二苯甲基亚砜基乙酰胺及硫代乙酰胺类化合物的合成与生物活性研究

Synthesis and biological evaluation of novel diphenyl methane sulfinyl and diphenylthio-acetamide derivatives

基于发作性睡病治疗药物莫达非尼的结构,设计并合成了两个系列的新化合物,分别为2-[(二苯甲基)亚砜基]乙酰胺类和2-[(二苯甲基)硫代]乙酰胺类化合物,并测定了这些化合物的生物活性。以二苯基甲醇为原料,经取代、氧化和酰化等反应合成了15个目标化合物(6a～6o),其结构经ESI-MS、1H NMR和元素分析确证。以小鼠自主活动实验测定了合成化合物对小鼠中枢神经的影响。初步构效关系表明,化合物6c、6f、6h和6n能提高小鼠的自主活动,其中6h的中枢兴奋活性略强于阳性对照药莫达非尼。

According to the structure-activity relationships （SARs） of modafinil, a therapeutic drug of hypnolepsy, we designed and synthesized two series of compounds 2-[（diphenylmethane）sulfinyl] acetamides and 2-[（diphenylmethyl）thio] acetamides, and measured their biological activities. The target compounds （6a-6o） were synthesized beginning with diphenyl carbinol by substitution, oxidation, acylation and so on. Their structures were confirmed by ESI-MS, ~H NMR and elemental analysis. The central stimulatory effects of the target compounds were determined by the independent activity assay on mice. Compounds 6e, 6f and 6n have considerable activities, while the central stimulative effect of 6h is slightly better than the positive control modafinil.