Rotationally restricted mimics of rigid molecules: nonspirocyclic hydantoin aldose reductase inhibitors.

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Rizzi JP, Schnur RC, Hutson NJ, Kraus KG, Kelbaugh PR

Rotationally restricted mimics of rigid molecules: nonspirocyclic hydantoin aldose reductase inhibitors.

J Med Chem. 1989 Jun;32(6):1208-13.

PubMed ID

2498517 [ View in PubMed

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Abstract

Sorbinil (1), a spirocyclic hydantoin, is a potent inhibitor of the enzyme aldose reductase. Simulation of the rigid spirocyclic ring orientation found in sorbinil was achieved with nonspirocyclic 5-[5'-chloro-2'-(alkylsulfonyl)-phenyl]hydantoins and 5-[5'-chloro-2'-[(N-alkylamino)sulfonyl]phenyl]hydantoins. The 2'-substituent (SO2R) was sufficiently large to hinder rotation of the hydantoin ring, forcing an orientation similar to that of a spirocyclic hydantoin. Calculated conformational preference, X-ray data, and inhibitory IC50 values for these nonspirocyclic 2'-substituted (SO2R) phenylhydantoins are in accord with what is expected for spirocyclic hydantoins and comparable to those of sorbinil.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Sorbinil	Aldose reductase	IC 50 (nM)	500	N/A	N/A	Details
Sorbinil	Aldose reductase	IC 50 (nM)	120	N/A	N/A	Details