Potassium channel activators based on the benzopyran substructure: synthesis and activity of the C-8 substituent

The synthesis of a series of methoxy bearing 2,2-dimethyl-2H-1-benzopyrans have been achieved for testing as potassium channel activators. The synthesis involves formation of 6-cyano-8-methoxy-2,2-dimethyl-2H-1-benzopyran from vanillin, epoxidation, then ring opening of the epoxide with nitrogen nucleophiles to produce the new benzopyrans. Biological testing showed a dramatic decrease in activity thus revealing an important site of activity in this class of compounds.