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 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.
Oh
C H
CH
Medicinal Chemistry Research Center, Korea Institute of Science and Technology, Seoul, Korea.
Lee
S C
SC
Lee
K S
KS
Woo
E R
ER
Hong
C Y
CY
Yang
B S
BS
Baek
D J
DJ
Cho
J H
JH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011687:Purines; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases