Design, syntheses, structure-activity relationships and docking studies of coumarin derivatives as novel selective ligands for the CB2 receptor

被引：24
|
作者：
Han, Shuang [1 ]
Zhang, Fei-Fei [2 ]
Qian, Hai-Yan [1 ]
Chen, Li-Li [1 ]
Pu, Jian-Bin [1 ]
Xie, Xin [2 ]
Chen, Jian-Zhong [1 ]
机构：
[1] Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China
[2] Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Key Lab Receptor Res, Shanghai 201203, Peoples R China
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 93卷
基金：
中国国家自然科学基金;
关键词：
GPCR; Cannabinoid CB2 receptor; Structure-activity relationship; Coumarin; CANNABINOID RECEPTOR; INVERSE AGONISTS; 2-OXOQUINOLINE DERIVATIVES; ENDOCANNABINOID SYSTEM; ANTIPRURITIC AGENT; IN-VITRO; ANTAGONISTS; DISCOVERY; PAIN; POTENT;
D O I：
10.1016/j.ejmech.2015.01.054
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The CB2 receptor has been considered as an inspiring drug target for the treatment of pain and immune-related diseases. In the current manuscript, a novel series of coumarin derivatives is reported to be designed and synthesized by combining the structural features of some known ligands for the cannabinoid receptors based on the CoMFA model of the lead compounds. The compounds were evaluated to be highly selective ligands for the CB2 receptor over the CBI receptor by calcium mobilization assays. Furthermore, SAR results indicate that the functionality of a ligand is controlled by the substituent on the nucleus. Therefore, molecular docking simulations were performed to calculate the receptor-ligand interactions of our synthesized compounds binding to the CB2 receptor. The understanding of the binding modes could be advantageous for further development of selective ligands for the CB2 receptor. (C) 2015 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：16 / 32
页数：17
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