Synthesis and biological evaluation of novel pteridin-7(8H)-one derivatives as potent CDK2 inhibitors.
Bioorg Med Chem Lett
; 88: 129284, 2023 05 15.
Article
em En
| MEDLINE
| ID: mdl-37060933
ABSTRACT
Cyclin-dependent kinase 2 (CDK2) is considered as an important target in the research of antitumor drugs. Taking the CDK2/4/6 inhibitor Ebvaciclib as the positive control and an in-house library compound (23) as the lead compound, three classes of 30 target compounds with pteridin-7(8H)-one as the core structure were designed to establish structure-activity relationships (SAR). In general, SAR of pteridin-7(8H)-one CDK2 inhibitors is systematically described in this paper, resulting in the discovery of two compounds (KII-17 and KII-21) with further research value. After the above compounds were tested for CDK2/4/6 kinase selectivity, we found that compound KII-21 was about 3 and 4 times more selective to CDK2-cyclinE2 than CDK4-cyclinD1 and CDK6-cyclinD3, respectively. This work also provides a reference basis for the subsequent research on CDK2 inhibitors.
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MEDLINE
Assunto principal:
Inibidores de Proteínas Quinases
/
Antineoplásicos
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article