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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
2000-9-8
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pubmed:abstractText |
A series of heteroaryl modified 1,2-diarylimidazoles has been synthesized and found to be potent and highly selective (1000-9000-fold) inhibitors of the human COX-2. 3-Pyridyl derived COX-2 selective inhibitor (25) exhibited excellent activity in acute (carrageenan induced paw edema, ED(50) = 5.4 mg/kg) and chronic (adjuvant induced arthritis, ED(50) = 0.25 mg/kg) models of inflammation. The relatively long half-life of 25 in rat and dog prompted investigation of the pyridyl and other heteroaromatic systems containing potential metabolic functionalities. A number of substituted pyridyl and thiazole containing compounds (e.g., 44, 46, 54, 76, and 78) demonstrated excellent oral activity in every efficacy model evaluated. Several orally active diarylimidazoles exhibited desirable pharmacokinetics profiles and showed no GI toxicity in the rat up to 100 mg/kg in both acute and chronic models. The paper describes facile and practical syntheses of the targeted diarylimidazoles. The structure-activity relationships and antiinflammatory properties of a series of diarylimidazoles are discussed.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2 Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nitriles,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides
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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:CogburnJ NJN,
pubmed-author:CollinsP WPW,
pubmed-author:GAYJ PJP,
pubmed-author:IsaksonP CPC,
pubmed-author:KhannaI KIK,
pubmed-author:KoboldtC MCM,
pubmed-author:KoszykF JFJ,
pubmed-author:LOWEC HCHJr,
pubmed-author:MasferrerJ LJL,
pubmed-author:PerkinsW EWE,
pubmed-author:SeibertKK,
pubmed-author:VeenhuizenA WAW,
pubmed-author:WeierR MRM,
pubmed-author:YangD CDC,
pubmed-author:YoSS,
pubmed-author:YuanJJ,
pubmed-author:ZhangY YYY
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3168-85
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pubmed:dateRevised |
2005-11-17
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pubmed:meshHeading |
pubmed-meshheading:10956225-Administration, Oral,
pubmed-meshheading:10956225-Animals,
pubmed-meshheading:10956225-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:10956225-Arthritis, Experimental,
pubmed-meshheading:10956225-Cyclooxygenase 2,
pubmed-meshheading:10956225-Cyclooxygenase 2 Inhibitors,
pubmed-meshheading:10956225-Cyclooxygenase Inhibitors,
pubmed-meshheading:10956225-Dogs,
pubmed-meshheading:10956225-Edema,
pubmed-meshheading:10956225-Gastrointestinal Hemorrhage,
pubmed-meshheading:10956225-Humans,
pubmed-meshheading:10956225-Hyperalgesia,
pubmed-meshheading:10956225-Imidazoles,
pubmed-meshheading:10956225-Intestines,
pubmed-meshheading:10956225-Isoenzymes,
pubmed-meshheading:10956225-Membrane Proteins,
pubmed-meshheading:10956225-Mice,
pubmed-meshheading:10956225-Nitriles,
pubmed-meshheading:10956225-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:10956225-Pyridines,
pubmed-meshheading:10956225-Rats,
pubmed-meshheading:10956225-Stomach,
pubmed-meshheading:10956225-Structure-Activity Relationship,
pubmed-meshheading:10956225-Sulfonamides
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pubmed:year |
2000
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pubmed:articleTitle |
Selective cyclooxygenase-2 inhibitors: heteroaryl modified 1,2-diarylimidazoles are potent, orally active antiinflammatory agents.
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pubmed:affiliation |
Discovery Medicinal Chemistry and Inflammatory Disease Research, Pharmacia Corporation, 4901 Searle Parkway, Skokie, Illinois 60077, USA. ish.k.khanna@monsanto.com
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pubmed:publicationType |
Journal Article
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