新型乙酰胆碱酯酶抑制剂的设计、合成与活性研究

Design, synthesis and evaluation of new acetylcholinesterase inhibitors

本文设计、合成了一类全新结构类型的2-氨基-4-苯基噻唑类化合物,并考察了这些化合物对乙酰胆碱酯酶活性的抑制作用。以α-溴代苯乙酮为起始原料,经Hantzsch、酰化和取代反应合成了2-氨基-4-苯基噻唑类化合物,并利用Ellman分光光度法考察了它们对乙酰胆碱酯酶(AChE)的体外抑制活性。实验结果表明目标化合物均具有一定的AChE抑制活性,其中化合物8a抑制活性最好,其IC50达到了3.54μmol·L-1,优于对照药利斯的明。2-氨基-4-苯基噻唑类化合物对乙酰胆碱酯酶具有较好的抑制活性,需要进一步深入研究。

A series of novel 2-amino-4-phenylthiazole derivatives were designed and synthesized, furthermore, their inhibition effect on acetylcholinesterase were investigated. 2-Amino-4-phenylthiazoles were prepared from a-bromoacetophenones by Hantzsch reaction, acylation reaction and substitution reaction. Moreover, their bioactivities as AChE inhibitors in vitro were measured with Ellman spectrophotometry. The results showed that most of them had a certain inhibition activity on ACHE, and the compound 8a was the best of them. The IC50 of 8a to AChE is 3.54 μmol·L^-1, and the value was better than that of rivastigmine. 2-Amino- 4-phenylthiazole derivatives showed a certain bioactivity in vitro, which were worth further investigation.