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 journalArticle

13 Citations (Scopus)

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

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Heptanes
Molecular modeling
Opioid Receptors
Ligands

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

Cite this

Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for the opioid receptors. / Loriga, Giovanni; Manca, Ilaria; Murineddu, Gabriele; Chelucci, Giorgio; Villa, Stefania; Gessi, Stefania; Toma, Lucio; Cignarella, Giorgio; Pinna, Gerard A.

In: Bioorganic and Medicinal Chemistry, Vol. 14, No. 3, 01.02.2006, p. 676-691.

Research output: Contribution to journalArticle

Loriga, G, Manca, I, Murineddu, G, Chelucci, G, Villa, S, Gessi, S, Toma, L, Cignarella, G & Pinna, GA 2006, 'Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for the opioid receptors', Bioorganic and Medicinal Chemistry, vol. 14, no. 3, pp. 676-691. https://doi.org/10.1016/j.bmc.2005.09.045
Loriga, Giovanni ; Manca, Ilaria ; Murineddu, Gabriele ; Chelucci, Giorgio ; Villa, Stefania ; Gessi, Stefania ; Toma, Lucio ; Cignarella, Giorgio ; Pinna, Gerard A. / Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for the opioid receptors. In: Bioorganic and Medicinal Chemistry. 2006 ; Vol. 14, No. 3. pp. 676-691.
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