Synthesis and biological properties of C-2, C-8, N-9 substituted 6-(3-chloroanilino)purine derivatives as cyclin-dependent kinase inhibitors. Part II.
Arch Pharm (Weinheim)
; 334(11): 345-50, 2001 Nov.
Article
em En
| MEDLINE
| ID: mdl-11822171
ABSTRACT
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 IC50 of 0.3 microM, 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-dependant diseases.
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Base de dados:
MEDLINE
Assunto principal:
Purinas
/
Quinases Ciclina-Dependentes
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article