Pyrano-[2,3b]-pyridines as potassium channel antagonists

The design and synthesis of a series of highly functionalized pyrano-2,3b]-pyridines is described. These compounds were assayed for their ability to block the I(Kur) channel encoded by the gene hKV1.5 in patch-clamped L-929 cells. Six of the compounds in this series showed sub-micromolar activity, the most potent being 4-(4-ethyl-benzenesulfonylamino)-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-pyrano2,3b]-pyridine-6-carboxylic acid ethyl-phenyl-amide with an IC(50) of 378 nM.