1607838-32-3Relevant academic research and scientific papers
NOVEL NAPHTHYRIDINES AND ISOQUINOLINES AND THEIR USE AS CDK8/19 INHIBITORS
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, (2016/02/12)
The present invention relates to naphthyridine and isoquinoline compounds, and pharmaceutically acceptable compositions thereof, useful as inhibitors of CDK8/19, and for the treatment of CDK8/19-related disorders.
Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19
Mallinger, Aurélie,Schiemann, Kai,Rink, Christian,Stieber, Frank,Calderini, Michel,Crumpler, Simon,Stubbs, Mark,Adeniji-Popoola, Olajumoke,Poeschke, Oliver,Busch, Michael,Czodrowski, Paul,Musil, Djordje,Schwarz, Daniel,Ortiz-Ruiz, Maria-Jesus,Schneider, Richard,Thai, Ching,Valenti, Melanie,De Haven Brandon, Alexis,Burke, Rosemary,Workman, Paul,Dale, Trevor,Wienke, Dirk,Clarke, Paul A.,Esdar, Christina,Raynaud, Florence I.,Eccles, Suzanne A.,Rohdich, Felix,Blagg, Julian
, p. 1078 - 1101 (2016/02/23)
The Mediator complex-associated cyclin-dependent kinase CDK8 has been implicated in human disease, particularly in colorectal cancer where it has been reported as a putative oncogene. Here we report the discovery of 109 (CCT251921), a potent, selective, and orally bioavailable inhibitor of CDK8 with equipotent affinity for CDK19. We describe a structure-based design approach leading to the discovery of a 3,4,5-trisubstituted-2-aminopyridine series and present the application of physicochemical property analyses to successfully reduce in vivo metabolic clearance, minimize transporter-mediated biliary elimination while maintaining acceptable aqueous solubility. Compound 109 affords the optimal compromise of in vitro biochemical, pharmacokinetic, and physicochemical properties and is suitable for progression to animal models of cancer.
PYRIDYL PIPERIDINES
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, (2015/12/31)
The invention provides novel substituted pyridyl piperidine compounds according to Formula (I) which are Wnt pathway inhibitors, their manufacture and use for the treatment of hyperproliferative diseases such as cancer, inflammatory or degenerative diseases.
2-AMINOPYRIDINE COMPOUNDS
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, (2014/05/24)
The invention provides novel substituted 2-aminopyridine compounds according to Formula (I), their manufacture and use for the treatment of hyperproliferative diseases such as cancer, inflammatory or degenerative diseases.
