Design,Synthesis,and Structure-Activity Relationship of Novel Potent and Highly Selective Cysteinyl Leukotriene Receptor 1(CysLT1R)Antagonists
Cysteinyl leukotrienes(CysLTs)are lipid mediators of inflammation,and their receptors(CysLTsR)play an essen-tial role in asthma,allergic rhinitis,cancer,andother diseases.According to earlier studies,3-substituted lH-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 com-pounds 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.
NETL
NSTL
万方数据
