Patent ID: 8841302
Filing Date: 2014-09-23
Classification: A61K,A61P

Abstract:
1. A combination product for treating or ameliorating HCV (hepatitis C virus) infection or disorders or symptoms associated therewith in a subject in need thereof comprising, a HCV inhibitor compound of Formula (I) or a free acid, free base, salt, isotopologue, racemate, enantiomer, diastereomer or stereoisomer form thereof: wherein X is hydrogen, halogen, cyano, nitro, carboxyl, C Ar is pyridinyl, pyrimidinyl or pyridazinyl; Z is C R R R R R R and a HCV protease inhibitor or a free acid, free base, salt, isotopologue, racemate, enantiomer, diastereomer or stereoisomer form thereof selected from: tert-butyl 1-((2S)-1-(1-amino-1,2-dioxohexan-3-ylamino)-4-methyl-1-oxopentan-2-ylamino)-3,3-dimethyl-1-oxobutan-2-ylcarbamate, (S)-2-acetamido-N-((S)-1-((S)-5-guanidino-1-oxopentan-2-ylamino)-4-methyl-1-oxopentan-2-yl)-4-methylpentanamide, tert-butyl (1S)-2-((2S)-2-(4-amino-1-cyclopropyl-3,4-dioxobutan-2-ylcarbamoyl)indolin-1-yl)-1-cyclohexyl-2-oxoethylcarbamate, (3S,18S)-N-[(3S)-1-amino-1,2-dioxohexan-3-yl]-18-cyclohexyl-16,19-dioxo-3,4-dihydro-1H-7,2-(eboxyheptanoiminoethano)isoguinoline-3-carboxamide, tert-butyl (3S)-1-((2S)-1-(4-amino-1-cyclopropyl-3,4-dioxobutan-2-ylamino)-4-methyl-1-oxopentan-2-yl)-2-oxoazonan-3-ylcarbamate, (2S)-isopropyl 2-(3-((3S)-1-((2S)-1-(4-amino-1-cyclobutyl-3,4-dioxobutan-2-ylamino)-4-methyl-1-oxopentan-2-yl)-2-oxoazonan-3-yl)ureido)-3,3-dimethylbutanoate, tert-butyl (1S)-2-((1S,3aR,6aS)-1-(4-amino-1-cyclopropyl-3,4-dioxobutan-2-ylcarbamoyl)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-cyclohexyl-2-oxoethylcarbamate, tert-butyl (S)-2-((1R,2S,5S)-2-((S)-4-amino-1-cyclopropyl-3,4-dioxobutan-2-ylcarbamoyl)-6,6,7,7-tetramethyl-3-azabicyclo[3.2.0]heptan-3-yl)-1-cyclohexyl-2-oxoethylcarbamate, (2S)-N-(4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)-3-((S)-2-(3-cyclohexylureido)-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-N-(4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)-3-((S)-2-(3-tert-butylureido)-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-N-((S)-4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)-3-((S)-2-(3-tert-butylureido)-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-N-((R)-4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)-3-((S)-2-(3-tert-butylureido)-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-3-((S)-2-(3-(1-(tert-butylsulfonylmethyl)cyclohexyl)ureido)-3,3-dimethylbutanoyl)-N-((S)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-3-((S)-2-(3-(1-(tert-butylsulfonylmethyl)cyclohexyl)ureido)-3,3-dimethylbutanoyl)-N-((S)-1-(cyclopropylamino)-1,2-dioxoheptan-3-yl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-3-((S)-2-(3-(1-(tert-butylsulfonylmethyl)cyclohexyl)ureido)-3,3-dimethylbutanoyl)-N-((R)-1-(cyclopropylamino)-1,2-dioxoheptan-3-yl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-3-((S)-2-(3-(1-(tert-butylsulfonylmethyl)cyclohexyl)ureido)-3,3-dimethylbutanoyl)-N-((S)-5-cyclopropyl-1-(cyclopropylamino)-1,2-dioxopentan-3-yl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-3-((S)-2-(3-(1-(tert-butylsulfonylmethyl)cyclohexyl)ureido)-3,3-dimethylbutanoyl)-N-((R)-5-cyclopropyl-1-(cyclopropylamino)-1,2-dioxopentan-3-yl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-N-((S)-1-(allylamino)-5-cyclopropyl-1,2-dioxopentan-3-yl)-3-((S)-2-(3-(1-(tert-butylsulfonylmethyl)cyclohexyl)ureido)-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-N-((S)-4-(allylamino)-1-cyclopropyl-3,4-dioxobutan-2-yl)-3-((S)-2-(3-(1-(tert-butylsulfonylmethyl)cyclohexyl)ureido)-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-N-((S)-4-(allylamino)-1-cyclopropyl-3,4-dioxobutan-2-yl)-3-((S)-2-(3-(1-(tert-butylsulfonylmethyl)cyclohexyl)ureido)-2-(1-methylcyclohexyl)acetyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-3-((S)-2-(3-(1-(tert-butylsulfonylmethyl)cyclohexyl)ureido)-2-(1-methylcyclohexyl)acetyl)-N-((S)-5-cyclopropyl-1-(cyclopropylamino)-1,2-dioxopentan-3-yl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-3-((S)-2-(3-(1-(tert-butylsulfonylmethyl)cyclohexyl)ureido)-2-(1-methylcyclohexyl)acetyl)-N-((S)-1-(cyclopropylamino)-1,2-dioxoheptan-3-yl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-N-((S)-1-(cyclopropylamino)-1,2-dioxoheptan-3-yl)-3-((S)-3,3-dimethyl-2-(3-(1-((4-methyltetrahydro-2H-pyran-4-ylsulfonyl)methyl)cyclohexyl)ureido)butanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-3-[N-({1-[(2S)-3,3-dioxido-1,3-oxathiolan-2-yl]cyclohexyl}carbamoyl)-3-methyl-L-valyl]-N-[(3S)-1,2-dioxo-1-(prop-2-en-1-ylamino)heptan-3-yl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)- N-[(3S)-1-(cyclopropylamino)-1,2-dioxoheptan-3-yl]-3-[N-({1-[(2R)-1,1-dioxidotetrahydrothiophen-2-yl]cyclohexyl}carbamoyl)-3-methyl-L-valyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-3-[N-({1-[(2R)-1,1-dioxidotetrahydrothiophen-2-yl]cyclohexyl}carbamoyl)-3-methyl-L-valyl]-N-[(3S)-1,2-dioxo-1-(prop-2-en-1-ylamino)heptan-3-yl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, (1R,2S,5S)-N-[(2S)-1-cyclopropyl-3,4-dioxo-4-(prop-2-en-1-ylamino)butan-2-yl]-3-[N-({1-[(2S)-1,1-dioxidotetrahydro-2H-thiopyran-2-yl]cyclohexyl}carbamoyl)-3-methyl-L-valyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide, or (1R,2S,5S)-3-[N-({1-[(3R)-4,4-dioxido-1,4-oxathian-3-yl]cyclohexyl}carbamoyl)-3-methyl-L-valyl]-N-[(3S)-1,2-dioxo-1-(prop-2-en-1-ylamino)heptan-3-yl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide.