915038-24-3

Usage

Uses

Used in Pharmaceutical Industry:
Cholan-24-oic acid,6-ethyl-3-hydroxy-7-oxo-,(3α,5β,6β)is used as an impurity in the synthesis of obeticholic acid for its potential therapeutic applications. Obeticholic acid is a farnesoid X receptor (FXR) agonist, which has been approved for the treatment of primary biliary cirrhosis and is being investigated for other liver-related diseases.
Used in Research and Development:
Cholan-24-oic acid,6-ethyl-3-hydroxy-7-oxo-,(3α,5β,6β)can be utilized in research and development for understanding the structure-activity relationship of bile acid derivatives and their potential applications in drug discovery. Its unique structural features may provide insights into the development of novel therapeutic agents targeting various diseases.
Used in Quality Control and Analysis:
As an impurity of obeticholic acid, Cholan-24-oic acid,6-ethyl-3-hydroxy-7-oxo-,(3α,5β,6β)is used in quality control and analysis to ensure the purity and safety of the final drug product. Analytical techniques such as high-performance liquid chromatography (HPLC), mass spectrometry, and nuclear magnetic resonance (NMR) can be employed to detect and quantify its presence in pharmaceutical formulations.

Upstream product

• 2862-62-6 3α-ol-6-oxo-5β-24-cholanoic acid methyl ester 
• 2868-48-6 methyl hyodeoxycholate 
• 83-49-8 Hyodeoxycholic Acid 
• 21066-15-9 methyl 3α-acetoxy-6-oxo-5β-cholanoate 
• 863239-58-1 3α,7α-bis((trimethylsilyl)oxy)-6-ene-5β-cholanic acid methyl ester 
• 83-46-5 β-sitosterol 
• 10538-59-7 7-ketolithocholic methyl ester 
• 75-07-0 acetaldehyde 
• 474-25-9 chenodeoxycholic acid 
• 859-97-2 3,7-diketocholanic acid 
• 122960-85-4 3α-tetrahydropyranyloxy-7-keto-5β-cholan-24-oic acid 

Downstream Products

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

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.

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.

PROCESS FOR THE PREPARATION OF 3α,7α-DIHYDROXY6α-ETHYL-5β-CHOLAN-24-OIC ACID

The present invention relates to an improved process for the preparation of 3α,7α-dihydroxy-6α-ethyl-5β-cholan-24-oic acid compound of formula-1, represented by the following structural formula: Formula-1 The present invention also relates to process for the preparation of ethylene diamine and tertiary butyl amine salts of 3α,7α-dihydroxy-6α-ethyl-5β-cholan-24-oic acid which are useful in the preparation of pure 3α,7α-dihydroxy-6α-ethyl-5β-cholan-24-oic acid.

Compound for treating metabolic diseases as well as preparation method and application thereof

The invention provides a compound for treating metabolic diseases, the compound has a structure represented by formula (I) or formula (II), or a racemate, a stereoisomer, a geometric isomer, a tautomer, a solvate, a hydrate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. The compounds provided by the invention are FXR and/or TGR5 receptor activators, and the compounds havethe activity of activating FXR and/or TGR5 receptors, and can be used for preparing medicines for treating chronic liver diseases, metabolic diseases or portal hypertension.

Preparation method of obeticholic acid and intermediate thereof

The invention discloses a preparation method of obeticholic acid and an intermediate thereof. The invention provides a preparation method of a compound V. The preparation method of the compound V comprises the following steps: carrying out hydroxyl protective reaction on a compound VI and a hydroxyl protective reagent to obtain the compound V. The preparation method is simple and convenient to operate, low in cost, gentle in condition, environmentally friendly and suitable for industrialization.

Preparation method of obeticholic acid and intermediate thereof

The invention discloses a preparation method of obeticholic acid and an intermediate thereof. The provided preparation method of the obeticholic acid comprises the following step: carrying out oxidizing reaction on a compound V and an oxidizing agent in an organic solvent to obtain a compound IV so as to obtain the final product. PG1 is a carboxyl protecting group, PG2 is a hydroxyl protecting group, and a component as shown in specification in the compound V and the compound IV independently shows that the ethidine is an E configuration, a Z configuration or a mixture of the E configuration and the Z configuration. The preparation method is simple and convenient to operate, low in cost, gentle in condition, environmentally friendly and suitable for industrialization.

STEROID DERIVATIVE FXR AGONIST

The present invention relates to a compound represented by formula (I), a tautomer thereof or a pharmaceutically acceptable salt thereof, and relates to applications thereof in the preparation of drugs for treating FXR related diseases.

Method for preparing intermediates of obeticholic acid and obeticholic acid

The invention discloses a method for preparing intermediates of obeticholic acid and the obeticholic acid. A synthetic route of the intermediates is shown as follows. The intermediates of the obeticholic acid have good stereoselectivity in the reaction process, so that difficulty of synthesis of the obeticholic acid is simplified greatly, and the synthesis cost of the obeticholic acid is reduced;the method has mild reaction conditions, and is industrially easy to implement, and the obeticholic acid intermediates and obeticholic acid which have low content of impurities can be obtained; the adopted raw materials are safe, and the cost is low, so that the production cost is reduced effectively.

3,7-di(t-butyldimethylsiloxy)-6-ene-5beta-cholan-24-oic acid methyl ester

The invention belongs to the technical field of medicines, relates to a method of preparing obeticholic acid through adopting 3,7-di(t-butyldimethylsiloxy)-6-ene-5beta-cholan-24-oic acid methyl ester as an intermediate, and particularly relates to the 3,7-di(t-butyldimethylsiloxy)-6-ene-5beta-cholan-24-oic acid methyl ester that is a chemical compound, a method of preparing the compound, and a use of the compound for preparation of the obeticholic acid. The invention also relates to a method of preparing the obeticholic acid. The method of preparing the obeticholic acid includes (1) preparing the 3,7-di(t-butyldimethylsiloxy)-6-ene-5beta-cholan-24-oic acid methyl ester and (2) preparing the obeticholic acid through adopting the 3,7-di(t-butyldimethylsiloxy)-6-ene-5beta-cholan-24-oic acid methyl ester as the intermediate.

METHODS FOR PREPARATION OF BILE ACIDS AND DERIVATIVES THEREOF

The present application relates to a method of preparing compounds of Formula (A) or a pharmaceutically acceptable salt, solvate, or amino acid conjugate thereof.