We have previously reported that N-(4-isopropyl-2, 2-dimethyl-3-oxo-3, 4-dihydro-2H-benzo [1, 4] oxazine-6-carbonyl) guanidine (4b) methanesulfonate salt (KB-R9032) is a potent and highly water-soluble Na/H exchange inhibitor. In a series of studies on Na/H exchange inhibitors, we designed and synthesized N-(3-oxo-3, 4-dihydro-2H-benzo [1, 4] thiazine-6- carbonyl) guanidines (5) as more potent inhibitors with high water-solubility. The design ...