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 ursodeoxycholic acid
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Paragraph 0023, (2020/06/24)
The invention discloses a preparation method of ursodesoxycholic acid, which comprises the following steps:using chenodeoxycholic acid as a raw material, oxidizing with sodium hypochlorite to obtain an intermediate 3alpha-hydroxy-7beta-carbonyl-5 beta-cholanic acid, carrying out hydrogenation reduction hydrogenation by using Raney nickel as a catalyst to obtain an ursodesoxycholic acid crude product, and carrying out triethylamine salifying refining to obtain the ursodesodesoxycholic acid bulk drug. The preparation method of ursodesoxycholic acid is stable and reliable in raw material source,high in reaction selectivity, easy in finished product refining, high in quality and short in process route; the method has the advantages of short synthesis steps, mild reaction conditions and cleanprocess, and is suitable for industrial production.