新型螺吡咯烷连接咪唑杂环混合化合物的设计、合成及乙酰胆碱酯酶抑制活性。
Design, synthesis and cholinesterase inhibitory activity of novel spiropyrrolidine tethered imidazole heterocyclic hybrids.
机构信息
Department of Chemistry, College of Science, King Saud University, P.O Box 2455, Riyadh 11451, Saudi Arabia.
Department of Chemistry, College of Science, King Saud University, P.O Box 2455, Riyadh 11451, Saudi Arabia.
出版信息
Bioorg Med Chem Lett. 2020 Jan 15;30(2):126789. doi: 10.1016/j.bmcl.2019.126789. Epub 2019 Nov 7.
A small library of structurally fascinating spiropyrrolidine tethered imidazole heterocylic hybrids has been synthesized regioselectively in good yields employing [bmim]Br mediated 1,3-diplar cycloaddition strategy. The new class of azomethine ylide generated in situ from l-histidine and 11H-indeno[1,2-b]quinoxalin-11-one reacts with various substituted β-nitrostyrenes affording the spiropyrrolidine tethered imidazole heterocylic hybrids. Compounds thus synthesized were assessed for their in vitro cholinesterase (ChEs) inhibitory activities, among them compounds possessing 4-methyl and 4-methoxy substituents on the aryl ring showed potent activities with IC values of 2.02 ± 0.05 and 2.05 ± 0.06 μM against AChE and 12.40 ± 0.14 and 11.45 ± 0.28 μM against BChE enzyme, respectively. In addition, the most active compounds were performed for their molecular docking simulation and the results revealed interesting binding templates to the active site channel of cholinesterase enzymes.
已通过[bmim]Br 介导的 1,3-双极化环加成策略，高区域选择性地合成了结构有趣的螺吡咯烷连接咪唑杂环的小型文库。由 l-组氨酸和 11H-茚并[1,2-b]喹喔啉-11-酮原位生成的新类氮杂叶立德与各种取代的β-硝基苯乙烯反应，得到螺吡咯烷连接的咪唑杂环杂合体。评估了如此合成的化合物对体外乙酰胆碱酯酶 (ChE) 的抑制活性，其中在芳环上带有 4-甲基和 4-甲氧基取代基的化合物对 AChE 的 IC 值分别为 2.02±0.05 和 2.05±0.06 μM，对 BChE 酶的 IC 值分别为 12.40±0.14 和 11.45±0.28 μM。此外，对最活性化合物进行了分子对接模拟，结果显示出与胆碱酯酶酶的活性部位通道结合的有趣模板。
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