Structure-based design and synthesis of substituted 2-butanols as nonpeptidic inhibitors of HIV protease: secondary amide series

SH Reich, M Melnick, MJ Pino, MAM Fuhry…

Index: Reich, Siegfried H.; Melnick, Michael; Pino, Mark J.; Fuhry, Mary Ann M.; Trippe, Anthony J.; Appelt, Krzysztof; Davies II, Jay F.; Wu, Bor-Wen; Musick, Linda Journal of Medicinal Chemistry, 1996 , vol. 39, # 14 p. 2781 - 2794

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Citation Number: 50

Abstract

The design, synthesis, and crystallographic analysis of protein-inhibitor complexes is described for a novel series of nonpeptidic HIV protease (HIV Pr) inhibitors. Beginning with a cocrystal structure of a Phe-Pro peptidomimetic bound to the HIV Pr, design was initiated that resulted in the substituted 2-butanol compound 8 as the lead compound (K i= 24.5 μM, racemic mixture). Modifications on the initial compound were then made on the basis of its ...