A novel series of arylpiperazinylalkyl 2-benzoxazolones and 2-benzothiazolones 18-38 was designed, synthesized and tested to evaluate their affinity for the 5-HT7 and 5-HT1A receptors. Compounds with a 2-benzothiazolone nucleus generally had affinity values higher than the corresponding 2-benzoxazolone compounds. In particular, derivatives possessing a six or seven carbon chain linker between 2- benzothiazolone and arylpiperazine had Ki values in the subnanomolar range for the 5-HT1A receptor and in the low nanomolar range for the 5-HT7 receptor, indicating that they may be interesting dual ligands. Molecular modeling studies revealed different docking poses for the investigated compounds in homology models of 5-HT1A and 5-HT7 receptors, which explained their experimentally determined affinities and general low selectivity. Additionally, structural interaction fingerprints analysis identified the important amino acid residues for the specific interactions of long-chain arylpiperazines within the binding pockets of both serotonin receptors.
|Titolo:||Structure-activity relationships and molecular modeling studies of novel arylpiperazinylalkyl 2-benzoxazolones and 2-benzothiazolones as 5-HT7 and 5-HT1A receptor ligands|
|Data di pubblicazione:||2014|
|Citazione:||Structure-activity relationships and molecular modeling studies of novel arylpiperazinylalkyl 2-benzoxazolones and 2-benzothiazolones as 5-HT7 and 5-HT1A receptor ligands / Salerno L; Pittalà V; Modica M; Siracusa M; Intagliata S; Cagnotto A; Salmona M; Kurczab R; Bojarski A J; Romeo G. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 85(2014), pp. 716-726.|
|Appare nelle tipologie:||1.1 Articolo in rivista|