Document Detail

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.
MedLine Citation:
PMID:  15857116     Owner:  NLM     Status:  MEDLINE    
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.
Gary T Wang; 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
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  48     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-28     Completed Date:  2005-06-03     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3118-21     Citation Subset:  IM    
Cancer Research, Global Pharmaceutical R and D, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
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MeSH Terms
Antineoplastic Agents / chemical synthesis*,  pharmacology
Camptothecin / pharmacology
Cell Cycle / drug effects
Crystallography, X-Ray
Doxorubicin / pharmacology
Drug Screening Assays, Antitumor
Hela Cells
Nitriles / chemical synthesis*,  pharmacology
Protein Kinase Inhibitors / chemical synthesis*,  chemistry,  pharmacology
Protein Kinases / metabolism*
Pyrazoles / chemical synthesis*,  pharmacology
Structure-Activity Relationship
Urea / analogs & derivatives*,  chemical synthesis*,  pharmacology
Reg. No./Substance:
0/Antineoplastic Agents; 0/Nitriles; 0/Protein Kinase Inhibitors; 0/Pyrazoles; 23214-92-8/Doxorubicin; 57-13-6/Urea; 7689-03-4/Camptothecin; EC 2.7.-/Protein Kinases; EC kinase 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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