title: Synthesis of novel phenylacetic acid derivatives with halogenated benzyl subunit and evaluation as aldose reductase inhibitors.
abstract: 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.
authors.affiliation: Institute of Pharmacy, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Rakowitz
authors.forename: Andreas
authors.initials: A
authors.lastname: Gmeiner
authors.forename: Nicole
authors.initials: N
authors.lastname: Schröder
authors.forename: Barbara
authors.initials: B
authors.lastname: Matuszczak
mesh_terms: 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
chemical_list: D001565:Benzoates; D004791:Enzyme Inhibitors; D006846:Hydrocarbons, Halogenated; D010648:Phenylacetates; D000449:Aldehyde Reductase