通过将不同的药效团合并到一个分子中，合理设计并合成了一系列基于三唑并吡啶的双JAK/HDAC抑制剂。所有三唑并吡啶衍生物均对这两个靶标均表现出有效的抑制活性，最好的化合物 4-(((5-(苯并[d][1, 3]二氧杂环戊醇-5-基)-[1, 2, 4]三唑并[1, 5]挖出-a]吡啶-2-基)氨基)甲基)-N-羟基苯甲酰胺(19)。 19被证明是一种泛HDAC和JAK1/2双重抑制剂，对两种癌细胞系MDA-MB-231和RPMI-8226表现出高细胞毒性，IC50值在亚微摩尔范围内。对接模拟显示 19 与 HDAC 和 JAK 蛋白的活性位点吻合良好。此外，19在体外表现出比SAHA更好的代谢稳定性。我们的研究表明，化合物 19 是进一步临床前研究的有希望的候选者。

A series of triazolopyridine-based dual JAK/HDAC inhibitors were rationally designed and synthesised by merging different pharmacophores into one molecule. All triazolopyridine derivatives exhibited potent inhibitory activities against both targets and the best compound 4-(((5-(benzo[d][1, 3]dioxol-5-yl)-[1, 2, 4]triazolo[1, 5-a]pyridin-2-yl)amino)methyl)-N-hydroxybenzamide (19) was dug out. 19 was proved to be a pan-HDAC and JAK1/2 dual inhibitor and displayed high cytotoxicity against two cancer cell lines MDA-MB-231 and RPMI-8226 with IC50 values in submicromolar range. Docking simulation revealed that 19 fitted well into the active sites of HDAC and JAK proteins. Moreover, 19 exhibited better metabolic stability in vitro than SAHA. Our study demonstrated that compound 19 was a promising candidate for further preclinical studies.