SYNTHESIS AND EVALUATION OF PYRIDYL ANALOGS OF L-735,524 - POTENT HIV-1 PROTEASE INHIBITORS

Two series of HIV protease inhibitors possessing a hydroxyaminopentana mide transition state isostere were prepared and evaluated in peptide cleavage and whole cell assays. These were found to be effective in lo w concentrations at halting the spread of the AIDS virus, and a number of these inhibitors were also found to provide reasonable plasma leve ls after oral The most promising, L-748,496 is potent (IC50 = 0.12 nM and IC95 = 6-12 nM) and comparable to L-735,524 which is currently in phase II human clinical trials.