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.
Pies
Tanja
T
Universität Hamburg, Institut für Pharmazie, Hamburg, Germany.
Schaper
Klaus-Jürgen
KJ
Leost
Maryse
M
Zaharevitz
Daniel W
DW
Gussio
Rick
R
Meijer
Laurent
L
Kunicke
Conrad
C
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
D001552:Benzazepines; D004791:Enzyme Inhibitors; D007211:Indoles; D016203:CDC2 Protein Kinase