51065-76-0Relevant articles and documents
Preparation method of pyrazolo[1,5-a]pyridine derivative
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Paragraph 0073-0081, (2021/04/21)
The invention discloses a preparation method of pyrazolo[1,5-a]pyridine derivatives, and belongs to the field of organic synthesis. The problems that an existing pyrazolo[1,5-a]pyridine structure synthesis method needs metal catalysis, the substrate range is limited, the total yield of multi-step reaction is low, stoichiometric additives, toxic oxidants and oxygen-free technologies are adopted, and reaction conditions are harsh are solved. The method comprises the steps: dissolving pyridinium salt, unsaturated alkene and 2,3-dichloro-5,6-dicyanobenzoquinone in an organic solvent, dropwise adding triethylamine to react, concentrating by a rotary evaporator to remove the solvent, and separating and purifying by silica gel column chromatography to obtain the pyrazolo[1,5-a]pyridine derivative.
Copper-mediated synthesis of pyrazolo[1,5-a]pyridines through oxidative linkage of C-C/N-N bonds
Mohan, Darapaneni Chandra,Ravi, Chitrakar,Rao, Sadu Nageswara,Adimurthy, Subbarayappa
supporting information, p. 3556 - 3560 (2015/03/30)
Copper-mediated synthesis of pyrazolo[1,5-a]pyridine-3-carboxylates through oxidative linkage of C-C and N-N bonds under mild reaction conditions is described. This protocol is applicable to a variety of pyridyl esters as well as various benzonitriles including nicotinonitrile, isonicotinonitrile and thiophene-2-carbonitrile. Better yields were observed with electron withdrawing substituted benzonitriles.
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.