ORGN 658 |
| We have identified a series of novel anthranilic acid derivatives that are potent, reversible inhibitors of Hepatitis C virus (HCV) NS5B polymerase, an essential enzyme for viral replication. The micromolar NS5B polymerase inhibitors belong to the N-phenoxyacetylanthranilic acid chemotype. X-ray crystallography determined that the inhibitors bind to a site on NS5B between the thumb and palm regions adjacent to the active site. Guided by crystallography, subsequent modifications to the hydrogen bonding and lipophilic regions of the inhibitors resulted in greatly improved activity against NS5B. Further SAR studies revealed a second, more potent sub-series where the phenoxy group was replaced by an anilino group. Analogs in both sub-series showed antiviral activity in a cell-based replicon model of HCV. |
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Technical Achievements in Organic Chemistry Award Symposium
9:00 AM-11:55 AM, Wednesday, August 22, 2007 BCEC -- 254 A/B, Oral
Division of Organic Chemistry |