Discovery of proline sulfonamides as potent and selective hepatitis C virus NS5b polymerase inhibitors. Evidence for a new NS5b polymerase binding site.
Article Details
- CitationCopy to clipboard
Gopalsamy A, Chopra R, Lim K, Ciszewski G, Shi M, Curran KJ, Sukits SF, Svenson K, Bard J, Ellingboe JW, Agarwal A, Krishnamurthy G, Howe AY, Orlowski M, Feld B, O'Connell J, Mansour TS
Discovery of proline sulfonamides as potent and selective hepatitis C virus NS5b polymerase inhibitors. Evidence for a new NS5b polymerase binding site.
J Med Chem. 2006 Jun 1;49(11):3052-5.
- PubMed ID
- 16722622 [ View in PubMed]
- Abstract
Through high throughput screening, substituted proline sulfonamide 6 was identified as HCV NS5b RNA-dependent RNA polymerase inhibitor. Optimization of various regions of the lead molecule resulted in compounds that displayed good potency and selectivity. The crystal structure of 6 and NS5b polymerase complex confirmed the binding near the active site region. The optimization approach and SAR are discussed in detail.