ABSTRACT
Among the manifold chemotypes described as cyclin-dependent kinase (CDK) inhibitors, the paullones are an exceptional compound family for at least two reasons. First, the series was discovered by systematic data mining in the National Cancer Institute’s (NCI’s) database of selectivity patterns from the Antitumor Drug Screening program. Therefore, the discovery of paullones is an example of a successful drug discovery program based on bioinformatics beyond virtual screening. Second, several groups have used the commercially available paullones as biochemical tools; consequently, a variety of interesting results from diverse research fields have been reported. As with the many other CDK inhibitor families, a number of qualitative and quantitative structure-activity relationship (QSAR) investigations and structure optimization programs were carried out on the paullone series, which will be summarized in this chapter. Short survey articles concentrating on special aspects of the paullone kinase inhibitor family have already been published elsewhere (Kunick and Lemcke, 2002; Meijer et al., 2005).
