Synthesis of novel phenylacetic acid derivatives with halogenated benzyl subunit and evaluation as aldose reductase inhibitors.
In the course of our ongoing studies several substituted benzyloxyphenylacetic acids were prepared. Comparison of their aldose reductase inhibition with the biological activity obtained for recently evaluated benzoic acid analogues revealed the critical role of a methylene spacer between the aromatic core and the acidic function. Starting from the most potent derivative (i.e. 5d, IC50 = 20.9 microM) further structural modifications were performed and their influence on the inhibitory effect was established.
Rakowitz
Dietmar
D
Institute of Pharmacy, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria.
Gmeiner
Andreas
A
Schröder
Nicole
N
Matuszczak
Barbara
B
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D000818:Animals; D001565:Benzoates / Q000737:chemistry; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006846:Hydrocarbons, Halogenated / Q000138:chemical synthesis* / Q000494:pharmacology; D010648:Phenylacetates / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001565:Benzoates; D004791:Enzyme Inhibitors; D006846:Hydrocarbons, Halogenated; D010648:Phenylacetates; D000449:Aldehyde Reductase