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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Synthesis and biological evaluation of 3-methyl-5-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione derivatives for the treatment of diet-induced obesity.
Triglycerides are the main part of fats and half of the lipids in hepatocytes, and play an important role in metabolism as energy sources and transporters of dietary fat. In this study, 33 derivatives based on 3-methyl-5-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione were synthesized and evaluated for their lipid-lowering activity. Among them, compound 1i was found to exhibit potent triglyceride-lowering potency in 3T3-L1 adipocytes which was comparable to that of the adenosine monophosphate-activated protein kinase (AMPK) agonist Acadesine (AIACR). Furthermore, oral administration of 1i at a dose of 50 mg kg(-1) d(-1) for 5 weeks could reduce the mean body weight and liver weight by 12.02% and 32.00%, respectively, and regulated serum levels of triglycerides in diet-induced obese mice. The results indicate that compound 1i is a potential small-molecule for the treatment of diet-induced obesity and related diseases.
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