isoxazol-4-yl)(4-(4-hydroxyphenyl)-piperazine-1-yl)methanone, (5-amino-3-(3-(trifluoromethyl)phenyl)isoxazol-4-yl)(4-(2-hydroxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(3-(trifluoromethyl)phenyl)isoxazol-4-yl)(4-(4-fluorophenyl)piperazine-1-yl)methanone, (5-amino-3-(3-(trifluoromethoxy)-phenyl)isoxazol-4-yl)(4-(2-fluorophenyl)piperazine-1-yl)methanone, (5-amino-3-(3-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(3,4-dichlorophenyl)piperazine-1-yl)methanone, (5-amino-3-(3-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(3-methoxyphenyl)piperazine-1-yl)-methanone, (5-amino-3-(3-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(2-methoxyphenyl)-piperazine-1-yl)methanone, (5-amino-3-(3-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(3-trifluoromethyl)phenyl)piperazine-1-yl)methanone, (5-amino-3-(3-(trifluoromethoxy)phenyl)-isoxazol-4-yl)(4-(4-hydroxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(3-(trifluoro-methoxy)phenyl)isoxazol-4-yl)(4-(2-hydroxyphenyl)piperazine-1-yl)methanone, (5-amino-3-(3-(trifluoromethoxy)phenyl)isoxazol-4-yl)(4-(4-fluorophenyl)piperazine-1-yl)methanone, ethyl-1-(5-amino-3-(2-chlorophenyl)isoxazol-4-carbonyl)piperidine-4-carboxylate, methyl-1-(5-amino-3-(2-fluorophenyl)isoxazol-4-carbonyl)piperidine-4-carboxylate, ethyl-1-(5-amino-3-(2-trifluoromethoxy)phenyl)isoxazol-4-carbonyl)piperidine-4-carboxylate, or ethyl-1-(5-amino-3-(2-(trifluoromethyl)phenyl)isoxazol-4-carbonyl)piperidine-4-carboxylate.