Synthesis and pharmacological evaluation of new arylpiperazines. 3-{4-[4-(3-chlorophenyl)-1-piperazinyl]butyl}-quinazolidin-4-one: A dual serotonin 5-HT1A/5-HT2A receptor ligand with an anxiolytic-like activity

摘要: On the basis of systematic studies on structure–activity relationships in arylpiperazine group serotonin ligands, 12 new derivatives containing quinazolidin-4(3H)-one (1–4), 2-phenyl-2,3-dihydrophthalazine-1,4-dione (5–8) or 1-phenyl-1,2-dihydropyridazine-3,6-dione (9–12) fragments were synthesized. The majority tested compounds (2, 4, 7, 8 and 10–12) showed a high affinity for 5-HT1A receptors (Ki=11–54 nM) two (1, 2) found active at 5-HT2A sites (16 68 nM, respectively). All ligands vivo revealed an antagonistic activity postsynaptic receptors, three them behaved as agonists presynaptic ones. Additionally, both meta-chlorophenylpiperazine quinazolidin-4-one fragment features receptor antagonists. dual 5-HT1A/5-HT2A ligand (2) was further its potential psychotropic activity. It distinct anxiolytic-like conflict drinking test rats observed effect more potent terms dose, than that produced by diazepam (used reference drug).