【摘要】 半胱氨酰白三烯（CysLTs）是炎症脂介质,其受体（CysLTsR）在哮喘、过敏性鼻炎和癌症等疾病的发生发展中发挥重要作用.已发现3-取代1H-吲哚-2-羧酸衍生物具有半胱氨酰白三烯受体1 （CysLT₁R）拮抗活性,但较差的溶解度限制了其进一步研究.基于已有研究基础继续进行结构优化,设计合成了多个系列化合物,其中3-{2-[（1E）-3-（{3-[（1E）-2-（7-氯喹啉-2-基）乙烯基]苯基}氨基）-3-氧亚基丙-1-烯基]苯基}丙酸（T9）展现出良好的选择性CysLT₁受体拮抗活性和改善的溶解度,其IC₅₀值为（0.0066±0.0023）μmol/L,在水中溶解度为4.16×10^-5 g/mL.更多还原

【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-carboxylic 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-chloroquinolin-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^-5g/mL.更多还原