Design, synthesis, and structure-activity relationship of substrate competitive, selective, and in vivo active triazole and thiadiazole inhibitors of the c-Jun N-terminal kinase

  • J Med Chem. 2009 Apr 9;52(7):1943-52. doi: 10.1021/jm801503n.
Surya K De  1 ,  John L Stebbins ,  Li-Hsing Chen ,  Megan Riel-Mehan ,  Thomas Machleidt ,  Russell Dahl ,  Hongbin Yuan ,  Aras Emdadi ,  Elisa Barile ,  Vida Chen ,  Ria Murphy ,  Maurizio Pellecchia
Affiliations
  • 1. Infectious and Inflammatory Disease Center and Cancer Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA.
PMID: 19271755 DOI: 10.1021/jm801503n
Abstract

We report comprehensive structure-activity relationship studies on a novel series of c-Jun N-terminal kinase (JNK) inhibitors. The compounds are substrate competitive inhibitors that bind to the docking site of the kinase. The reported medicinal chemistry and structure-based optimizations studies resulted in the discovery of selective and potent thiadiazole JNK inhibitors that display promising in vivo activity in mouse models of Insulin insensitivity.

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