Title of article :
Design, synthesis, and biological evaluation of monopyrrolinone-based HIV-1 protease inhibitors possessing augmented P2′ side chains
Author/Authors :
Amos B. Smith III، نويسنده , , Adam K. Charnley، نويسنده , , Hironori Harada، نويسنده , , Jason J. Beiger، نويسنده , , Louis-David Cantin، نويسنده , , Craig S. Kenesky، نويسنده , , Ralph Hirschmann، نويسنده , , Sanjeev Munshi، نويسنده , , David B. Olsen، نويسنده , , Mark W. Stahlhut، نويسنده , , William A. Schleif، نويسنده , , Lawrence C. Kuo، نويسنده ,
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.
