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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2008-8-7
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:BlockMichael HMH,
pubmed-author:DaviesAudrey MAM,
pubmed-author:GuFeiF,
pubmed-author:HaiyunWangW,
pubmed-author:HanYongxinY,
pubmed-author:HoffmannEthanE,
pubmed-author:JoseyJohn AJA,
pubmed-author:KausRobert JRJ,
pubmed-author:LambMichelle LML,
pubmed-author:LeeJohn WJW,
pubmed-author:LynePaul DPD,
pubmed-author:MacintyreTerryT,
pubmed-author:MohrPeter JPJ,
pubmed-author:OmerCharles ACA,
pubmed-author:ScottDavid ADA,
pubmed-author:ThouinLL,
pubmed-author:WangHaixiaH,
pubmed-author:WangTaoT,
pubmed-author:WoodR WRW,
pubmed-author:YuDingweiD,
pubmed-author:ZhangHai-JunHJ,
pubmed-author:ZhuYanyiY
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pubmed:issnType |
Electronic
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pubmed:day |
14
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pubmed:volume |
51
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4672-84
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18646745-Amines,
pubmed-meshheading:18646745-Animals,
pubmed-meshheading:18646745-Cell Line,
pubmed-meshheading:18646745-Humans,
pubmed-meshheading:18646745-Male,
pubmed-meshheading:18646745-Models, Molecular,
pubmed-meshheading:18646745-Molecular Structure,
pubmed-meshheading:18646745-Protein Kinase Inhibitors,
pubmed-meshheading:18646745-Pyrazoles,
pubmed-meshheading:18646745-Pyrimidines,
pubmed-meshheading:18646745-Rats,
pubmed-meshheading:18646745-Rats, Wistar,
pubmed-meshheading:18646745-Receptor, trkA,
pubmed-meshheading:18646745-Structure-Activity Relationship
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pubmed:year |
2008
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pubmed:articleTitle |
Identification of 4-aminopyrazolylpyrimidines as potent inhibitors of Trk kinases.
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pubmed:affiliation |
Department of Cancer Chemistry, AstraZeneca R&D Boston, Waltham, Massachusetts 02451, USA. tao.wang@astrazeneca.com
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pubmed:publicationType |
Journal Article
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