The Synthesis And The Anti-senil Dementia Effects Study Of The Derivates Of 2-Substituted Clausenamide Esters

Clausenamide is isolated from aqueous extract of leaves of Clausena lansium. Based on the pharmacological study, clausenamide could markedly decrease the activity of mice serum ALT caused by CCl4, enhance the synaptic transmission in the dentate gyrus and protect the cerebrum in hypoxia and ischemia damage. It can be used as liver protectant or nootropics. According to the basic principle of the optimization of the lead compound, such as molecular diversity, molecular similarity and molecular complementarity, using clausenamide as the lead compound, fourteen target compounds were designed and synthesized in this article, all of which have not been reported yet. The systematically biological screening of these compounds is to find some higher biological activity compounds.The selection of acylating agents and the study in the condition of acylation reaction were reported in this thesis. In terms of the ability, price, acquisition, reaction mechanism and coproduct, acy lchloride, acid anhydride and isocyanate were selected. The bettered reaction routes were definited through studying the effect factor to the acylation reaction, for instance, the molar ratio of the reactant, reaction temperature, reaction time, catalyst, and postprocessing of the reaction. All of the target compounds were characterized by means of IR , 1H-NMR, MS and elemental analysis.The result of the acetylcholinesterase(AchE) inhibitor screening in vitro suggested that fourteen target compounds showed very limited inhibitory activity or even none. Additionally, there were no statistic differences between the model group and observed groups coming to changes of alanine aminotransferase(ALT) values and icteric index. Further anti-senil dementia activity estimate is under processs.