2276-93-9

Usage

Uses

Used in Pharmaceutical Industry:
(4R)-4-[(3S,5S,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid is used as a steroid compound for modulating T regulatory lymphocytes. This application is particularly relevant for the treatment of inflammatory or autoimmune disorders, as it can help regulate the immune system and reduce inflammation.
Used in Drug Delivery Systems:
In the field of drug delivery, (4R)-4-[(3S,5S,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid can be utilized as a carrier or component in the development of novel drug delivery systems. Its unique structure and functional groups may allow for targeted delivery of therapeutic agents, potentially improving the efficacy and bioavailability of various medications.
Used in Chemical Research:
Due to its complex structure and multiple stereocenters, (4R)-4-[(3S,5S,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid can serve as a valuable compound in chemical research. It may be used to study stereochemistry, synthesis, and the development of new methodologies for the preparation of complex organic molecules.

InChI:InChI=1/C24H40O3/c1-15(4-9-22(26)27)19-7-8-20-18-6-5-16-14-17(25)10-12-23(16,2)21(18)11-13-24(19,20)3/h15-21,25H,4-14H2,1-3H3,(H,26,27)/t15-,16-,17-,18-,19-,20-,21-,23-,24+/m0/s1

Upstream product

• 91509-44-3 4-[(3R,5S,8R,9S,10S,13R,14S,17R)-3-(2,2-Dimethyl-propionyloxy)-10,13-dimethyl-7,12-dioxo-hexadecahydro-cyclopenta[a]phenanthren-17-yl]-pentanoic acid methyl ester 
• 81-25-4 3α,7α,12α-trihydroxy-5β-cholanic acid 
• 861-83-6 methyl chlolate 
• 106714-00-5 3β-hydroxy-5β.17βH.20ξH-cholen-(14)-oic acid-(24) 
• 64-19-7 acetic acid 
• 1452-33-1 methyl 3-oxo-4-cholenolate 
• 141-52-6 sodium ethanolate 
• 1553-56-6 dehydrolithocholic acid 
• 7647-01-0 hydrogenchloride 
• 104538-82-1 C₃₂H₄₆O₄ 
• 1255-51-2 methyl 3β-acetyloxy-5β-cholan-24-oate 
• 81938-70-7 methyl O-mesyllithocholate 
• 1249-75-8 methyl lithocholate 
• 434-13-9 Lithocholic acid 

Downstream Products

• 28083-35-4 5β.14β.17βH.20ξH-cholen-(3)-oic acid-(24) 
• 1249-75-8 methyl 3β-hydroxy-5α-cholan-24-oate 
• 434-13-9 Lithocholic acid 
• 5405-42-5 methyl 3β-hydroxy-5β-cholan-24-oate 
• 1553-56-6 dehydrolithocholic acid 
• 1249-75-8 3α-Hydroxy-5β-cholansaeure-methylester 
• 84573-10-4 N-(methoxycarbonylmethyl)-3-oxo-5β-cholan-24-oic acid amide 
• 1249-75-8 4-((R)-3-Hydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoic acid methyl ester 
• 117899-79-3 3β-hydroxy-24-phenyl-5α-cholanone-(24) 
• 15074-03-0 (R)-methyl 4-((5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-3-oxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoate 
• 1249-75-8 methyl 3α-hydroxy-5α-cholan-24-oate 

Relevant academic research and scientific papers

Triplet energy management between two signaling units through cooperative rigid scaffolds

Through-bond triplet exciplex formation in donor-acceptor systems linked through a rigid bile acid scaffold has been demonstrated on the basis of kinetic evidence upon population of the triplet acceptors (naphthalene, or biphenyl) by through-bond triplet-

ISOLITHOCHOLIC ACID OR ISOALLOLITHOCHOLIC ACID AND DEUTERATED DERIVATIVES THEREOF FOR PREVENTING AND TREATING CLOSTRIDIUM DIFFICILE-ASSOCIATED DISEASES

The present invention relates to isolithocholic acid (3?-hydroxy-5?-cholan-24-oic acid, iso-LCA) and isoallolithocholic acid (3?-hydroxy-5α-cholan-24-oic acid) and their deuterated analogs for preventing or treating Clostridium difficile-associated disease in a mammalian subject.

3-MODIFIED ISO-/ISOALLO-LITHOCHOLIC ACID DERIVATIVES OR THEIR HOMO-ANALOGS FOR PREVENTING AND TREATING CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DISEASES

The present invention relates to isolithocholic acid (3β-hydroxy-5β-cholan-24-oic acid) and isoallolithocholic acid (3β-hydroxy-5α-cholan-24-oic acid) together with the respective 22-homo-analogs or the deuterated analogs, which are modified in 3-position

Optimization of EphA2 antagonists based on a lithocholic acid core led to the identification of UniPR505, a new 3α-carbamoyloxy derivative with antiangiogenetic properties

The EphA2 receptor has been validated in animal models as new target for treating tumors depending on angiogenesis and vasculogenic mimicry. In the present work, we extended our current knowledge on structure-activity relationship (SAR) data of two related classes of antagonists of the EphA2 receptor, namely 5β-cholan-24-oic acids and 5β-cholan-24-oyl L-β-homotryptophan conjugates, with the aim to develop new antiangiogenic compounds able to efficiently prevent the formation of blood vessels. As a result of our exploration, we identified UniPR505, N-[3α-(Ethylcarbamoyl)oxy-5β-cholan-24-oyl]-L-β-homo-tryptophan (compound 14), as a submicromolar antagonist of the EphA2 receptor capable to block EphA2 phosphorylation and to inhibit neovascularization in a chorioallantoic membrane (CAM) assay.

