Discovery of [3-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3-b]pyridin-1-yl]acetic acids as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.
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Van Zandt MC, Doan B, Sawicki DR, Sredy J, Podjarny AD
Discovery of [3-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3-b]pyridin-1-yl]acetic acids as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.
Bioorg Med Chem Lett. 2009 Apr 1;19(7):2006-8. doi: 10.1016/j.bmcl.2009.02.037. Epub 2009 Feb 12.
- PubMed ID
- 19250825 [ View in PubMed]
- Abstract
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]acetic 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 microM), a related enzyme involved in the detoxification of reactive aldehydes.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) 2-(3-((4,5,7-trifluorobenzo[d]thiazol-2-yl)methyl)-1H-pyrrolo[2,3-b]pyridin-1-yl)acetic acid Aldose reductase IC 50 (nM) >100000 N/A N/A Details Lidorestat Aldose reductase IC 50 (nM) 27000 N/A N/A Details