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

Basic Information

ID: ALA1124482

Journal: J Med Chem

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

Authors: Rizzi JP, Schnur RC, Hutson NJ, Kraus KG, Kelbaugh PR.

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.

CiteXplore: 2498517

DOI: 10.1021/jm00126a011

Patent ID: ┄