香豆素-3-甲酰胺类化合物的合成及其对乙酰胆碱酯酶的抑制活性。
Synthesis and anticholinesterase activity of coumarin-3-carboxamides bearing tryptamine moiety.
机构信息
Department of Chemistry, Arak Branch, Islamic Azad University, Arak, Iran.
Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medicinal Sciences, Tehran, Iran.
出版信息
Eur J Med Chem. 2016 Oct 4;121:40-46. doi: 10.1016/j.ejmech.2016.05.014. Epub 2016 May 7.
A number of N-(2-(1H-indol-3-yl)ethyl)-2-oxo-2H-chromene-3-carboxamides were synthesized and tested against AChE and BuChE. The in vitro assessment of the synthesized compounds 4a-o revealed that most of them had significant activity toward AChE. The SAR study demonstrated that the introduction of benzyloxy moiety on the 7-position of coumarin scaffold can improve the anti-AChE activity. The best result was obtained with 7-(4-fluorobenzyl)oxy moiety in the case of compound 4o, displaying IC50 value of 0.16 μM. Based on the docking study of AChE, the prototype compound 4o was laid across the active site and occupied both peripheral anionic site (PAS) and catalytic anionic site (CAS).
许多 N-(2-(1H-吲哚-3-基)乙基)-2-氧代-2H-色烯-3-甲酰胺被合成并针对 AChE 和 BuChE 进行了测试。对合成化合物 4a-o 的体外评估表明，它们中的大多数对 AChE 具有显著的活性。SAR 研究表明，在香豆素支架的 7-位引入苯甲氧基可以提高抗 AChE 活性。在化合物 4o 的情况下，最好的结果是引入 7-(4-氟苯甲氧基)，其 IC50 值为 0.16 μM。基于 AChE 的对接研究，原型化合物 4o 横跨活性位点，并占据外周阴离子部位 (PAS) 和催化阴离子部位 (CAS)。
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