Design and synthesis of 3,4-dihydro-1 H-[1]-benzothieno[2,3- c]pyran and 3,4-dihydro-1 H-pyrano[3,4- b]benzofuran derivatives as non-nucleoside inhibitors of HCV NS5B RNA dependent RNA polymerase

Abstract

A novel class of HCV NS5B RNA dependent RNA polymerase inhibitors containing 3,4-dihydro-1 H-[1]-benzothieno[2,3- c]pyran and 3,4-dihydro-1 H-pyrano[3,4- b]benzofuran scaffolds were designed and synthesized. Optimization of the alkyl substituent in the pyran ring showed preference for an n-propyl group, while 5,8-disubstitution pattern is preferred for the aromatic region. Analog 19 displayed potent activity with an IC 50 of 50 nM against HCV NS5B enzyme and was selective over a panel of polymerases.