Article ID Journal Published Year Pages File Type
1375945 Bioorganic & Medicinal Chemistry Letters 2009 4 Pages PDF
Abstract

In an effort to find a potent xanthine oxidoreductase (XO) inhibitor, we discovered the best compound 2-[2-(2-methoxy-ethoxy)-ethoxy]-5-[5-(2-methyl-pyridin-4-yl)-1H-[1,2,4]triazol-3-yl]-benzonitrile 28. Here, we describe the following: (1) the design, synthesis, and structure–activity relationship of a series of 3-phenyl-5-pyridyl-1,2,4-triazole derivatives by in vitro studies of XO inhibitory activity in bovine milk and in vivo studies of serum uric acid (UA) reductive activity in rats, (2) a drug interaction study by a cytochrome P450 3A4 (CYP3A4) assay, and (3) a pharmacokinetic (PK) study. Compound 28 exhibits potent XO inhibitory activity, serum UA-lowering activity in rats, weak CYP3A4 inhibitory activity, and moderate PK profile.

Graphical abstractA series of 3-phenyl-5-pyridyl-1,2,4-triazole derivatives was synthesized and evaluated as xanthine oxidoreductase inhibitors. The best compound (28) had the most potent serum UA-lowering activity and moderate PK profile without CYP3A4 inhibition.Figure optionsDownload full-size imageDownload as PowerPoint slide

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Physical Sciences and Engineering Chemistry Organic Chemistry
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