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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
17
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pubmed:dateCreated |
2002-8-8
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pubmed:abstractText |
Adenosine (ADO) is an extracellular signaling molecule within the central and peripheral nervous system. Its concentration is increased at sites of tissue injury and inflammation. One of the mechanisms by which antinociceptive and antiinflammatory effects of ADO can be enhanced consists of inhibition of adenosine kinase (AK), the primary metabolic enzyme for ADO. Novel nonnucleoside AK inhibitors based on 4-amino-6-alkynylpyrimidines were prepared, and the importance of the length of the linker at the 5-position for high affinity AK inhibition was demonstrated. Compounds with 2- and 3-atom linkers were the most potent AK inhibitors. Optimization of their physicochemical properties led to 31a and 37a that effectively reduced pain and inflammation in animal models.
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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 |
0022-2623
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pubmed:author |
pubmed-author:BhagwatShripad SSS,
pubmed-author:DidomenicoStanleyS,
pubmed-author:GomtsyanArthurA,
pubmed-author:JarvisMichael FMF,
pubmed-author:KohlhaasKathyK,
pubmed-author:KowalukElizabeth AEA,
pubmed-author:LeeChih-HungCH,
pubmed-author:MatulenkoMark AMA,
pubmed-author:MikusaJoeJ,
pubmed-author:MucJJ,
pubmed-author:WismerCarol TCT,
pubmed-author:YuHaixiaH
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
45
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3639-48
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:12166937-Adenosine,
pubmed-meshheading:12166937-Adenosine Kinase,
pubmed-meshheading:12166937-Analgesics,
pubmed-meshheading:12166937-Animals,
pubmed-meshheading:12166937-Anti-Inflammatory Agents,
pubmed-meshheading:12166937-Enzyme Inhibitors,
pubmed-meshheading:12166937-Humans,
pubmed-meshheading:12166937-Magnetic Resonance Spectroscopy,
pubmed-meshheading:12166937-Models, Molecular,
pubmed-meshheading:12166937-Morpholines,
pubmed-meshheading:12166937-Pain Measurement,
pubmed-meshheading:12166937-Phosphorylation,
pubmed-meshheading:12166937-Pyridines,
pubmed-meshheading:12166937-Pyrimidines,
pubmed-meshheading:12166937-Rats,
pubmed-meshheading:12166937-Structure-Activity Relationship,
pubmed-meshheading:12166937-Tumor Cells, Cultured
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pubmed:year |
2002
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pubmed:articleTitle |
Design, synthesis, and structure-activity relationship of 6-alkynylpyrimidines as potent adenosine kinase inhibitors.
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pubmed:affiliation |
Neuroscience Research, Global Pharmaceutical Products Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA. authur.r.gomtsyan@abbott.com
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pubmed:publicationType |
Journal Article
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