Partyka Anna, Kurczab Rafał, Canale Vittorio, Satała Grzegorz, Marciniec Krzysztof, Pasierb Agnieszka, Jastrzębska-Więsek Magdalena, Pawłowski Maciej, Wesołowska Anna, Bojarski Andrzej J, Zajdel Paweł
Department of Clinical Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
Institute of Pharmacology, Polish Academy of Sciences, Department of Medicinal Chemistry, 12 Smętna Street, 31-343 Krakow, Poland.
Bioorg Med Chem. 2017 Jul 15;25(14):3638-3648. doi: 10.1016/j.bmc.2017.04.046. Epub 2017 May 4.
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 and serotoninergic 5-HT, 5-HT, 5-HT and 5-HT 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, 5-HT and 5-HT 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.).
设计、合成了一系列具有半刚性亚烷基间隔基的长链芳基哌嗪衍生物的吖嗪磺酰胺，并采用体外方法对其与多巴胺能D受体和5-羟色胺能5-HT、5-HT、5-HT和5-HT受体的亲和力进行了生物学评价。与同源模型对接显示，在最有效的配体与靶受体的复合物中可能形成卤键。该研究鉴定出化合物5-({4-(2-[4-(2,3-二氯苯基)哌嗪-1-基]乙基)哌啶-1-基}磺酰基)喹啉(21)，其表现为D、5-HT和5-HT受体拮抗剂。在初步体内研究中，化合物21在10mg/kg剂量下对小鼠MK-801诱发的多动试验显示出明显的抗精神病特性，并在小鼠强迫游泳试验中发挥抗抑郁样作用(MED=0.625mg/kg，腹腔注射)。
