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.
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Authors | Michael C Van Zandt, Brian Doan, Diane R Sawicki, Janet Sredy, Alberto D Podjarny |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 19
Issue 7
Pg. 2006-8
(Apr 01 2009)
ISSN: 1464-3405 [Electronic] England |
PMID | 19250825
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- (6-methyl-3-(4,5,7-trifluorobenzothiazol-2-ylmethyl)pyrrolo(2,3-b)pyridin-1-yl)acetic acid
- Acetates
- Benzothiazoles
- Enzyme Inhibitors
- Aldehyde Reductase
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Topics |
- Acetates
(chemical synthesis, chemistry, pharmacology)
- Aldehyde Reductase
(antagonists & inhibitors, metabolism)
- Benzothiazoles
(chemical synthesis, chemistry, pharmacology)
- Catalytic Domain
- Chronic Disease
- Computer Simulation
- Crystallography, X-Ray
- Diabetes Complications
(drug therapy)
- Enzyme Inhibitors
(chemical synthesis, chemistry, pharmacology)
- Humans
- Inhibitory Concentration 50
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