Cyclic HIV protease inhibitors: synthesis, conformational analysis, P2/P2'structure-activity relationship, and molecular recognition of cyclic ureas

…, PE Aldrich, GV DeLucca, CJ Eyermann…

Index: Lam, Patrick Y. S.; Ru, Yu; Jadhav, Prabhakar K.; Aldrich, Paul E.; DeLucca, George V.; Eyermann, Charles J.; Chang, Chong-Hwan; Emmett, George; Holler, Edward R.; Daneker, Wayne F.; Li, Liangzhu; Confalone, Pat N.; McHugh, Robert J.; Han, Qi; Li, Renhua; Markwalder, Jay A.; Seitz, Steven P.; Sharpe, Thomas R.; Bacheler, Lee T.; Rayner, Marlene M.; Klabe, Ronald M.; Shum, Linyee; Winslow, Dean L.; Kornhauser, David M.; Jackson, David A.; Erickson-Viitanen, Susan; Hodge, C. Nicholas Journal of Medicinal Chemistry, 1996 , vol. 39, # 18 p. 3514 - 3525

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Citation Number: 204

Abstract

High-resolution X-ray structures of the complexes of HIV-1 protease (HIV-1PR) with peptidomimetic inhibitors reveal the presence of a structural water molecule which is hydrogen bonded to both the mobile flaps of the enzyme and the two carbonyls flanking the transition-state mimic of the inhibitors. Using the structure-activity relationships of C 2- symmetric diol inhibitors, computed-aided drug design tools, and first principles, we ...