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

Mariela Bollini; Ricardo Gallardo‐Macias; Krasimir A. Spasov; Julian Tirado‐Rives; Karen S. Anderson; William L. Jorgensen

doi:10.1016/j.bmcl.2012.11.115

Abstract

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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 1–7nM potency towards both the wild-type virus and a Tyr181C variant.

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

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