Novel aldose reductase inhibitors derived from 6-[[(diphenylmethylene)amino]oxy]hexanoic acid.
Starting from the recently identified aldose reductase inhibitor 6-[[(diphenylmethylene)amino]oxy]hexanoic acid 1, the following systematic structural modifications were performed: (a) formal substitution of the phenyl rings, (b) isosteric replacement of the benzene core by the heteroarenes pyridine and thiophene, (c) formal reduction of the aromatic substructure and subsequent diminution of the cyclohexyl ring, (d) introduction of methylene spacer between C=N and the phenyl rings, and finally (e) formal ring closure in order to get derivatives of the tricycles fluorenone, xanthone, and thioxanthone, respectively. Out of these series, compounds 22-24 bearing disubstituted phenyl rings exhibit the highest inhibitory activity (IC(50 )value approx. 3 muM) which lie almost in the range of the reference sorbinil.
Rakowitz
Dietmar
D
Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria. dietmar.rakowitz@uibk.ac.at
Piccolruaz
Grete
G
Pirker
Cornelia
C
Matuszczak
Barbara
B
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000478:Alkylation; D000818:Animals; D002208:Caproates / Q000138:chemical synthesis* / Q000494:pharmacology*; D002417:Cattle; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D010091:Oximes / Q000138:chemical synthesis / Q000494:pharmacology; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D002208:Caproates; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D010091:Oximes; D000449:Aldehyde Reductase