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Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Novel aldose reductase inhibitors derived from 6-[[(diphenylmethylene)amino]oxy]hexanoic acid
Dietmar Rakowitz1, Grete Piccolruaz, Cornelia Pirker
1Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria. dietmar.rakowitz@uibk.ac.at
Abstract:
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.
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