Aiming to identify new optimization strategy effective for ALK-mutations, two series of pyrroformyl-containing 2,4-diaminopyrimidine compounds (11a-o, 12a-o) were designed, synthesized and evaluated for their anti-proliferative activities against three cancer cell lines in vitro by MTT assay. The biological evaluations on cellular assay resulted in discovery of compound 11k, which performed considerable activity with IC₅₀ value of 0.034 μM against H2228 cell. Meanwhile, 11k exhibited outstanding enzymatic inhibitory potency with IC₅₀ values of 1.9 nM and 3.1 nM against ALK^WT and ALK^L1196M, respectively, surpassing the reference ceritinib (IC₅₀=1.9 nM and 7.6 nM). Ultimately, the binding mode of 11k with ALK was established to explore the SARs. Overall, 11k was considered as a promising ALK inhibitor for mutation treatment.

为了确定对ALK突变有效的新优化策略，设计，合成并评估了两个系列含吡咯甲酰基的2,4-二氨基嘧啶化合物（11a-o，12a-o）对三种癌细胞的抗增殖活性在体外通过MTT测定。细胞分析的生物学评估导致发现化合物11k，该化合物对H2228细胞表现出相当大的活​​性，IC ₅₀值为0.034μM。同时，11k对ALK ^WT和ALK ^L1196M表现出出色的酶抑制效能，IC ₅₀值为1.9 nM和3.1 nM。分别超过参考赛立替尼（IC ₅₀ = 1.9 nM和7.6 nM）。最终，建立了11k与ALK的结合模式以探索SAR。总的来说，11k被认为是用于突变治疗的有希望的ALK抑制剂。