Hepatitis C virus NS3-4A serine protease inhibitors:: SAR of P′2 moiety with improved potency

We have discovered that introduction of appropriate amino acid derivatives at P-2(') position improved the binding potency of P-3-capped alpha-ketoamide inhibitors of HCV NS3 serine protease. X-ray crystal structure of one of the inhibitors (43) bound to the protease revealed the importance of the P-2(') moiety. (c) 2005 Elsevier Ltd. All rights reserved.