A new series of β₂-adrenoceptor agonists bearing the 2-amino-2-phenylethanol scaffold was synthesized. Evaluation of the compounds using cell assays and an in vitro guinea pig trachea relaxation assay showed that 8-hydroxy-5-(2-hydroxy-1-((4-hydroxyphenethyl)amino)ethyl)quinolin-2(1H)-one (compound 5j) has the best pharmacological profile among all the evaluated compounds. The (S)-isomer of 5j was subsequently found to be the active enantiomer with a promising EC₅₀ value of 1.26 nM in stimulating β₂-adrenoceptor-mediated cAMP accumulation and a substantially higher selectivity for the β₂ than for the β₁ subtype. The putative binding mode of (S)-5j revealed by molecular docking of the β₂-adrenoceptor resembles that in agonist binding. Taken together, these results showed that compound (S)-5j is a promising hit worthy of further study for the development of β₂-adrenoceptor agonists.

一系列新的β ₂ -肾上腺素受体激动剂轴承2-氨基-2-苯基乙醇的支架来合成。使用细胞测定法和体外豚鼠气管松弛测定法对化合物的评估表明，8-hydroxy-5-（2-hydroxy-1-（（4-hydroxyphenethyl）amino）ethyl）quinolin-2（1 H）-one （化合物5j）在所有评估的化合物中均具有最佳的药理作用。的（S） -异构体5j上，随后发现是活性对映体有前途的EC ₅₀ 1.26纳米的值在刺激β ₂ -肾上腺素受体介导的cAMP累积和用于β显着更高的选择性₂比对β_1个亚型。的推定的结合模式（小号）-5j揭示的β的分子对接₂ -肾上腺素受体类似于在激动剂结合。总之，这些结果表明，化合物（小号）-5j是一种很有前途的命中值得的β的发展进一步研究的₂ -肾上腺素受体激动剂。