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 journalArticle

5 Citations (Scopus)

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

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Octanes
Opioid Analgesics
Analgesics
octane

Keywords

  • Analgesic activity
  • Diazabicyclooctanes
  • Opioid receptors

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmaceutical Science

Cite this

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

In: Farmaco, Vol. 53, No. 10-11, 11.1998, p. 667-674.

Research output: Contribution to journalArticle

Cignarella, G. ; Barlocco, D. ; Vianello, P. ; Villa, S. ; Pinna, G. A. ; Fadda, P. ; Fratta, W. ; Toma, L. ; Gessi, S. / 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. In: Farmaco. 1998 ; Vol. 53, No. 10-11. pp. 667-674.
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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.",
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AU - Cignarella, G.

AU - Barlocco, D.

AU - Vianello, P.

AU - Villa, S.

AU - Pinna, G. A.

AU - Fadda, P.

AU - Fratta, W.

AU - Toma, L.

AU - Gessi, S.

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