Malinka W, Rutkowska M
Department of Chemistry of Drugs, Wrocław University of Medicine, Poland.
Farmaco. 1997 Oct;52(10):595-601.
The synthesis of 2H-4,6-dimethyl-2-[(4- phenylpiperazin-1-yl)methyl]-3-oxo-2,3-dihydroisothiazolo[5, 4-b]pyridine. (3) and its biological properties are described. Compound 3 pharmacologically evaluated in vivo by use of behavioral tests showed to have a profile of activity characteristic of stimulation of the central serotoninergic system, mostly 5-HT52A receptors (anorectic action: 2 mg/kg i.p., 8.5 mg/kg po) However, receptor activity of isothiazolopyridine 3 was not confirmed in vitro using 5-HT2A and 5-HT1A receptor binding technique. Molecular modeling studies demonstrated that it is difficult to predict bioactive conformation of title molecule 3.
2H-4,6-二甲基-2-[(4-苯基哌嗪-1-基)甲基]-3-氧代-2,3-二氢异噻唑并[5,4-b]吡啶(3)的合成及其生物学性质已被描述。通过行为测试在体内进行药理评估的化合物3显示出具有刺激中枢5-羟色胺能系统的活性特征,主要是5-HT52A受体(厌食作用:腹腔注射2mg/kg,口服8.5mg/kg)。然而,使用5-HT2A和5-HT1A受体结合技术在体外未证实异噻唑并吡啶3的受体活性。分子模拟研究表明,难以预测标题分子3的生物活性构象。