Spiro hydantoin aldose reductase inhibitors.

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Sarges R, Schnur RC, Belletire JL, Peterson MJ

Spiro hydantoin aldose reductase inhibitors.

J Med Chem. 1988 Jan;31(1):230-43.

PubMed ID
3121857 [ View in PubMed
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Abstract

Sorbitol formation from glucose, catalyzed by the enzyme aldose reductase, is believed to play a role in the development of certain chronic complications of diabetes mellitus. Spiro hydantoins derived from five- and six-membered ketones fused to an aromatic ring or ring system inhibit aldose reductase isolated from calf lens. In vivo these compounds are potent inhibitors of sorbitol formation in sciatic nerves of streptozotocinized rats. Optimum in vivo activity is reached in spiro hydantoins derived from 6-halogenated 2,3-dihydro-4H-1-benzopyran-4-ones (4-chromanones). In 2,4-dihydro-6-fluorospiro[4H-1-benzopyran-4,4'-imidazolidine]-2',5 '-dione, the activity resides exclusively in the 4S isomer, compound 115 (CP-45,634, USAN: sorbinil). This compound is currently being used to test, in humans, the value of aldose reductase inhibitors in the therapy of diabetic complications.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AlrestatinAldose reductaseIC 50 (nM)10000N/AN/ADetails
SorbinilAldose reductaseIC 50 (nM)500N/AN/ADetails