476660-69-2Relevant academic research and scientific papers
AMINO-QUINOLINES AS KINASE INHIBITORS
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Page/Page column 56; 57, (2018/06/22)
Disclosed are compounds having the formula:wherein R 1 , R 2 , R 3 and Z are as defined herein, and methods of making and using the same.
NOVEL COMPOUNDS
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Paragraph 0129-0130, (2018/05/26)
The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for
Identification of Quinoline-Based RIP2 Kinase Inhibitors with an Improved Therapeutic Index to the hERG Ion Channel
Haile, Pamela A.,Casillas, Linda N.,Bury, Michael J.,Mehlmann, John F.,Singhaus, Robert,Charnley, Adam K.,Hughes, Terry V.,Demartino, Michael P.,Wang, Gren Z.,Romano, Joseph J.,Dong, Xiaoyang,Plotnikov, Nikolay V.,Lakdawala, Ami S.,Convery, Maire A.,Votta, Bartholomew J.,Lipshutz, David B.,Desai, Biva M.,Swift, Barbara,Capriotti, Carol A.,Berger, Scott B.,Mahajan, Mukesh K.,Reilly, Michael A.,Rivera, Elizabeth J.,Sun, Helen H.,Nagilla, Rakesh,Lepage, Carol,Ouellette, Michael T.,Totoritis, Rachel D.,Donovan, Brian T.,Brown, Barry S.,Chaudhary, Khuram W.,Gough, Peter J.,Bertin, John,Marquis, Robert W.
supporting information, p. 1039 - 1044 (2018/10/15)
RIP2 kinase was recently identified as a therapeutic target for a variety of autoimmune diseases. We have reported previously a selective 4-aminoquinoline-based RIP2 inhibitor GSK583 and demonstrated its effectiveness in blocking downstream NOD2 signaling in cellular models, rodent in vivo models, and human ex vivo disease models. While this tool compound was valuable in validating the biological pathway, it suffered from activity at the hERG ion channel and a poor PK/PD profile thereby limiting progression of this analog. Herein, we detail our efforts to improve both this off-target liability as well as the PK/PD profile of this series of inhibitors through modulation of lipophilicity and strengthening hinge binding ability. These efforts have led to inhibitor 7, which possesses high binding affinity for the ATP pocket of RIP2 (IC50 = 1 nM) and inhibition of downstream cytokine production in human whole blood (IC50 = 10 nM) with reduced hERG activity (14 μM).
COMPOUNDS FOR THE MODULATION OF RIP2 KINASE ACTIVITY
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Page/Page column 50, (2017/04/11)
The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of RIP2 kinase, including degrading RIP2 kinase, the treatment of diseases and conditions mediated by the RIP2 kinase, in particular for the treatment of inflammatory diseases or conditions.
AMINO-QUINOLINES AS KINASE INHIBITORS
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Page/Page column 66; 67, (2018/05/15)
Disclosed are compounds having the formula: wherein R1, R2, R3 and Z are as defined herein, and methods of making and using the same.
IAP E3 LIGASE DIRECTED PROTEOLYSIS TARGETING CHIMERIC MOLECULES
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Page/Page column 54, (2016/11/14)
Proteolysis Targeting Chimeric molecules (Protacs) are bifunctional molecules which which can simultaneously bind a target protein and an E3 ubiquitin ligase thereby bringing the ligase and target in close proximity These bifunctional molecules allow the
AMINO-QUINOLINES AS KINASE INHIBITORS
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Paragraph 0123, (2016/10/31)
Disclosed are compounds having the formula: wherein R1, R2, R3 and Z are as defined herein, and methods of making and using the same.
Structure-based design of novel class II c-Met inhibitors: 2. SAR and kinase selectivity profiles of the pyrazolone series
Liu, Longbin,Norman, Mark H.,Lee, Matthew,Xi, Ning,Siegmund, Aaron,Boezio, Alessandro A.,Booker, Shon,Choquette, Debbie,D'Angelo, Noel D.,Germain, Julie,Yang, Kevin,Yang, Yajing,Zhang, Yihong,Bellon, Steven F.,Whittington, Douglas A.,Harmange, Jean-Christophe,Dominguez, Celia,Kim, Tae-Seong,Dussault, Isabelle
, p. 1868 - 1897 (2012/05/04)
As part of our effort toward developing an effective therapeutic agent for c-Met-dependent tumors, a pyrazolone-based class II c-Met inhibitor, N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-1,5-dimethyl-3-oxo-2- phenyl-2,3-dihydro-1H-pyrazole-4-c
