Oh C H, Lee S C, Lee K S, Woo E R, Hong C Y, Yang B S, Baek D J, Cho J H
Medicinal Chemistry Research Center, Korea Institute of Science and Technology, Seoul, Korea.
Arch Pharm (Weinheim). 1999 Jun;332(6):187-90. doi: 10.1002/(sici)1521-4184(19996)332:6<187::aid-ardp187>3.0.co;2-d.
In this study, C-2, N-9 substituted 6-benzylaminopurine derivatives were synthesized and their inhibitory effects on cyclin-dependent kinase (CDK2) were evaluated. The effect of substituents at the C-2 and N-9 positions of substituted purine was investigated. Among the compounds tested, compound 7b-iii (6-benzylamino-2-thiomorpholinyl-9-isopropylpurine) was the most active inhibitor (IC50 = 0.9 microM). Compound 7b-iii showed 10-fold higher activity compared to olomoucine and almost the same activity as roscovitine. Results from structure-activity relationship studies should allow the design of more potent and selective CDK inhibitors, which may provide an effective therapy for cancer or other CDK dependent diseases.
在本研究中，合成了C-2、N-9取代的6-苄基氨基嘌呤衍生物，并评估了它们对细胞周期蛋白依赖性激酶（CDK2）的抑制作用。研究了取代嘌呤的C-2和N-9位取代基的影响。在所测试的化合物中，化合物7b-iii（6-苄基氨基-2-硫代吗啉基-9-异丙基嘌呤）是活性最高的抑制剂（IC50 = 0.9 microM）。与olomoucine相比，化合物7b-iii的活性高10倍，与roscovitine的活性几乎相同。构效关系研究的结果应有助于设计更有效和更具选择性的CDK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。
