The discovery of 2-amino-3,5-diarylbenzamide inhibitors of IKK-α and IKK-β kinases

A potent and selective series of 2-amino-3,5-diarylbenzamide inhibitors of IKK-α and IKK-β is described. The most potent compounds are 8h, 8r and 8v, with IKK-β inhibitory potencies of pIC50 7.0, 6.8 and 6.8, respectively. The series has excellent selectivity, both within the IKK family over IKK-ε, and across a wide variety of kinase assays. The potency of 8h in the IKK-β enzyme assay translates to significant cellular activity (pIC50 5.7–6.1) in assays of functional and mechanistic relevance.

A potent and selective series of 2-amino-3,5-diarylbenzamide inhibitors of IKK-α and IKK-β is described. The most potent compounds are 8h, 8r and 8v, with IKK-β inhibitory potencies of pIC50 7.0, 6.8 and 6.8, respectively. The series has excellent selectivity, both within the IKK family over IKK-ε, and across a wide variety of kinase assays. The potency of 8h in the IKK-α and IKK-β enzyme assay translates to significant cellular activity (pIC50 5.7–6.1) in assays of functional and mechanistic relevance.Figure optionsDownload as PowerPoint slide