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.

Absolute configuration and biological profile of two thiazinooxadiazol-3-ones with L-type calcium channel activity: a study of the structural effects

IOAN, PIERFRANCO;BUDRIESI, ROBERTA;CHIARINI, ALBERTO;SPINELLI, DOMENICO;
2012

Abstract

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.
ORGANIC & BIOMOLECULAR CHEMISTRY
Pierfranco Ioan; Alessia Ciogli; Francesco Sirci; Roberta Budriesi; Barbara Cosimelli; Marco Pierini; Elda Severi; Alberto Chiarini; Gabriele Cruciani; Francesco Gasparrini; Domenico Spinelli; Emanuele Carosati
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/144345
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