2. Academic Validation
  3. 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

  • Bioorg Med Chem Lett. 2013 Feb 15;23(4):1110-3. doi: 10.1016/j.bmcl.2012.11.115.
Mariela Bollini 1,  Ricardo Gallardo-Macias,  Krasimir A Spasov,  Julian Tirado-Rives,  Karen S Anderson,  William L Jorgensen
Affiliations

Affiliation

  • 1 Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA.
PMID: 23298809 DOI: 10.1016/j.bmcl.2012.11.115
Abstract

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.

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