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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
1997-6-27
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pubmed:abstractText |
Series of 1,2-diarylimidazoles has been synthesized and found to contain highly potent and selective inhibitors of the human COX-2 enzyme. The paper describes a short synthesis of the target 1,2-diarylimidazoles starting with aryl nitriles. Different portions of the diarylimidazole (I) were modified to establish SAR. Systematic variations of the substituents in the aryl ring B have yielded very potent (IC50 = 10-100 nm) and selective (1000-12500) inhibitors of the COX-2 enzyme. The study on the influence of substituents in the imidazole ring established that a CF3 group at position 4 gives the optimum oral activity. A number of the diarylimidazoles showed excellent inhibition in the adjuvant induced arthritis model (e.g., ED50 = 0.02 mpk for 22 and 34). The diarylimidazoles are also potent inhibitors of carrageenan-induced edema (ED50 = 9-30 mpk) and hyperalgesia (ED50 = 11-40 mpk). Several orally active diarylimidazoles show no GI toxicity in the rat and mouse up to 200 mpk.
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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/Carrageenan,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 1,
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/PTGS1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Ptgs1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ptgs1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfones
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:CaslerJ JJJ,
pubmed-author:CollinsP WPW,
pubmed-author:GregoryS ASA,
pubmed-author:IsaksonP CPC,
pubmed-author:KhannaI KIK,
pubmed-author:KoboldtC MCM,
pubmed-author:KoszykF JFJ,
pubmed-author:MasferrerJ LJL,
pubmed-author:PerkinsW EWE,
pubmed-author:SeibertKK,
pubmed-author:VeenhuizenA WAW,
pubmed-author:WeierR MRM,
pubmed-author:XuX DXD,
pubmed-author:YoSS,
pubmed-author:ZhangY YYY
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pubmed:issnType |
Print
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pubmed:day |
23
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1634-47
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pubmed:dateRevised |
2005-11-17
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pubmed:meshHeading |
pubmed-meshheading:9171873-Animals,
pubmed-meshheading:9171873-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:9171873-Arthritis, Experimental,
pubmed-meshheading:9171873-Carrageenan,
pubmed-meshheading:9171873-Cyclooxygenase 1,
pubmed-meshheading:9171873-Cyclooxygenase 2,
pubmed-meshheading:9171873-Cyclooxygenase 2 Inhibitors,
pubmed-meshheading:9171873-Cyclooxygenase Inhibitors,
pubmed-meshheading:9171873-Edema,
pubmed-meshheading:9171873-Gastrointestinal Diseases,
pubmed-meshheading:9171873-Humans,
pubmed-meshheading:9171873-Imidazoles,
pubmed-meshheading:9171873-Isoenzymes,
pubmed-meshheading:9171873-Membrane Proteins,
pubmed-meshheading:9171873-Mice,
pubmed-meshheading:9171873-Molecular Structure,
pubmed-meshheading:9171873-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:9171873-Rats,
pubmed-meshheading:9171873-Structure-Activity Relationship,
pubmed-meshheading:9171873-Sulfonamides,
pubmed-meshheading:9171873-Sulfones
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pubmed:year |
1997
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pubmed:articleTitle |
1,2-Diarylimidazoles as potent, cyclooxygenase-2 selective, and orally active antiinflammatory agents.
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pubmed:affiliation |
Searle Research and Development, Skokie, Illinois 60077, USA.
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pubmed:publicationType |
Journal Article
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