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 | |
| Publication status | Published - Nov 1998 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Benzocondensed derivatives as rigid analogues of the μ-opioid agonist 3(8)-cinnamyl-8(3)-propionyl-3,8-diazabicyclo[3,2,1]octanes
T2 - Synthesis, modeling, and affinity
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.
PY - 1998/11
Y1 - 1998/11
N2 - 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.
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.
KW - Analgesic activity
KW - Diazabicyclooctanes
KW - Opioid receptors
UR - http://www.scopus.com/inward/record.url?scp=0032453580&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032453580&partnerID=8YFLogxK
U2 - 10.1016/S0014-827X(98)00084-6
DO - 10.1016/S0014-827X(98)00084-6
M3 - Article
VL - 53
SP - 667
EP - 674
JO - Farmaco
JF - Farmaco
SN - 0014-827X
IS - 10-11
ER -