Synthesis and biological evaluation of novel pteridin-7(8H)-one derivatives as potent CDK2 inhibitors.

Basic Information

ID: ALA5257095

Journal: Bioorg Med Chem Lett

Title: Synthesis and biological evaluation of novel pteridin-7(8H)-one derivatives as potent CDK2 inhibitors.

Authors: Wang X, Ding L, Jiang H, Yuan X, Xiang L, Tang C.

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.

CiteXplore: 37060933

DOI: 10.1016/j.bmcl.2023.129284

Patent ID: ┄