31823-53-7Relevant academic research and scientific papers
Synthesis and activity evaluation of a series of cholanamides as modulators of the liver X receptors
Martínez, Mario D.,Ghini, Alberto A.,Dansey, M. Virginia,Veleiro, Adriana S.,Pecci, Adali,Alvarez, Lautaro D.,Burton, Gerardo
, p. 1092 - 1101 (2018)
The Liver X receptors (LXRs) are members of the nuclear receptor family, that play fundamental roles in cholesterol transport, lipid metabolism and modulation of inflammatory responses. In recent years, the synthetic steroid N,N-dimethyl-3β-hydroxycholenamide (DMHCA) arised as a promising LXR ligand. This compound was able to dissociate certain beneficial LXRs effects from those undesirable ones involved in triglyceride metabolism. Here, we synthetized a series of DMHCA analogues with different modifications in the steroidal nucleus involving the A/B ring fusion, that generate changes in the overall conformation of the steroid. The LXRα and LXRβ activity of these analogues was evaluated by using a luciferase reporter assay in BHK21 cells. Compounds were tested in both the agonist and antagonist modes. Results indicated that the agonist/antagonist profile is dependent on the steroid configuration at the A/B ring junction. Notably, in contrast to DMHCA, the amide derived from lithocholic acid (2) with an A/B cis configuration and its 6,19-epoxy analogue 4 behaved as LXRα selective agonists, while the 2,19-epoxy analogues with an A/B trans configuration were antagonists of both isoforms. The binding mode of the analogues to both LXR isoforms was assessed by using 50 ns molecular dynamics (MD) simulations. Results revealed conformational differences between LXRα- and LXRβ-ligand complexes, mainly in the hydrogen bonding network that involves the C-3 hydroxyl. Overall, these results indicate that the synthetized DMHCA analogues could be interesting candidates for a therapeutic modulation of the LXRs.
Stereoselective Introduction of Steroid Side Chains at C(17) and C(20)
Batcho, Andrew D.,Berger, Donald E.,Davoust, Stephen G.,Wovkulich, Peter M.,Uskokovic, Milan R.
, p. 1682 - 1688 (1981)
A simple and efficient new method for the highly stereoselective (at C(17) and C(20)) introduction of steroid side chains which are suitably functionalized for further elaboration is presented.The ene reaction of (17 Z)-ethylidene steroids, which are read
Synthesis and biological activity of cyclopropyl Δ7-dafachronic acids as DAF-12 receptor ligands
Carotti, Andrea,Ceccarelli, Giada,Gioiello, Antimo,Goracci, Laura,Mancino, Valentina,Passeri, Daniela,Pellicciari, Roberto,Sardella, Roccaldo
, p. 5403 - 5412 (2021/06/30)
The four cyclopropyl stereoisomers of Δ7-dafachronic acids were prepared from the bile acid hyodeoxycholic acid and employed as chemical tools to exploit the importance of the orientation and spatial disposition of the carboxyl tail and the C25-methyl gro
OXYSTEROLS AND METHODS OF USE THEREOF
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Paragraph 00143, (2016/04/26)
Compounds are provided according to Formula (I) and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X, Y, R1, R2a, R2b, R4a, R4b, R5a, R5b/
Stereoselective construction of steroidal side chain from 16-dehydropregnenolone acetate
Aher, Nilkanth G.,Gonnade, Rajesh G.,Pore, Vandana S.
body text, p. 2005 - 2009 (2010/04/03)
Stereoselective construction of steroidal side chain at C-20 having 'natural' configuration using 16-dehydropregnalone acetate (16-DPA) as a starting material has been carried out. Palladiumcatalyzed carbon-carbon bond-forming Heck reaction between C-20 vinyl iodide with methyl acrylate and transfer hydrogenation with triethylsilane and Pd/C are the key steps for stereoselective sidechain synthesis. Georg Thieme Verlag Stuttgart.
Chemical synthesis of the 3-sulfooxy-7-N-acetylglucosaminyl-24-amidated conjugates of 3β,7β-dihydroxy-5-cholen-24-oic acid, and related compounds: Unusual, major metabolites of bile acid in a patient with Niemann-Pick disease type C1
Iida, Takashi,Kakiyama, Genta,Hibiya, Yohei,Miyata, Shohei,Inoue, Takehiko,Ohno, Kohsaku,Goto, Takaaki,Mano, Nariyasu,Goto, Junichi,Nambara, Toshio,Hofmann, Alan F.
, p. 18 - 29 (2007/10/03)
The chemical synthesis of 3β,7β-dihydroxy-5-cholen-24-oic acid, triply conjugated by sulfuric acid at C-3, by N-acetylglucosamine (GlcNAc) at C-7, and by glycine or taurine at C-24, is described. These are unusual, major metabolites of bile acid found to
Production method of steroid compound
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Page/Page column 61, (2008/06/13)
An object of the present invention is to provide a novel method for producing a steroid compound. The present invention provides a method for producing 3,7-dioxo-5β-cholanic acid or ester derivatives thereof, which uses, as raw materials, sterols having d
Technical-scale homologation of a cholanic acid derivative through the barton ester. A practical approach to 25-hydroxy vitamin D3 and congeners
Kutner, Andrzej,Chodynski, Michal,Masnyk, Marek,Wicha, Jerzy
, p. 290 - 293 (2013/09/08)
A novel method was developed of the homologation of a cholanic acid derivative using the Barton ester, as a practical approach to 25-hydroxy vitamin D and congeners. The method involves transformation of a cholanic acid derivative into a nor-bromidc by using 2-mercaptopyridine N-oxide sodium salt and bromotrichloromethane and then alkylation of the bromide with dimethylmalonate followed by demethoxycarbonylation by Krapcho procedure. The major byproducts of the synthesis were isolated, and their structures were identified by spectroscopic and chemical methods. Our method is designed especially for the large-scale manufacturing of vitamin D compounds because it involves an intermediate that can be easily purified and it avoids the use of toxic and explosive diazomethane that is employed in the classical synthesis of vitamins D from natural steroids.
Studies on vitamin D (Calciferol)and its analogues. 10. Side chain analogues of 25 hydroxyvitamin D3
Johnson,Carey,Norman,Okamura
, p. 5 - 11 (2007/10/06)
A homologous series of side chain analogues of 25 hydroxyvitamin D3 (25 hydroxycholecalciferol) in which the length of the side chain is modified while maintaining its characteristic tertiary hydroxyl moiety has been synthesized. The following five analogues have been prepared and characterized: pentanor 25 OH D3 (2a), trinor 25 OH D3 (2b), dinor 25 OH D3 (2c), nor 25 OH D3 (2d), and homo 25 OH D3 (2e). Biological assays in vivo of intestinal calcium absorption and bone calcium mobilization in the chick of the five analogues revealed that the homo analogue 2e exhibited a significant biological response relative to the -D (-vitamin D3) control. Compared to the natural vitamin D3, 2e is as active in its ability to mobilize bone calcium and is about half as effective in stimulating intestinal calcium transport. The remaining analogues (2a d) exhibited no significant activity in either assay, although the nor analogue 2d was previously observed to exhibit antimetabolite activity.
