| 摘要 |
The present invention covers microcylic compounds of formula active in-vitro and in cellular assays against NS3 protease of the hepatitis C virus when W is CH or N; R21 is H, halo, C1-6 alkyl, cycloalkyl, haloalkyl, C1-6 alkoxy, cycloalkoxy, hydroxy, or N(R23)2, wherein each R23 is independently H, C1-6 alkyl or cycloalkoxy; and R22 is H, halo, C1-6 alkyl, C3-6 cycloalkyl, C1-6thioalkyl, C1-6 alkoxy, C3-6 cycloalkoxy, C2-7 alkoxyalkyl, C3-6 cycloalkyl, C6 or 10 aryl or Het, wherein Het is a five-, six- or seven-membered saturated or unsaturated heterocycle containing from one to four heteroatoms selected from nitrogen, oxygen and sulfur, said cycloalkyl, aryl or Het being substituted with R24, wherein R24 is H, C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, C3-6 cycloalkoxy, NO2, N(R25)2, NH-C(O)-R25; or NH-C(O)-NH-R25, wherein each R25 is independently: H, C1-6 alkyl or C3-6cycloalkyl; or R24 is NH-C(O)-OR26 wherein R26 is C1-6 alkyl or C3-6 cycloalkyl; R3 is hydroxy, NH2, or a group of formula -NH-R31, wherein R31 is C6 or 10 aryl, heteroaryl, -C(O)-R32, -C(O)-OR32 or -C(O)-NHR32, wherein R32 is: C1-6 alkyl or C3-6 cycloalkyl; D is a 5 to 10-atom saturated or unsaturated alkylene chain optionally containing one to three heteroatoms independently selected from O, S, or NR41, wherein R41 is H, C1-6 alkyl, cycloalkyl or -C(O)-R42, wherein R42 is C1-6 alkyl, cycloalkyl or C6 to 10 aryl; R4 is H or from one to three substituents at any carbon atom of said chain D, said substituent independently selected from the group consisting of: C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, hydroxy, halo, amino, oxo, thio, or C1-6 thioalkyl, and A is an amide of formula -C(O)-NH-R5, wherein R5 is selected from the group consisting of: C1-8 alkyl, C3-6 cycloalkyl, C6 or 10 aryl or C7-16 aralkyl; or A is a carboxylic acid or a pharmaceutically acceptable salt of ester thereof. |
