Design and synthesis of ethyl pyrrolidine-5,5-trans-lactams as inhibitors of hepatitis C virus NS3/4A protease.

Abstract Using a pyrrolidine-5,5- trans -lactam template, we have designed small, neutral, mechanism-based inhibitors of hepatitis C NS3/4A protease. Compound 11a , with an alpha-ethyl P1 substituent and a Boc-valine substituent at the pyrrolidine nitrogen, has an IC 50 =30 μM.