In this study, C‐2, C‐8, N‐9 substituted 6‐(3‐chloroanilino)purine derivatives were synthesized and their inhibitory effects on cyclin‐dependent kinases (CDK2, 4) as well as their cytotoxicities were evaluated. The effects of substituents at the C‐2, C‐8, and N‐9 positions of the substituted purine were investigated. Among the compounds tested, [6‐(3‐chloroanilino)‐2‐(2‐hydroxymethyl‐4‐hydroxypyrrolidyl)‐9‐isopropylpurine] (4h) was the most active inhibitor of CDK2 with IC50 of 0.3μM, i.e. a two‐fold increased inhibitory activity as compared to roscovitine. Results from structure‐activity relationship studies should allow the design of more potent and selective CDK2 inhibitors, which may provide an effective therapy for cancer or other CDK‐dependent diseases.

中文翻译：

---

作为细胞周期蛋白依赖性激酶抑制剂的 C-2、C-8、N-9 取代的 6-(3-氯苯胺基)-嘌呤衍生物的合成和生物学特性。第二部分

在这项研究中，合成了 C-2、C-8、N-9 取代的 6-(3-氯苯胺基)嘌呤衍生物，并评估了它们对细胞周期蛋白依赖性激酶 (CDK2, 4) 的抑制作用及其细胞毒性。研究了取代嘌呤的 C-2、C-8 和 N-9 位取代基的影响。在测试的化合物中，[6-(3-chloroanilino)-2-(2-hydroxymethyl-4-hydroxypyrrolidyl)-9-isopropylpurine] (4h) 是最有效的 CDK2 抑制剂，IC50 为 0.3μM，即双-与roscovitine相比，抑制活性成倍增加。构效关系研究的结果应该允许设计更有效和选择性的 CDK2 抑制剂，这可能为癌症或其他 CDK 依赖性疾病提供有效的治疗方法。