Synthesis and alpha4beta2 nicotinic affinity of unichiral 5-(2-pyrrolidinyl)oxazolidinones and 2-(2-pyrrolidinyl)benzodioxanes.
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.
Pallavicini
Marco
M
Istituto di Chimica Farmaceutica e Tossicologica, Università di Milano, viale Abruzzi 42, I-20131 Milano, Italy. marco.pallavicini@unimi.it
Moroni
Barbara
B
Bolchi
Cristiano
C
Cilia
Antonio
A
Clementi
Francesco
F
Fumagalli
Laura
L
Gotti
Cecilia
C
Meneghetti
Fiorella
F
Riganti
Loredana
L
Vistoli
Giulio
G
Valoti
Ermanno
E
D004146:Dioxanes / Q000138:chemical synthesis* / Q000378:metabolism*; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000378:metabolism*; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000378:metabolism*
D004146:Dioxanes; D023303:Oxazolidinones; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2