Synthesis of novel benzoic acid derivatives with benzothiazolyl subunit and evaluation as aldose reductase inhibitors.
Several methyl benzothiazolyloxybenzoates, S-isosters, and the corresponding benzoic acids were synthesized and tested as aldose reductase inhibitors (ARIs). Out of this series, the ester derivative 2a-7 was found to exhibit the highest enzyme-inhibitoric activity. In order to investigate this unexpected result, further modifications were carried out which allowed us to explain this finding and to open a path to a novel class of ARIs.
Rakowitz
Dietmar
D
Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria. dietmar.rakowitz@uibk.ac.at
Hennig
Barbara
B
Nagano
Marietta
M
Steger
Stefan
S
Costantino
Luca
L
Matuszczak
Barbara
B
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D019817:Benzoic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D052160:Benzothiazoles; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000201:enzymology; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry*
D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D013844:Thiazoles; D019817:Benzoic Acid; D000449:Aldehyde Reductase; C005465:benzothiazole