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.

中文翻译：

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3-甲基-5-苯基噻吩并[2,3-d]嘧啶-2,4（1H，3H）-二酮衍生物的合成和生物学评价用于治疗饮食性肥胖。

甘油三酸酯是肝细胞中脂肪的主要部分和一半的脂质，在代谢中起着重要的作用，它是膳食脂肪的能量来源和转运体。在这项研究中，合成了33种基于3-甲基-5-苯基硫代[2,3-d]嘧啶-2,4（1H，3H）-二酮的衍生物，并评估了它们的降脂活性。其中，发现化合物1i在3T3-L1脂肪细胞中具有有效的降低甘油三酸酯的功效，与腺苷单磷酸激活的蛋白激酶（AMPK）激动剂Acadesine（AIACR）相当。此外，以50 mg kg（-1）d（-1）的剂量口服1i 5周可分别使平均体重和肝脏重量降低12.02％和32.00％，并调节血清甘油三酯水平。饮食诱导的肥胖小鼠。