CDK1-inhibitory activity of paullones depends on electronic properties of 9-substituents

Multiple linear regression analysis was employed in an effort to establish a quantitative structure-activity relationship model for the CDK1-inhibitory activity of a series of 9-substituted paullones. While the electronic properties of the 9-substituents proved to be of high relevance for CDK1 inhibition, both lipophilic and a steric parameters could not be included in a meaningful equation for the calculation of biological properties. The equation solely based on the electronic parameter was successfully used for the prediction of the CDK1-inhibitory activity of a small test set comprising novel paullones with sulfur-containing 9-substituents. Among these new derivatives, 2-methoxy-9-methylsulfonylpaullone proved to be superior to the standard alsterpaullone with respect to CDK1 inhibition.