4651-67-6Relevant articles and documents
Ido,Sakurai
, p. 51,53 (1939)
An expedient synthesis of 6α-fluoroursodeoxycholic acid
Koenigsberger, Kurt,Chen, Guang-Pei,Vivelo, James,Lee, George,Fitt, John,McKenna, Joseph,Jenson, Todd,Prasad, Kapa,Repic, Oljan
, p. 665 - 669 (2002)
Optimization of the synthesis of 6α-fluoroursodeoxycholic acid 1 is described starting from the commercially available 2. The penultimate intermediate 16 was made in eight synthetic steps but in only four operations in an overall yield of 57%. The highlights are flourination of hydroxyketo acid 11 using Selectfluor through the intermediacy of silyl enol ether 12, conversion of 13 to 14 via equilibration of fluoroketone, esterification, and acylation. The drug substance 1 was prepared from mesylate 16 using potassium superoxide followed by a mild reductive workup using methoxydiethylborane.
(E)-7-Ethylidene-lithocholic Acid (7-ELCA) Is a Potent Dual Farnesoid X Receptor (FXR) Antagonist and GPBAR1 Agonist Inhibiting FXR-Induced Gene Expression in Hepatocytes and Stimulating Glucagon-like Peptide-1 Secretion From Enteroendocrine Cells
Dracinsky, Martin,Drastik, Martin,Kaspar, Miroslav,Klepetarova, Blanka,Kronenberger, Thales,Kudova, Eva,Micuda, Stanislav,Pavek, Petr,Stefela, Alzbeta
, (2021/09/08)
Bile acids (BAs) are key signaling steroidal molecules that regulate glucose, lipid, and energy homeostasis via interactions with the farnesoid X receptor (FXR) and G-protein bile acid receptor 1 (GPBAR1). Extensive medicinal chemistry modifications of the BA scaffold led to the discovery of potent selective or dual FXR and GPBAR1 agonists. Herein, we discovered 7-ethylidene-lithocholic acid (7-ELCA) as a novel combined FXR antagonist/GPBAR1 agonist (IC50 = 15?μM/EC50 = 26?nM) with no off-target activation in a library of 7-alkyl substituted derivatives of BAs. 7-ELCA significantly suppressed the effect of the FXR agonist obeticholic acid in BSEP and SHP regulation in human hepatocytes. Importantly, 7-ELCA significantly stimulated the production of glucagon-like peptide-1 (GLP-1), an incretin with insulinotropic effect in postprandial glucose utilization, in intestinal enteroendocrine cells. We can suggest that 7-ELCA may be a prospective approach to the treatment of type II diabetes as the dual modulation of GPBAR1 and FXR has been supposed to be effective in the synergistic regulation of glucose homeostasis in the intestine.
Preparation method of low-cost, high-yield and high-purity 7-ketolithocholic acid
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Paragraph 0048-0055, (2020/07/24)
The invention discloses a preparation method of low-cost, high-yield and high-purity 7-ketolithocholic acid, which is characterized by comprising the following steps: adding chenodeoxycholic acid intoa mixed solution of an organic solvent and water, and performing stirring to dissolve; adding bromide and acid, and performing stirring and dissolving; adding bromate for reaction; adding a terminating agent, and performing stirring to terminate the reaction; adding water to crystallize the product; and carrying out solid-liquid separation, washing a solid product with water for multiple times, and performing drying to obtain 7-ketolithocholic acid. According to the method, a common and safe reagent is adopted, chenodeoxycholic acid is selectively oxidized into 7-ketolithocholic acid under arelatively mild condition, the product purity is greater than 98.0%, and the yield is greater than 85%. The method has the advantages of cheap reagents, simple operation, high process reproducibility,simple post-treatment, high product purity and the high yield, and can easily implement industrial production.