AIMS Design of sulfonamide-triazine derivatives as JAK1 inhibitors. BACKGROUND JAK1 is a kinase involved in different autoimmune diseases. JAK1 inhibitors have shown promising results in treating autoimmune diseases. OBJECTIVES To design new JAK1 inhibitors based on sulfonamides-triazine conjugates capable of binding interactions comparable to observed interactions anchoring potent crystallographic JAK1 inhibitors. METHODS The crystallographic structures of 4 diverse nanomolar inhibitors complexed within JAK1 were used to guide the synthesis of new diaminotriazine-sulfonamide-based JAK1 inhibitors. RESULTS Nineteen compounds have been prepared, some of which exhibited low micromolar IC50 values against JAK1. CONCLUSIONS Crystallographic complexes of diverse JAK1 inhibitors were successfully used to guide the synthesis of novel sulfonamide-triazine-based low micromolar JAK1 inhibitors.

中文翻译：

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基于磺胺-三嗪偶联物的新型 JAK1 抑制剂的设计和合成。

AIMS 磺胺三嗪衍生物作为 JAK1 抑制剂的设计。背景 JAK1是一种涉及不同自身免疫疾病的激酶。JAK1 抑制剂在治疗自身免疫性疾病方面已显示出可喜的结果。目的 设计基于磺胺-三嗪共轭物的新型 JAK1 抑制剂，其结合相互作用与观察到的锚定有效晶体学 JAK1 抑制剂的相互作用相当。方法 使用 JAK1 内复合的 4 种不同纳摩尔抑制剂的晶体结构来指导合成新的基于二氨基三嗪-磺酰胺的 JAK1 抑制剂。结果 制备了 19 种化合物，其中一些对 JAK1 表现出低微摩尔 IC50 值。