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Design and synthesis of ethyl pyrrolidine-5,5-trans-lactams as inhibitors of hepatitis C virus NS3/4A protease |
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| Authors: | Slater Martin J Andrews David M Baker Graham Bethell Susanne S Carey Seb Chaignot Helene Clarke Berwyn Coomber Barry Ellis Malcolm Good Andrew Gray Norman Hardy George Jones Paul Mills Gail Robinson Ed |
| Institution: | GlaxoSmithKline Medicines Research Centre, Stevenage, UK. mjs40312@gsk.com |
| 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 microM. |
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