Synthesis and binding affinities of 4-diarylaminotropanes, a new class of delta opioid agonists

Bioorg Med Chem Lett. 2000 May 15;10(10):1109-11. doi: 10.1016/s0960-894x(00)00182-7.

Abstract

A series of 4-diarylaminotropanes has been prepared. Both endo and exo diastereomeric forms bound to the delta opioid receptor but the endo isomers were more potent and selective versus the mu opioid receptor than the exo isomers. The most potent delta opioid agonist (14) exhibited a delta opioid Ki of 0.2 nM and was 860-fold selective over mu.

MeSH terms

  • Animals
  • Benzamides / metabolism
  • Binding Sites
  • Diphenylamine / analogs & derivatives*
  • Diphenylamine / chemistry
  • Diphenylamine / metabolism
  • Diphenylamine / pharmacology
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / metabolism
  • Enkephalin, D-Penicillamine (2,5)- / metabolism
  • Morphine / metabolism
  • Piperazines / metabolism
  • Rats
  • Receptors, Opioid, delta / agonists*
  • Receptors, Opioid, delta / metabolism*
  • Receptors, Opioid, mu / agonists
  • Receptors, Opioid, mu / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tropanes / chemistry*
  • Tropanes / metabolism*
  • Tropanes / pharmacology

Substances

  • Benzamides
  • Piperazines
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Tropanes
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • 4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide
  • Morphine
  • Enkephalin, D-Penicillamine (2,5)-
  • Diphenylamine