A series of 4(5)-(6-methylpyridin-2-yl)imidazoles 16–19 and -pyrazoles 22–29, 33, and 34 have been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in cell-based luciferase reporter assays. The 6-quinolinyl imidazole analogs 16 and 18 inhibited ALK5 phosphorylation with IC₅₀ values of 0.026 and 0.034 μM, respectively. In a luciferase reporter assay using HaCaT cells transiently transfected with p3TP-luc reporter construct, 18 displayed 66% inhibition at 0.05 μM, while competitor compounds 2 and 3 showed 44% inhibition. The binding mode of 18 generated by flexible docking studies with ALK5:18 complex shows that it fits well into the active site cavity of ALK5 by forming broad and tight interactions.

一系列的4（5） - （6-甲基吡啶-2-基）咪唑类16-19和-pyrazoles 22-29，33和34都在酶测定法和细胞中被合成并评价了它们的ALK5抑制活性基于荧光素酶报告基因的检测。6-喹啉基咪唑类似物16和18抑制ALK5磷酸化，IC ₅₀值分别为0.026和0.034μM。在使用p3TP-luc报告基因构建体瞬时转染的HaCaT细胞进行的荧光素酶报告基因分析中，18个在0.05μM时显示66％的抑制，而竞争化合物2和3在显示44％时被抑制。的绑定方式18通过柔性对接研究与ALK5生成：18复杂的显示，它通过形成广泛的和紧密的相互作用很符合ALK5的活性位点空腔。