31823-53-7Relevant articles and documents
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.
Stereocontrolled Synthesis of Steroidal Side Chains
Dauben, William G.,Brookhart, Todd
, p. 237 - 238 (1981)
-
OXYSTEROLS AND METHODS OF USE THEREOF
-
, (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/
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
