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

J Med Chem. 1996 May 10;39(10):1991-2007. doi: 10.1021/jm950717a.

P Chen ¹, P T Cheng, M Alam, B D Beyer, G S Bisacchi, T Dejneka, A J Evans, J A Greytok, M A Hermsmeier, W G Humphreys, G A Jacobs, O Kocy, P F Lin, K A Lis, M A Marella, D E Ryono, A K Sheaffer, S H Spergel, C Q Sun, J A Tino, G Vite, R J Colonno, R Zahler, J C Barrish

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Affiliation

1 Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.

PMID: 8642558 DOI: 10.1021/jm950717a

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.

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