[Benzimidazole 5-carboxylic amide derivatives -- Boehringer Ingelheim]
Not content with BILN 2061, BI is working on this class. The following is a result of medicinal chemistry applied to the leads discovered in the full text freebie linked below (if memory serves, BI purchased Biochem Pharma of early HIV fame, and this effort is coming from there) . . .
>>Bioorg Med Chem Lett. 2004 Feb 23;14(4):967-71.
Non-nucleoside inhibitors of the hepatitis C virus NS5B polymerase: discovery of benzimidazole 5-carboxylic amide derivatives with low-nanomolar potency.
Beaulieu PL, Bos M, Bousquet Y, DeRoy P, Fazal G, Gauthier J, Gillard J, Goulet S, McKercher G, Poupart MA, Valois S, Kukolj G.
Department of Chemistry, Boehringer Ingelheim (Canada) Ltd, Research and Development, 2100 Cunard Street, Laval, Quebec, Canada H7S 2G5. pbeaulieu@lav.boehringer-ingelheim.com
Optimization of benzimidazole 5-carboxamide derivatives previously identified as specific inhibitors of the NS5B polymerase of the hepatitis C virus (HCV) has led to the discovery of potent analogues that inhibit the enzyme at low-nanomolar concentrations. Greater than 800-fold improvement in potency from the original lead structure was achieved through the combined effects of conformational rigidification, molecular size extension and the identification of previously unexploited interactions. Furthermore, these inhibitors retain specificity for HCV polymerase relative to other viral and mammalian RNA polymerases.<<
nar.oupjournals.org
Cheers, Tuck |
