title: Synthesis and alpha4beta2 nicotinic affinity of unichiral 5-(2-pyrrolidinyl)oxazolidinones and 2-(2-pyrrolidinyl)benzodioxanes.
abstract: The RS and SR enantiomers of 2-oxazolidinone and 1,4-benzodioxane bearing a 2-pyrrolidinyl substituent at the 5- and 2-position, respectively, were synthesized as candidate nicotinoids. One of the two benzodioxane stereoisomers reasonably fits the pharmacophore elements of (S)-nicotine and binds at alpha4beta2 nicotinic acetylcholine receptor with submicromolar affinity. Interestingly, both the synthesized pyrrolidinylbenzodioxanes exhibit analogous affinity at alpha(2) adrenergic receptor resembling the behaviour of some known alpha(2)-AR ligands recently proved to possess neuronal nicotinic affinity.
authors.affiliation: Istituto di Chimica Farmaceutica e Tossicologica, Università di Milano, viale Abruzzi 42, I-20131 Milano, Italy. marco.pallavicini@unimi.it
authors.forename: Marco
authors.initials: M
authors.lastname: Pallavicini
authors.forename: Barbara
authors.initials: B
authors.lastname: Moroni
authors.forename: Cristiano
authors.initials: C
authors.lastname: Bolchi
authors.forename: Antonio
authors.initials: A
authors.lastname: Cilia
authors.forename: Francesco
authors.initials: F
authors.lastname: Clementi
authors.forename: Laura
authors.initials: L
authors.lastname: Fumagalli
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gotti
authors.forename: Fiorella
authors.initials: F
authors.lastname: Meneghetti
authors.forename: Loredana
authors.initials: L
authors.lastname: Riganti
authors.forename: Giulio
authors.initials: G
authors.lastname: Vistoli
authors.forename: Ermanno
authors.initials: E
authors.lastname: Valoti
mesh_terms: D004146:Dioxanes / Q000138:chemical synthesis* / Q000378:metabolism*; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000378:metabolism*; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D004146:Dioxanes; D023303:Oxazolidinones; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2