Phenylaminopyrimidines as inhibitors of Janus kinases (JAKs)

Details of SAR studies leading to CYT387, a potent and selective dual JAK1 and JAK2 inhibitor, are reported. A series of phenylaminopyrimidines has been identified as inhibitors of Janus kinases (JAKs). Development of this initial series led to the potent JAK2/JAK1 inhibitor CYT387 ( N-(cyanomethyl)...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2009-10, Vol.19 (20), p.5887-5892
Hauptverfasser:	Burns, Christopher J., Bourke, David G., Andrau, Laura, Bu, Xianyong, Charman, Susan A., Donohue, Andrew C., Fantino, Emmanuelle, Farrugia, Michelle, Feutrill, John T., Joffe, Max, Kling, Marcel R., Kurek, Margarita, Nero, Tracy L., Nguyen, Thao, Palmer, James T., Phillips, Ian, Shackleford, David M., Sikanyika, Harrison, Styles, Michelle, Su, Stephen, Treutlein, Herbert, Zeng, Jun, Wilks, Andrew F.
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antineoplastic agents Benzamides - chemical synthesis Benzamides - chemistry Benzamides - pharmacology Binding Sites Biological and medical sciences Caco-2 Cells Cell Line, Tumor Computer Simulation CYT387 General aspects Humans Inhibitor JAK2 Janus Janus Kinase 2 - antagonists & inhibitors Janus Kinase 2 - metabolism Kinase Male Medical sciences Myeloproliferative Pharmacology. Drug treatments Protein Isoforms - antagonists & inhibitors Protein Isoforms - metabolism Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacokinetics Pyrimidines - chemical synthesis Pyrimidines - chemistry Pyrimidines - pharmacokinetics Pyrimidines - pharmacology Rats Rats, Sprague-Dawley Structure-Activity Relationship
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Zusammenfassung:	Details of SAR studies leading to CYT387, a potent and selective dual JAK1 and JAK2 inhibitor, are reported. A series of phenylaminopyrimidines has been identified as inhibitors of Janus kinases (JAKs). Development of this initial series led to the potent JAK2/JAK1 inhibitor CYT387 ( N-(cyanomethyl)-4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]-benzamide). Details of synthesis and SAR studies of these compounds are reported.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2009.08.071