Cdk1 inhibitors of acetyl chrysin mannich base derivatives, synthesis and use thereof

Abstract

Provided is a series of acetyl Chrysin Mannich base derivatives with the structures illustrated in the following scheme: wherein Ris acetyl and Ris cycloalkylamine-methyl, or Ris acetyl and Ris cycloalkylamine-methyl. Such derivatives are cyclin-dependent protein kinases 1 (CDK1) selective inhibitors. Base on the levels of .Oand Feare higher 5-15 times in cancer cells than in normal cells, the action mechanism of such derivatives by regulating intracellular reactive oxygen species (ROS) is activating mitochondria apoptosis pathway without the death receptor pathway, thus selectively inducing apoptosis of cancer cells and protecting normal cells. Inside, CH-j has a good druggability for the selectivity of solid cancers. Moreover, CH-f has also a good druggability for the systemic cancers.