Studies on Uricosuric Diuretics. I. 6, 7-Dichloro-5-sulfamoyl-2, 3-dihydrobenzofuran-2-carboxylic Acids

• Published in: Chemical & pharmaceutical bulletin Vol. 35; no. 8; pp. 3195 - 3214
• Main Authors: HARADA, HIROSHI, MATSUSHITA, YOSHIHIRO, YODO, MITSUAKI, NAKAMURA, MASUHISA, YONETANI, YUKIO
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1987; Maruzen; Japan Science and Technology Agency
• Subjects: 2, 3-dihydrobenzofuran-5-sulfonamide; Animals; antihypertensive activity; Benzofurans - chemical synthesis; Benzofurans - pharmacology; Chemical Phenomena; Chemistry; diuretic activity; Diuretics - chemical synthesis; Diuretics - pharmacology; Exact sciences and technology; Female; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Male; Mice; Mice, Inbred Strains; Organic chemistry; Preparations and properties; Rats; Rats, Inbred Strains; S-8666; saluretic activity; Species Specificity; Structure-Activity Relationship; Sulfonamides; uricosuric activity; Uricosuric Agents - chemical synthesis; Uricosuric Agents - pharmacology; Sulfonamide; Rat; Rodentia; Oxygen heterocycle; Uricosuric agent; Biological activity; Diuretic; Vertebrata; Mammalia; Mouse; Animal; Enantiomer; Bicyclic compound; Antihypertensive agent; Aromatic compound
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.35.3195

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. Structureactivity relationships are presented. The 6, 7-dichloro-5-N, N-disubstituted 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.