1-(5-Chloro-2-alkoxyphenyl)-3-(5-cyano-pyrazi-2-yl)ureas as Potent and SelectiveInhibitors of Chk1 Kinase: Synthesis,Preliminary SAR, and BiologicalActivities
The discovery of 1-(5-chloro-2-alkoxyphenyl)-3-(5-cyanopyrazin-2-yl)ureas as a new class of potent (IC50 valuesof 3−10 nM) and selective inhibitors of Chk1 kinase wasdescribed. One of these compounds (2e) potentiates HeLa cellsby over 22-fold against doxorubicin in an antiproliferationassay, and SW620 cells against camptothecin by 20-fold in anantiproliferation assay and 14-fold in a soft agar assay. Flowcytometry (FACS) analysis confirmed that 2e abrogated G2checkpoint arrest of H1299 cells caused by doxorubicin and Scheckpoint arrest caused by camptothecin.
