Studies on uricosuric diuretics. I. 6,7-Dichloro-5-sulfamoyl-2,3-dihydrobenzofuran-2-carboxylic acids
| Autor: | Yukio Yonetani, Hiroshi Harada, Masuhisa Nakamura, Mitsuaki Yodo, Yoshihiro Matsushita |
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| Rok vydání: | 1987 |
| Předmět: |
Male
Uricosuric Chemical Phenomena Stereochemistry medicine.medical_treatment Mice Inbred Strains Mice Structure-Activity Relationship Species Specificity Uricosuric Agent Drug Discovery medicine Animals Structure–activity relationship Diuretics Benzofurans chemistry.chemical_classification Sulfonamides Bicyclic molecule Chemistry Rats Inbred Strains Biological activity General Chemistry General Medicine Uricosuric Agents Rats Sulfonamide Female Diuretic Enantiomer |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 35:3195-3214 |
| ISSN: | 1347-5223 0009-2363 |
| DOI: | 10.1248/cpb.35.3195 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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