Studies on Uricosuric Diuretics. I. : 6,7-Dichloro-5-sulfamoyl-2,3-dihydrobenzofuran-2-carboxylic Acids(Medeicinal Chemistry,Chemical)

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2,3-Dihydrobenzofuran derivatives having various sulfamoyl groups at the 5-position were synthesized and tested for oral diuretic and saluretic activities in rats and mice. Intraperitoneal uricosuric activity was also tested by a clearance method using oxonate-treated rats. Structure-activity relationships are presented. The 6,7-dichlora-5-N,N-disubsntuted sulfamoyl-2,3-dihydro-benzofuran-2-carboxylic acids (9ab, ac, 13a and b) having lower alkyl substituents showed the most potent diuretic and saluretic activities among the compounds synthesized. Hyperuricosuric activity was observed in 6,7-dichloro-2,3-dihydrobenzofuran-2-carboxylic acids and 2-hydroxymethyl-6,7-dichloro-2,3-dihydrobenzofurans having a 5-sulfamoyl group, with relatively small substituents (9aa-ac, af, ak, al, an, ao and 16a-c). The saluretic activity of 9ab showed a high-ceiling profile. Examination of the enantiomers of 9ab revealed that the (-)-enantiomer is responsible for most of the diuretic and saluretic activities, while the (+)-enantiomer is responsible for most of the uricosuric activity.
公益社団法人日本薬学会の論文
1987-08-25