Steroid compound 3-site hydroxyl configuration inversion method

The invention discloses a steroid compound 3-site hydroxyl configuration inversion method. The method specifically comprises the following steps that (1) a steroid compound containing a 3-site hydroxyl reacts with an acyl chloride compound; (2) the product obtained in the step (1) and a substituting agent are subjected to SN2 nucleophilic substitution reaction under existing of a phase transfer catalyst; and (3) the product obtained in the step (2) is subjected to a hydrolysis reaction. Compared with a Mitsunobu method, the method does not need to use triphenylphosphine and azodiformate pricedhigher, and accordingly the production cost is greatly lowered; meanwhile, a p-nitrobenzoic acid derivative which seriously affects the water environment does not need to be used, and therefore the method is more environmentally friendly. The method adopts cesium acetate/18-crown ether-6 system to conduct 3-site hydroxyl configuration inversion, can remarkably reduce occurrence of side reactions,accordingly a higher reaction yield is obtained, and the method is finally applicable to industrialized production.

Structure-Activity Relationships and Mechanism of Action of Eph-ephrin Antagonists: Interaction of Cholanic Acid with the EphA2 Receptor

The Eph-ephrin system, including the EphA2 receptor and the ephrinA1 ligand, plays a critical role in tumor and vascular functions during carcinogenesis. We previously identified (3α,5β)-3-hydroxycholan-24-oic acid (lithocholic acid) as an Eph-ephrin antagonist that is able to inhibit EphA2 receptor activation; it is therefore potentially useful as a novel EphA2 receptor-targeting agent. Herein we explore the structure-activity relationships of a focused set of lithocholic acid derivatives based on molecular modeling investigations and displacement binding assays. Our exploration shows that while the 3-α-hydroxy group of lithocholic acid has a negligible role in recognition of the EphA2 receptor, its carboxylate group is critical for disrupting the binding of ephrinA1 to EphA2. As a result of our investigation, we identified (5β)-cholan-24-oic acid (cholanic acid) as a novel compound that competitively inhibits the EphA2-ephrinA1 interaction with higher potency than lithocholic acid. Surface plasmon resonance analysis indicates that cholanic acid binds specifically and reversibly to the ligand binding domain of EphA2, with a steady-state dissociation constant (KD) in the low micromolar range. Furthermore, cholanic acid blocks the phosphorylation of EphA2 as well as cell retraction and rounding in PC3 prostate cancer cells, two effects that depend on EphA2 activation by the ephrinA1 ligand. These findings suggest that cholanic acid can be used as a template structure for the design of effective EphA2 antagonists, and may have potential impact in the elucidation of the role played by this receptor in pathological conditions.

Characterization of rabbit aldose reductase-like protein with 3β-hydroxysteroid dehydrogenase activity

In this study, we isolated the cDNA for a rabbit aldose reductase-like protein that shared an 86% sequence identity to human aldo-keto reductase (AKR)1 1B10 and has been assigned as AKR1B19 in the AKR superfamily. The purified recombinant AKR1B19 was similar to AKR1B10 and rabbit aldose reductase (AKR1B2) in the substrate specificity for various aldehydes and α-dicarbonyl compounds. In contrast to AKR1B10 and AKR1B2, AKR1B19 efficiently reduced 3-keto-5α/β-dihydro-C19/C21/C24-steroids into the corresponding 3β-hydroxysteroids, showing Km of 1.3-9.1 μM and kcat of 1.1-7.6 min-1. The stereospecific reduction was also observed in the metabolism of 5α- and 5β- dihydrotestosterones in AKR1B19-overexpressing cells. The mRNA for AKR1B19 was ubiquitously expressed in rabbit tissues, and the enzyme was co-purified with 3β-hydroxysteroid dehydrogenase activity from the lung. Thus, AKR1B19 may function as a 3-ketoreductase, as well as a defense system against cytotoxic carbonyl compounds in rabbit tissues. The molecular determinants for the unique 3-ketoreductase activity were investigated by replacement of Phe303 and Met304 in AKR1B19 with Gln and Ser, respectively, in AKR1B10. Single and double mutations (F303Q, M304S and F303Q/M304S) significantly impaired this activity, suggesting the two residues play critical roles in recognition of the steroidal substrate.

Anchoring cationic amphiphiles for nucleotide delivery significance of DNA release from cationic liposomes for transfection

We have designed and synthesized lithocholic acid-based cationic amphiphile molecules as components of cationic liposomes for gene transfection (lipofection). To study the relationship between the molecular structures of those amphiphilic molecules, particularly the extended hydrophobic appendant (anchor) at the 3-hydroxyl group, and transfection efficiency, we synthesized several lithocholic and isolithocholic acid derivatives, and examined their transfection efficiency. We also compared the physico-chemical properties of cationic liposomes prepared from these derivatives. We found that isolithocholic acid derivatives exhibit higher transfection efficiency than the corresponding lithocholic acid derivatives. This result indicates that the orientation and extension of hydrophobic regions influence the gene transfection process. Isolithocholic acid derivatives showed a high ability to encapsulate DNA in a compact liposome-DNA complex and to protect it from enzymatic degradation. Isolithocholic acid derivatives also facilitated the release of DNA from the liposome-DNA complex, which is a crucial step for DNA entry into the nucleus. Our results show that the transfection efficiency is directly influenced by the ability of the liposome complex to release DNA, rather than by the DNA-encapsulating ability. Molecular modeling revealed that isolithocholic acid derivatives take relatively extended conformations, while the lithocholic acid derivatives take folded structures. Thus, the efficiency of release of DNA from cationic liposomes in the cytoplasm, which contributes to high transfection efficiency, appears to be dependent upon the molecular shape of the cationic amphiphiles.