Xi:Irritant;4402-83-9Relevant articles and documents
PPARs-FXR multi-target micromolecular agonist as well as preparation method and application thereof
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Paragraph 0092; 0095; 0097; 0125-0129, (2021/05/22)
The invention discloses a PPARs-FXR multi-target micromolecule agonist and a preparation method and application thereof, the structure is shown in a general formula I, and the definition of each substituent group is shown in the description and claims. Th
Highly Modular Flow Cell for Electroorganic Synthesis
Gütz, Christoph,Stenglein, Andreas,Waldvogel, Siegfried R.
, p. 771 - 778 (2017/05/29)
A highly modular electrochemical flow cell and its application in electroorganic synthesis is reported. This innovative setup facilitates many aspects: an easy adjustment of electrode distance, quick exchange of electrode material, and the possibility to easily switch between a divided or undivided cell. However, the major benefit of the cell is the exact thermal positioning of the electrode material into a Teflon piece. Thereby, the application of expensive and nonmachinable electrode materials like boron-doped diamond or glassy carbon can easily be realized in flow cells. By this geometry, the maximum surface of such valuable electrode materials is exploited. The cell size can compete with classical preparative approaches in terms of performance and productivity. The optimization of reaction parameters and an easy up-scaling to larger flow cells is possible. By using this cell, the starting material can be saved in the development of the electroorganic transformations. To demonstrate the utility of this particular cell, two transformations of important building blocks for the fine chemical and pharmaceutical industry were established including an efficient and simple workup protocol.
Design, Synthesis, and Biological Evaluation of Novel Nonsteroidal Farnesoid X Receptor (FXR) Antagonists: Molecular Basis of FXR Antagonism
Huang, Huang,Si, Pei,Wang, Lei,Xu, Yong,Xu, Xin,Zhu, Jin,Jiang, Hualiang,Li, Weihua,Chen, Lili,Li, Jian
, p. 1184 - 1199 (2015/07/07)
Farnesoid X receptor (FXR) plays an important role in the regulation of cholesterol, lipid, and glucose metabolism. Recently, several studies on the molecular basis of FXR antagonism have been reported. However, none of these studies employs an FXR antagonist with nonsteroidal scaffold. On the basis of our previously reported FXR antagonist with a trisubstituted isoxazole scaffold, a novel nonsteroidal FXR ligand was designed and used as a lead for structural modification. In total, 39 new trisubstituted isoxazole derivatives were designed and synthesized, which led to pharmacological profiles ranging from agonist to antagonist toward FXR. Notably, compound 5s (4′-[(3-{[3-(2-chlorophenyl)-5-(2-thienyl)isoxazol-4-yl]methoxy}-1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid), containing a thienyl-substituted isoxazole ring, displayed the best antagonistic activity against FXR with good cellular potency (IC50=12.2±0.2μM). Eventually, this compound was used as a probe in a molecular dynamics simulation assay. Our results allowed us to propose an essential molecular basis for FXR antagonism, which is consistent with a previously reported antagonistic mechanism; furthermore, E467 on H12 was found to be a hot-spot residue and may be important for the future design of nonsteroidal antagonists of FXR. X marks the spot: 39 trisubstituted isoxazoles were designed and synthesized, leading to compounds with pharmacological profiles ranging from agonist to antagonist at the farnesoid X receptor (FXR). By using the most potent antagonist as a probe, the essential molecular basis of FXR antagonism is proposed, and E467 on H12 can be regarded as a hot-spot residue for the future design of nonsteroidal antagonists of FXR.
