摘要
A series of substituted benzofuropyrimidinones with pan-PIM activities and excellent selectivity against a panel of diverse kinases is described. Initial exploration identified aryl benzofuropyrimidinones that were potent, but had cell permeability limitation. Using X-ray crystal structures of the bound PIM-1 complexes with g class="boldFont">3g>, g class="boldFont">5mg>, and g class="boldFont">6dg>, we were able to guide the SAR and identify the alkyl benzofuropyrimidinone (g class="boldFont">6lg>) with good PIM potencies, permeability, and oral exposure.