Use of medium-sized cycloalkyl rings to enhance secondary binding: Discovery of a new class of human immunodeficiency virus (HIV) protease inhibitors

KR Romines, KD Watenpaugh, PK Tomich…

Index: Romines, Karen R.; Watenpaugh, Keith D.; Tomich, Paul K.; Howe, W. Jeffrey; Morris, Jeanette K.; et al. Journal of Medicinal Chemistry, 1995 , vol. 38, # 11 p. 1884 - 1891

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Citation Number: 39

Abstract

A unique strategy for the enhancement of secondary binding of an inhibitor to an enzyme has been demonstrated in the design of new human immunodeficiency virus (HIV) protease inhibitors. When the planar benzene ring of a 4-hydroxycoumarin lead compound (la, Ki= 0.800 pM) was replaced with medium-sized (ie, 7-9), conformationally-flexible, alkyl rings, the enzyme inhibitory activity of the resulting compounds was dramatically improved, and ...