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.
|Titolo:||Synthesis of new arylpiperazinylalkylthiobenzimidazole, benzothiazole, or benzoxazole, derivatives as potent and selective 5-HT1A serotonin receptor ligands|
|Data di pubblicazione:||2008|
|Citazione:||Synthesis of new arylpiperazinylalkylthiobenzimidazole, benzothiazole, or benzoxazole, derivatives as potent and selective 5-HT1A serotonin receptor ligands / SIRACUSA M A; SALERNO L; MODICA M N; PITTALA' V; ROMEO G; AMATO M E; NOWAK M; BOJARSKI A J; MEREGHETTI I; CAGNOTTO A; MENNINI T. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 51(2008), pp. 4529-4538.|
|Appare nelle tipologie:||1.1 Articolo in rivista|