915038-26-5

Basic information

• Product Name: 3α-hydroxy-6-ethyl-7-keto-5β-cholan-24-oic acid
• Synonyms: 3α-hydroxy-6-ethyl-7-keto-5β-cholan-24-oic acid;3α-hydroxy-6-ethyl-7-keto-5β-cholan-24-oic acid-o;(3alpha,5beta,6alpha)-6-Ethyl-3-hydroxy-7-oxocholan-24-oic acid;Obeticholic Acid Intermediate G;Intermediate 3;Obeticholic Acid Impurity 8;route 2 N-1 intermediate;(3α,5β,6α)--6-Ethyl-3-hydroxy-7-oxocholan-24-oic acid
• CAS NO: 915038-26-5
• Molecular Formula: C₂₆H₄₂O₄
• Molecular Weight: 418.60928
• EINECS: 1592732-453-0
• Product Categories: Ocaliva intermediate
• Mol File: 915038-26-5.mol
• Article Data: 15

Chemical Properties

• Boiling Point: 561.5±25.0 °C(Predicted)
• Appearance: /
• Density: 1.087±0.06 g/cm3(Predicted)
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 4.76±0.10(Predicted)
• CAS DataBase Reference: 3α-hydroxy-6-ethyl-7-keto-5β-cholan-24-oic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 3α-hydroxy-6-ethyl-7-keto-5β-cholan-24-oic acid(915038-26-5)
• EPA Substance Registry System: 3α-hydroxy-6-ethyl-7-keto-5β-cholan-24-oic acid(915038-26-5)

Safety Data

• Hazardous Substances Data: 915038-26-5(Hazardous Substances Data)

Usage

General Description

3α-hydroxy-6-ethyl-7-keto-5β-cholan-24-oic acid is a compound that belongs to the category of bile acids, which are essential for the digestion and absorption of dietary fats. This particular bile acid is synthesized in the liver and stored in the gallbladder, where it is released into the small intestine to aid in the emulsification and absorption of fats. It plays a key role in the formation of micelles, which are crucial for the absorption of fat-soluble vitamins and other lipid-soluble nutrients. Additionally, 3α-hydroxy-6-ethyl-7-keto-5β-cholan-24-oic acid has also been shown to have potential therapeutic properties, particularly in the treatment of liver and gastrointestinal disorders.

Upstream product

• 863239-59-2 3α-hydroxy-6-ethylidene-7-keto-5β-cholan-24-carboxylic acid methyl ester 

Downstream Products

• 1537866-42-4 6α-ethyl-3α-formyloxy-7-keto-5β-cholan-24-oic acid 
• 865244-30-0 (3α,5β,6α,7β)-6-ethyl-3,7-dihydroxycholan-24-oic acid 

Relevant articles and documents

3β-Isoobeticholic acid efficiently activates the farnesoid X receptor (FXR) due to its epimerization to 3α-epimer by hepatic metabolism

Bile acids (BAs) are important signaling molecules acting via the farnesoid X nuclear receptor (FXR) and the membrane G protein-coupled bile acid receptor 1 (GPBAR1). Besides deconjugation of BAs, the oxidoreductive enzymes of colonic bacteria and hepatocytes enable the conversion of BAs into their epimers or dehydrogenated forms. Obeticholic acid (OCA) is the first-in-class BA-derived FXR agonist approved for the treatment of primary biliary cholangitis. Herein, a library of OCA derivatives, including 7-keto, 6-ethylidene derivatives and 3β-epimers, was synthetized and investigated in terms of interactions with FXR and GPBAR1 in transaction assays and evaluated for FXR target genes expression in human hepatocytes and C57BL/6 mice. The derivatives were further subjected to cell-free analysis employing in silico molecular docking and a TR-FRET assay. The conversion of the 3βhydroxy epimer and its pharmacokinetics in mice were studied using LC–MS. We found that only the 3β-hydroxy epimer of OCA (3β-isoOCA) possesses significant activity to FXR in hepatic cells and mice. However, in a cell-free assay, 3β-isoOCA had about 9-times lower affinity to FXR than did OCA. We observed that 3β-isoOCA readily epimerizes to OCA in hepatocytes and murine liver. This conversion was significantly inhibited by the hydroxy-Δ5-steroid dehydrogenase inhibitor trilostane. In addition, we found that 3,7-dehydroobeticholic acid is a potent GPBAR1 agonist. We conclude that 3β-isoOCA significantly activates FXR due to its epimerization to the more active OCA by hepatic metabolism. Other modifications as well as epimerization on the C3/C7 positions and the introduction of 6-ethylidene in the CDCA scaffold abrogate FXR agonism and alleviate GPBAR1 activation.

Preparation method of obeticholic acid

The invention relates to a preparation method of obeticholic acid, in particular to a compound shown as a formula III which is described in the specification, a preparation method of the compound anda method for preparing obeticholic acid through the compound III. The method has the advantages of mild reaction conditions, few byproducts, simplicity and convenience in operation, high total yield and the like, and is suitable for large-scale production.

Process Research and Impurity Control Strategy for Obeticholic Acid, a Farnesoid X Receptor Agonist

The process to obtain ICH-grade quality obeticholic acid (OCA) was improved, and the overall yield was 25.9%. The critical process parameters were established to reduce or avoid process-related impurities. The formation mechanisms, purge pathways, and control strategies for these impurities were also discussed for the first time. An high-performance liquid chromatography instrument utilizing the charged aerosol detection technique was applied for an impurity content assay in OCA for the first time. The developed process was robust and suitable for manufacturing scale-up.