Transforming growth factor (TGF-β), a key mediator of tumor growth and metastasis, has been recognized as an important cancer drug target. A series of benzo[c][1,2,5]thiadiazol-5-yl imidazoles (14a–g) and thieno[3,2-c]-pyridin-2-yl imidazoles (20a–g) were designed, synthesized, and evaluated for their activin receptor-like kinase 5 (ALK5) activities. Among these compounds, 14c showed the highest activity (IC₅₀ = 0.008 μM) against ALK5 kinase, which was 16.1-fold and 1.8-fold higher than those of positive control compounds LY-2157299 (IC₅₀ = 0.129 μM) and EW-7197 (IC₅₀ = 0.014 μM), respectively. Compound 14g (350) showed the highest selectivity index of ALK5 against p38α MAP kinase, which was significantly higher than that of positive control compounds LY-2157299 (4) and EW-7197 (211). The inhibitory effects of compound 14c on TGF-β-induced Smad signaling and cell motility were studied in SPC-A1, HepG2 and HUVEC cells using western blot analysis and wound healing assay. ADMET prediction analysis showed that compounds 14c and 14g had good pharmacokinetics and drug-likeness behaviors.

转化生长因子（TGF-β）是肿瘤生长和转移的关键介质，已被认为是重要的抗癌药物。设计，合成了一系列苯并[ c ] [1,2,5]噻二唑-5-基咪唑（14a – g）和噻吩并[3,2- c ]-吡啶-2-基咪唑（20a – g）。 ，并评估其激活素受体样激酶5（ALK5）的活性。在这些化合物中，14c显示出最高的 针对ALK5激酶的活性（IC ₅₀ = 0.008μM），比阳性对照化合物LY - 2157299（IC ₅₀  = 0.129μM）高出16.1倍和1.8倍。分别为EW-7197（IC ₅₀  = 0.014μM）。化合物14g（350）显示出ALK5对p38αMAP激酶的最高选择性，显着高于阳性对照化合物LY - 2157299（4）和EW - 7197（211）。使用蛋白质印迹分析和伤口愈合试验研究了化合物14c对SPC-A1，HepG2和HUVEC细胞中TGF-β诱导的Smad信号转导和细胞运动的抑制作用。ADMET预测分析表明，化合物14c和14g具有良好的药代动力学和类似药物的行为。