Synthesis, modelling, and mu-opioid receptor affinity of N-3(9)-arylpropenyl-N-9(3)-propionyl-3,9-diazabicycl

Farmaco. 2000 Aug;55(8):553-62. doi: 10.1016/s0014-827x(00)00036-7.

Abstract

A series of N-3-arylpropenyl-N-9-propionyl-3,9-diazabicyclo[3.3.1]nonanes (1a-g) and of reverted N-3-propionyl-N-9-arylpropenyl isomers (2a-g), as homologues of the previously reported analgesic 3,8-diazabicyclo[3.2.1]octanes (I-II), were synthesized and evaluated for the binding affinity towards opioid receptor subtypes mu, delta and kappa. Compounds 1a-g and 2a-g exhibited a strong selective mu-affinity with Ki values in the nanomolar range, which favourably compared with those of I and II. In addition, contrary to the trend observed for DBO-I, II, the mu-affinity of series 2 is markedly higher than that of the isomeric series 1. This aspect was discussed on the basis of the conformational studies performed on DBN which allowed hypotheses on the mode of interaction of these compounds with the mu receptor.

MeSH terms

  • Analgesics / chemical synthesis*
  • Analgesics / chemistry
  • Analgesics / pharmacology*
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / chemistry
  • Bridged Bicyclo Compounds / metabolism
  • Bridged Bicyclo Compounds / pharmacology*
  • Guinea Pigs
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Male
  • Models, Molecular*
  • Rats
  • Rats, Wistar
  • Receptors, Opioid, mu / drug effects*
  • Receptors, Opioid, mu / metabolism

Substances

  • Analgesics
  • Bridged Bicyclo Compounds
  • Receptors, Opioid, mu