935667-21-3Relevant academic research and scientific papers
Use of ω-transaminase enzyme chemistry in the synthesis of a JAK2 kinase inhibitor
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.
, p. 1123 - 1130 (2013/10/08)
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.
Efficient synthesis of (S)-1-(5-fluoropyrimidin-2-yl)ethylamine using an ω-transaminase biocatalyst in a two-phase system
Meadows, Rebecca E.,Mulholland, Keith R.,Schuermann, Martin,Golden, Michael,Kierkels, Hans,Meulenbroeks, Elise,Mink, Daniel,May, Oliver,Squire, Christopher,Straatman, Harrie,Wells, Andrew S.
, p. 1117 - 1122 (2013/10/08)
Screening of 60 transaminases using three different amine donors found that the ω-transaminase from Vibrio fluvialis together with (S)-α-methylbenzylamine to be the most promising combination to deliver the desired (S)-1-(5-fluoropyrimidin-2-yl)-ethylamine (2) in almost quantitative conversion. The process was further improved by the addition of immiscible organic solvents with toluene identified as most suitable concerning the distribution of the reactants without negatively impacting the performance of the biocatalyst. Further process optimization using commercial enzyme preparations of V. fluvialis led to product/catalyst ratios of 15 g/g cell dry weight. This approach led to a process that provided (S)-1-(5-fluoropyrimidin-2- yl)ethylamine (2) in 77% yield with 99.8% ee. In addition, a recombinant E. coli-based whole-cell biocatalyst was also designed and applied to this process. The use of this low cost enzyme formulation gave product of similar quality to that obtained using the commercial formulation of V. fluvialis. This process was further optimized and scaled-up to deliver (S)-1-(5-fluoropyrimidin-2-yl) ethylamine (2)with a yield of 66% and an optical purity of 97.3% ee. These results confirm the efficiency and competitiveness of the transaminase technology for the production of chiral amines.
HETEROCYCLIC JAK KINASE INHIBITORS
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Page/Page column 67, (2010/04/27)
The present invention relates to compounds of Formula (I) and to their salts, pharmaceutical compositions, methods of use, and methods for their preparation. These compounds provide a treatment for myeloproliferative disorders and cancer
TRICYCLIC 2,4-DIAMIN0-L,3,5-TRIAZINE DERIVATIVES USEFUL FOR THE TREATMENT OF CANCER AND MYELOPROLIFERATIVE DISORDERS
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Page/Page column 75, (2010/01/07)
The present invention relates to compounds of Formula (I): (I) and to their salts, pharmaceutical compositions, methods of use, and methods for their preparation. These compounds provide a treatment for myeloproliferative disorders and cancer.
Discovery of pyrazol-3-ylamino pyrazines as novel JAK2 inhibitors
Ioannidis, Stephanos,Lamb, Michelle L.,Davies, Audrey M.,Almeida, Lynsie,Su, Mei,Bebernitz, Geraldine,Ye, Minwei,Bell, Kirsten,Alimzhanov, Marat,Zinda, Michael
scheme or table, p. 6524 - 6528 (2010/05/18)
The design, synthesis and biological evaluation of a series of pyrazol-3-ylamino pyrazines as potent and selective JAK2 kinase inhibitors is reported, along with the pharmacokinetic and pharmacodynamic properties of lead compounds.
Identification of 4-aminopyrazolylpyrimidines as potent inhibitors of Trk kinases
Wang, Tao,Lamb, Michelle L.,Scott, David A.,Wang, Haixia,Block, Michael H.,Lyne, Paul D.,Lee, John W.,Davies, Audrey M.,Zhang, Hai-Jun,Zhu, Yanyi,Gu, Fei,Han, Yongxin,Wang, Bin,Mohr, Peter J.,Kaus, Robert J.,Josey, John A.,Hoffmann, Ethan,Thress, Ken,MacIntyre, Terry,Wang, Haiyun,Omer, Charles A.,Yu, Dingwei
experimental part, p. 4672 - 4684 (2009/07/25)
The design, synthesis and biological evaluation of a series of 4-aminopyrazolylpyrimidines as potent Trk kinase inhibitors is reported. High-throughput screening identified a promising hit in the 4- aminopyrazolylpyrimidine chemotype. Initial optimization of the series led to more potent Trk inhibitors. Further optimization using two strategies resulted in significant improvement of physical properties and led to the discovery of 10z (AZ-23), a potent, orally bioavailable Trk A/B inhibitor. The compound offers the potential to test the hypothesis that modulation of Trk activity will be of benefit in the treatment of cancer and other indications in vivo.
PYRAZOLYL-AMINO-SUBSTITUTED PYRAZINES AND THEIR USE FOR THE TREATMENT OF CANCER
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Page/Page column 63, (2008/12/04)
The present invention relates to compounds of Formula (I): and to their pharmaceutical compositions, and to their methods of use. These novel compounds provide a treatment for myeloproliferative disorders and cancer.
5-AMINOPYRAZOL-3-YL-3H-IMIDAZO [4,5-B] PYRIDINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF CANCER
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Page/Page column 72, (2008/12/08)
The present invention relates to compounds of Formula (I) and to their pharmaceutical compositions, and to their methods of use. These novel compounds provide a treatment for myeloproliferative disorders and cancer.
9- (PYRAZOL- 3 -YL) - 9H- PURINE-2 -AMINE AND 3- (PYRAZ0L-3-YL) -3H-IMIDAZ0 [4, 5-B] PYRIDIN-5-AMINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF CANCER
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Page/Page column 52, (2009/01/20)
The present invention relates to compounds of Formula (I): and to their pharmaceutical compositions, and to their methods of use. These compounds provide a treatment for myeloproliferative disorders and cancer.
AMINO-THIAZOLYL- PYRIMIDINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF CANCER
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Page/Page column 52, (2009/01/20)
The present invention relates to compounds of Formula (I): and to their pharmaceutical compositions, and to their methods of use. These compounds provide a treatment for myeloproliferative disorders and cancer.
