Synthesis of 2,3,4a,11b-tetrahydro-oxazino[2,3-c]benzopyran-9-carbonitriles as ATP-sensitive potassium channel openers

A series of optically active tetrahydro-oxazino[2,3-c]benzopyran derivatives have been synthesized and evaluated for potassium channel opening activity. (4aR,11bR)-1-Benzoyl-5,5-dimethyl-2,3,4a,11b-tetrahydro-oxazino[2,3-c]benzopyran-9-carbonitrile ((−)-11e) was identified as a bladder-selective potassium channel opener (IC50, bladder = 8.15 μM, IC50, portal vein = 34.5 μM).