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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
18
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pubmed:dateCreated |
2003-8-27
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pubmed:abstractText |
Src tyrosine kinase is a therapeutic target for bone diseases that has been validated by gene knockout studies. Furthermore, in vitro cellular studies implicate that Src has a positive regulatory role in osteoclasts and a negative regulatory role in osteoblasts. The potential use of Src inhibitors for osteoporosis therapy has been previously shown by novel bone-targeted ligands of the Src SH2 (e.g., AP22408) and non-bone-targeted, ATP-based inhibitors of Src kinase. Significant to this study, compounds 2-12 exemplify novel analogues of known pyrrolopyrimidine and pyrazolopyrimidine template-based Src kinase inhibitors that incorporate bone-targeting group modifications designed to provide tissue (bone) selectivity and diminished side effects. Accordingly, we report here the structure-based design, synthetic chemistry and biological testing of these compounds and proof-of-concept studies thereof.
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pubmed:commentsCorrections |
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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 |
Sep
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pubmed:issn |
0960-894X
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pubmed:author |
pubmed-author:AdamsSusanS,
pubmed-author:BohacekRegine SRS,
pubmed-author:DalgarnoDavid CDC,
pubmed-author:KeatsJeffrey AJA,
pubmed-author:KeenanTerence PTP,
pubmed-author:LiouShuennS,
pubmed-author:LiuShuangyingS,
pubmed-author:ManiUktiU,
pubmed-author:MetcalfChester ACA3rd,
pubmed-author:NarulaSurinder SSS,
pubmed-author:RamMary KMK,
pubmed-author:SawyerTomi KTK,
pubmed-author:ShakespeareWilliam CWC,
pubmed-author:SundaramoorthiRajiR,
pubmed-author:TaylorMerryM,
pubmed-author:VioletteSheila MSM,
pubmed-author:WangYihanY,
pubmed-author:WeigeleManfredM,
pubmed-author:WeigleManfredM,
pubmed-author:van SchravandijkMarie RoseMR
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3063-6
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12941334-Adenosine Triphosphate,
pubmed-meshheading:12941334-Animals,
pubmed-meshheading:12941334-Bone Diseases,
pubmed-meshheading:12941334-Drug Design,
pubmed-meshheading:12941334-Enzyme Inhibitors,
pubmed-meshheading:12941334-Humans,
pubmed-meshheading:12941334-Inhibitory Concentration 50,
pubmed-meshheading:12941334-Models, Molecular,
pubmed-meshheading:12941334-Osteoporosis,
pubmed-meshheading:12941334-Purines,
pubmed-meshheading:12941334-Pyrimidines,
pubmed-meshheading:12941334-Structure-Activity Relationship,
pubmed-meshheading:12941334-src-Family Kinases
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pubmed:year |
2003
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pubmed:articleTitle |
Bone-targeted Src kinase inhibitors: novel pyrrolo- and pyrazolopyrimidine analogues.
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pubmed:affiliation |
ARIAD Pharmaceuticals, Inc., 26 Landsdowne Street, Cambridge, MA 02139-4234, USA. raji.sundaramoorthi@ariad.com
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pubmed:publicationType |
Journal Article
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