6159-50-8

Usage

Uses

Used in Pharmaceutical Industry:
(R)-4-((3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-bis(formyloxy)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid is used as an intermediate in the synthesis of various pharmaceutical compounds. Its unique structure and functional groups make it a valuable building block for the development of new drugs with potential therapeutic applications.
Used in Chemical Research:
In the field of chemical research, (R)-4-((3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-bis(formyloxy)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid serves as a subject for studying the synthesis, properties, and reactivity of complex organic molecules. Its chiral centers and functional groups provide opportunities for exploring enantioselective reactions and the development of novel synthetic methods.
Used in Material Science:
The structural features of (R)-4-((3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-bis(formyloxy)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid may also find applications in material science. Its formyloxy groups can potentially be utilized in the formation of polymers or other materials with specific properties, such as improved stability or biocompatibility.

Upstream product

• 64-18-6 formic acid 
• 128-13-2 ursodeoxycholic acid 
• 64986-84-1 7-formylchenodeoxycholic acid 
• 50-00-0 formaldehyd 
• 474-25-9 chenodeoxycholic acid 
• 60354-42-9 methyl 7α-acetoxy-3,12-dioxo-5β-cholanoate 
• 106351-12-6 3-keto-7α-formyloxy-5β-cholan-24-oic acid 
• 4651-67-6 7-Ketolithocholic acid 
• 1434-27-1 7α-acetoxy-3,3-ethanediyldioxy-12-oxo-5β-cholan-24-oic acid methyl ester 

Downstream Products

• 80724-93-2 chenooxazoline 
• 38636-78-1 3α,7α-dihydroxy-26,27-dinor-5β-cholestan-25-oic acid 
• 80724-93-2 2-(3α,7β-dihydroxy-24-nor-5β-cholanyl)-4,4-dimethyl-2-oxazoline 
• 77060-26-5 3-keto-7β-hydroxy-5β-cholan-24-oic acid 
• 1260542-93-5 24-α-methylbenzyl-3α,7β-dihydroxy-5β-cholanamide 
• 1260542-94-6 24-(2-phenethyl)-3α,7β-dihydroxy-5β-cholanamide 
• 1260542-95-7 24-(3-phenpropyl)-3α,7β-dihydroxy-5β-cholanamide 
• 99697-24-2 Norursodeoxycholic acid 
• 118316-12-4 3α,7β-dihydroxy-24-nor-5β-cholan-23-nitrile 
• 102044-28-0 homo-ursodeoxycholic acid 
• 1612191-86-2 6α-ethyl-3α,7α-dihydroxy-24-nor-5β-cholan-23-ol 
• 17974-66-2 (25RS)-3α,7α-dihydroxy-5β-cholestan-26-oic acid 

Relevant academic research and scientific papers

Synthesis and olfactory activity of unnatural, sulfated 5β-bile acid derivatives in the sea lamprey (Petromyzon marinus)

A variety of unnatural bile acid derivatives (9a-9f) was synthesized and used to examine the specificity with which the sea lamprey (Petromyzon marinus) olfactory system detects these compounds. These compounds are analogs of petromyzonol sulfate (PS, 1), a component of the sea lamprey migratory pheromone. Both the stereochemical configuration at C5 (i.e., 5α vs. 5β) and the extent and sites of oxygenation (hydroxylation or ketonization) of the bile acid derived steroid skeleton were evaluated by screening the compounds for olfactory activity using electro-olfactogram recording. 5β-Petromyzonol sulfate (9a) elicited a considerable olfactory response at sub-nanomolar concentration. In addition, less oxygenated systems (i.e., 9b-9e) elicited olfactory responses, albeit with less potency. The sea lamprey sex pheromone mimic 9f (5β-3-ketopetromyzonol sulfate) was also examined and found to produce a much lower olfactory response. Mixture studies conducted with 9a and PS (1) suggest that stimulation is occurring via similar modes of activation, demonstrating a relative lack of specificity for recognition of the allo-configuration (i.e., 5α) in sea lamprey olfaction. This attribute could facilitate design of pheromone analogs to control this invasive species.

A novel bile acid analog, A17, ameliorated non-alcoholic steatohepatitis in high-fat diet-fed hamsters

Being endocrine signaling molecules that regulate lipid metabolism and affect energy balance, bile acids are potential drug candidates for non-alcoholic steatohepatitis (NASH). Obeticholic acid (OCA) could improve NASH accompanied by significant side effects. Therefore, it is worthwhile to develop safer and more effective bile acid analogs. In this study, a new bile acid analog A17 was synthesized and its potential anti-NASH effects were assessed in vitro and in vivo. The impact of A17 on steatosis was investigated in the rat primary hepatocytes challenged with oleic acid. It was found that A17 alleviated lipid accumulation by reducing fatty acid (FA) uptake and promoting FA oxidation. The reduction of FA uptake came from inhibiting fatty acid translocase (Cd36) expression. The promotion of FA oxidation came from stimulating the phosphorylation of adenosine monophosphate (AMP)-activated protein kinase alpha (AMPKα). In addition, A17 reduced lipopolysaccharide-induced inflammation in Raw264.7 cells by activating Takeda G protein-coupled receptor 5 (TGR5). In in vivo study, male Golden Syrian hamsters were fed with high fat (HF) diet and then treated with 50 mg/kg/d A17 for 6 weeks. A17 lowered the lipid profiles and liver enzyme levels in serum and improved liver pathological conditions with less side effects compared with OCA. Further studies confirmed that the molecular mechanisms of A17 in vivo were similar to those in vitro. In conclusion, a novel bile acid analog A17 was identified to ameliorate NASH in HF-fed hamsters. The potential mechanisms could be contributed to reducing FA uptake, stimulating FA oxidation and relieving inflammation.

METHOD FOR PREPARING CHOLIC ACID COMPOUND

The present application belongs to the field of pharmaceutical chemistry, and relates to a method for preparing a cholic acid compound. Specifically, the present application provides a process for preparing a compound as shown in formula I, comprising subjecting a compound of formula 2 to an oxidization reaction to obtain a compound of formula 3; attaching a trimethylsilyl group to the compound of formula 3 to obtain a compound of formula 4; reacting the compound of formula 4 with acetaldehyde to obtain a compound of formula 5; subjecting the compound of formula 5 to a catalytic hydrogenation reaction to obtain a compound of formula 6; and converting a cyano group of the compound of formula 6 to a carboxyl group to give the compound of formula I. The preparation method has high yield, requires less purification operations, and is suitable for industrial application.

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.

COMPOSITIONS AND METHODS FOR TREATING CLOSTRIDIUM ASSOCIATED DISEASES

The present disclosure provides compounds for preventing, treating, and/or reducing the risk of developing a Clostridium-associated disease in a mammalian subject. Also provided are pharmaceutically acceptable salts of such compounds and compositions that include such compounds and/or pharmaceutically acceptable salts thereof.

Synthesis and Biological Evaluation of Bile Acid Analogues Inhibitory to Clostridium difficile Spore Germination

Standard antibiotic-based strategies for the treatment of Clostridium difficile infections disrupt indigenous microbiota and commonly fail to eradicate bacterial spores, two key factors that allow recurrence of infection. As an alternative approach to controlling C. difficile infection, a series of bile acid derivatives have been prepared that inhibit taurocholate-induced spore germination. These analogues have been evaluated in a highly virulent NAP1 strain using optical density and phase-contrast microscopy assays. Heterocycle substitutions at C24 were well-tolerated and several tetrazole-containing derivatives were highly potent inhibitors in both assays, with complete inhibition of spore germination observed at 10-25 μM. To limit intestinal absorption, C7-sulfated analogues designed to avoid active and passive transport pathways were prepared. One of these derivatives, compound 21b, was found to be a potent inhibitor of C. difficile spore germination and poorly permeable in a Caco-2 model of intestinal epithelial absorption, suggesting that it is likely to be gut-restricted.

Rational design of nucleoside-bile acid conjugates incorporating a triazole moiety for anticancer evaluation and SAR exploration

Herein we report a study on the synthesis and biological evaluation of a library of nucleoside-bile acid conjugates prepared by combining 20-deoxyadenosine, 20-deoxyguanosine, 20-deoxyuridine as well as adenosine and guanosine derivatives with cheno-, urso-, nor-cheno-, nor-urso- and taurourso-desoxycholic acid derivatives by means of the click reaction. The new nucleoside-bile acid conjugates incorporating a triazole moiety were tested in vitro against leukemic K562 and HCT116 colon carcinoma, as well as on normal fibroblast cells. Six compounds displayed interesting anti-proliferative activity against the selected cancer lines and no cytotoxic effects against normal fibroblasts. A possible structure activity relationship was also investigated.

CHOLANE DERIVATIVES FOR USE IN THE TREATMENT AND/OR PREVENTION OF FXR AND TGR5/GPBAR1 MEDIATED DISEASES

13073PTWO 56 ABSTRACT The present invention relates to compounds having cholane scaffolds of formula (I), said compounds for use in the treatment and/or prevention of FXR and TGR5/GPBAR1 mediated diseases. 5

Modification on ursodeoxycholic acid (UDCA) scaffold. Discovery of bile acid derivatives as selective agonists of cell-surface G-protein coupled bile acid receptor 1 (GP-BAR1)

Bile acids are signaling molecules interacting with the nuclear receptor FXR and the G-protein coupled receptor 1 (GP-BAR1/TGR5). GP-BAR1 is a promising pharmacological target for the treatment of steatohepatitis, type 2 diabetes, and obesity. Endogenous bile acids and currently available semisynthetic bile acids are poorly selective toward GP-BAR1 and FXR. Thus, in the present study we have investigated around the structure of UDCA, a clinically used bile acid devoid of FXR agonist activity, to develop a large family of side chain modified 3,7 dihydroxyl cholanoids that selectively activate GP-BAR1. In vivo and in vitro pharmacological evaluation demonstrated that administration of compound 16 selectively increases the expression of pro-glucagon 1, a GP-BAR1 target, in the small intestine, while it had no effect on FXR target genes in the liver. Further, compound 16 results in a significant reshaping of bile acid pool in a rodent model of cholestasis. These data demonstrate that UDCA is a useful scaffold to generate novel and selective steroidal ligands for GP-BAR1.

Optimized synthesis of pure, non-polymorphic, crystalline bile acids with defined particle size

The present invention relates to a pure polymorph of Nor-UDCA or Bis-nor-UDCA, or of a pharmaceutically acceptable salt thereof. The invention further provides a pharmaceutical composition comprising the polymorph of the invention, and a method for preparing the polymorph. The invention includes the pharmaceutical use of the polymorph or of the pharmaceutical composition of the invention.