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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetates / chemical synthesis*
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Acetates / chemistry
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Acetates / pharmacology*
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Aldehyde Reductase / antagonists & inhibitors*
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Aldehyde Reductase / metabolism
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Benzothiazoles / chemical synthesis*
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Benzothiazoles / chemistry
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Benzothiazoles / pharmacology
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Catalytic Domain
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Chronic Disease
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Computer Simulation
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Crystallography, X-Ray
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Diabetes Complications / drug therapy
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Humans
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Inhibitory Concentration 50
Substances
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(6-methyl-3-(4,5,7-trifluorobenzothiazol-2-ylmethyl)pyrrolo(2,3-b)pyridin-1-yl)acetic acid
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Acetates
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Benzothiazoles
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Enzyme Inhibitors
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Aldehyde Reductase