Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase

Won Gil Lee, Kathleen M. Frey, Ricardo Gallardo-Macias, Krasimir A. Spasov, Albert H. Chan, Karen S. Anderson, William L. Jorgensen

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Non-nucleoside inhibitors of HIV-1 reverse transcriptase (HIV-RT) are reported that incorporate a 7-indolizinylamino or 2-naphthylamino substituent on a pyrimidine or 1,3,5-triazine core. The most potent compounds show below 10 nanomolar activity towards wild-type HIV-1 and variants bearing Tyr181Cys and Lys103Asn/Tyr181Cys resistance mutations. The compounds also feature good aqueous solubility. Crystal structures for two complexes enhance the analysis of the structure-activity data.

Original languageEnglish (US)
Pages (from-to)4824-4827
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number21
DOIs
StatePublished - Nov 1 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.

Keywords

  • Drug solubility
  • HIV-1 reverse transcriptase
  • NNRTI
  • Protein crystallography
  • Structure-based drug design

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