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Design and synthesis of lactam-thiophene carboxylic acids as potent hepatitis C virus polymerase inhibitors.

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Barnes-Seeman D,Boiselle C,Capacci-Daniel C,Chopra R,Hoffmaster K,Jones CT,Kato M,Lin K,Ma S,Pan G,Shu L,Wang J,Whiteman L,Xu M,Zheng R,Fu J

doi

10.1016/j.bmcl.2014.06.031

subject

Has Abstract

pub_date

2014-08-15 00:00:00

pages

3979-85

issue

16

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(14)00659-3

journal_volume

24

pub_type

杂志文章

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