Novel, potent aldose reductase inhibitors: 3,4-Dihydro-4-oxo-3-((5-(trifluoromethyl)-2-benzothiazolyl)methyl) -1-phthalazine-acetic acid (Zopolrestat) and congeners

A new working hypothesis that there is a hitherto unrecognized binding site on the aldose reductase enzyme with strong affinity for benzothiazoles was pursued for the design of novel, potent aldose reductase inhibitors. The first application of this hypothesis led to a novel series of 3,4-dihydro-4-oxo-3-(benzothiazolylmethyl)-1-phthalazineacetic acids.