Benzocondensed derivatives as rigid analogues of the μ-opioid agonist 3(8)-cinnamyl-8(3)-propionyl-3,8-diazabicyclo[3,2,1]octanes: Synthesis, modeling, and affinity

G. Cignarella, D. Barlocco, P. Vianello, S. Villa, G. A. Pinna, P. Fadda, W. Fratta, L. Toma, S. Gessi

Research output: Contribution to journalArticlepeer-review

Abstract

A new series of rigid analogues (1a-g, 2a-g) of the previously reported analgesic 3-cinnamyl-8-propionyl-3,8-diazabicyclo[3.2.1]octane (I) and its reverted isomer 3-propionyl-8-cinnamyl (II) were synthesized, in which the cinnamyl substituent is incorporated in benzocondensed bicyclic systems. Binding assays for the affinity towards μ receptors indicated that, while in the reverted series 2 the β-naphthylmethyl (2d) and the benzocycloheptenylmethyl derivative (2g) favorably compared with II, all compounds 1 displayed a μ-affinity lower than that of the parent I. Modeling studies suggest that the flexibility of the cinnamyl side chain plays an important role for activity.

Original languageEnglish
Pages (from-to)667-674
Number of pages8
JournalFarmaco
Volume53
Issue number10-11
DOIs
Publication statusPublished - Nov 1998

Keywords

  • Analgesic activity
  • Diazabicyclooctanes
  • Opioid receptors

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmaceutical Science

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