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

Identification 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. 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.