Imidazo[1,2-a]pyridin-3-amines as potential HIV-1 non-nucleoside reverse transcriptase inhibitors

Bioorg Med Chem. 2011 Jul 15;19(14):4227-37. doi: 10.1016/j.bmc.2011.05.062. Epub 2011 Jun 21.

Abstract

During random screening of a small in-house library of compounds, certain substituted imidazo[1,2-a]pyridines were found to be weak allosteric inhibitors of HIV-1 reverse transcriptase (RT). A library of these compounds was prepared using the Groebke reaction and a subset of compounds prepared from 2-chlorobenzaldehyde, cyclohexyl isocyanide and a 6-substituted 2-aminopyridine showed good inhibitory activity in enzymatic (RT) and HIV anti-infectivity MAGI whole cell assays. The compound showing the best anti-HIV-1 IIIB whole cell activity (MAGI IC(50)=0.18 μM, IC(90)=1.06 μM), along with a good selectivity index (>800), was 2-(2-chlorophenyl)-3-(cyclohexylamino)imidazo[1,2-a]pyridine-5-carbonitrile 38.

MeSH terms

  • Cell Line
  • Cell Survival / drug effects
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV-1 / drug effects
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Small Molecule Libraries
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 2-(2-chlorophenyl)-3-(cyclohexylamino)imidazo(1,2-a)pyridine-5-carbonitrile
  • Imidazoles
  • Pyridines
  • Reverse Transcriptase Inhibitors
  • Small Molecule Libraries
  • HIV Reverse Transcriptase