Novel non-benzimidazole chk2 kinase inhibitors

A number of benzimidazole replacements were synthesized and examined to gain a greater understanding of the SAR around this novel series of chk2 kinase inhibitors. In a recent paper, [Arienti, K. L.; Brunmark, A.; Axe, F. U.; McClure, K. M.; Lee, A.; Blevitt, J.; Neff, D. K.; Huang, L.; Crawford, S....

Full description

Saved in:
Bibliographic Details
Published inBioorganic & medicinal chemistry letters Vol. 16; no. 7; pp. 1924 - 1928
Main Authors McClure, Kelly J., Huang, Liming, Arienti, Kristen L., Axe, Frank U., Brunmark, Anders, Blevitt, Jon, Guy Breitenbucher, J.
Format Journal Article
LanguageEnglish
Published Oxford Elsevier Ltd 01.04.2006
Elsevier
Subjects
Benzimidazoles - chemistry
Benzimidazoles - pharmacology
Biological and medical sciences
Checkpoint Kinase 2
Medical sciences
Miscellaneous
Models, Molecular
Pharmacology. Drug treatments
Protein Kinase Inhibitors - chemistry
Protein Kinase Inhibitors - pharmacology
Protein-Serine-Threonine Kinases - antagonists & inhibitors
Radiation therapy and radiosensitizing agent
Radiation-Protective Agents - chemistry
Radiation-Protective Agents - pharmacology
Structure-Activity Relationship
Treatment with physical agents
Treatment. General aspects
Tumors
Human
Radioprotector
Enzyme
Transferases
Enzyme inhibitor
Organic chlorine compounds
In vitro
Modeling
Biological activity
Signal transduction
Protein kinase
T-Lymphocyte
Molecular model
Binding mode
Carboxamide
Chemical synthesis
Online AccessGet full text

Cover

More Information
Summary:A number of benzimidazole replacements were synthesized and examined to gain a greater understanding of the SAR around this novel series of chk2 kinase inhibitors. In a recent paper, [Arienti, K. L.; Brunmark, A.; Axe, F. U.; McClure, K. M.; Lee, A.; Blevitt, J.; Neff, D. K.; Huang, L.; Crawford, S.; Chennagiri, R. P.; Karlsson, L.; Brietenbucher, J. G. J. Med. Chem. 2005, 48, 1873], we described the discovery of a class of benzimidazole chk2 kinase inhibitors, exemplified by compound 1, which had radio-protective effects in human T-cells subjected to ionizing radiation. Here, a series of non-benzimidazole analogs intended to define the scope of the SAR about this new series of inhibitor, and allow for refinement of the binding model of these compounds to the chk2 kinase is described.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2005.12.096