title: Synthesis and alpha4beta2 nicotinic affinity of 2-pyrrolidinylmethoxyimines and prolinal oxime ethers.
abstract: Homochiral E and Z isomers of N-methylprolinal O-isopropyloxime and (1-methyl-2-pyrrolidinyl)methoxyimines were synthesized as candidate bioisosteres of nicotine and its isoxazolic analogue ABT 418. Two of them, namely (S)-2-isopropylideneaminooxymethyl- and (Z)-(S)-2-ethylideneaminooxymethyl-1-methylpyrrolidine, proved to bind at alpha4beta2 nicotinic acetylcholine receptor with submicromolar affinity and remarkable selectivity over alpha7 and muscarinic receptors thus supporting the hypothesized bioisosteric relationship between their methyloxyimino group and the aromatic heterocycles of the reference ligands.
authors.affiliation: Istituto di Chimica Farmaceutica e Tossicologica, Università di Milano, viale Abruzzi 42, I-20131 Milano, Italy. marco.pallavincini@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: 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: Silvia
authors.initials: S
authors.lastname: Vailati
authors.forename: Ermanno
authors.initials: E
authors.lastname: Valoti
authors.forename: Luigi
authors.initials: L
authors.lastname: Villa
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D007097:Imines / Q000138:chemical synthesis* / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D007097:Imines; D011759:Pyrrolidines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D011392:Proline; C046026:prolinal