96740-93-1Relevant articles and documents
Discovery of new and highly effective quadruple FFA1 and PPARα/γ/δ agonists as potential anti-fatty liver agents
Zhou, Zongtao,Ren, Qiang,Jiao, Shixuan,Cai, Zongyu,Geng, Xinqian,Deng, Liming,Wang, Bin,Hu, Lijun,Zhang, Luyong,Yang, Ying,Li, Zheng
supporting information, (2021/12/27)
Non-alcoholic fatty liver disease (NAFLD) has become the most common hepatic disease, while no drug was approved until now. The previous study reported that the quadruple FFA1/PPAR-α/γ/δ agonist RLA8 provided better efficacy than obeticholic acid on NASH. In the present study, two design strategies were introduced to explore better quadruple FFA1/PPAR-α/γ/δ agonists with improved metabolic stability. These efforts ultimately resulted in the identification of ZLY18, a quadruple FFA1/PPAR-α/γ/δ agonist with twice higher metabolic half-life than RLA8 in the liver microsome. In the triton-1339W-induced hyperlipidemic model, ZLY18 reversed hyperlipidemia to an almost normal level, which exhibited far stronger lipid-lowering effects than that of RLA8. Moreover, ZLY18 significantly decreased steatosis, hepatocellular ballooning, inflammation and liver fibrosis in NASH model even better than RLA8. Further mechanism studies suggested that ZLY18 exerts stronger effects than RLA8 on the regulation of the gene related to lipid synthesis, oxidative stress, inflammation and fibrosis. In addition, ZLY18 is more effective than pirfenidone in the prevention of CCl4-induced liver fibrosis. Besides, ZLY18 has an acceptable safety profile in the acute toxicity study at a high dose of 500 mg/kg. Therefore, ZLY18 represents a novel and highly promising quadruple FFA1/PPAR-α/γ/δ agonist worth of further investigation and development.
Solid-phase synthesis of serine-based glycosphingolipid analogues for preparation of glycoconjugate arrays
Wallner, Fredrik K.,Norberg, Henrik A.,Johansson, Annika I.,Mogemark, Mickael,Elofsson, Mikael
, p. 309 - 315 (2007/10/03)
Synthetic glycolipids with defined structures are important tools in the study of glycolipid biology. In this paper we describe a solid-phase synthesis of three galactosylated serine-based glycosphingolipid analogues using the novel linker 2-fluoro-4-(hydroxymethyl)-phenoxyacetic acid. Gel-phase 19F-NMR spectroscopy was used to measure the yield and stereochemical outcome of the solid-phase glycosylations. Under NIS-TfOH promotion, α- and β-selective glycosylations were performed at room temperature with thioglycoside donors carrying fluorine labelled protective groups. Finally, the glycolipids were covalently linked to microtiter plates and labelled lectins with different selectivity for α- and β-galactosides could bind to the glycolipid arrays.
Solid-phase synthesis of oligoribonucleotides
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, (2008/06/13)
A process for the preparation of oligoribonucleotides of the formula STR1 in which n, L, BB, W, T, Y', U, C1 and C2 are as defined in the description, by solid-phase synthesis is described, as are intermediates of the oligoribonucleo
