(Acylaryloxy)acetic acid diuretics. 3. 2,3-Dihydro-5-acyl-2-benzofurancarboxylic acids, a new class of uricosuric diuretics

Abstract

The discovery that dihydroethacrynic acid and other (4-acylphenoxy)acetic acids possessed modest but significant uricosuric and diuretic activity prompted the investigation of the related 2,3-dihydro-5-acyl-2-benzofurancarboxylic acids. Synthetic routes to a number of the 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 in the chimpanzee revealed that all diuretic and saluretic activity is due to the (+) enantiomer while the (-) enantiomer is responsible for all of the uricosuric activity. X-ray analysis showed that the (-) enantiomer possesses the 2R configuration.