Discovery of novel aldose reductase inhibitors characterized by an alkoxy-substituted phenylacetic acid core.
In continuation of our effort aimed towards the development of novel aldose reductase inhibitors, several phenylacetic acids bearing an alkoxy substituent in position 3 or 4, respectively, were prepared and screened. The latter represent formal ring opening products of the cyclohexylmethyloxyphenylacetic acids IIa and IIb, recently elaborated in our group. Out of these series, compounds 4aa and 4ba characterized by an n-heptyloxy subunit turned out to be the most potent inhibitors. Based on these unexpected results, we suggest that such an alkyl side chain acts as a useful surrogate for the 4-bromo-2-fluorobenzyl residue often found in potent aldose reductase inhibitors.
Rakowitz
Dietmar
D
Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria. dietmar.rakowitz@uibk.ac.at
Gmeiner
Andreas
A
Matuszczak
Barbara
B
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D002417:Cattle; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D010648:Phenylacetates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
C026245:3-hydroxyphenylacetate; D004791:Enzyme Inhibitors; D010648:Phenylacetates; C008070:4-hydroxyphenylacetic acid; D000449:Aldehyde Reductase