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Chinese Journal of Organic Chemistry >

2024 , Vol. 44 >Issue 1: 259 - 276

DOI: https://doi.org/10.6023/cjoc202306001

ARTICLES

Design, Synthesis, and Structure-Activity Relationship of Novel Potent and Highly Selective Cysteinyl Leukotriene Receptor 1 (CysLT1R) Antagonists

  • Jingyi Wang ,
  • Jinyu Liu ,
  • Dongsheng Chen ,
  • Huayan Chen ,
  • Xin Xie ,
  • Fajun Nan
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  • a University of Chinese Academy of Sciences, Beijing 100049
    b Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203
    c Nanjing University of Chinese Medicine, Nanjing 210023
*E-mail: ;
E-mail:

Received date: 2023-06-01

  Revised date: 2023-07-18

  Online published: 2023-09-08

Supported by

National Natural Science Foundation of China(82003571)

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Abstract

Cysteinyl leukotrienes (CysLTs) are lipid mediators of inflammation, and their receptors (CysLTsR) play an essential role in asthma, allergic rhinitis, cancer, and other diseases. According to earlier studies, 3-substituted 1H-indole-2-car- boxylic acid derivatives displayed selective cysteinyl leukotriene receptor 1 (CysLT1R) antagonistic activity, while their poor water solubility restricted their further evaluation. Hence, structural optimization was continued and multiple series of compounds were designed and synthesized based on existing research foundations. Among them, 3-(2-((E)-3-((3-((E)-2-(7-chloro- quinolin-2-yl)vinyl)phenyl)amino)-3-oxoprop-1-en-1-yl)phenyl)propanoic acid (T9) exhibits good selective CysLT1 receptor antagonistic activity and improved solubility, with IC50 value of (0.0066±0.0023) μmol/L and water solubility of 4.16×10－5 g/mL.

Key words： cysteinyl leukotriene; cysteinyl leukotriene receptor 1 (CysLT1R); selective antagonists

Cite this article

Jingyi Wang , Jinyu Liu , Dongsheng Chen , Huayan Chen , Xin Xie , Fajun Nan . Design, Synthesis, and Structure-Activity Relationship of Novel Potent and Highly Selective Cysteinyl Leukotriene Receptor 1 (CysLT1R) Antagonists[J]. Chinese Journal of Organic Chemistry, 2024 , 44(1) : 259 -276 . DOI: 10.6023/cjoc202306001

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