10538-59-7

Basic information

• Product Name: 7-ketolithocholic Methyl ester
• Synonyms: 7-ketolithocholic Methyl ester;Methyl 7-keto-3alpha-hydroxy-5beta-cholanoate;Methyl 3alpha-hydroxy-7-oxo-5beta-cholan-24-oate;Obeticholic Acid N-4;obeticholic acid intermediate 2;5β-Cholanic acid, 3α-hydroxy-7-oxo-, methyl ester;route 3 intermediate2;7-Ketolithocholic acid methyl ester (BTC-E1)
• CAS NO: 10538-59-7
• Molecular Formula: C₂₅H₄₀O₄
• Molecular Weight: 404.5827
• Product Categories: Obeticholic Acid;Ocaliva intermediate
• Mol File: 10538-59-7.mol

Chemical Properties

• Melting Point: 107-109℃
• Boiling Point: 505.7±25.0 °C(Predicted)
• Appearance: /
• Density: 1.085±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• PKA: 15.02±0.70(Predicted)
• CAS DataBase Reference: 7-ketolithocholic Methyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 7-ketolithocholic Methyl ester(10538-59-7)
• EPA Substance Registry System: 7-ketolithocholic Methyl ester(10538-59-7)

Safety Data

• Hazardous Substances Data: 10538-59-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
7-ketolithocholic Methyl ester is used as a TGR5 modulator for its potential role in regulating various physiological processes. TGR5 is a bile acid receptor that has been linked to the regulation of glucose and energy homeostasis, as well as other functions such as inflammation and cell proliferation. By modulating TGR5, 7-ketolithocholic Methyl ester may have therapeutic applications in treating metabolic disorders, liver diseases, and other conditions related to bile acid metabolism.
Used in Research Applications:
7-ketolithocholic Methyl ester is used as a research tool for studying the role of bile acids and their receptors in cellular processes. It can help researchers understand the mechanisms underlying the actions of TGR5 and its potential as a therapeutic target for various diseases.
Used in Drug Development:
7-ketolithocholic Methyl ester may be used in the development of new drugs targeting TGR5. As a modulator of this receptor, it could potentially be used to create medications that improve metabolic health, reduce inflammation, or treat specific liver diseases. Further research and development would be necessary to determine its efficacy and safety as a drug candidate.

Upstream product

• 75-75-2 methanesulfonic acid 
• 4651-67-6 7-Ketolithocholic acid 
• 7753-72-2 methyl 3,7-dioxocholan-24-oate 
• 10190-22-4 3α,6α,7α-triol-5β-24-cholanoic acid methyl ester 
• 547-75-1 hyocholic acid 
• 15073-97-9 methyl 3α,12α-dihydroxy-7-oxo-5β-cholate 
• 81-25-4 cholic acid 
• 911-40-0 7-ketodeoxycholic acid 
• 336099-76-4 methyl 3α-[(1,1-dimethylethyl)dimethylsilyloxy]-7-oxocholan-24-oate 
• 83-46-5 β-sitosterol 
• 859-97-2 3,7-diketocholanic acid 
• 67-56-1 methanol 

Downstream Products

• 10538-55-3 3α,7β-dihydroxy-5β-cholan-24-oic acid methyl ester 
• 3057-04-3 chenodeoxycholic acid methyl ester 
• 124729-57-3 3α,7α-dihydroxy-7β-ethyl-5β-cholanoic acid 
• 124729-58-4 3α,7α-dihydroxy-7β-n-propyl-5β-cholanoic acid 
• 95749-50-1 3-oxo-6,7-seco-5β-cholane-6,7,24-trioic acid 
• 83-49-8 Hyodeoxycholic Acid 
• 1537866-42-4 6α-ethyl-3α-formyloxy-7-keto-5β-cholan-24-oic acid 
• 863239-59-2 3α-hydroxy-6-ethylidene-7-keto-5β-cholan-24-carboxylic acid methyl ester 
• 4651-67-6 7-Ketolithocholic acid 
• 1516887-31-2 3α-hydroxy-6-ethylidene-7-keto-5β-cholanoic acid-24-methyl ester 
• 915038-24-3 (E/Z)-3α-hydroxy-6-ethylidene-7-keto-5β-cholan-24-oic acid 
• 1516887-33-4 (E)-3α-hydroxy-6-ethylidene-7-keto-5β-cholan-24-oic acid 
• 1516887-31-2 (E)-3α-hydroxy-6-ethylidene-7-keto-5β-cholan-24-oic acid methyl ester 
• 52759-80-5 methyl 3α-7α-ditrimethylsilyloxy-5β-chol-6-en-24-oate 

Relevant articles and documents

Facial synthesis of key intermediate of obeticholic acid via Pd-catalyzed Kumada-Tamao-Corriu cross-coupling reaction

Obeticholic acid (OCA) is used to treatment for Primary Biliary Cholangitis and other Famesoid X Receptor related diseases. Through the palladium catalyzed Kumada-Tamao-Corriu cross-coupling reaction, a novel and efficient method for synthesis of OCA with satisfied yield was successfully developed. The absolute configuration of the key intermediate was confirmed by Single-crystal X-ray Diffraction. It affords good strategy for large-scale synthesis of OCA.

