二氟代苯甲亚砜基乙酰胺类化合物的合成与生物活性  

Synthesis and biological evaluation of novel difluorophenyl methanesulfinyl acetamide derivatives

作　　者：朱雄[1] 黄文龙[2] 皋聪[3] 朱炎[1] 张印广 凌勇[5] 

机构地区：[1]中国药科大学医药化工研究所,南京210009 [2]中国药科大学新药研究中心,南京210009 [3]中国药科大学药理学教研室,南京210009 [4]北京协和药厂,北京102600 [5]南通大学医学院,南通226001

出　　处：《中国药科大学学报》2012年第1期16-20,共5页Journal of China Pharmaceutical University

摘　　要：在莫达非尼的结构基础上设计并合成了一系列新的二氟代苯甲亚砜基乙酰胺类化合物,并对这些化合物的中枢兴奋活性进行了测定。以二(4-氟苯基)甲醇为原料,经取代、酯化、胺解和氧化等反应合成了二氟代苯甲亚砜基乙酰胺类衍生物,共计16个目标化合物(5a～5p),其结构经ESI-MS、1H NMR、IR和元素分析确证,然后以小鼠自主活动实验测定了其中枢兴奋活性。初步研究表明,化合物5a,5b,5c,5e以及5j能提高小鼠的自主活动,其中化合物5b的中枢兴奋活性与莫达非尼相当。Based on the study results of known structure-activity relationships（SARs） of modafinil derivatives,a series of difluorophenyl methanesulfinyl acetamide compounds were designed and synthesized,and their central stimulative activities were investigated.The target compounds were synthesized starting from dis（4-fluorophenyl） methanol by substitution,esterification,amination and oxidation.Sixteen target compounds（5a-5p） were synthesized and their structures were confirmed by ESI-MS,1H NMR,IR and elemental analysis.Their central stimulative effects were evaluated by the independent activity assay in mice.Preliminary results of pharmacological test showed that compounds 5a,5b,5c,5e and 5j enhanced activities of healthy mice,and the central stimulative activity of 5b was comparable to that of the positive control modafinil.

关 键 词：莫达非尼 亚砜基乙酰胺 合成 中枢兴奋活性 

分 类 号：R914.5[医药卫生—药物化学] R965[医药卫生—药学]