Structure-based design of a novel thiazolone scaffold as HCV NS5B polymerase allosteric inhibitors

Shunqi Yan; Todd Appleby; Gary Larson; Jim Z Wu; Robert Hamatake; Zhi Hong; Nanhua Yao

doi:10.1016/j.bmcl.2006.08.056

Structure-based design of a novel thiazolone scaffold as HCV NS5B polymerase allosteric inhibitors

Bioorg Med Chem Lett. 2006 Nov 15;16(22):5888-91. doi: 10.1016/j.bmcl.2006.08.056. Epub 2006 Aug 24.

Authors

Shunqi Yan¹, Todd Appleby, Gary Larson, Jim Z Wu, Robert Hamatake, Zhi Hong, Nanhua Yao

Affiliation

¹ Valeant Pharmaceuticals Research and Development, 3300 Hyland Ave. Costa Mesa, CA 92626, USA. [email protected]

PMID: 16934455
DOI: 10.1016/j.bmcl.2006.08.056

Abstract

A structure-based approach was performed to design a novel thiazolone scaffold as HCV NS5B inhibitors. A focused library was designed and docked by GOLD. One of the top-scored molecules was synthesized and shown to have similar potency to the initial hit. The X-ray complex structure was determined and validated our design rationale.

Publication types

Validation Study

MeSH terms

Allosteric Regulation
Antiviral Agents / chemistry
Antiviral Agents / pharmacology*
Computational Biology
Crystallography, X-Ray
DNA-Directed RNA Polymerases / antagonists & inhibitors*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Structure-Activity Relationship
Thiazoles / chemistry
Thiazoles / pharmacology*
Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

Antiviral Agents
Enzyme Inhibitors
Thiazoles
Viral Nonstructural Proteins
NS-5 protein, hepatitis C virus
DNA-Directed RNA Polymerases