6,7-二氧代-4-芳胺香豆素的设计、合成及分子对接研究
收稿日期: 2014-11-03
修回日期: 2014-11-28
网络出版日期: 2014-12-23
基金资助
国家自然科学基金(No. 21271036)资助项目.
Design, Synthesis and Molecular Docking Study of 6,7-Dioxo-4-aryl-aminocoumarin
Received date: 2014-11-03
Revised date: 2014-11-28
Online published: 2014-12-23
Supported by
Project supported by the National Natural Science Foundation of China (No. 21271036).
茶酚-氧位-甲基转移(COMT)酶抑制剂在治疗帕金森病中起到重要作用. 通过对现有COMT酶抑制剂托卡朋和恩托卡朋结构与活性关系分析, 推断含有儿茶酚结构的香豆素类化合物可能具有潜在的COMT酶抑制活性, 因此设计合成了一类新型的6,7-二氧代-4-芳胺香豆素, 通过理论计算, 研究了此类化合物对COMT酶抑制活性. 结果表明, 设计的10种6,7-二氧代-4-芳胺香豆素与COMT酶的对接效果均较好, 其中具有甲氧基乙基保护的儿茶酚结构化合物6,7-二[2-(甲氧基)乙氧]-4-(苯胺)香豆素(6b4)和6,7-二[2-(甲氧基)乙氧]-4-[(3-乙炔基)苯胺]香豆素(6b5)与COMT酶的对接效果尤为显著.
王爱玲 , 陶波 , 艾纯芝 , 郑学仿 . 6,7-二氧代-4-芳胺香豆素的设计、合成及分子对接研究[J]. 有机化学, 2015 , 35(4) : 843 -850 . DOI: 10.6023/cjoc201411004
Catechol-O-methyltransferase (COMT) inhibitors play an important role in the treatment of Parkinson's disease (PD). On the basis of the structure-activity relation (SAR) analysis of existing COMT inhibitors, entacapone and tolcapone, it has been derived that coumarin compounds containing catechol structures may have inhibitory bioactivities on COMT. Thus, the novel COMT inhibitors, 6,7-dioxo-4-arylaminocoumarin compounds, were designed, and their inhibitory bioactivities on COMT were investigated by theoretical calculation. The results show that ten 6,7-dioxo-4-aryl-aminocoumarin compounds exhibit good docking effect, especially 6,7-bis(2-methoxyethoxy)-4-phenylamino-2H-chromen-2-one (6b4) and 4-(3-ethynyl- phenyl)amino-6,7-bis(2-methoxyethoxy)-2H-chromen-2-one (6b5) which have the structure of catechol protected by methoxy ethyl group.
Key words： coumarin; COMT inhibitor; L-dopa; SAR; Parkinson's disease
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