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 / P., Ioan; Ciogli, Alessia; F., Sirci; R., Budriesi; B., Cosimelli; Pierini, Marco; E., Severi; A., Chiarini; G., Cruciani; Gasparrini, Francesco; D., Spinelli; E., Carosati. - In: ORGANIC & BIOMOLECULAR CHEMISTRY. - ISSN 1477-0520. - STAMPA. - 10:(2012), pp. 8994-9003. [10.1039/C2OB25946J]

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

CIOGLI, Alessia;PIERINI, MARCO;GASPARRINI, Francesco;
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.
2012
Absolute configuration, Calcium channel blockers, Calcium channels, Hydrophilic and hydrophobic interactions, In-silico, Long chains, Pharmacological profiles, Short chain compound, Structural effect
01 Pubblicazione su rivista::01a Articolo in rivista
Absolute configuration and biological profile of two thiazinooxadiazol-3-ones with L-type calcium channel activity: a study of the structural effects / P., Ioan; Ciogli, Alessia; F., Sirci; R., Budriesi; B., Cosimelli; Pierini, Marco; E., Severi; A., Chiarini; G., Cruciani; Gasparrini, Francesco; D., Spinelli; E., Carosati. - In: ORGANIC & BIOMOLECULAR CHEMISTRY. - ISSN 1477-0520. - STAMPA. - 10:(2012), pp. 8994-9003. [10.1039/C2OB25946J]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/487273
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