Author/Authors :
Ramnarayan S. Randad، نويسنده , , Lucyna Lubkowska، نويسنده , , Michael A. Eissenstat، نويسنده , , Sergei V. Gulnik، نويسنده , , Betty Yu، نويسنده , , T. Narayana Bhat، نويسنده , , David J. Clanton، نويسنده , , Tyra House، نويسنده , , Sherman F. Stinson، نويسنده , , John W. Erickson، نويسنده ,
Abstract :
A series of novel unsymmetrical anthranilamide-containing HIV protease inhibitors was designed. The structure-activity studies revealed a series of potent P2–P3′ inhibitors that incorporate an anthranilamide group at the P2′ position. A reduction in molecular weight and lipophilicity is achieved by a judicious choice of P2 ligands (i.e., aromatic, heteroaromatic, carbamate, and peptidic). A systematic investigation led to the 5-thiazolyl carbamate analog 8m, which exhibited a favorable Cmax/EC50 ratio (>30), plasma half-life (>8 h), and potent in vitro antiviral activity (EC50 = 0.2 uM).
