硫色满-4-酮类乙酰胆碱酯酶抑制剂的设计、合成及活性评价  

Design,Synthesis and Evaluation of Thiochroman-4-ones as Acetylcholinesterase Inhibitors

作　　者：马正月[1] 张仕国[1] 张元功[1] 申蕊[1] 王伟华[1] 杨琦[1] 杨更亮[1] 

机构地区：[1]河北大学药学院,河北省药物质量分析控制重点实验室,河北保定071002

出　　处：《中国药学杂志》2013年第20期1774-1778,共5页Chinese Pharmaceutical Journal

基　　金：国家"重大新药创制"科技重大专项资助项目(2012ZX09103-101-057);国家自然科学基金资助项目(21175031;20905019)

摘　　要：目的为了研究硫色满-4-酮衍生物对乙酰胆碱酯酶的活性作用。方法采用取代的苯硫酚为原料,经取代反应和浓硫酸环合反应制备了6-羟基硫色满-4-酮,与苄基哌嗪反应制备3-(4-苄基哌嗪-1-甲基)硫色满-4-酮Mannich碱类盐酸盐,并将其用于乙酰胆碱酯酶(AChE)体外活性抑制实验。结果目标化合物具有AChE抑制活性,在微摩尔范围内,化合物8a的IC50=0.96μmol·L-1,优于对照组利斯的明。结论 3-(4-苄基哌嗪-1-甲基)硫色满-4-酮Mannich碱对乙酰胆碱酯酶有抑制活性,有进一步研究意义。OBJECTIVE To research the effect of thiochroman-4-one derivatives on acetylcholine esterase activity. METHODS Substituted thiophenols as the starting materials were transformed into 6-hydroxythioehroman-4-ones by substitution reaction and cycliza- tion reaction with concentrated sulfuric acid, and the resultant compounds were reacted with benzylpiperazins to prepare 3-（ 4- benzylpiperazine-l-methyl） thiochroman-4-ones hydrochloride, and their bioactivities as AChE inhibitors were measured in vitro. RESULTS The target compounds had AChE inhibitive activity in micromolar range, and compound 8a was better than rivastigmine with ICs0 = 0. 96μmol L-l. CONCLUSION 3-（4-Benzylpiperazine-l-methyl） thiochroman-4-ones show anti-acetylcholinesterase activity in vitro, which are worth further research.

关 键 词：硫色满-4-酮 乙酰胆碱酯酶抑制剂 哌嗪 阿尔茨海默病 

分 类 号：R97[医药卫生—药品]