Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency.

Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency.

Bioorganic & medicinal chemistry letters (2013-01-10)

Mariela Bollini, Ricardo Gallardo-Macias, Krasimir A Spasov, Julian Tirado-Rives, Karen S Anderson, William L Jorgensen

摘要

Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved activity towards Tyr181Cys containing variants was pursued with the assistance of free energy perturbation (FEP) calculations. Optimization of the 4-R substituent in 1 led to ethyl and isopropyl analogs 1e and 1f with 1-7 nM potency towards both the wild-type virus and a Tyr181C variant.