Novel Potassium Chennel Activators. II. Synthesis and Pharmacological Evaluation of 3,4-Dihydro-2H-1,4-benzoxazine Derivatives : Modificaiton of the Aromatic Part

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Three new series of analogues related to 3,4-dihydro-2H-1,4-benzoxazine derivative 1a were synthesized and evaluated for their potassium channel activating activity. In the first series I, where the 6,7-positions were disubstituted, it was found that an electron-withdrawing substituent was preferable at the 6 position, bet either an electron-withdrawing or releasing substituent without bulkiness was tolerated at the 7 position. In the second series II, where several heterocycles were introduced into the 6,7-positions, the oxadiazole derivative 6 showed more potent activity than cromakalin. In the third series III, where the benzene ring was replaced by pyridine ring, borane complex 16 had equivalent activity to cromakalim. Especially, compound 6 showed a potent hypotensive effect with a long duration of action in the spontaneous hypertensive rat and had a lesser increasing effect on intracranial pressure in dogs than 1a and levcromakalim, showing a good profile as a antihypertensive agent.
公益社団法人日本薬学会の論文
1999-07-15