Potential aldose reductase inhibitors: 1,2,4-triazolidine-3,5-diones and 2-(3,4,5-trimethoxybenzoyl)-4,4-diethyl-3,5-isoxazolidinedione .
1,2,4-Triazolidine-3,5-diones and the 3,5-isoxazolidinedione were observed to be potent inhibitors of rat lens aldose reductase activity. In vivo in streptozotocin-diabetic rats, selected agents at 20 mg/kg/day, orally for 21 days reduced significantly the sorbitol levels of rbc, lens and sciatic nerves, suggesting that these derivatives may have some usefulness to treat clinical complications of diabetes mellitus.
Hall
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Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
Izydore
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Simlot
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Wong
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D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007908:Lens, Crystalline / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism*; D013012:Sorbitol / Q000097:blood / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use
D001786:Blood Glucose; D007555:Isoxazoles; D014230:Triazoles; C074534:2-(3,4,5-trimethoxybenzoyl)-4,4-diethyl-3,5-isoxazolidinedione; D013012:Sorbitol; D000449:Aldehyde Reductase