Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 52, Issue 10, Pages 3317-3327Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm900251a
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Funding
- NIDDK NIH HHS [R43 DK065423, 1R43DK65423] Funding Source: Medline
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The incidence of obesity and other diseases associated with an increased triacylglycerol mass is growing rapidly, particularly in the United States. Glycerol 3-phosphate acyltransferase (GPAT) catalyzes the rate-limiting step of glycerolipid biosynthesis, the acylation of glycerol 3-phosphate with saturated long-chain acyl-CoAs. In an effort to produce small molecule inhibitors of this enzyme, a series of benzoic and phosphonic acids was designed and synthesized. In vitro testing of this series has led to the identification of several compounds, in particular 2-(nonylsulfonamido)benzoic acid (15g), possessing moderate GPAT inhibitory activity in an intact mitochondrial assay.
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