Cyclin-dependent kinases 4/6 play an important role in regulation of cell cycle, and overexpress in a variety of cancers. Up to now, new CDK inhibitors still need to be developed due to its poor selectivity. Herein we report a novel series of 4-(2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazole-7-yl)-N-(5-(piperazin-1-ylmethyl)pyridine-2-yl)pyrimidin-2-amine anologues as potent CDK 4/6 inhibitors based on LY2835219 (Abemaciclib). Compound 10d, which exhibits approximate potency on CDK4/6 (IC₅₀ = 7.4/0.9 nM), has both good pharmacokinetic characters and high selectivity on CDK1 compared with LY2835219. Overall, compound 10d could be a promising candidate and a good starting point as anticancer drugs.

细胞周期蛋白依赖性激酶4/6在调节细胞周期中起重要作用，并在多种癌症中过表达。迄今为止，由于其选择性差，仍需要开发新的CDK抑制剂。在这里，我们报告了一系列新的4-（2,3-二氢-1 H-苯并[ d ]吡咯并[1,2 - a ]咪唑-7-基）-N-（5-（哌嗪-1-基甲基）吡啶-2-基）嘧啶-2-胺类似物，作为基于LY2835219（Abemaciclib）的有效CDK 4/6抑制剂。 与LY2835219相比，在CDK4 / 6上具有近似效价（IC ₅₀ = 7.4 / 0.9 nM）的化合物10d具有良好的药代动力学特征和对CDK1的高选择性。总体而言，化合物10d 有望成为抗癌药物的有希望的候选者和良好的起点。