Bifenilil - 1H imidazole derivatives and bifenildiil - bis (1h imidazole - 4.2) dilaurate as inhibitors of hepatitis C virus, compositions containing same and Use thereof in the treatment of hcv infection.

摘要

Compounds, compositions and their use in the treatment of infection with hepatitis C virus (HCV). Also Pharmaceutical compositions containing such compounds and Methods of using such compounds in the treatment of hcv infection.Claim 1, characterized in that: a compound selected from ((1S) - 2 - ((1R, 3S, 5R) - 3 - (4 - (4 '- (2 - ((1R, 3S, 5R) - 2 - (N - (Methoxycarbonyl) - l-alanyl) - 2-azabicyclo 3,1.0 [Hex] - 3 - yl) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 2-azabicyclo [3.1.0] hex - 2 - methyl - 1 - il) - 2-oxoethyl) methyl carbamate (4,4' -; Bifenildiilbis (1h imidazole - 4.2 - diyl (1R, 3S, 5R) - 2-azabicyclo [3.1.0 - 3.2 - diyl) hexane ((2S) - 2 - oxo - 1.2 - butanodiil) biscarbamato Dimethyl (2 - ((1R, 3S, 5R) - 3 - (4 - (4 '- (2 - ((1R, 3S, 5R) - 2 - (((Methoxycarbonyl) amino) Acetyl) - 2-azabicyclo [3.1.0] hex - 3 - yl) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 2-azabicyclo [3.1.0] hex - 2 - yl) - 2-oxoethyl) methylcarbamate; (4,4' - bifen Ildiilbis (1h imidazole - 4.2 - diyl (1R, 3S, 5R) - 2-azabicyclo [3.1.0] hexane - 3.2 - diyl cyclopropyl - (1S) - 1 - 2 - oxo - 2.1 - etanediil biscarbamato) dimethyl ((1R) - 1 - ((1R, 3S, 5R) - 3 - (4 - (4 '- (2 - ((1R, 3S, 5R) - 2 - ((2R) - 2 - (Methoxycarbonyl) amino) - 3 - metilbutanoil) - 2-azabicyclo [3.1.0] hex - 3 - yl) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 2-azabicyclo [3.1.0] hex - 2 - il) carbonyl) - 2 - M Etilopropil) methylcarbamate; (4,4 '- bifenildiilbis (1h imidazole - 4.2 - diyl (1R, 3S, 5R) - 2-azabicyclo [3.1.0 3.2 - diyl] hexane - ((1R) - 2 - oxo - 1 - phenyl - 2.1 - etanediil biscarbamato dedimetilo;))) ((1S) - 1 - ((1R, 3S, 5R) - 3 - (4 - (4 '- (2 - ((1R, 3S, 5R) - 2 - acetyl - 2-azabicyclo [3.1.0) hex - 3 - yl) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 2-azabicyclo [3.1.0] hex - 2 - il) carbonyl) - 2 - metilopropil) methylcarbamate; (1S) - 2 - methyl - 1 - ((1R, 3S) - 3 - (4 - (4 '- (2 - ((1R, 3S, 5R) - 5 - (2 - [(3aS, 4S, 6aR) - 2 - oxohexahidro - 1H thieno [3,4-d] imidazole-4-pentanoic - il) pentanoil) - 2-azabicyclo [3.1.0] hex - 3 - yl) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 2-azabicyclo [3.1.0] hex - 2 - il) carbonyl) - 2 - metilopropil methylcarbamate; n - ((1S) - 1 - ((1R, 3S, 5R) - 3 - (4 - (4 '- (2 - ((1R, 3S, 5R) - 2 - ((2S) - 