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

JP Rizzi, RC Schnur, NJ Hutson, KG Kraus…

Index: Rizzi, James P.; Schnur, Rodney C.; Hutson, Nancy J.; Kraus, Kenneth G.; Kelbaugh, Paul R. Journal of Medicinal Chemistry, 1989 , vol. 32, # 6 p. 1208 - 1213

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Citation Number: 17

Abstract

Sorbinil (l), 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 (S02R) was sufficiently large to hinder rotation of the hydantoin ring, forcing an orientation similar to that of a spirocyclic ...