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Design, synthesis, and structure-activity relationship studies of thiophene-3-carboxamide derivatives as dual 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. Intriguingly, the compounds have a dual inhibitory activity by functioning as both ATP and JIP mimetics, possibly by binding to both the ATP binding site and to the docking site of the kinase. Several of such novel compounds display potent JNK inhibitory profiles both in vitro and in cell.

SUBMITTER: De SK

PROVIDER: S-EPMC3089059 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Design, synthesis, and structure-activity relationship studies of thiophene-3-carboxamide derivatives as dual inhibitors of the c-Jun N-terminal kinase.

De Surya K SK Barile Elisa E Chen Vida V Stebbins John L JL Cellitti Jason F JF Machleidt Thomas T Carlson Coby B CB Yang Li L Dahl Russell R Pellecchia Maurizio M

Bioorganic & medicinal chemistry 20110312 8

We report comprehensive structure-activity relationship studies on a novel series of c-Jun N-terminal kinase (JNK) inhibitors. Intriguingly, the compounds have a dual inhibitory activity by functioning as both ATP and JIP mimetics, possibly by binding to both the ATP binding site and to the docking site of the kinase. Several of such novel compounds display potent JNK inhibitory profiles both in vitro and in cell. ...[more]

PMID: 21458276

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