AMINODIOL HIV PROTEASE INHIBITORS - SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF P-1 P-1' COMPOUNDS - CORRELATION BETWEEN LIPOPHILICITY AND CYTOTOXICITY/

A series of novel aminodiol inhibitors of HIV protease based on the le ad compound 1 with structural modifications at P-1' were synthesized i n order to reduce the cytotoxicity of 1. We have observed a high degre e of correlation between the lipophilicity and the cytotoxicity of thi s series of inhibitors. It was found that appropriate substitution at the para position of the P-1' phenyl group of 1 resulted in the identi fication of equipotent (both against the enzyme and in cell culture) c ompounds (101, 10m, 10n, and 15c) which possess significantly decrease d cytotoxicity.