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CDK1‐Inhibitory Activity of Paullones Depends on Electronic Properties of 9‐Substituents
Author(s) -
Pies Tanja,
Schaper KlausJürgen,
Leost Maryse,
Zaharevitz Daniel W.,
Gussio Rick,
Meijer Laurent,
Kunicke Conrad
Publication year - 2004
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200300870
Subject(s) - steric effects , chemistry , electronic effect , cyclin dependent kinase 1 , inhibitory postsynaptic potential , stereochemistry , computational chemistry , biochemistry , biology , cell , neuroscience , cell cycle
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.