The scaffold was further evaluated for off-target liabilities against the human Ether-á-gogo related gene (hERG) potassium channel and a select group of kinases. First, the pyrimidinone moiety bears resemblance to previously reported kinase inhibitors. To determine the potential liability that off-target kinase inhibition may render we selected four kinases that are earmarked by pharmaceutical companies as 'sentinel representatives' of kinase families that should be assessed for pre-clinical profiling to reduce safety-related drug attrition. Analogs 20, 38, and 39