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

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

  • Eur J Med Chem. 2015 Mar 26:93:16-32. doi: 10.1016/j.ejmech.2015.01.054.
Shuang Han 1,  Fei-Fei Zhang 2,  Hai-Yan Qian 1,  Li-Li Chen 1,  Jian-Bin Pu 1,  Xin Xie 3,  Jian-Zhong Chen 4
Affiliations

Affiliations

  • 1 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • 2 CAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 3 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.
  • 4 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: chjz@zju.edu.cn.
PMID: 25644673 DOI: 10.1016/j.ejmech.2015.01.054
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.

Keywords

Cannabinoid CB2 receptor; Coumarin; GPCR; Structure–activity relationship.

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