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.

BILE ACIDS LXIX. SELECTIVE K-SELECTRIDE REDUCTION OF 3,7-DIKETO STEROIDS

The K-Selectride reduction at low temperature (-45 C) of 7-oxo-5α-cholestan-3β-yl acetate and methyl 7-oxo-3α-hydroxy-5β-cholanoate resulted in almost quantitative yield of the 7α-alcohol in the 5α-compound but only moderate yield of the 5β-analog.The simultaneous reduction of two carbonyl in the 3 and 7 positions afforded good to excellent yields of the diaxial diol in planar steroids (methyl 3,7-dioxo-5α-cholanoate, 3,7-dioxo-5α-cholestane and methyl 3,7-dioxo-5α-cholestan-27-oate) and only 14percent of 3α,7α-(OH)2 from methyl 3,7-dioxo-5β-cholanoate.

(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

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.

Method for preparing obeticholic acid

The invention discloses a method for preparing obeticholic acid or pharmaceutically acceptable salt thereof, the method comprises the following steps: (c) carrying out hydrolysis reaction on a compound 5 to remove a carboxyl protecting group Q so as to generate a compound 6; (d) subjecting the compound 6 to a hydrogenation reaction to produce a compound 7; (e) carrying out carbonyl reduction reaction and hydrolysis reaction for removing a hydroxyl protecting group P on the compound 7 by a one-step method to generate obeticholic acid, wherein P is a hydroxyl protecting group, and Q is a carboxyl protecting group. The key intermediate product in a solid form at normal temperature is obtained through design of a synthesis route, separation and purification of the intermediate product and subsequent synthesis operation are facilitated, and the yield of each step and the purity of the intermediate product and the final product are improved.

SYNTHETIC DERIVATIVES OF CHOLIC ACID 7-SULFATE AND USES THEREOF

The compositions and methods provided herein are related, in part, to the discovery of cholic acid 7-sulfate as a treatment for diabetes. Provided herein is a method for treating a metabolic disorder (e.g., diabetes, obesity), or an inflammatory disease (e.g., Crohn's disease, inflammatory bowel disease, ulcerative colitis, pancreatitis, hepatitis, appendicitis, gastritis, diverticulitis, celiac disease, food intolerance, enteritis, ulcer, gastroesophageal reflux disease (GERD), psoriatic arthritis, psoriasis, and rheumatoid arthritis) in a subject in need thereof comprising administering to a subject a compound of Formulae (I)-(XVII).

7-ketolithocholic acid intermediate and preparation process and application thereof

The invention discloses a 7-ketolithocholic acid intermediate and a preparation process and an application thereof. Hyocholic acid is utilized as a starting material, an esterification reaction is carried out first, then a silane protection group protects a 3-hydroxyl group with high selectivity, then a specific spatial structure of 6,7-hydroxyl group of the hyocholic acid is utilized, a conventional protection method can be selectively connected to a strong leaving group at 6-position to obtain the 7-ketolithocholic acid intermediate, and the 7-ketolithocholic acid intermediate is subjected to oxidation, removal, reduction, and hydrolysis to remove a protection group to obtain a target product 7-ketolithocholic acid. The 7-ketolithocholic acid prepared by the process is high in degree ofpurity, is also simple in process step, enables a synthetize route to be greatly simplified, and enables the industrialization cost to be saved.

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.

Synthesis method of obeticholic acid and intermediate

The invention discloses a synthesis method of obeticholic acid and an intermediate. The method specifically comprises seven steps: an oxidation reaction, an esterification reaction, a protection reaction, an Aldol reaction, hydrogenation reduction, hydrolysis and a carbonyl reduction reaction with raw materials including chenodeoxycholic acid, NBS, concentrated sulfuric acid, methanol, sodium iodide, trimethyl silicon chloride, trimethylamine, acetaldehyde, boron trifluoride diethyl etherate, palladium on carbon, hydrogen, NaOH and NaBH4. The synthesis method of obeticholic acid and the intermediate is high in yield, low in cost, environmentally friendly, easy to operate 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.