Synthesis and biological activities of C-2, N-9 substituted 6-benzylaminopurine derivatives as cyclin-dependent kinase inhibitor

In this study, C-2, N-9 substituted 6-benzylaminopurine derivatives were sy nthesized and their inhibitory effects on cyclin-dependent kinase (CDK2) we re evaluated. The effect of substituents at the C-2 and N-9 positions of su bstituted purine was investigated. Among the compounds tested, compound 7b- iii (6-benzylamino-2-thiomorpholinyl-9-isopropylpurine) was the most active inhibitor (IC50 = 0.9 mu M). Compound 7b-iii showed 10-fold higher activit y compared to olomoucine and almost the same activity as roscovitine. Resul ts from structure-activity relationship studies should allow the design of more potent and selective CDK inhibitors, which may provide an effective th erapy for cancer or other CDK dependent diseases.