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Synthesis and Biological Activities of C‐2, N‐9 Substituted 6‐Benzylaminopurine Derivatives as Cyclin‐Dependent Kinase Inhibitor
Author(s) -
Oh ChangHyun,
Lee SuChul,
Lee KiSoo,
Woo EunRhan,
Hong Chang Yong,
Yang BoemSeok,
Baek Dae Jin,
Cho JungHyuck
Publication year - 1999
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/(sici)1521-4184(19996)332:6<187::aid-ardp187>3.0.co;2-d
Subject(s) - cyclin dependent kinase , cdk inhibitor , chemistry , kinase , cyclin dependent kinase 2 , ic50 , stereochemistry , structure–activity relationship , enzyme inhibitor , cyclin , biological activity , purine , biochemistry , enzyme , pharmacology , protein kinase a , in vitro , cell cycle , biology , cell
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 mM). 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.