HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF HEPATITIS C

摘要

The present invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.(I);

主权项

1. A compound having the formula:or a pharmaceutically acceptable salt thereof,wherein:
X is a 5 or 6-membered saturated monocyclic ring with 1 or 2 heteroatom ring atoms independently selected from N and O; A is fluorophenyl; B is a) hydrogen;
b) —C(O)CH═C(CH3)2;c) Ar;d) —C(O)—Ar;e) —C(O)CHRy—Ar;f) —C(O)CH(NHRx)—Ar;g) —SO2(CH2)0-2—Ar;h) —SO2—CH═CH—Ar;i) —CO-Cyc;j) —COCH2—Cyc;k) —SO2-Cyc; Ar is an aromatic ring system selected from:
(i) 5-6 membered monocyclic ring with 0, 1, or 2 heteroatom ring atoms independently selected from N or O, optionally substituted with 1 or 2 substituents independently selected from fluorophenyl, C1-C6 alkyl, and halo; and(ii) 8-10 membered bicyclic rings with 1, 2 or 3 heteroatom ring atoms selected from N, O and S, optionally substituted with 1, 2 or 3 substituents independently selected from C1-C6 alkyl, C1-C6 alkoxy, halo, CF3, cyano, oxo, —NH2, and cyclopropylmethyl; Cyc is C3-C6 cycloalkyl optionally substituted with fluorophenyl or pyridine; or 3-oxabicyclo[3.1.0]hexane; D is H or NR3SO2R4; R2, R3, and R4 are independently C1-C6 alkyl; Ra is hydrogen or C1-C6 alkyl; Rx is hydrogen or C(O)OC(CH3)3; and Ry is hydrogen, morpholinyl or Ar.