- Use of ω-transaminase enzyme chemistry in the synthesis of a JAK2 kinase inhibitor
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ω-Transaminase enzyme chemistry provides an excellent methodology to build synthetically useful chiral amines from their corresponding ketones. An application of this methodology, providing a long-term commercial manufacturing route to a JAK2 kinase inhibitor, is reported herein.
- Frodsham, Lianne,Golden, Michael,Hard, Susan,Kenworthy, Martin N.,Klauber, David J.,Leslie, Kevin,Macleod, Claire,Meadows, Rebecca E.,Mulholland, Keith R.,Reilly, Julie,Squire, Christopher,Tomasi, Simone,Watt, Denise,Wells, Andrew S.
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p. 1123 - 1130
(2013/10/08)
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- 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
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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.
- 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
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experimental part
p. 262 - 276
(2011/03/20)
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- 4- (3-AMINOPYRAZOLE) PYRIMIDINE DERIVATIVES FOR USE AS TYROSINE KINASE INHIBITORS IN THE TREATMENT OF CANCER
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This invention relates to novel compounds having the formula (I) and to their pharmaceutical compositions and to their methods of use. These novel compounds provide a treatment for cancer.
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Page/Page column 43
(2010/11/27)
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