Design, synthesis, and biological evaluation of monopyrrolinone-based HIV-1 protease inhibitors possessing augmented P2' side chains |
| |
| Authors: | Smith Amos B Charnley Adam K Harada Hironori Beiger Jason J Cantin Louis-David Kenesky Craig S Hirschmann Ralph Munshi Sanjeev Olsen David B Stahlhut Mark W Schleif William A Kuo Lawrence C |
| |
| Institution: | Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA. smithhab@sas.upenn.edu |
| |
| Abstract: | A series of monopyrrolinone-based HIV-1 protease inhibitors possessing rationally designed P2' side chains have been synthesized and evaluated for activity against wild-type HIV-1 protease. The most potent inhibitor displays subnanomolar potency in vitro for the wild-type HIV-1 protease. Additionally, the monopyrrolinone inhibitors retain potency in cellular assays against clinically significant mutant forms of the virus. X-ray structures of these inhibitors bound in the wild-type enzyme reveal important insights into the observed biological activity. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ |
