Discovery of [3-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3-b]pyridin -1-yl]ace tic acids as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications

Efforts to identify treatments for chronic diabetic complications have resulted in the discovery of a novel series of highly potent and selective [3-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3-b]pyridin -1-yl]ace tic acid aldose reductase inhibitors. The lead candidate, [6-methyl-3-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3- b]pyridin -1-yl]acetic acid example 16, inhibits aldose reductase with an IC50 of 8 nM, while being inactive against aldehyde reductase (IC50 > 100 is a subset of M), a related enzyme involved in the detoxification of reactive aldehydes.