Identification of [(naphthalene-1-carbonyl)-amino]-acetic acid derivatives as nonnucleoside inhibitors of HCV NS5B RNA dependent RNA polymerase.

作者信息

Gopalsamy Ariamala, Lim Kitae, Ellingboe John W, Krishnamurthy Girija, Orlowski Mark, Feld Boris, van Zeijl Marja, Howe Anita Y M

机构信息

Chemical and Screening Sciences, Wyeth Research, 401 N Middletown Road, Pearl River, NY 10965, USA.

出版信息

Bioorg Med Chem Lett. 2004 Aug 16;14(16):4221-4. doi: 10.1016/j.bmcl.2004.06.013.

DOI:10.1016/j.bmcl.2004.06.013

PMID:15261274

Abstract

A novel series of HCV NS5B RNA dependent RNA polymerase inhibitors containing a naphthalene carboxamide scaffold were identified by high throughput screening. Optimization of substituents by parallel synthesis and the iterative design towards understanding structure-activity relationship to improve potency are described. Tetra substituted naphthalene 31 displayed potent activity with IC(50) of 120 nM against HCV NS5B enzyme and was selective over a panel of polymerases.

摘要

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