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Synthesis and biological properties of C‐2, C‐8, N‐9 substituted 6‐(3‐chloroanilino)‐purine derivatives as cyclin‐dependent kinase inhibitors. Part II
Author(s) -
Oh ChangHyun,
Kim HeeKwon,
Lee SuChul,
Oh Changsok,
Yang BoemSeok,
Rhee Hak June,
Cho JungHyuck
Publication year - 2001
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 - 10.1002/1521-4184(200112)334:11<345::aid-ardp345>3.0.co;2-1
Subject(s) - cyclin dependent kinase , chemistry , cyclin dependent kinase 2 , stereochemistry , kinase , purine analogue , purine , ic50 , enzyme inhibitor , structure–activity relationship , cdk inhibitor , hydroxymethyl , enzyme , biochemistry , in vitro , protein kinase a , cell cycle , cell
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 IC 50 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.