Identification of small molecule inhibitors of the hepatitis C virus RNA-dependent RNA polymerase from a pyrrolidine combinatorial mixture

George Burton; Thomas W Ku; Thomas J Carr; Terry Kiesow; Robert T Sarisky; Juili Lin-Goerke; Audrey Baker; David L Earnshaw; Glenn A Hofmann; Richard M Keenan; Dashyant Dhanak

doi:10.1016/j.bmcl.2005.01.076

Identification of small molecule inhibitors of the hepatitis C virus RNA-dependent RNA polymerase from a pyrrolidine combinatorial mixture

Bioorg Med Chem Lett. 2005 Mar 15;15(6):1553-6. doi: 10.1016/j.bmcl.2005.01.076.

Authors

George Burton¹, Thomas W Ku, Thomas J Carr, Terry Kiesow, Robert T Sarisky, Juili Lin-Goerke, Audrey Baker, David L Earnshaw, Glenn A Hofmann, Richard M Keenan, Dashyant Dhanak

Affiliation

¹ GlaxoSmithKline Pharmaceuticals, 1250 South Collegeville Road, PO Box 5089, Collegeville, PA 19426-0989, USA. [email protected]

PMID: 15745795
DOI: 10.1016/j.bmcl.2005.01.076

Abstract

HTS of the compound collection for inhibition of the HCV RNA dependent RNA polymerase identified two 168 member N-acyl pyrrolidine combinatorial mixture hits. Deconvolution and expansion of these mixtures by solid phase synthesis to establish initial SAR and identify a potent inhibitor is reported.

MeSH terms

Combinatorial Chemistry Techniques
Hepacivirus / enzymology*
Molecular Structure
Pyrrolidines / chemistry*
Pyrrolidines / pharmacology*
RNA-Dependent RNA Polymerase / antagonists & inhibitors*

Substances

Pyrrolidines
RNA-Dependent RNA Polymerase