Lenalidomide is a cereblon modulator known for its antitumor, anti‐inflammatory, and immunomodulatory properties in clinical applications. Recently, some reported lenalidomide analogs could exhibit a significant bioactivity through various modifications in the isoindolinone ring. In this study, we designed and synthesized a series of novel lenalidomide analogs on the basis of the installation of a methylene chain at the C‐4 position of isoindolinone via the Suzuki cross‐coupling reaction. These new compounds were further evaluated for their in vitro antiproliferative activities against two tumor cell lines (MM.1S and Mino). Specifically, compound 4c displayed the strongest antiproliferative activity against the MM.1S (IC50 = 0.27 ± 0.03 μM) and Mino (IC50 = 5.65 ± 0.58 μM) tumor cell lines. In summary, we have developed a new synthetic strategy for C‐4 derivatization of lenalidomide, providing a bioactive scaffold that could be used to discover further potential antitumor lead compounds in pharmaceutical research.

中文翻译：

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通过 Suzuki 交叉偶联反应设计和合成新的来那度胺类似物

来那度胺是一种脑调节剂，以其在临床应用中的抗肿瘤、抗炎和免疫调节特性而闻名。最近，一些报道的来那度胺类似物可以通过异吲哚啉酮环的各种修饰表现出显着的生物活性。在这项研究中，我们通过铃木交叉偶联反应在异吲哚啉酮的 C-4 位安装亚甲基链，设计并合成了一系列新型来那度胺类似物。进一步评估了这些新化合物对两种肿瘤细胞系（MM.1S 和 Mino）的体外抗增殖活性。具体而言，化合物 4c 对 MM.1S (IC50 = 0.27 ± 0.03 μM) 和 Mino (IC50 = 5.65 ± 0.58 μM) 肿瘤细胞系显示出最强的抗增殖活性。总之，