8-Hydroxyquinolin-2(1H)-one analogues as potential β2-agonists: Design, synthesis and activity study
8-Hydroxyquinolin-2(1H)-one analogues as potential β2-agonists: Design, synthesis and activity study
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8-Hydroxyquinolin-2(1H)-one 类似物作为潜在的 β2-激动剂：设计、合成和活性研究
DOI：
10.1016/j.ejmech.2021.113697
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发表时间：
2021
影响因子：
6.7
通讯作者：
Maosheng Cheng
中科院分区：
文献类型：
--
作者：
Gang Xing;Zhengxing Zhi;Ce Yi;Jitian Zou;Xuefeng Jing;Anthony Yiu-Ho Woo;Bin Lin;Li Pan;Yuyang Zhang;Maosheng Cheng
β-2激动剂与血浆β-2-肾上腺素能受体结合，引起cAMP积聚，被广泛用作慢性呼吸系统疾病的支气管扩张剂。在这里，我们设计并合成了一组8-羟基喹啉-2(1H)-酮类似物，并用细胞cAMP实验研究了它们的β-2-激动剂活性。在所测试的化合物中，化合物B05和C08被鉴定为有效的(EC50)和选择性的β-2激动剂。它们在非过表达的HEK293细胞中表现为部分β-2激动剂，在豚鼠离体气管条标本中具有快速的平滑肌松弛作用和较长的作用时间。综上所述，B05和C08是β-2激动剂，在慢性呼吸道疾病中具有潜在的应用前景。
β2-Agonists that bind to plasmalemmal β2-adrenoceptors causing cAMP accumulation are widely used as bronchodilators in chronic respiratory diseases. Here, we designed and synthesized a group of 8-hydroxyquinolin-2(1H)-one analogues and studied their β2-agonistic activities with a cellular cAMP assay. CompoundsB05andC08were identified as potent (EC50< 20 pM) and selective β2-agonists among the compounds tested. They behaved as partial β2-agonists in non-overexpressed HEK293 cells, and possessed rapid smooth muscle relaxant actions and long duration of action in isolated guinea pig tracheal strip preparations. In summary,B05andC08are β2-agonists with potential applicability in chronic respiratory diseases.