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Journal of Chinese Pharmaceutical Sciences ›› 2017, Vol. 26 ›› Issue (7): 504-511.DOI: 10.5246/jcps.2017.07.056

• Original articles • Previous Articles     Next Articles

Design, synthesis and bioevaluation of isoflavone derivative as a novel CLR/RAMP1 antagonist

Junjie Wang, Chao Wang, Peng Lü, Yan Niu*, Hongyue Li, Wenhui Huang, Can Li, Fengrong Xu, Lei Liang, Ping Xu*   

  1. Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2017-04-29 Revised:2017-05-20 Online:2017-07-28 Published:2017-06-19
  • Contact: Tel.: +86-010-82805281, E-mail: yanniu@bjmu.edu.cn
  • Supported by:

    National Basic Research Program of China (Grant No. 2012CB518000), Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20120001110010).

Abstract:

CGRP receptor (CLR) is a B class GPCR that functions only when combined with RAMPs. CLR/RAMP1 has been regarded as a promising target for migraine treatment, as its antagonists have been proved to be effective recently. In the present study we designed and synthesized small molecular antagonists against CLR/RAMP1, resulting in a novel type of structure with acceptable high potency. The molecules were designed via virtual screening. Afterwards, a series of modification were conducted on the hit compounds, resulting in compound 8 as the best scored compound in docking, which was further validated in vitro by cell-based functional assay. 

Key words: Isoflavone, CLR/RAMP1 antagonist, Research

CLC Number: 

Supporting: