56363-84-9Relevant articles and documents
Copper and L-(?)-quebrachitol catalyzed hydroxylation and amination of aryl halides under air
Bao, Xuefei,Chen, Guoliang,Dong, Jinhua,Du, Fangyu,Li, Hui,Liang, Xinjie,Wu, Ying,Zhang, Yongsheng
supporting information, (2020/08/03)
L-(?)-Quebrachitol, a natural product obtained from waste water of the rubber industry, was utilized as an efficient ligand for the copper-catalyzed hydroxylation and amination of aryl halides to selectively give phenols and aryl amines in water or 95percent ethanol. In addition, the hydroxylation of 2-chloro-4-hydroxybenzoic acid was validated on a 100-g scale under air.
Target hopping as a useful tool for the identification of novel EphA2 protein-protein antagonists
Tognolini, Massimiliano,Incerti, Matteo,Pala, Daniele,Russo, Simonetta,Castelli, Riccardo,Hassan-Mohamed, Iftiin,Giorgio, Carmine,Lodola, Alessio
supporting information, p. 67 - 72 (2014/01/17)
Lithocholic acid (LCA), a physiological ligand for the nuclear receptor FXR and the G-protein-coupled receptor TGR5, has been recently described as an antagonist of the EphA2 receptor, a key member of the ephrin signalling system involved in tumour growth. Given the ability of LCA to recognize FXR, TGR5, and EphA2 receptors, we hypothesized that the structural requirements for a small molecule to bind each of these receptors might be similar. We therefore selected a set of commercially available FXR or TGR5 ligands and tested them for their ability to inhibit EphA2 by targeting the EphA2-ephrin-A1 interface. Among the selected compounds, the stilbene carboxylic acid GW4064 was identified as an effective antagonist of EphA2, being able to block EphA2 activation in prostate carcinoma cells, in the micromolar range. This finding proposes the "target hopping" approach as a new effective strategy to discover new protein-protein interaction inhibitors. Target hopping: Given the ability of lithocholic acid to recognize FXR, TGR5 and EphA2 receptors, we hypothesized the structural requirements to bind each of these receptors might be similar. We selected a set of commercially available FXR or TGR5 ligands and tested them for their ability to inhibit EphA2 by targeting the EphA2-ephrin-A1 interface. Moreover, a small panel of GW4064 derivatives was synthesized. Copyright
Optimization of alkylidene hydrazide based human glucagon receptor antagonists. Discovery of the highly potent and orally available 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6-tetramethylbenzyl)-1h-indol-4ylmethylene]hydrazide
Madsen, Peter,Ling, Anthony,Plewe, Michael,Sams, Christian K.,Knudsen, Lotte B.,Sidelmann, Ulla G.,Ynddal, Lars,Brand, Christian L.,Andersen, Birgitte,Murphy, Douglas,Teng, Min,Truesdale, Larry,Kiel, Dan,May, John,Kuki, Atsuo,Shi, Shenghua,Johnson, Michael D.,Teston, Kimberly Ann,Feng, Jun,Lakis, James,Anderes, Kenna,Gregor, Vlad,Lau, Jesper
, p. 5755 - 5775 (2007/10/03)
Highly potent human glucagon receptor (hGluR) antagonists have been prepared employing both medicinal chemistry and targeted libraries based on modification of the core (proximal) dimethoxyphenyl group, the benzyl ether linkage, as well as the (distal) benzylic aryl group of the lead 2, 3-cyano-4-hydroxybenzoic acid (3,5-dimethoxy-4-isopropylbenzyloxybenzylidene)hydrazide. Electron-rich proximal aryl moieties such as mono- and dimethoxy benzenes, naphthalenes, and indoles were found to be active. The SAR was found to be quite insensitive regarding the linkage to the distal aryl group, since long and short as well as polar and apolar linkers gave highly potent compounds. The presence of a distal aryl group was not crucial for obtaining high binding affinity to the hGluR. In many cases, however, the affinity could be further optimized with substituted distal aryl groups. Representative compounds have been tested for in vitro metabolism, and structure - metabolism relationships are described. These efforts lead to the discovery of 74, NNC 25-2504, 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6tetramethylbenzyl)-1H-indol-4-ylmethylene]hydrazide, with low in vitro metabolic turnover. 74 was a highly potent noncompetitive antagonist of the human glucagon receptor (IC50 = 2.3 nM, KB = 760 pM) and of the isolated rat receptor (IC50 = 430 pM, KB = 380 pM). Glucagonstimulated glucose production from isolated primary rat hepatocytes was inhibited competitively by 74 (Ki = 14 nM). This compound was orally available in dogs (Fpo = 15%) and was active in a glucagon-challenged rat model of hyperglucagonemia and hyperglycemia.
