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 m receptors indicated that, while in the reverted series 2 the b-naphthylmethyl (2d) and the benzocycloheptenylmethyl derivative (2g) favorably compared with II, all compounds 1 displayed a m-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.
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
GESSI, Stefania
1998
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 m receptors indicated that, while in the reverted series 2 the b-naphthylmethyl (2d) and the benzocycloheptenylmethyl derivative (2g) favorably compared with II, all compounds 1 displayed a m-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.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
