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.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A Practical Method for the Preparation of α'-Chloroketones of N-Carbamate Protected-α-Amino Acids.-Kowalski homologation of protected amino acid esters with chloroiodomethane leads to formation of chloroketones (III). They can be converted into the corresponding chlorohydrins and epoxides present in several HIV protease inhibitors. The procedure is amenable to large scale and avoids the use of hazardous reagents. -(CHEN, P.; CHENG, P. T. W.; SPERGEL, S. H.; ZAHLER, R.; WANG, X.; THOT-TATHIL, J.; BARRISH, J. C.; POLNIASZEK, R. P.; Tetrahedron Lett. 38 (1997) 18, 3175-3178; Discovery Chem., Bristol-Myers Squibb Pharm. Res.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.