title: Design, syntheses, structure-activity relationships and docking studies of coumarin derivatives as novel selective ligands for the CB2 receptor.
abstract: 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 CB1 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.
authors: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors: Shuang
authors: S
authors: Han
authors: CAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors: Fei-Fei
authors: FF
authors: Zhang
authors: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors: Hai-Yan
authors: HY
authors: Qian
authors: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors: Li-Li
authors: LL
authors: Chen
authors: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors: Jian-Bin
authors: JB
authors: Pu
authors: CAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: xxie@simm.ac.cn.
authors: Xin
authors: X
authors: Xie
authors: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: chjz@zju.edu.cn.
authors: Jian-Zhong
authors: JZ
authors: Chen
mesh_terms: D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003412:Cricetulus; D015195:Drug Design; D008024:Ligands; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000235:genetics; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D003374:Coumarins; D008024:Ligands; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D002118:Calcium
keywords: Cannabinoid CB2 receptor; Coumarin; GPCR; Structure–activity relationship