title: CDK1-inhibitory activity of paullones depends on electronic properties of 9-substituents.
abstract: 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.
authors.affiliation: Universität Hamburg, Institut für Pharmazie, Hamburg, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Pies
authors.forename: Klaus-Jürgen
authors.initials: KJ
authors.lastname: Schaper
authors.forename: Maryse
authors.initials: M
authors.lastname: Leost
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Zaharevitz
authors.forename: Rick
authors.initials: R
authors.lastname: Gussio
authors.forename: Laurent
authors.initials: L
authors.lastname: Meijer
authors.forename: Conrad
authors.initials: C
authors.lastname: Kunicke
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors*; D004583:Electrons; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016014:Linear Models; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013215:Starfish / Q000201:enzymology
chemical_list: D001552:Benzazepines; D004791:Enzyme Inhibitors; D007211:Indoles; D016203:CDC2 Protein Kinase