FEP-guided selection of bicyclic heterocycles in lead optimization for non-nucleoside inhibitors of HIV-1 reverse transcriptase

Joseph T. Kim, Andrew D. Hamilton, Christopher M. Bailey, Robert A. Domoal, Ligong Wang, Karen S. Anderson, William L. Jorgensen

Research output: Contribution to journalArticle

Abstract

Monte Carlo simulations using free energy perturbation theory have been used to guide the selection of bicyclic heterocycles in the lead optimization of non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). Good correlation is found between predicted and observed activities. Six compounds are reported with EC50 values below 20 nM for protection of human MT-2 cells against the cytopathogenicity of HIV-1. Striking variation in activity is found and analyzed for an isomeric pyrrolopyrimidine and pyrrolopyrazine pair.

Original languageEnglish (US)
Pages (from-to)15372-15373
Number of pages2
JournalJournal of the American Chemical Society
Volume128
Issue number48
DOIs
StatePublished - Dec 6 2006

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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