A series of N-(3-((1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)benzenesulfonamides were designed as the first class of highly selective ZAK inhibitors. The representative compound 3h strongly inhibits the kinase activity of ZAK with an IC₅₀ of 3.3 nM and dose-dependently suppresses the activation of ZAK downstream signals in vitro and in vivo, while it is significantly less potent for the majority of 403 nonmutated kinases evaluated. Compound 3h also exhibits orally therapeutic effects on cardiac hypertrophy in a spontaneous hypertensive rat model.

中文翻译：

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的结构设计基于ñ - （3 - （（1 ħ -吡唑并[3,4- b ]吡啶-5-基）乙炔基）苯磺酰胺作为选择性亮氨酸拉链和无菌-α基序激酶（ZAK）抑制剂

设计了一系列N-（3-（（1 H-吡唑并[3,4- b ]吡啶基-5-基）乙炔基）苯磺酰胺作为第一类高选择性ZAK抑制剂。代表性化合物3h强烈抑制该激酶ZAK的活性为IC ₅₀为3.3 nM，并在体内和体外剂量依赖性地抑制ZAK下游信号的激活，而对大多数403种未突变激酶的效价则明显较低，化合物3h还在以下方面表现出口服治疗作用：自发性高血压大鼠模型中的心脏肥大。