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设计、合成、对接研究及一些新型四氢色烯[3',4':5,6]吡喃并[2,3-b]喹啉-6(7H)-酮衍生物对乙酰胆碱酯酶和丁酰胆碱酯酶的抑制活性评价。

Design, synthesis, docking study and biological evaluation of some novel tetrahydrochromeno [3',4':5,6]pyrano[2,3-b]quinolin-6(7H)-one derivatives against acetyl- and butyrylcholinesterase.

机构信息

Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.

出版信息

Eur J Med Chem. 2013 Oct;68:291-300. doi: 10.1016/j.ejmech.2013.07.045. Epub 2013 Aug 11.

Abstract

Novel hybrid derivatives of two known scaffolds; tetrahydroaminoquinoline and coumarin were synthesized and evaluated for both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities. By means of an efficient nanocatalyst, the reaction time for the syntheses of the target compounds was reduced. Subsequently, Ellman's modified method was used to evaluate the enzyme inhibitory activity of the synthesized structures. It was observed that most hybrid structures were moderate to potent inhibitors of AChE compared to Tacrine as the reference drug among which 7f with 4-fluorophenyl substituent was the most active compound (IC50=5 nM).

摘要

新型混合衍生物的两个已知的支架;四氢氨基喹啉和香豆素的合成和评价为乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BuChE)的活性。通过一种高效的纳米催化剂,反应时间的合成目标化合物减少。随后,埃勒曼的改良方法用于评价酶抑制活性的合成结构。结果表明,大多数混合结构是中度至强效抑制剂的乙酰胆碱酯酶相比,他克林作为参考药物其中 7f 与 4-氟苯基取代基是最活跃的化合物(IC50 = 5 nM)。

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