苯氧茚酮类衍生物的合成和乙酰胆碱酯酶抑制活性

Synthesis and AchE inhibitory activity of 2-phenoxyindan-1-one derivatives

目的设计、合成新型的AchE抑制剂。方法在K2CO3和乙腈存在下,将2-溴-5,6-二甲氧基-1-茚酮与多种胺烷基苯酚缩合得到一系列苯氧茚酮类衍生物,并采用改进的E llm an方法研究它们的体外AchE和BchE抑制活性。结果合成了16个未见文献报道的化合物8a^p,结构经IR,1H NMR,MS及元素分析确证。初步体外AchE,BchE抑制活性试验表明,绝大部分化合物都显示出良好的抑制AchE活性,其中8h的IC50为50.0 nmol.L-1,与石杉碱甲相近(IC50=53.0 nmol.L-1);而所有化合物基本都无BchE抑制活性。结论该类衍生物具有较强的AchE抑制活性,有进一步研究的价值。

Aim To design and synthesize novel AchE inhibitors. Methods The condensation of 2- bromo-5,6-dimethoxy-indan-1-one with various aminoalkyl phenols in the presence of K2CO3 and acetonitrile gave the corresponding title compounds, and the in vitro AchE and BchE inhibitory activities were evaluated by the modified Ellman method. Results Sixteen novel target compounds 8a - p were synthesized, their structures were confirmed by ^1 H NMR, MS, IR and elemental analysis. Preliminary pharmacological test demonstrated that most of these compounds displayed high Ache inhibitory activities, the IC50 of the most potent inhibitor 8h was 50. 0 nmol · L^-1, similar to that of Huperzine A （ IC50 = 53.0 nmol · L^-1 ）, while all the compounds were almost inactive against BchE. Conclusion 2-Phenoxy-indan- 1-one derivatives exhibit high activities of AchE inhibition and are worthy of further investigation.