Strong potassium channel-activating effects were found among a series of novel 4-substituted 3,4-dihydro-2H-1,4-benzoxazine derivatives. The key step in preparation was the nucleophilic substitution of 3,4-dihydro-2H-1,4-benzoxazine (3) with activated halogenopyridines, such as halogenopyridine N-oxides (15a--c) and the borane adduct (15d) of 4-bromopyridine. Structure-activity relationship studies identified 2-(3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazin-4-yl)pyridin e-1-oxide (16a: YM934) as the optimal compound. This compound (16a) showed a more potent oral antihypertensive effect than cromakalim in conscious spontaneously hypertensive rats.