The impact of the halogen bonding on D 2 and 5-HT 1A /5-HT 7 receptor activity of azinesulfonamides of 4-[(2-ethyl)piperidinyl-1-yl]phenylpiperazines with antipsychotic and antidepressant properties.

Autor: Partyka A; Department of Clinical Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland., Kurczab R; Institute of Pharmacology, Polish Academy of Sciences, Department of Medicinal Chemistry, 12 Smętna Street, 31-343 Krakow, Poland., Canale V; Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland., Satała G; Institute of Pharmacology, Polish Academy of Sciences, Department of Medicinal Chemistry, 12 Smętna Street, 31-343 Krakow, Poland., Marciniec K; Department of Organic Chemistry, Medical University of Silesia, 4 Jagiellońska Street, 41-200 Sosnowiec, Poland., Pasierb A; Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland., Jastrzębska-Więsek M; Department of Clinical Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland., Pawłowski M; Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland., Wesołowska A; Department of Clinical Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland., Bojarski AJ; Institute of Pharmacology, Polish Academy of Sciences, Department of Medicinal Chemistry, 12 Smętna Street, 31-343 Krakow, Poland., Zajdel P; Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland. Electronic address: pawel.zajdel@uj.edu.pl.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2017 Jul 15; Vol. 25 (14), pp. 3638-3648. Date of Electronic Publication: 2017 May 04.
DOI: 10.1016/j.bmc.2017.04.046
Abstrakt: 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 D 2 and serotoninergic 5-HT 1A , 5-HT 2A , 5-HT 6 and 5-HT 7 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-HT 1A and 5-HT 7 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.).
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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