476660-67-0Relevant academic research and scientific papers
COMPOUNDS FOR THE TREATMENT OF KINASE-DEPENDENT DISORDERS
-
Paragraph 000474; 000475, (2019/08/12)
Disclosed herein are compounds of Formula I'. Compounds of Formula I' inhibit, regulate and/or modulate kinase receptor, particularly Axl and Mer signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase- dependent diseases and conditions. The present invention also provides methods for making compounds as mentioned above, and compositions which contain these compounds.
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).
AMINO-QUINOLINES AS KINASE INHIBITORS
-
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
-
Paragraph 0127-0128, (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
AMINO-QUINOLINES AS KINASE INHIBITORS
-
Page/Page column 66, (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.
COMPOUNDS FOR THE MODULATION OF RIP2 KINASE ACTIVITY
-
Page/Page column 49; 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.
IAP E3 LIGASE DIRECTED PROTEOLYSIS TARGETING CHIMERIC MOLECULES
-
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
-
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.
1,4-DISUBSTITUTED PYRIDAZINE DERIVATIVES AND THEIR USE FOR TREATING SMN-DEFICIENCY-RELATED CONDITIONS
-
Page/Page column 46, (2015/02/25)
The present invention provides a compound of formula IA or a pharmaceutically acceptable salt thereof; 5 (IA) a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
COMPOUND HAVING TGF-BETA INHIBITORY ACTIVITY AND PHARMACEUTICAL COMPOSITION CONTAINING SAME
-
Page/Page column 82, (2010/11/24)
The present invention provides compounds of formula (I) or compounds of formula (II) and pharmaceutically acceptable salts or solvates thereof. An objective of the present invention is to provide compounds having TGF2 inhibitory activity.
