732981-76-9Relevant articles and documents
Discovery of 5-chloro- N 2-[(1 S)-1-(5-fluoropyrimidin-2-yl) ethyl]- N 4-(5-methyl-1 H -pyrazol-3-yl)pyrimidine-2,4-diamine (AZD1480) as a novel inhibitor of the jak/stat pathway
Ioannidis, Stephanos,Lamb, Michelle L.,Wang, Tao,Almeida, Lynsie,Block, Michael H.,Davies, Audrey M.,Peng, Bo,Su, Mei,Zhang, Hai-Jun,Hoffmann, Ethan,Rivard, Caroline,Green, Isabelle,Howard, Tina,Pollard, Hannah,Read, Jon,Alimzhanov, Marat,Bebernitz, Geraldine,Bell, Kirsten,Ye, Minwei,Huszar, Dennis,Zinda, Michael
, p. 262 - 276 (2011/03/20)
The myeloproliferative neoplasms, polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis are a heterogeneous but related group of hematological malignancies characterized by clonal expansion of one or more myeloid lineages. The discovery of the Jak2 V617F gain of function mutation highlighted Jak2 as a potential therapeutic target in the MPNs. Herein, we disclose the discovery of a series of pyrazol-3-yl pyrimidin-4-amines and the identification of 9e (AZD1480) as a potent Jak2 inhibitor. 9e inhibits signaling and proliferation of Jak2 V617F cell lines in vitro, demonstrates in vivo efficacy in a TEL-Jak2 model, has excellent physical properties and preclinical pharmacokinetics, and is currently being evaluated in Phase I clinical trials.
PYRAZOLE DERIVATIVES AS INHIBITORS OF RECEPTOR TYROSYNE KINASES
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Page/Page column 118, (2008/06/13)
Compounds of formula (I): and their use in the inhibition of Trk activity are described.
