Substituted 5,6-dihydrofuro[3,2-f]-1,2-benzisoxazole-6-carboxylic acids: high-ceiling diuretics with uricosuric activity.
A series of substituted 5,6-dihydrofuro[3,2-f]-1,2-benzisoxazoles was prepared and evaluated for their saluretic and uricosuric properties. Pharmacological evaluation of the title compounds was carried out in mice, rats, dogs, and monkeys. The diuretic/saluretic nature of these compounds was observed in all species, whereas the uricosuric activity was best seen in the Cebus monkey. Evaluation of the enantiomers of 8-chloro-3-(o-fluorophenyl)-5,6-dihydrofuro [3,2-f]-1,2-benzisoxazole-6-carboxylic acid (15k) revealed that only the (+) enantiomer (29) displayed diuretic and saluretic activity, whereas both enantiomers possessed uricosuric activity. X-ray analysis showed that the (-) enantiomer (30) possesses the 2R configuration.
D000818:Animals; D002712:Chlorides / Q000652:urine; D004232:Diuretics / Q000138:chemical synthesis*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology; D000882:Haplorhini; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D008958:Models, Molecular; D009318:Natriuresis / Q000187:drug effects; D010080:Oxazoles / Q000138:chemical synthesis*; D011188:Potassium / Q000652:urine; D051381:Rats; D012964:Sodium / Q000652:urine; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014528:Uricosuric Agents / Q000138:chemical synthesis*
D002712:Chlorides; D004232:Diuretics; D005663:Furans; D007555:Isoxazoles; D010080:Oxazoles; D014528:Uricosuric Agents; D012964:Sodium; D011188:Potassium