A series of 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazoles and -pyrazoles 14a–c, 15a–c, 16a, 16b, 19a–d, 21a, and 21b has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. Among them, the pyrazole derivative 21b inhibited ALK5 phosphorylation with an IC₅₀ value of 0.018 μM and showed 95% inhibition at 0.03 μM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct. The 21b showed a high selectivity index of 284 against p38α MAP kinase. The binding pose of 21b generated by docking analysis reveals that it fits well into the ATP binding cavity of ALK5 by forming several hydrogen bond interactions.

一系列的4-（[1,2,4] triazolo [1,5 - a ] pyridin-6-yl）-5（3）-（6-methylpyridin-2-yl）imidazoles和-pyrazoles 14a – c，已合成15a – c，16a，16b，19a – d，21a和21b并在酶测定法和基于细胞的萤光素酶报告基因测定法中评估了它们对ALK5的抑制活性。其中，吡唑衍生物21b用IC ₅₀抑制ALK5磷酸化使用永久转染了p3TP-luc报告基因构建体的HaCaT细胞进行的荧光素酶报告基因测定中，其值为0.018μM，在0.03μM处显示95％的抑制作用。在图21B显示了对284p38αMAP激酶的高选择性指数。通过对接分析产生的21b的结合态表明，通过形成多个氢键相互作用，它与ALK5的ATP结合腔非常吻合。