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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.

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.

SUBMITTER: De SK

PROVIDER: S-EPMC2667321 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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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.

De Surya K SK Stebbins John L JL Chen Li-Hsing LH Riel-Mehan Megan M Machleidt Thomas T Dahl Russell R Yuan Hongbin H Emdadi Aras A Barile Elisa E Chen Vida V Murphy Ria R Pellecchia Maurizio M

Journal of medicinal chemistry 20090401 7

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. ...[more]

PMID: 19271755

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