Structure-based drug design of a highly potent CDK1,2,4,6 inhibitor with novel macrocyclic quinoxalin-2-one structure

The design of a novel series of cyclin-dependent kinase (CDK) inhibitors containing a macrocyclic quinoxaline-2-one is reported. Structure-based drug design and optimization from the starting point of diarylurea 2, which we previously reported as a moderate CDK1,2,4,6 inhibitor [J. Biol.Chem.2001, 276, 27548], led to the discovery of potent CDK1,2,4,6 inhibitor that were suitable for iv administration for in vivo study.

Graphical abstractIdentification of a novel series of CDK1,2,4,6 inhibitor with macrocyclic quinoxalin-2-one is reported. The structure-based designs and optimizations led to the potent CDK1,2,4,6 inhibitor that could be available as iv administration for in vivo studies from the lead compound with diarylurea scaffold.Figure optionsDownload full-size imageDownload as PowerPoint slide