Targeting Transcriptional CDKs 7, 8, and 9 with Anilinopyrimidine Derivatives as Anticancer Agents: Design, Synthesis, Biological Evaluation and In Silico Studies.

ABSTRACT: Cyclin-dependent kinases (CDKs) are promising targets in chemotherapy. In this study, we report a series of 2-anilinopyrimidine derivatives with CDK inhibitory activity. Twenty-one compounds were synthesized and their CDK inhibitory and cytotoxic activities were evaluated. The representative compounds demonstrate potent antiproliferative activities toward different solid cancer cell lines and provide a promising strategy for the treatment of malignant tumors. Compound 5f was the most potent CDK7 inhibitor (IC₅₀ = 0.479 µM), compound 5d was the most potent CDK8 inhibitor (IC₅₀ = 0.716 µM), and compound 5b was the most potent CDK9 inhibitor (IC₅₀ = 0.059 µM). All the compounds satisfied the Lipinski's rule of five (mo

SUBMITTER: Eskandrani R 

PROVIDER: S-EPMC10254914 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature