Phenolic modification as an approach to improve the pharmacology of the 3-acyloxy-2-benzylpropyl homovanillic amides and thioureas, a promising class of vanilloid receptor agonists and analgesics

Bioorg Med Chem. 2002 Apr;10(4):1171-9. doi: 10.1016/s0968-0896(01)00387-x.

Abstract

In order to improve the analgesic activity and pharmacokinetics of thioureas 2 and 3, which we previously developed as potent vanilloid receptor (VR) agonists, we prepared and characterized phenolic modifications of them and of their amide surrogates (7, 8). The aminoethyl analogue of the amide template 13 was a potent analgesic with an EC50=0.96 microg/kg in the AA-induced writhing test and with better in vivo stability than the parent phenol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Amides / pharmacokinetics
  • Amides / pharmacology
  • Analgesics / blood
  • Analgesics / chemistry
  • Analgesics / pharmacokinetics
  • Analgesics / pharmacology*
  • Animals
  • Calcium / metabolism
  • Homovanillic Acid / analogs & derivatives*
  • Homovanillic Acid / chemical synthesis
  • Homovanillic Acid / pharmacokinetics
  • Male
  • Neurons / drug effects
  • Phenol / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Drug / agonists*
  • Structure-Activity Relationship
  • Thiourea / chemistry
  • Thiourea / pharmacokinetics
  • Thiourea / pharmacology

Substances

  • Amides
  • Analgesics
  • Receptors, Drug
  • Phenol
  • Thiourea
  • Calcium
  • Homovanillic Acid