The Delta(2)-isoxazoline derivatives 3a- c and 4a- c, structurally related to epibatidine, and the simplified analogues 5a-c were synthesized by means of a 1,3-dipolar cycloaddition of regioisomeric pyridinenitrile oxides to suitable dipolarophiles. Target compounds were assayed at alpha 4 beta 2 and alpha 7 neuronal acetylcholine receptor (nAChR) subtypes. Competition binding experiments at alpha 4 beta 2 nAChRs showed an overall significant reduction in affinity for the compounds under study in comparison to the reference radioligand [H-3]-epibatidine. On the other hand, compounds 3b, 3c, and 4b exhibited a noticeable affinity for the alpha 7 receptors and 3c showed also a slight degree of alpha 7 over alpha 4 beta 2 selectivity.
Synthesis of novel epibatidine-related derivatives through 1,3-dipolar cycloaddition of pyridinenitrile oxides / C.M.L. Dallanoce, P. Bazza, G. Grazioso, M. De Amici, C. De Micheli. - In: ARKIVOC. - ISSN 1551-7004. - 2006:8(2006 May 12), pp. 17-23.
|Titolo:||Synthesis of novel epibatidine-related derivatives through 1,3-dipolar cycloaddition of pyridinenitrile oxides|
BAZZA, PAOLA (Secondo)
DE AMICI, MARCO (Penultimo)
DE MICHELI, CARLO (Ultimo)
|Parole Chiave:||1,3-dipolar cycloaddition; Binding affinity; Epibatidine analogues; Neuronal nicotinic receptors; Nitrile oxides; Synthesis|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||12-mag-2006|
|Appare nelle tipologie:||01 - Articolo su periodico|