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

doi:10.1016/S0014-827X(98)00084-6

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 journal › Article › peer-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 language	English
Pages (from-to)	667-674
Number of pages	8
Journal	Farmaco
Volume	53
Issue number	10-11
DOIs	https://doi.org/10.1016/S0014-827X(98)00084-6
Publication status	Published - Nov 1998

Keywords

Analgesic activity
Diazabicyclooctanes
Opioid receptors

ASJC Scopus subject areas

Drug Discovery
Pharmaceutical Science

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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 journal › Article › peer-review

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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.",

keywords = "Analgesic activity, Diazabicyclooctanes, Opioid receptors",

author = "G. Cignarella and D. Barlocco and P. Vianello and S. Villa and Pinna, {G. A.} and P. Fadda and W. Fratta and L. Toma and S. Gessi",

year = "1998",

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doi = "10.1016/S0014-827X(98)00084-6",

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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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AB - 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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KW - Diazabicyclooctanes

KW - Opioid receptors

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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

Abstract

Keywords

ASJC Scopus subject areas

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