PDF(Pubmed)
Abstract：
Selective butyrylcholinesterase inhibitors are considered promising drug candidates for the treatment of Alzheimer\'s disease. In this work, one rivastigmine-bambuterol hybrid (MTR-1) and fourteen of its analogues were synthesized, purified, and characterized. In vitro cholinesterase assays showed that all the compounds were more potent inhibitors of BChE when compared to AChE. Further investigations indicated that MTR-3 (IC50(AChE) > 100,000 nM, IC50(BChE) = 78 nM) was the best compound in the series, showing high butyrylcholinesterase selectivity and inhibition potency, the potential to permeate the blood-brain barrier, and longer-lasting BChE inhibition than bambuterol. These compounds could be used to discover novel specific BChE inhibitors for the treatment of Alzheimer\'s disease.
摘要：
选择性丁酰胆碱酯酶抑制剂被认为是治疗阿尔茨海默病的有希望的候选药物。在这项工作中,合成了一种利伐斯的明-班布特罗杂种（MTR-1）及其14种类似物，纯化,和特点。体外胆碱酯酶测定显示,与AChE相比,所有化合物都是更有效的BChE抑制剂。进一步的研究表明，MTR-3（IC50（AChE）>100,000nM，IC50(BChE)=78nM)是该系列中最好的化合物，显示出高的丁酰胆碱酯酶选择性和抑制效力，渗透血脑屏障的潜力，和比班布特罗更持久的BChE抑制作用。这些化合物可用于发现用于治疗阿尔茨海默病的新型特异性BChE抑制剂。
