Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for the opioid receptors

Giovanni Loriga, Ilaria Manca, Gabriele Murineddu, Giorgio Chelucci, Stefania Villa, Stefania Gessi, Lucio Toma, Giorgio Cignarella, Gerard A. Pinna

Research output: Contribution to journalArticlepeer-review

Abstract

In an effort to improve diazabicycloalkane-based opioid receptor ligands, N-3(6)-arylpropenyl-N-6(3)-propionyl-3,6-diazabicyclo[3.1.1]heptanes (3A,Ba-i) were synthesized and their affinity and selectivity towards μ-, δ- and κ-receptors were evaluated. The results of the current study revealed a number of compounds (3Bb, 3Bg and 3Bh) having a high affinity for μ (K i at μ-receptors ranging from 2.7 to 7.9 nM) versus δ (Ki at δ-receptors >2000 nM) and versus κ (K i at κ-receptors >5000 nM) receptors. Molecular modelling carried out on the pair 3Aa/3Ba and on the 3Bh was consistent with the hypothesis that the two series of compounds 3A and 3B interact with the μ-receptor in very different ways.

Original languageEnglish
Pages (from-to)676-691
Number of pages16
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number3
DOIs
Publication statusPublished - Feb 1 2006

Keywords

  • Molecular modelling
  • Opioid receptors affinities and selectivities
  • Synthesis of 3,6-diazabicyclo[3.1.1]heptanes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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