2-acetamido-3 - metilbutanoil) - 2-azabicyclo (3.1.0] hex - 3 - yl) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 2-azabicyclo [3.1.0] hex - 2 - il) carbonyl) - 2 - metilopropil) acetamide (1S) - 1 - ((1R, 3S, 5R) - 3 - (4 - (4 '- (2 - ((1R, 3S, 5R) - 2 - ((2S) - 2 - ((tert Butoxycarbonyl) amino) - 3 - metilbutanoil) - 2-azabicyclo [3.1.0) hex - 3 - yl) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 2-azabicyclo [3.1.0] hex - 2 - il) carbonyl) - 2 - metilopropil) carbamate TERT B Utilo; (2S) - 1 - ((1R, 3S, 5R) - 3 - (4 - (4 '- (2 - ((1R, 3S, 5R) - 2 - ((2S) - 2 - amino - 4 - metilbutanoil) - 2-azabicyclo [3.1.Hex - 3 0) - yl) - 1H imidazole - 5 - il) - 4 - bifenilil) - 1H imidazole - 2 - il) - 2-azabicyclo [3.1.0] hex - 2 - il) - 3 - methyl - 1 - 2 - oxo - butanamina; n - ((1S) 1 - ((1R, 3S, 5R) - 3 - (4 - (4 '- (2 - ((1R, 3S, 5R) - 2 - ((2S) - 2 - ((ciclopropilcarbonil) amino) - 3 - metilbutanoil) - 2-azabicyclo [3.1.0] hex - 3 - il) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 2-azabicyclo [3.1.0] hex - 2 - il) carbonyl) - metilopropil) ciclopropanocarbamato; 2 - ((1R) - 1 - ((1R, 3S, 5R) - 3 - (4 - (4 '- (2 - ((1R, 3S, 5R) - 2 - ((2R) - 2 - ((tert Butoxycarbonyl) amino) - 3 - metilbutanoil) - 2-azabicyclo [3.1.0] hex - 3 - yl) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 2-azabicyclo [3.1.0] hex - 2 - il) carbonyl) - 2 - metilopropil) carbamate Tert Butyl N - ((1R) - 1 - ((1R, 3S, 5R) - 3 - (4 - (4 '- (2 - ((1R, 3S, 5R) - 2 - ((2R) - 2-acetamido-3 - metilbutanoil) - 2-azabicyclo [3.1.0] hex - 3 - yl) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 2-azabicyclo [3.1.0] hex - 2 - il) carbonyl) - 2 - metilopropil) acetamide; n, n' - (4, 4 '- bifenildiilbis (1h imidazole - 4.2 - diyl (1R, 3S, 5R) - 2-azabicyclo [3.1.0] hexane - 3.2 - diyl ((2S) - 3 - methyl - 1 - 2 - oxo - butanodiil) di (2) - pirimidinamina); ((1S) - 1 - (((6S) - 6 - (4 - (4 '- (2 - ((6S) - 5 - (2S) - 2 - (Methoxycarbonyl) amino) - 3 - metilbutanoil) - 5 - azaspiro [2.4] hept-3-ene - 6 - yl) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 5 - [2 azaspiro.4] hept-3-ene - 5 - il) carbonyl) - 2 - metilopropil) methylcarbamate; (1S) - 1 - ((2S, 5S) - 2 - (4 - (4 '- (2 - ((2S, 5S) - 1 - ((2S) - 2 - (Methoxycarbonyl) - metilbutanoil) amino) - 3 - 5 - methyl - 2 - pirrolidinil) - 1H imidazole - 4-yl) - 4 - bifenilil) - H - imidazole - 2 - il) - 5 - methyl - 1 - pirrolidinil) carbonyl) - 2 - metilopropil) methylcarbamate; 2 - (((6S) - 6 - (4 - (4 '- (2 - ((6S) - 5 - (Methoxycarbonyl) amino) Acetyl) - 5 - [2 azaspiro.4 - 6 hept-2-yl) - yl) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 5 - azaspiro [2.4] hept-3-ene - 5 - yl) - 2-oxoethyl) methylcarbamate; ((1S) - 2 - ((6S) - 6 - (4 - (4 '- (2 - ((6S) - 5 - (N - (Methoxycarbonyl) - l-alanyl) - 5 - azaspiro [2.4] hept-3-ene (IL - 6) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 5 - azaspiro [2.4] hept-2-yl) - il - 5 - 1 - methyl - 2 - oxoe Methyl carbamate (TIL); 4,4 '- bifenildiilbis (1h imidazole - 4.2 - diyl (6S) - 5 - [2 azaspiro.4 - 6.5 - diyl] heptane ((2S) - 2 - oxo - 1,2 - dimethyl biscarbamato butanodiil))), ((1R) - 1 - (((6S) - 6 - (4 - (4 '- (2 - ((6S) - 5 - ((2R) - 2 - (Methoxycarbonyl) amino) - 3 - metilbutanoil) - 5 - [azaspiro plates 2.4) - 6 - yl) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 5 - azaspiro [2.4] hept-2-yl) carbonyl) - il - 5 - 2 - metilopropil MET) carbamate ILO; (4,4 '- bifenildiilbis (1h imidazole - 4.2 - diyl (6S) - 5 - [2 azaspiro.4 - 6.5 - diyl] heptane ((1R) - 2 - oxo - 1 - phenyl - 2.1 - etanediil) biscarbamato Dimethyl ((1R) - 1 - ((2S, 5S) - 2 - (4 - (4 - (2 - ((2S, 5S) - 1 - ((2R) - 2 - (Methoxycarbonyl) amino) - 3 - metilbutanoil) - 5-methyl-2 - pirrolidinil) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 5 - methyl - 1 - pirrolidinil) carbonyl) - 2 - metilopropil) carbama To Methyl; (4,4 '- bifenildiilbis (1h imidazole - 4.2 - diyl ((2S, 5S) - 5 - methyl - 2Pirrolidinediil) 1 - ((1R) - 2 - oxo - 1 - phenyl - 2.1 - etanediil) dimethyl (biscarbamato; 4,4 '- bifenildiilbis (1h imidazole - 4.2 - diyl ((2S, 5S) - 5 - methyl - 2.1 - pirrolidinediil) ((2S) - 2 - oxo - butanodiil) biscarbamato 1,2 - Dimethyl (2 - ((2S, 5S) - 2 - (4 - (4' - (2 - ((2S,(5S) - 1 - (Methoxycarbonyl) amino) Acetyl) - 5-methyl-2 - pirrolidinil) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 5 - methyl - 1 - pirrolidinil) - 2-oxoethyl) methylcarbamate; (2 - ((2S, 5S) - 2 - (4 - (4 '- (2 - ((2S, 5S) - 1 - (2 - (Methoxycarbonyl) amino) - 2 - metilopropanoil) - 5 - metii - 2 - pirrolidinil) - 1H imidazole - 4-yl) - 4 - bifenili L) - 1H imidazole - 2 - il) - 5 - methyl - 1 - 1 - pirrolidinil)1 - dimethyl - 2-oxoethyl) methylcarbamate; ((1S) - 2 - ((2S, 5S) - 2 - (4 - (4 '- (2 - ((2S, 5S) - 1 - (N - (Methoxycarbonyl) - l-alanyl) - 5 - methyl - 2 - pirrolidinil) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole - 2 - il) - 5 - methyl - 1 - methyl - 1 - pirrolidinil) - 2-oxoethyl) methylcarbamate; 4,4' - (4,4 '- bifenildiil) bis (2 - ((2S, 5S) - 5 - methyl - 1 - (3 - Metilbutanoil) - 2 - pirrolidinil) - 1H imidazole); 4,4 '- (4,4' - bifenildiil) bis (2 - ((2S,5S) - 5 - methyl - 1 - (phenylacetyl) - 2 - pirrolidinil) - 1H imidazole; (2) 2R, R ') - 1,1' - (4,4 '- bifenildiilbis (1h imidazole - 4.2 - diyl ((2S, 5S) - 5 - methyl - 2.1 - pirrolidinediil))) bis (3 - methyl - 1 - 2 - oxo - butanol; (2) 2S, S') - 1,1' - (4,4 '- bifenildiilbis (1h imidazole - 4.2 - diyl ((2S, 5S) - 5 - methyl - 2.1 - pirrolidinediil) bis (3 - methyl - 1 - 2 - oxo - bu Tanol); 2 - ((2S, 5S) - 1 - acetyl - 5 - methyl - 2 - pirrolidinil) - 4 - (4 '- (2 - ((2S,5S) - 1 - acetyl - 5 - methyl - 2 - pirrolidinil) - 1H imidazole - 5 - il) - 4 - bifenilil) - 1H imidazole; (2S) - 2 - (4 - (4 '- (2 - ((2S) - 1 - (tert Butoxycarbonyl) - 2 - pirrolidinil) - 4 - (1,3-dioxan-2-yl ilmetilo) - 1H imidazole - 5 - il) - 4 - bifenilil) - 1H imidazole - il - 2) - 1 - pirrolidincarboxilato Tert Butyl (2S) - 2 - (4 - (4' - (2 - ((2S) - 1 - (tert butoxicar - pirrolidinil Bonil) - 2 - (1, - 4)Dioxolan - 2 - 3 - ilmetilo) - 1H imidazole - 5 - il) - 4 - bifenilil) - 1H imidazole - il - 2) - 1 - pirrolidincarboxilato Tert Butyl (2S) - 2 - (4 - (4 '- (2 - ((2S) - 1 - (tert Butoxycarbonyl) - 2 - pirrolidinil) - 1H imidazole - 4-yl) - 4 - bifenilil) - 5 - (2 - methoxy - 2-oxoethyl) - 1H imidazole - il - 2) - 1 - pirrolidincarboxilato Tert Butyl (2S) - 2 - (4 - ( 4 '- (2 - ((2S) - 1 - (tert Butoxycarbonyl) - 2 - pirrolidinil) - 1H imidazole - 4-yl) - 4 - bifenilil) - 5 - propyl - 1H - ImideZol - il - 2) - 1 - pirrolidincarboxilato Tert Butyl 2 - ((2S) - 1 - (tert Butoxycarbonyl) - 2 - pirrolidinil) - 5 - (4 '- (2 - ((2S) - 1 - (tert Butoxycarbonyl) - 2 - pirrolidinil) - 1H imidazole - 5 - il) - 4 - bifenilil) - 1H imidazole carboxylate Ethyl 4 - (2S) - 2 - (4 - (4' - (2 - ((2S) - 1 - (tert Butoxycarbonyl) - 2 - pirrolidinil) - 1H imidazole - 4 - IL) - 3 '- fluoro-4 - bifenilil) - 1H imidazole - 2 - il) - 4,4 - difluoro - 1 - pirrolidincarboxilato Tert Butyl 2 - ((2S) - 4,4 '- difluoro - 2 - pirrolidinil) - 4 - (3' - fluoro-4 '- (2 - (2S) - 2 - pirrolidinil) - 1H imidazole - 4-yl) - 4 - bifenilil) - 1H imidazole, (1R) - 2 - ((2S) - 2 - (4 - (4' - (2 - ((2S) - 1 - ((2R) - 2 - (Diethylamino) - 2 - phenylacetyl) - 2 - pirrolidinil) - 1H imidazole - 4-yl) bifenilil - 4 - 5 - methyl) - 1H Imidazole - il - 2) - 1 - pirrolidinil) - n,N-diethyl - 2 - oxo - feniletanamina 1; 1 - ((1R) - 2 - ((2S) - 2 - (4 - (4 - (4 '- methyl - 2 - ((2S) - 1 - ((2R) - 2 - phenyl - 2 - (piperidinyl) Acetyl) - 