396653-31-9Relevant articles and documents
Synthesis of trisubstituted alkenes by Ni-catalyzed hydroalkylation of internal alkynes with cycloketone oxime esters
Lu, Xiao-Yu,Liu, Chuang-Chuang,Jiang, Run-Chuang,Yan, Lu-Yu,Liu, Qi-Le,Wang, Qing-Qing,Li, Jia-Mei
supporting information, p. 14191 - 14194 (2020/11/24)
A method for Ni-catalyzed hydroalkylation of internal alkynes with cycloketone oxime esters was developed. The reaction has a broad substrate scope. This hydroalkylation shows excellent regio-and stereo-selectivity. This method enables readily available starting materials to be used to access a range of cyano-substituted single-configuration trisubstituted alkenes. These are valuable feedstock chemicals and are widely used in synthetic and medicinal chemistry.
FXR RECEPTOR MODULATOR, PREPARATION METHOD THEREFOR, AND USES THEREOF
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Paragraph 0047; 0048; 0055, (2018/11/27)
The present disclosure disclosed a modulator of FXR receptor and preparation and use thereof, which relates to the technical filed of medicinal chemistry. The present disclosure provides a modulator of FXR receptor having a structural formula I or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof, which can combine with FXR receptor (that is NR1H4) and be acted as a FXR agonist or a partial agonist for preventing and treating the disease mediated by FXR, such as chronic intrahepatic or extrahepatic cholestasis, hepatic fibrosis caused by chronic cholestasis or acute intrahepatic cholestasis, chronic hepatitis B, gallstone, hepatic carcinoma, colon cancer or intestinal inflammatory disease, etc. Specifically, for some chemical compounds, their EC50 for FXR agonist activity reach below 100nM, which show an excellent FXR agonist activity and an excellent prospect to provide a new pharmaceutical selection in clinical treatment for the disease mediated by FXR.
Discovery of spirofused piperazine and diazepane amides as selective histamine-3 antagonists with in vivo efficacy in a mouse model of cognition
Brown, Dean G.,Bernstein, Peter R.,Griffin, Andrew,Wesolowski, Steve,Labrecque, Denis,Tremblay, Maxime C.,Sylvester, Mark,Mauger, Russell,Edwards, Phillip D.,Throner, Scott R.,Folmer, James J.,Cacciola, Joseph,Scott, Clay,Lazor, Lois A.,Pourashraf, Mehrnaz,Santhakumar, Vijayaratnam,Potts, William M.,Sydserff, Simon,Giguère, Pascall,Lévesque, Carine,Dasser, Mohammed,Groblewski, Thierry
, p. 733 - 758 (2014/03/21)
A new series of potent and selective histamine-3 receptor (H3R) antagonists was identified on the basis of an azaspiro[2.5]octane carboxamide scaffold. Many scaffold modifications were largely tolerated, resulting in nanomolar-potent compounds in the H3R functional assay. Exemplar compound 6s demonstrated a selective profile against a panel of 144 secondary pharmacological receptors, with activity at only σ2 (62% at 10 μM). Compound 6s demonstrated free-plasma exposures above the IC50 (～50×) with a brain-to-plasma ratio of ～3 following intravenous dosing in mice. At three doses tested in the mouse novel object recognition model (1, 3, and 10 mg/kg s.c.), 6s demonstrated a statistically significant response compared with the control group. This series represents a new scaffold of H3 receptor antagonists that demonstrates in vivo exposure and efficacy in an animal model of cognition.
