Barnes, David, Boiselle, Carri, Chopra, Rajiv, Hoffmaster, Keith, Kato, Mitsunori, Lin, Kai, Pan, Guoyu, Zheng, Rui, Shu, Lei, Ma, Sue, Wang, Jianling, Whiteman, Leah, Xu, Mei and Fu, Jiping (2014) Design and synthesis of lactam-thiophene carboxylic acids as potent hepatitis C virus polymerase inhibitors. Bioorganic & Medicinal Chemistry Letters, 24 (16). pp. 3979-3985. ISSN 0960894X

Abstract

Herein we report the successful incorporation of a lactam as an amide replacement in the design of hepatitis C virus NS5B Site II thiophene carboxylic acid inhibitors. Optimizing potency in a replicon assay and minimizing potential risk for CYP3A4 induction led to the discovery of inhibitor 22a. This lead compound has a favorable pharmacokinetic profile in rats and dogs.

Item Type:	Article
Keywords:	NS5B polymerase, PXR
Date Deposited:	27 Apr 2016 23:45
Last Modified:	27 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/21393