Macrocyclic compounds as antiviral agents

摘要

A class of macrocyclic compounds of formula (I), wherein R1, R3, R4, Ra, Rb, A, Z, Y, X, M, W, n and m are defined herein, that are useful as inhibitors of viral proteases, particularly the hepatitis C virus (HCV) NS3 protease, are provided. Also provided are processes 5 for the synthesis and use of such macrocyclic compounds for treating or preventing HCV infection. Formula (I):;

主权项

1. A compound of formula (I):or a pharmaceutically acceptable salt thereof,wherein:
m is 0, 1, 2 or 3; n is 0; R1 is CO2R5, CONR5SO2R5, CONR5SO2N(R5)2 or tetrazolyl; Ra is C2-6alkylene-R2; Rb is hydrogen; or Ra and Rb, together with the carbon atom to which they are attached, form a C3-6cycloalkyl group, optionally substituted by R2; R2 is C1-6alkyl, C2-6alkenyl or C3-8cycloalkyl, wherein said alkyl, alkenyl or cycloalkyl is optionally substituted with 1 to 3 halo; R3 is C1-6alkyl, (CH2)0-3C3-8cycloalkyl, (CH2)0-3aryl or (CH2)0-3Het, optionally substituted by halo, OR5, SR5, N(R5)2, C1-6alkyl, NO2, CN, CF3, NR5SO2R5, SO2N(R5)2, NHCO2R5, NHCOR5, NHCONHR5, CO2R5, C(O)R5 or CON(R5)2; each W is independently halo, OR5, C1-6alkyl, CN, NO2, CF3, CO2R5 or CON(R5)2; each R5 is independently hydrogen, C1-6alkyl or C3-8cycloalkyl; Z is O or NR6; R6 is hydrogen or C1-6alkyl; Y is C═O, SO2 or CRcRd; X is O, NRe or CReRf; Rc, Rd, Re and Rf are independently hydrogen, halo or C1-6alkyl; M is C4-12alkylene, C4-12alkenylene or C4-12alkynylene, optionally substituted by C1-6alkyl, (CH2)0-3C3-8cycloalkyl, (CH2)0-3aryl, and optionally containing one O or S atom or one NH or NC1-6alkyl group, and optionally spiro-fused to a C3-7cycloalkyl group, and optionally fused to a 3- to 8-membered ring, which ring optionally contains 1 or 2 heteroatoms selected from N, O and S; ring A is  optionally substituted by R4; and R4 is halo, hydroxy, C1-6alkyl, C1-6alkoxy, CN, NO2, oxo, C3-8cycloalkyl, N(R5)2, aryl or heteroaryl, optionally substituted by 1 to 8 halo or C1-4alkyl.