39676-14-7Relevant academic research and scientific papers
FUSED BICYCLIC ALKYLENE LINKED IMIDODICARBONIMIDIC DIAMIDES, METHODS FOR SYNTHESIS, AND USES IN THERARY
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Paragraph 0214-0215, (2018/06/30)
The present invention provides novel fused bicyclic alkylene linked imidodicarbonimidic diamides. In particular, described herein are N-[2-(indol-3- yl)alkylene]-linked imidodicarbonimidic diamides and N-[2-(pyrrolopyridin-3- yl)alkylene]-linked imidodicarbonimidic diamides (compound of formula (I) or formula (II)), and uses therefor. The compounds of the present invention are believed to be organic cation transporter selective compounds, useful for the treatment of diseases and conditions caused by reduced activity of 5' adenosine monophosphate-activated protein kinase (AMPK).
FXR MODULATORS AND METHODS OF THEIR USE
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Page/Page column 20-21; 27, (2017/09/08)
The present disclosure is directed to modulators of farnesoid X receptor. Methods of making and using these modulators is also described.
Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors
Shultz, Michael D.,Cao, Xueying,Chen, Christine H.,Cho, Young Shin,Davis, Nicole R.,Eckman, Joe,Fan, Jianmei,Fekete, Alex,Firestone, Brant,Flynn, Julie,Green, Jack,Growney, Joseph D.,Holmqvist, Mats,Hsu, Meier,Jansson, Daniel,Jiang, Lei,Kwon, Paul,Liu, Gang,Lombardo, Franco,Lu, Qiang,Majumdar, Dyuti,Meta, Christopher,Perez, Lawrence,Pu, Minying,Ramsey, Tim,Remiszewski, Stacy,Skolnik, Suzanne,Traebert, Martin,Urban, Laszlo,Uttamsingh, Vinita,Wang, Ping,Whitebread, Steven,Whitehead, Lewis,Yan-Neale, Yan,Yao, Yung-Mae,Zhou, Liping,Atadja, Peter
experimental part, p. 4752 - 4772 (2011/09/20)
Histone deacetylase (HDAC) inhibitors have shown promise in treating various forms of cancer. However, many HDAC inhibitors from diverse structural classes have been associated with QT prolongation in humans. Inhibition of the human ether a-go-go related gene (hERG) channel has been associated with QT prolongation and fatal arrhythmias. To determine if the observed cardiac effects of HDAC inhibitors in humans is due to hERG blockade, a highly potent HDAC inhibitor devoid of hERG activity was required. Starting with dacinostat (LAQ824), a highly potent HDAC inhibitor, we explored the SAR to determine the pharmacophores required for HDAC and hERG inhibition. We disclose here the results of these efforts where a high degree of pharmacophore homology between these two targets was discovered. This similarity prevented traditional strategies for mitigating hERG binding/modulation from being successful and novel approaches for reducing hERG inhibition were required. Using a hERG homology model, two compounds, 11r and 25i, were discovered to be highly efficacious with weak affinity for the hERG and other ion channels.
Azaindolylalkylamine derivatives as 5-hydroxytryptamine-6 ligands
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, (2008/06/13)
The present invention provides a compound of formula I and the use thereof for the therapeutic treatment of disorders relating to or affected by the 5-HT6 receptor.
