A series of cyano-substituted 2,4-diarylaminopyrimidines was designed and synthesized as potent non-covalent JAK3 inhibitors. Among the derivatives synthesized, 9o (IC₅₀ = 22.86 nM), 9 k (IC₅₀ = 21.58 nM), and 9j (IC₅₀ = 20.66 nM) demonstrated inhibitory potencies against JAK3 similar to the known JAK3 inhibitor tofacitinib (IC₅₀ = 20.10 nM). Moreover, 9o displayed potent anti-proliferative activities against Raji and Ramos cells, with IC₅₀ values of 0.9255 μM and 1.405 μM, respectively. In addition, 9o demonstrated low toxicity in normal HBE (human bronchial epithelial cells, IC₅₀ > 10 μΜ) and L-02 (human liver cells, IC₅₀ = 3.104 μΜ) cells. Analysis of the mode of action by flow cytometry indicated that 9o effectively arrested Raji cells at the G2/M phase. Taken together, these results suggested that 9o might be a promising candidate for development as a potential treatment for B-cell lymphoma.

设计并合成了一系列氰基取代的 2,4-二芳基氨基嘧啶作为有效的非共价 JAK3 抑制剂。在合成的衍生物中，9o (IC ₅₀  = 22.86 nM)、9 k (IC ₅₀  = 21.58 nM) 和9j (IC ₅₀  = 20.66 nM) 对 JAK3 的抑制效力类似于已知的 JAK3 抑制剂托法替尼 (IC ₅₀  = 20.10)毫）。此外，9o对 Raji 和 Ramos 细胞显示出有效的抗增殖活性，IC ₅₀值分别为 0.9255 μM 和 1.405 μM。此外，9o在正常 HBE（人支气管上皮细胞，IC₅₀  > 10 μM）和 L-02（人肝细胞，IC ₅₀  = 3.104 μM）细胞。流式细胞术对作用方式的分析表明，9o在 G2/M 期有效地阻止了 Raji 细胞。综上所述，这些结果表明9o可能是作为 B 细胞淋巴瘤潜在治疗方法开发的有希望的候选者。