title: Epiboxidine and novel-related analogues: a convenient synthetic approach and estimation of their affinity at neuronal nicotinic acetylcholine receptor subtypes.
abstract: Racemic exo-epiboxidine 3, endo-epiboxidine 6, and the two unsaturated epiboxidine-related derivatives 7 and 8 were efficiently prepared taking advantage of a palladium-catalyzed Stille coupling as the key step in the reaction sequence. The target compounds were assayed for their binding affinity at neuronal alpha4beta2 and alpha7 nicotinic acetylcholine receptors. Epiboxidine 3 behaved as a high affinity alpha4beta2 ligand (K(i)=0.4 nM) and, interestingly, evidenced a relevant affinity also for the alpha7 subtype (K(i)=6 nM). Derivative 7, the closest analogue of 3 in this group, bound with lower affinity at both receptor subtypes (K(i)=50 nM for alpha4beta2 and K(i)=1.6 microM for alpha7) evidenced a gain in the alpha4beta2 versus alpha7 selectivity when compared with the model compound.
authors.affiliation: Istituto di Chimica Farmaceutica e Tossicologica Pietro Pratesi, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Rizzi
authors.forename: Clelia
authors.initials: C
authors.lastname: Dallanoce
authors.forename: Carlo
authors.initials: C
authors.lastname: Matera
authors.forename: Pietro
authors.initials: P
authors.lastname: Magrone
authors.forename: Luca
authors.initials: L
authors.lastname: Pucci
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gotti
authors.forename: Francesco
authors.initials: F
authors.lastname: Clementi
authors.forename: Marco
authors.initials: M
authors.lastname: De Amici
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002384:Catalysis; D002540:Cerebral Cortex / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D009474:Neurons / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013696:Temperature
chemical_list: D007555:Isoxazoles; D008024:Ligands; D011978:Receptors, Nicotinic; C106388:epiboxidine