Design, synthesis, and SAR analysis of novel selective sigma1 ligands.
A new series of arylalkyl- and alkenylamines was designed, synthesized, and evaluated for binding to sigma(1) and sigma(2) receptors. Many compounds exhibited nanomolar affinity for sigma(1) subtype receptor with good selectivity over sigma(2). A molecular modeling study was conducted in order to rationalize the experimental data, and the structure-receptor affinities are discussed.
Collina
Simona
S
Dipartimento di Chimica Farmaceutica, Università di Pavia, Viale Taramelli 12, 27100 Pavia, Italy. simona.collina@unipv.it
Loddo
Guya
G
Urbano
Mariangela
M
Linati
Laura
L
Callegari
Athos
A
Ortuso
Francesco
F
Alcaro
Stefano
S
Laggner
Christian
C
Langer
Thierry
T
Prezzavento
Orazio
O
Ronsisvalle
Giuseppe
G
Azzolina
Ornella
O
D000818:Animals; D001921:Brain / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D015195:Drug Design; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008566:Membranes / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D011869:Radioligand Assay; D017480:Receptors, sigma / Q000187:drug effects*; D013329:Structure-Activity Relationship; D000097605:Sigma-1 Receptor
D007202:Indicators and Reagents; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor