Deregulation of the cell cycle is a common feature in human cancer. The inhibition of cyclin-dependent kinases (CDKs), which play a crucial role in control of the cell cycle, has always been one of the most promising areas in cancer chemotherapy. This review first summarizes the biology of CDKs and then focuses on the recent advances in both broad-range and selective CDK inhibitors during the last 5 years. The design rationale, structural optimization and structure-activity relationships analysis of these small molecules have been discussed in detail and the key interactions with the amino-acid residues of the most important compounds are highlighted. Future perspectives for CDKs inhibitors will be defined in the development of highly selective CDK inhibitors, an accurate knowledge of gene control mechanism and further predictive biomarker research.
A scalable and practical route to
wogonin, a bioactive natural
product with multiple pharmacological activities which is currently
under phase I/II clinical studies, is described. Wogonin was obtained
via a four-step process starting from commercially available chrysin
and including the Elbs oxidation, benzylation, methylation, and the
final debenzylation. The whole procedure gives the target product
in a 38% overall yield with >99% purity. Key steps in this process
including oxidation and methylation are discussed in detail. The optimized
process has been successfully demonstrated on the kilogram scale to
support ongoing clinical development of wogonin.
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