New HIV-1 reverse transcriptase inhibitors based on a tricyclic benzothiophene scaffold: synthesis, resolution, and inhibitory activity

Bioorg Med Chem Lett. 2006 Jun 1;16(11):3034-8. doi: 10.1016/j.bmcl.2006.02.049. Epub 2006 Mar 9.

Abstract

We synthesized, separated into enantiomers, and tested for the HIV-1 reverse transcriptase inhibitory activity a group of analogs of dimethyl-1-(1-piperidynyl)cyclobuta[b][1]benzothiophene-2,2a(7bH)-dicarboxylate (NSC-380292). Absolute configurations of the enantiomers were determined based on absolute X-ray structures and analysis of CD spectra. Within pairs of enantiomers the (R,R)-enantiomer was always much more potent HIV-1 reverse transcriptase inhibitor.

Publication types

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

MeSH terms

  • Circular Dichroism
  • Cyclization
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / metabolism
  • Molecular Structure
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Thiophenes / chemical synthesis
  • Thiophenes / chemistry*
  • Thiophenes / pharmacology*

Substances

  • NSC-380292
  • Reverse Transcriptase Inhibitors
  • Thiophenes
  • benzothiophene
  • HIV Reverse Transcriptase