Structure-based design of achiral, nonpeptidic hydroxybenzamide as a novel P2/P2′ replacement for the symmetry-based HIV protease inhibitors

RS Randad, L Lubkowska, AM Silva…

Index: Randad, Ramnarayan S.; Lubkowska, Lucyna; Silva, Abelardo M.; Guerin, Diego M. A.; Gulnik, Sergei V.; Yu, Betty; Erickson, John W. Bioorganic and Medicinal Chemistry, 1996 , vol. 4, # 9 p. 1471 - 1480

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Citation Number: 5

Abstract

A combination of structure-activity studies, kinetic analysis, X-ray crystallographic analysis, and modeling were employed in the design of a novel series of HIV-1 protease (HIV PR) inhibitors. The crystal structure of a complex of HIV PR with SRSS-2, 5-bis [N-(tert- butyloxycarbonyl) amino]-3, 4-dihydroxy-1, 6-diphenylhexane (1) delineated a crucial water- mediated hydrogen bond between the ter-butyloxy group of the inhibitor and the amide ...