2 - pirrolidinil) - 1H imidazole - 5 - il) - 4 - bifenilil) - 1H imidazole - yl) - 2 - 1 - 2 - oxo - pirrolidinil) - 1-phenylethyl) piperidine; ((1R) - 2 - ((2S) - 2 - (4 - (4 - (2 - ((2S) - 1 - ((2R) - 2 - (Methoxycarbonyl) amino) - 2 - F Enilacetil) - 2 - pirrolidinil) - 1H imidazole - 4-yl) - 4 - bifenilil - 5 - methyl) - 1H imidazole - il - 2) - 1 - pirrolidinil) -2 - oxo - 1-phenylethyl) methylcarbamate; (1S) - 2 - ((2S) - 2 - (4 - (4 '- (2 - ((2S) - 1 - (N - (Methoxycarbonyl) - l-alanyl) - 2 - pirrolidinil) - 4 - methyl - 1H imidazole - 5 - il) - 4 - bifenilil) - 1H imidazole - yl) - 2 - 1 - 1 - methyl - pirrolidinil) - 2-oxoethyl) methylcarbamate; ((1S) - 1 - ((2S) - 2 - (4 - (4' - (2 - (2S) - 1 - ((2S) - 2 - (Methoxycarbonyl) amino) - 3 - metilbutanoil) - 2 - pirrolidinil) - 1H imidazole - 4-yl) - 4 - bifenilil) - 5 - metii - 1H imidazole - il - 2) - 1 - pirrolidiNil) carbonyl) - 2 - metilopropil) methylcarbamate; ((1S, 2R) - 2 - methoxy - (1 - ((2S) - 2 - (4 - (4 '- (2 - ((2S) - 1 - (N - (Methoxycarbonyl - O - methyl - L - treonil - pirrolidinil) - 2 - 4 - methyl) - 1H imidazole - 5 - il) - 4 - bifenilil) - 1H imidazole - il - 2) - 1 - pirrolidinil) carbonyl) propyl) methylcarbamate; (1, 1' - (R) - 2,2 ', 4,4' - (bifenildiilbis 4 - methyl) - 1H imidazole - 5.2 - diyl) (2S) - 2.1 - pirrolidinediil)) bis (n, N - dimethyl - 2 - oxo - 1 - (1R, feniletanamina);1 '- (R) - 2,2', 4,4 '- (bifenildiilbis (4 - methyl - 1H imidazole - 5.2 - diyl) (2S) - 2.1 - pirrolidinediil)) bis (n, n-diethyl - 2 - oxo - 1 - feniletanamina); 1,1' - (4,4 '- bifenildiilbis (4 - methyl) - 1H imidazole - 5.2 - diyl) (2S) - 2 - ((1R) - pirrolidinediil 1 - phenyl - 2 - oxo - 2.1 - etanediil) dipiperidina; bifenildiilbis (4,4' - (4 - (methyl) - 1H imidazole - 5.2 - diyl) pirrolidinediil (2S) - 2.1 - ((1R) - 2 - oxo - phenyl - 2 - 1,1 - etanediil) biscarbamato Dimethyl ((1S) - 2 - ((2S) - 2 - (4 - (4 '- (2 - ((2S) - 1 - (N - (Methoxycarbonyl) - l-alanyl) - 2 - pirrolidinil) - 5 - methyl - 1 - imidazole - 4-yl) - 4 - bifenilil) - 5 - methyl - 1 - il) imidazole - 2 - 1 - 1 - methyl - pirrolidinil) - 2-oxoethyl) methylcarbamate; ((1S) - 1 - ((2S) - 2 - (4 - (4' - (2 - ((2S) - 1 - ((2S) - 2 - ((metoxicarbon IL) amino) - 3 - metilbutanoil) - 2 - pirrolidinil) - 4 - methyl imidazole - H - - 5 - yl) - 4 - bifenilil - 5 - methyl) - 1H imidazole -2 - yl) - 1 - pirrolidinil) carbonyl) - 2 - metilopropil) methylcarbamate; ((1S, 2R) - 2 - methoxy - (1 - ((2S) - 2 - (4 - (4 '- (2 - ((2S) - 1 - (N - (metoxicarb