639520-83-5Relevant articles and documents
Acetic Acid Accelerated Visible-Light Photoredox Catalyzed N-Demethylation of N,N-Dimethylaminophenyl Derivatives
Wu, Guolin,Li, Yazhen,Yu, Xuemei,Gao, Yu,Chen, Haijun
supporting information, p. 687 - 692 (2017/02/23)
N,N-Dimethylaminophenyl moiety is a common fragment in medicinal chemistry as several pharmaceuticals bearing this privileged motif are on the market and under clinical evaluation. Oxidative N-demethylation is generally regarded as the major metabolic pathway. However, pharmacokinetics, metabolites studies as well as the further structural modification are precluded by the impracticality of chemical synthesis. Here we report that acetic acid can significantly accelerate visible-light photoredox catalyzed N-demethylation of N,N-dimethylaminophenyl derivatives. This approach is easy for large scale reaction and even for potential industrial manufacture. (Figure presented.).
Liver-selective glucocorticoid antagonists: A novel treatment for type 2 diabetes
Von Geldern, Thomas W.,Tu, Noah,Kym, Philip R.,Link, James T.,Jae, Hwan-Soo,Lai, Chunqiu,Apelqvist, Theresa,Rhonnstad, Patrik,Hagberg, Lars,Koehler, Konrad,Grynfarb, Marlena,Goos-Nilsson, Annika,Sandberg, Johnny,Osterlund, Marie,Barkhem, Tomas,H?glund, Marie,Wang, Jiahong,Fung, Steven,Wilcox, Denise,Nguyen, Phong,Jakob, Clarissa,Hutchins, Charles,F?rnegf?rdh, Mathias,Kauppi, Bj?rn,?hman, Lars,Jacobson, Peer B.
, p. 4213 - 4230 (2007/10/03)
Hepatic blockade of glucocorticoid receptors (GR) suppresses glucose production and thus decreases circulating glucose levels, but systemic glucocorticoid antagonism can produce adrenal insufficiency and other undesirable side effects. These hepatic and systemic responses might be dissected, leading to liver-selective pharmacology, when a GR antagonist is linked to a bile acid in an appropriate manner. Bile acid conjugation can be accomplished with a minimal loss of binding affinity for GR. The resultant conjugates remain potent in cell-based functional assays. A novel in vivo assay has been developed to simultaneously evaluate both hepatic and systemic GR blockade; this assay has been used to optimize the nature and site of the linker functionality, as well as the choice of the GR antagonist and the bile acid. This optimization led to the identification of A-348441, which reduces glucose levels and improves lipid profiles in an animal model of diabetes.
GLUCOCORTICOID RECEPTOR LIGANDS FOR THE TREATMENT OF METABOLIC DISORDERS
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Page 27; 28, (2008/06/13)
This invention relates to novel compounds that are liver selective glucocorticoid receptor antagonists, to methods of preparing such compounds, and to methods for using such compounds in the regulation of metabolism, especially lowering serum glucose levels, insulin levels, or lipid levels, and/or decreasing body weight.
