The impact of the halogen bonding on D-2 and 5-HT1A/5-HT7 receptor activity of azinesulfonamides of 4-[(2-ethyl)piperidinyl-1-yl] phenylpiperazines with antipsychotic and antidepressant properties

作者：Partyka Anna; Kurczab Rafal; C****e Vittorio; Satala Grzegorz; Marciniec Krzysztof; Pasierb Agnieszka; Jastrzebska Wiesek Magdalena; Pawlowski Maciej; Wesolowska Anna; Bojarski Andrzej J; Zajdel Pawel^*

来源：Bioorganic & Medicinal Chemistry, 2017, 25(14): 3638-3648.

DOI：10.1016/j.bmc.2017.04.046

• Azinesulfonamides
• Semi-rigid long-chain arylpiperazines
• Multimodal dopamine/serotonin ligands
• Multi-target ligands
• Halogen bonding
• Schizophrenia
• Depression

A series of azinesulfonamides of long-chain arylpiperazine derivatives with semi-rigid alkylene spacer was designed, synthesized, and biologically evaluated using in vitro methods for their affinity for dopaminergic D2 and serotoninergic 5-HT1A, 5-HT2A, 5-HT6 and 5-HT7 receptors. Docking to homology models revealed a possible halogen bond formation in complexes of the most potent ligands and the target receptors. The study allowed for the identification of compound 5-({4-(2-[4-(2,3-dichlorophenyl) piperazin-1-yl]ethyl)piperidin-1-yl}sulfonyl)quinoline (21), which behaved as D-2, 5-HT1A and 5-HT7 receptor antagonist. In preliminary in vivo studies, compound 21 displayed distinct antipsychotic properties in the MK-801-evoked hyperactivity test in mice at a dose of 10 mg/kg, and exerted antidepressant -like effect in a forced swim test in mice (MED = 0.625 mg/kg, i.p.).

• 出版日期2017-7-15