Document Report Card

ID: ALA1129312

Journal: J Med Chem

Title: Aminodiol HIV protease inhibitors. Synthesis and structure-activity relationships of P1/P1' compounds: correlation between lipophilicity and cytotoxicity.

Authors: Chen P, Cheng PT, Alam M, Beyer BD, Bisacchi GS, Dejneka T, Evans AJ, Greytok JA, Hermsmeier MA, Humphreys WG, Jacobs GA, Kocy O, Lin PF, Lis KA, Marella MA, Ryono DE, Sheaffer AK, Spergel SH, Sun CQ, Tino JA, Vite G, Colonno RJ, Zahler R, Barrish JC.

Abstract: A series of novel aminodiol inhibitors of HIV protease based on the lead compound 1 with structural modifications at P1' were synthesized in order to reduce the cytotoxicity of 1. We have observed a high degree of correlation between the lipophilicity and cytotoxicity of this series of inhibitors. It was found that appropriate substitution at the para position of the P1' phenyl group of 1 resulted in the identification of equipotent (both against the enzyme and in cell culture) compounds (10l, 10m, 10n, and 15c) which possess significantly decreased cytotoxicity.

CiteXplore: 8642558

DOI: 10.1021/jm950717a