N,N-Diethyl-4-[(3-hydroxyphenyl)(piperidin-4-yl)amino] benzamide derivatives: the development of diaryl amino piperidines as potent delta opioid receptor agonists with in vivo anti-nociceptive activity in rodent models

Bioorg Med Chem Lett. 2009 Nov 1;19(21):5994-8. doi: 10.1016/j.bmcl.2009.09.072. Epub 2009 Sep 22.

Abstract

We have investigated a series of phenolic diaryl amino piperidine delta opioid receptor agonists, establishing the importance of the phenol functional group and substitution on the piperdine nitrogen for delta agonist activity and selectivity versus the mu and kappa opioid receptors. This study uncovered compounds with improved agonist potency and selectivity compared to the standard, non-peptidic delta agonist SNC-80. In vivo anti-nociceptive activity of analog 8e in two rodent models is discussed, demonstrating the potential of delta agonists to provide a novel mechanism for pain relief.

MeSH terms

  • Analgesics / chemical synthesis
  • Analgesics / chemistry*
  • Analgesics / pharmacology
  • Animals
  • Benzamides / chemical synthesis
  • Benzamides / chemistry*
  • Benzamides / pharmacology
  • Diphenylamine / analogs & derivatives*
  • Diphenylamine / chemical synthesis
  • Diphenylamine / chemistry
  • Diphenylamine / pharmacology
  • Disease Models, Animal
  • Mice
  • Piperidines / chemical synthesis
  • Piperidines / chemistry*
  • Piperidines / pharmacology
  • Rats
  • Receptors, Opioid, delta / agonists*
  • Receptors, Opioid, delta / metabolism
  • Structure-Activity Relationship

Substances

  • Analgesics
  • Benzamides
  • Piperidines
  • Receptors, Opioid, delta
  • Diphenylamine