Substituted imidazoles as glucagon receptor antagonists

  • Bioorg Med Chem Lett. 2001 Sep 17;11(18):2549-53. doi: 10.1016/s0960-894x(01)00498-x.
L L Chang  1 ,  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
Affiliations
  • 1. Department of Medicinal Chemical Research, Merck Research Laboratories, Rahway, NJ 07065, USA. [email protected]
PMID: 11549467 DOI: 10.1016/s0960-894x(01)00498-x
Abstract

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.

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