A series of new compounds containing a benzimidazole, benzothiazole, or benzoxazole nucleus linked to an arylpiperazine by different thioalkyl chains was prepared. They were tested in radioligand binding experiments to evaluate their affinity for 5-HT 1A and 5-HT 2A serotonergic, alpha 1 adrenergic, D1, and D2 dopaminergic receptors. Many of tested compounds showed an interesting binding profile; in particular, 36 displayed very high 5-HT 1A receptor affinity and selectivity over all the other investigated receptors. Selected compounds, evaluated in functional assays, showed antagonistic or partial agonistic activity at 5-HT 1A receptor. An extensive conformational research using both NMR and modeling techniques indicated that extended conformations predominated in vacuum, in solution and during interactions with 5-HT 1A receptor. Finally, the elaborated binding mode of selected compounds at 5-HT 1A receptor was used to explain the influence of spacer length on ligands affinity.

Synthesis of new arylpiperazinylalkylthiobenzimidazole, benzothiazole, or benzoxazole, derivatives as potent and selective 5-HT1A serotonin receptor ligands

SIRACUSA, Maria Angela;SALERNO, Loredana;MODICA, Maria Nunziata;PITTALA', Valeria;ROMEO, Giuseppe;AMATO, Maria Emanuela;
2008

Abstract

A series of new compounds containing a benzimidazole, benzothiazole, or benzoxazole nucleus linked to an arylpiperazine by different thioalkyl chains was prepared. They were tested in radioligand binding experiments to evaluate their affinity for 5-HT 1A and 5-HT 2A serotonergic, alpha 1 adrenergic, D1, and D2 dopaminergic receptors. Many of tested compounds showed an interesting binding profile; in particular, 36 displayed very high 5-HT 1A receptor affinity and selectivity over all the other investigated receptors. Selected compounds, evaluated in functional assays, showed antagonistic or partial agonistic activity at 5-HT 1A receptor. An extensive conformational research using both NMR and modeling techniques indicated that extended conformations predominated in vacuum, in solution and during interactions with 5-HT 1A receptor. Finally, the elaborated binding mode of selected compounds at 5-HT 1A receptor was used to explain the influence of spacer length on ligands affinity.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/5550
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