Anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors with sub-micromolar potency in the cell-based replicon assay

作者：Stammers Timothy A^*; Coulombe Rene; Duplessis Martin; Fazal Gulrez; Gagnon Alexandre; Garneau Michel; Goulet Sylvie; Jakalian Araz; LaPlante Steven; Rancourt Jean; Thavonekham Bounkham; Wernic Dominik; Kukolj George; Beaulieu Pierre L

来源：Bioorganic & Medicinal Chemistry Letters, 2013, 23(24): 6879-6885.

DOI：10.1016/j.bmcl.2013.09.102

• HCV NS5B polymerase
• Thumb Pocket 2
• Non-nucleoside inhibitor
• Structure-based drug design
• Direct-acting antiviral

Optimization efforts on the anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors 1 and 2 resulted in the identification of multiple structural elements that contributed to improved cell culture potency. The additive effect of these elements resulted in compound 46, an inhibitor with enzymatic (IC50) and cell culture (EC50) potencies of less than 100 nanomolar.

• 出版日期2013-12-15