Document Detail

Substituted imidazoles as glucagon receptor antagonists.
MedLine Citation:
PMID:  11549467     Owner:  NLM     Status:  MEDLINE    
A modestly active, nonselective triarylimidazole lead was optimized for binding affinity with the human glucagon receptor. This led to the identification of a 2- and/or 4-alkyl or alkyloxy substituent on the imidazole C4-aryl group as a structural determinant for significant enhancement in binding with the glucagon receptor (e.g., 41, IC(50)=0.053 microM) and selectivity (>1000x) over p38MAP kinase in this class of compounds.
L L Chang; K L Sidler; M A Cascieri; S de Laszlo; G Koch; B Li; M MacCoss; N Mantlo; S O'Keefe; M Pang; A Rolando; W K Hagmann
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  11     ISSN:  0960-894X     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2001 Sep 
Date Detail:
Created Date:  2001-09-10     Completed Date:  2002-03-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  2549-53     Citation Subset:  IM    
Department of Medicinal Chemical Research, Merck Research Laboratories, Rahway, NJ 07065, USA.
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MeSH Terms
CHO Cells
Drug Design
Drug Evaluation, Preclinical
Imidazoles / chemistry
Inhibitory Concentration 50
Magnesium / metabolism,  pharmacology
Mitogen-Activated Protein Kinases / drug effects,  metabolism
Pyridines / chemistry*,  metabolism,  pharmacology*
Receptors, Glucagon / antagonists & inhibitors*,  metabolism
Structure-Activity Relationship
p38 Mitogen-Activated Protein Kinases
Reg. No./Substance:
0/Imidazoles; 0/Pyridines; 0/Receptors, Glucagon; 7439-95-4/Magnesium; EC Protein Kinases; EC Mitogen-Activated Protein Kinases

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