Absolute configuration and biological profile of two thiazinooxadiazol-3-ones with L-type calcium channel activity: a study of the structural effects.
In the framework of our interest in racemic thiazinooxadiazol-3-ones we determined the absolute configuration and the biological activity as L-type calcium channel blockers of two compounds that differ in the length of the acetal chain, which could affect the pharmacological profile. We observed an interesting inversion of the stereoselectivity, with the activity residing on the R-form for a short chain compound (n = 1) and on the S-form for a long chain one (n = 12). The length of the linear acetal chain appears to be able to invert the stereoselectivity of such a class of compounds, and in silico simulations suggested that this different behaviour might be explained by different hydrophilic and hydrophobic interactions with the binding site.
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
Pierfranco
P
Ioan
Alessia
A
Ciogli
Francesco
F
Sirci
Roberta
R
Budriesi
Barbara
B
Cosimelli
Marco
M
Pierini
Elda
E
Severi
Alberto
A
Chiarini
Gabriele
G
Cruciani
Francesco
F
Gasparrini
Domenico
D
Spinelli
Emanuele
E
Carosati
D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D004583:Electrons; D008958:Models, Molecular; D008968:Molecular Conformation; D010069:Oxadiazoles / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D010069:Oxadiazoles; C522526:oxadiazol-3-one