Synthesis, modelling, and μ-opioid receptor affinity of N-3(9)-arylpropenyl-N-9(3)-propionyl-3,9-diazabicyclo[3.3.1]nonanes

G. A. Pinna, G. Murineddu, M. M. Curzu, S. Villa, P. Vianello, P. A. Borea, S. Gessi, L. Toma, D. Colombo, G. Cignarella

Research output: Contribution to journalArticle

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 μ, δ and κ. Compounds 1a-g and 2a-g exhibited a strong selective μ-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 μ-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 μ receptor.

Original languageEnglish
Pages (from-to)553-562
Number of pages10
JournalFarmaco
Volume55
Issue number8
DOIs
Publication statusPublished - 2000

Keywords

  • μ-Affinity
  • Diazabicyclononanes
  • Modelling

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmaceutical Science

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