Azabenzthiazole inhibitors of leukotriene A4 hydrolase

Previously, benzthiazole containing LTA4H inhibitors were discovered that were potent (1-3), but were associated with the potential for a hERG liability. Utilizing medicinal chemistry first principles (e.g., introducing rigidity, lowering c Log D) a new benzthiazole series was designed, congeners of 1-3, which led to compounds 7a, 7c, 12a-d which exhibited LTA4H IC50 = 3-6 nM and hERG Dofetilide Binding IC50 = 8.9-> >10 μM.