(Acylaryloxy)acetic acid diuretics. 3. 2,3-Dihydro-5-acyl-2-benzofurancarboxylic acids, a new class of uricosuric diuretics.
The discovery that dihydroethacrynic acid and other (4-acylphenoxy)acetic acids possessed modest but significant uricosuric and diuretic activity prompted our investigation of the related 2,3-dihydro-5-acyl-2-bensofurancarboxylic acids. Synthetic routes to a number of these compounds are presented along with the structure-activity relationships generated from studies in rats, dogs, and chimpanzee. Examination of the enantiomers of 6,7-dichloro-2,3-dihydro-5-(2-thienylcarbonyl)-2-benzofurancarboxylic acid (10c) in the chimpanzee revealed that all diuretic and saluretic activity is due to the (+) enantiomer 10d, while the (-) enantiomer 10e is responsible for all of the uricosuric activity. X-ray analysis showed that the (-) enantiomer 10e possesses the 2R configuration.
D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004232:Diuretics / Q000138:chemical synthesis*; D004285:Dogs; D002679:Pan troglodytes; D051381:Rats; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014528:Uricosuric Agents / Q000138:chemical synthesis*; D014961:X-Ray Diffraction
D001572:Benzofurans; D004232:Diuretics; D014528:Uricosuric Agents