Targeting CDK4/6 has been identified as an effective therapeutics for treatment of cancer. We herein reported the discovery of a series of 6-(2-(methylamino)ethyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-2-amine derivatives as CDK4/6 inhibitors against cancer. Compound 3c, which displayed high potency and selectivity on CDK4/6 (IC₅₀ = 0.710/1.10 nM) over a variety of other kinases, possessed desirable antiproliferative activities, excellent metabolic properties, and favorable pharmacokinetic characters. In MCF-7, Colo-205, and A549 xenograft models, compound 3c exhibited significant tumor growth inhibitions with low toxicities, which could be a promising drug candidate for further development.

靶向CDK4 / 6已被确定为治疗癌症的有效疗法。我们在本文中报道了发现一系列6-（2-（甲基氨基）乙基）-5,6,7,8-四氢-1,6-萘啶-2-胺衍生物作为抗癌CDK4 / 6抑制剂。化合物3c在CDK4 / 6（IC ₅₀  = 0.710 / 1.10 nM）上对多种其他激酶显示出高效能和选择性，具有所需的抗增殖活性，出色的代谢特性和良好的药代动力学特性。在MCF-7，Colo-205和A549异种移植模型中，化合物3c表现出明显的肿瘤生长抑制作用，且毒性低，这可能是进一步开发的有希望的候选药物。