The Aurora kinases are essential for cell mitosis and the dysregulation of Aurora A and B have been linked to the etiology of human cancers. The p-carboxylic acid substituted 2,7-diphenyl-5H-benzo[c]pyrimido[4,5-e]azepine 1 (MLN8054) has been previously identified as a potent Aurora A kinase inhibitor (Aurora A Delfia IC50 = 31 nM). Structure–activity relationship (SAR) guided studies of carboxamide derivatives of 1 led to inhibitors of Aurora A such as 2 that demonstrate increased potency in enzyme (Aurora A Delfia IC50 = 3 nM) and cell-based assays and display comparable efficacy to 1 in certain xenograft models.

Identification of 2-(4-benzamidophenyl)-7-phenyl-5H-benzo[c]pyrimido[4,5-e]azepines as potent aurora kinase inhibitors

249th National Meeting (2015)

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