abstract |
HEPATITIS C VIRUS MACROCYCLIC INHIBITORS, COMBINATION AND PHARMACEUTICAL COMPOSITION UNDERSTANDING THEREOF, AND HOW TO USE AND PROCESS TO PREPARE THESE INHIBITORS. The present invention relates to HCV replication inhibitors of Formula (I) and their N-oxides, salts, or stereoisomers, wherein each dashed line (represented by) represents an optional double bond; X is N, CH and where X supports a double bond it is c; R 13 is -OR 6 6, -NH-SO 2 R 7 7; R 2 is hydrogen, and where X is O or CH, R 2 may also be C 1-6 alkyl; R 13 is hydrogen, C 1-6 alkyl, C 1-6 alkoxyC 1-6 alkyl, or C 3-7 cycloalkyl; n is 3, 4, 5, or 6; R 4 and R 5 independently of each other are hydrogen, halo, hydroxy, nitro, cyano, carboxyl, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, amino, azido, mercapto, C 1-6 alkylthio, polyhaloC 1-6 alkyl, aryl or Het; W is aryl or Het; R6 is hydrogen; arila; Het; C 3-7 cycloalkyl optionally substituted with C 1-6 alkyl; or C 1-6 alkyl optionally substituted with C 3-7 cycloalkyl, aryl or Het; R17 is aryl; Het; C 3-7 cycloalkyl optionally substituted with C 1-6 alkyl; or C 1-6 alkyl optionally substituted with C 3-7 cycloalkyl, aryl or Het; aryl is phenyl or naphthyl, each optionally substituted with 1-3 substituents; Het is a saturated, partially unsaturated or fully unsaturated 5 or 6 membered heterocyclic ring containing 1 - 4 heteroatoms each independently selected from N, O or S, and optionally substituted with 1 - 3 substituents; pharmaceutical compositions containing compounds (1) and processes (I). Bioavailable combinations of HCV inhibitors of Formula (I) with ritonavir are also provided. |