Discovery of dimeric inhibitors by extension into the entrance channel of HIV-1 reverse transcriptase

Bioorg Med Chem Lett. 2012 Feb 15;22(4):1565-8. doi: 10.1016/j.bmcl.2011.12.132. Epub 2012 Jan 5.

Abstract

Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase is being pursued with computational guidance. Extension of azine-containing inhibitors into the entrance channel between Lys103 and Glu138 has led to the discovery of potent and structurally novel derivatives including dimeric inhibitors in an NNRTI-linker-NNRTI motif.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Motifs
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Computer Simulation*
  • Crystallography, X-Ray
  • Dimerization
  • Drug Discovery*
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV-1 / drug effects
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology
  • Triazenes / chemical synthesis
  • Triazenes / chemistry
  • Triazenes / pharmacology

Substances

  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • Triazenes
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase