2. Academic Validation
  3. 1-(5-Chloro-2-alkoxyphenyl)-3-(5-cyanopyrazin-2-yl)ureas [correction of cyanopyrazi] as potent and selective inhibitors of Chk1 kinase: synthesis, preliminary SAR, and biological activities

1-(5-Chloro-2-alkoxyphenyl)-3-(5-cyanopyrazin-2-yl)ureas [correction of cyanopyrazi] as potent and selective inhibitors of Chk1 kinase: synthesis, preliminary SAR, and biological activities

  • J Med Chem. 2005 May 5;48(9):3118-21. doi: 10.1021/jm048989d.
Gary T Wang 1,  Gaoquan Li,  Robert A Mantei,  Zehan Chen,  Peter Kovar,  Wendy Gu,  Zhan Xiao,  Haiying Zhang,  Hing L Sham,  Thomas Sowin,  Saul H Rosenberg,  Nan-Horng Lin
Affiliations

Affiliation

  • 1 Cancer Research, Global Pharmaceutical R and D, Abbott Laboratories, Abbott Park, Illinois 60064, USA. [email protected]
PMID: 15857116 DOI: 10.1021/jm048989d
Abstract

The discovery of 1-(5-chloro-2-alkoxyphenyl)-3-(5-cyanopyrazin-2-yl)ureas as a new class of potent (IC(50) 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.

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