Portal de Periódicos da CAPES

1-(5-Chloro-2-alkoxyphenyl)-3-(5-cyano- pyrazi-2-yl)ureas as Potent and Selective Inhibitors of Chk1 Kinase: Synthesis, Preliminary SAR, and Biological Activities

2005; American Chemical Society; Volume: 48; Issue: 9 Linguagem: Inglês

10.1021/jm048989d

1520-4804

Gary T. Wang, Gaoquan Li, Robert A. Mantei, Zehan Chen, Peter Kovar, Wendy Gu, Zhan Xiao, Haiying Zhang, Hing L. Sham, Thomas J. Sowin, Saul H. Rosenberg, Nan‐Horng Lin,

Cell death mechanisms and regulation

The discovery of 1-(5-chloro-2-alkoxyphenyl)-3-(5-cyanopyrazin-2-yl)ureas as a new class of potent (IC50 values of 3−10 nM) and selective inhibitors of Chk1 kinase was described. One of these compounds (2e) potentiates HeLa cells by over 22-fold against doxorubicin in an antiproliferation assay, and SW620 cells against camptothecin by 20-fold in an antiproliferation assay and 14-fold in a soft agar assay. Flow cytometry (FACS) analysis confirmed that 2e abrogated G2 checkpoint arrest of H1299 cells caused by doxorubicin and S checkpoint arrest caused by camptothecin.