Document Report Card

Basic Information

ID: ALA1137885

Journal: Bioorg Med Chem Lett

Title: P4 and P1' optimization of bicycloproline P2 bearing tetrapeptidyl alpha-ketoamides as HCV protease inhibitors.

Authors: Yip Y, Victor F, Lamar J, Johnson R, Wang QM, Glass JI, Yumibe N, Wakulchik M, Munroe J, Chen SH.

Abstract: With the aim of improving HCV protease inhibitors reported in our previous manuscripts, we synthesized and evaluated a series of 1a-based tetrapeptidyl alpha-ketoamides with additional P4 modification. The promising analog discovered through this SAR, 5a, was further derivatized at P1' or P1 position. As a result of these efforts, we found that replacement of the P4 valine as seen in 1a with cyclohexylglycine (Chg) resulted in the discovery of 5a, 5c, and 5e endowed with improved cellular activity in comparison to 1a.

CiteXplore: 15341970

DOI: 10.1016/j.bmcl.2004.07.007