Chinese Journal of Organic Chemistry >
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).
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
Wang Ailing , Tao Bo , Ai Chunzhi , Zheng Xuefang . Design, Synthesis and Molecular Docking Study of 6,7-Dioxo-4-aryl-aminocoumarin[J]. Chinese Journal of Organic Chemistry, 2015 , 35(4) : 843 -850 . DOI: 10.6023/cjoc201411004
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