CDK4/6 has been identified as an attractive therapeutic target for treatment of cancer. For unmet clinical needs, a novel class of imidazo [1′,2':1,6]pyrido [2,3-d]pyrimidin derivatives, which had distinctive triheteroaryl structure, had been discovered as CDK4/6 inhibitors. The compounds 10b and 10c, displayed the low nanomolar range activities on CDK4/6, desirable antiproliferative activities, excellent metabolic properties, and acceptable pharmacokinetic characters. In Colo-205 and U87MG xenograft models, compounds 10b and 10c also showed significant tumor growth inhibitions with controllable toxicities. All data confirmed that imidazo [1′,2':1,6]pyrido [2,3-d]pyrimidin derivatives 10b and 10c could be promising drug candidates for cancer therapy.

CDK4 / 6已被确定为治疗癌症的有吸引力的治疗靶标。为满足未满足的临床需求，已发现具有独特的三杂芳基结构的一类新型咪唑并[1'，2'：1,6]吡啶并[2,3- d ]嘧啶衍生物作为CDK4 / 6抑制剂。化合物10b和10c显示出对CDK4 / 6的低纳摩尔范围的活性，所需的抗增殖活性，优异的代谢特性和可接受的药代动力学特征。在Colo-205和U87MG异种移植模型中，化合物10b和10c还显示出明显的肿瘤生长抑制作用，且毒性可控。所有数据均证实咪唑[1'，2'：1,6]吡啶[2,3- d]嘧啶衍生物10b和10c可能是有希望的癌症治疗药物。