Optimization of pyrimidinyl- and triazinyl-amines as non-nucleoside inhibitors of HIV-1 reverse transcriptase

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

Research output: Contribution to journalArticle

Abstract

Non-nucleoside inhibitors of HIV-1 reverse transcriptase are being pursued through synthesis and assaying for anti-viral activity. Following computational analyses, the focus has been on the motif Het-NH-Ph-U, where Het is an aromatic heterocycle and U is an unsaturated, hydrophobic group. Previous investigations with Het = 2-thiazoyl and 2-pyrimidinyl are extended here to triazinyl derivatives. The result is several NNRTIs in the 2-20 nM range with negligible cytotoxicity and auspicious predicted pharmacological properties.

Original languageEnglish (US)
Pages (from-to)5664-5667
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number21
DOIs
StatePublished - Nov 1 2006

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Keywords

  • 2-Pyrimidinylamine
  • Anti-HIV
  • Free energy perturbation
  • NNRTI
  • Structure-based drug design
  • Triazinylamine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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