Structure guided design of a series of selective pyrrolopyrimidinone MARK inhibitors

Article abstract of DOI:10.1016/j.bmcl.2016.08.068

The initial structure activity relationships around an isoindoline uHTS hit will be described. Information gleaned from ligand co-crystal structures allowed for rapid refinements in both MARK potency and kinase selectivity. These efforts allowed for the identification of a compound with properties suitable for use as an in vitro tool compound for validation studies on MARK as a viable target for Alzheimer's disease.[Figure presented]