Design and Synthesis of Spiro-cyclopentenyl and Spiro-[1,3]-dithiolanyl Substituted Pyrrolidine-5,5-trans-lactams as Inhibitors of Hepatitis C Virus NS3/4A Protease.

Abstract Using the pyrrolidine-5,5- trans -lactam template, we have designed small, neutral, mechanism-based inhibitors of hepatitis C NS3/4A protease. Compound 2b , with a spiro-cyclobutyl P1 substituent and an isopropyl carbonyl substituent at the lactam nitrogen, has an IC 50 value in the replicon cell-based assay of 3 μM.