28936-94-9Relevant articles and documents
PROGRANULIN MODULATORS AND METHODS OF USING THE SAME
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Paragraph 0400, (2021/04/30)
Provided herein are compounds of formula (I) that modulate progranulin and methods of using the compounds in progranulin- associated disorders, such as Frontotemperal lobe dementia (FTLD).
Opioid receptor agonists and application thereof
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Paragraph 1683; 1686-1691, (2019/01/24)
The invention discloses compounds and salts thereof that can be used as opioid receptor ligands, a preparation method of the compounds, compositions containing the compounds, and a use of the compounds as [mu] opioid receptor agonists; the compounds are used for treatment of [mu] opioid receptor-mediated related diseases, such as pains and pain-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
supporting information, 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.