title: The enantiomers of epiboxidine and of two related analogs: synthesis and estimation of their binding affinity at α4β2 and α7 neuronal nicotinic acetylcholine receptors.
abstract: Epiboxidine hydrochlorides (+)-2 and (-)-2, which are the structural analogs of the antipodes of epibatidine (±)-1, as well as the enantiomeric pairs (+)-3/(-)-3 and (+)-4/(-)-4 were synthesized and tested for binding affinity at α4β2 and α7 nicotinic acetylcholine receptor (nAChR) subtypes. Final derivatives were prepared through the condensation of racemic N-Boc-7-azabicyclo[2.2.1]heptane-2-one (±)-5 with the resolving agent (R)-(+)-2-methyl-2-propanesulfinamide. The pharmacological analysis carried out on the three new enantiomeric pairs evidenced an overall negligible degree of enantioselectivity at both nAChRs subtypes, a result similar to that reported for both natural and unnatural epibatidine enantiomers at the same investigated receptor subtypes.
authors.affiliation: Dipartimento di Scienze Farmaceutiche Pietro Pratesi, Università degli Studi di Milano, Milano, Italy. clelia.dallanoce@unimi.it
authors.forename: Clelia
authors.initials: C
authors.lastname: Dallanoce
authors.forename: Carlo
authors.initials: C
authors.lastname: Matera
authors.forename: Marco
authors.initials: M
authors.lastname: De Amici
authors.forename: Luca
authors.initials: L
authors.lastname: Rizzi
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: Carlo
authors.initials: C
authors.lastname: De Micheli
mesh_terms: D000818:Animals; D060326:Chemistry Techniques, Synthetic; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013237:Stereoisomerism; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579165:Chrna7 protein, rat; D007555:Isoxazoles; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C106388:epiboxidine; C403531:nicotinic receptor alpha4beta2