Design, synthesis, and biological evaluation of 3,4,5-trimethoxyphenyl acrylamides as antinarcotic agents

J Enzyme Inhib Med Chem. 2010 Feb;25(1):38-43. doi: 10.3109/14756360902932784.

Abstract

The synthesis and biological evaluation of 3,4,5-trimethoxyphenyl acrylamides 1a-f as novel antinarcotic agents are described. The molecules were prepared by the Wittig reaction, followed by a coupling reaction between 3,4,5-trimethoxycinnamic acid (9) and aliphatic amines, which resulted in good yields. When tested for biological activity, compounds 1d-f exhibited strong inhibitory effects on the morphine withdrawal syndrome in mice due to their high binding affinities with serotonergic 5-HT1A receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / chemical synthesis*
  • Acrylamides / chemistry
  • Acrylamides / metabolism
  • Acrylamides / pharmacology*
  • Animals
  • Cells, Cultured
  • Drug Design
  • Drug Evaluation, Preclinical
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Inbred C57BL
  • Narcotic Antagonists / chemical synthesis*
  • Narcotic Antagonists / chemistry
  • Narcotic Antagonists / metabolism
  • Narcotic Antagonists / pharmacology*
  • Radioligand Assay
  • Receptor, Serotonin, 5-HT1A / drug effects
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Acrylamides
  • Narcotic Antagonists
  • Receptor, Serotonin, 5-HT1A