P1 and P1; Optimization of [3,4]-Bicycloproline P2 Incorporated Tetrapeptidyl α-Ketoamide Based HCV Protease Inhibitors

Title: P1 and P1; Optimization of [3,4]-Bicycloproline P2 Incorporated Tetrapeptidyl α-Ketoamide Based HCV Protease Inhibitors

Volume: 2 Issue: 2

Author(s): Shu-Hui Chen, Jason Lamar, Yvonne Yip, Frantz Victor, Robert B. Johnson, Q. May Wang, John I. Glass, Beverly Heinz, Joseph Colacino, Deqi Guo, Mark Tebbe and John E. Munroe

Affiliation:

Keywords: hcv infection, ns3 protease, enzyme inhibition, replicon assay, cytotoxicity, alpha-ketoamide

Abstract: We describe herein tetrapeptidyl α-ketoamide 4A based systematic P1 modifications alone or/and in combination with further P1; variations. These SAR efforts led to the discovery of a number of potent and selective HCV NS3 protease inhibitors such as 4B, 9, and 12 endowed with impressive cellular activity as measured in the replicon assay and very good therapeutic indexes. On the basis of its overall profile, compound 4B (VX-950) has been selected for human clinical trials.

Cite this article as:

Chen Shu-Hui, Lamar Jason, Yip Yvonne, Victor Frantz, Johnson B. Robert, Wang May Q., Glass I. John, Heinz Beverly, Colacino Joseph, Guo Deqi, Tebbe Mark and Munroe E. John, P1 and P1; Optimization of [3,4]-Bicycloproline P2 Incorporated Tetrapeptidyl α-Ketoamide Based HCV Protease Inhibitors, Letters in Drug Design & Discovery 2005; 2 (2) . https://dx.doi.org/10.2174/1570180053175115