2. Academic Validation
  3. Design, synthesis, and biological evaluations of 5-aryl-pyrazole-3-carboxamide derivatives as selective CB2 receptor agonists for the treatment of colitis

Design, synthesis, and biological evaluations of 5-aryl-pyrazole-3-carboxamide derivatives as selective CB2 receptor agonists for the treatment of colitis

  • Eur J Med Chem. 2025 Feb 5:283:117117. doi: 10.1016/j.ejmech.2024.117117.
Bei-Er Jiang 1,  Ying He 2,  Jie Chen 3,  Xing-Wu Jiang 4,  Zi-Liang Qiu 4,  Qiu-Wen Liang 4,  Xin-Long Gao 2,  Han-Kun Zhang 4,  Hai-Gang Tian 3,  Ming-Yao Liu 4,  Wei-Qiang Lu 5,  Li-Fang Yu 6
Affiliations

Affiliations

  • 1 Naval Medical Center, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, PR China; Drug Discovery Unit, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, PR China.
  • 2 Naval Medical Center, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, PR China.
  • 3 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, PR China.
  • 4 Drug Discovery Unit, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, PR China.
  • 5 Drug Discovery Unit, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, PR China. Electronic address: wqlu@bio.ecnu.edu.cn.
  • 6 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, PR China. Electronic address: lfyu@sat.ecnu.edu.cn.
PMID: 39653620 DOI: 10.1016/j.ejmech.2024.117117
Abstract

Synthetic CB2 receptor agonists exhibit great potential in the treatment of neurodegenerative diseases, chronic and neuropathic pain, Cancer, and inflammation-associated pathologies while avoiding adverse psychoactive effects caused by interactions with CB1 receptors. Herein, a class of 5-aryl-pyrazole-3-carboxamide derivatives was thus designed, synthesized, and biologically evaluated. Among the compounds tested, compound 33, one of the most potent leads, showed a remarkably high potency and selectivity at the CB2 receptor (EC50, CB2 = 16.2 nM, EC50, CB1 > 105 nM). Furthermore, 33 treatment significantly attenuate colon inflammation in a dextran sodium sulfate (DSS)-induced mouse model of colitis, supporting that CB2 receptor agonists might serve as potential therapeutics for treating colitis.

Keywords

5-aryl-pyrazole-3-carboxamide derivatives; CB2 receptor; Colitis.

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