The impact of the halogen bonding on D2 and 5-HT1A/5-HT7 receptor activity of azinesulfonamides of 4-[(2-ethyl)piperidinyl-1-yl]phenylpiperazines with antipsychotic and antidepressant properties

Bioorganic & Medicinal Chemistry
Anna PartykaPaweł Zajdel

Abstract

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 D2, 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 10mg/kg, and exerted antidepressant-like effect in a forced swim test in mice (MED=0.625mg/kg, i.p.).

Citations

Sep 19, 2019·European Journal of Medicinal Chemistry·Giuseppe RomeoMaria Nunziata Modica
Oct 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ivana I JevtićRodrigo Teodoro
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Vittorio CanalePaweł Zajdel
Oct 24, 2018·Journal of Medicinal Chemistry·Márton VassChris de Graaf

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