| pubmed-article:14584938 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:14584938 | lifeskim:mentions | umls-concept:C1257954 | lld:lifeskim |
| pubmed-article:14584938 | lifeskim:mentions | umls-concept:C0220781 | lld:lifeskim |
| pubmed-article:14584938 | lifeskim:mentions | umls-concept:C0220825 | lld:lifeskim |
| pubmed-article:14584938 | lifeskim:mentions | umls-concept:C1883254 | lld:lifeskim |
| pubmed-article:14584938 | lifeskim:mentions | umls-concept:C0456387 | lld:lifeskim |
| pubmed-article:14584938 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
| pubmed-article:14584938 | lifeskim:mentions | umls-concept:C1707689 | lld:lifeskim |
| pubmed-article:14584938 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
| pubmed-article:14584938 | lifeskim:mentions | umls-concept:C0205460 | lld:lifeskim |
| pubmed-article:14584938 | pubmed:issue | 23 | lld:pubmed |
| pubmed-article:14584938 | pubmed:dateCreated | 2003-10-30 | lld:pubmed |
| pubmed-article:14584938 | pubmed:abstractText | A group of 6-alkyl (alkoxy or alkylthio)-4-aryl-3-(4-methanesulfonylphenyl)pyran-2-ones (14a-v), possessing either a H or F substituent at the para-position of the C-4 phenyl ring, were designed for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors with in vivo antiinflammatory-analgesic activities. Although 6-ethylthio-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-one (14s) exhibited a very high in vitro COX-2 inhibitory potency (IC(50) = 0.0032 muM) and COX-2 selectivity (SI > 120 000), 14s exhibited moderate antiinflammatory activity compared to celecoxib in a carrageenan-induced rat paw edema assay. In contrast, the less potent (IC(50) = 0.10 muM), and less selective (SI = 2880) COX-2 inhibitor 6-ethoxy-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-one (14i) exhibited good antiinflammatory activity where a 1 mg/kg oral dose reduced inflammation 32 and 67% at 3 and 5 h postdrug administration relative to the reference drug celecoxib where a 50 mg/kg oral dose reduced inflammation by 79 and 58% at the respective 3 and 5 h time periods. Molecular modeling studies, where 14i was docked in the active site of both COX-1 and COX-2, reveals that the C-6 ethoxy substituent orients the pyran-2-one ring to position the SO(2)Me pharmacophore in the vicinity of the secondary pocket in COX-2. The absence of this COX-2 secondary pocket in the COX-1 binding site is due to the presence of the bulky Ile(523) in COX-1 such that access to the amino acid residues (Ile(517), Phe(518), Gln(192), and His(90)), which line the COX-2 secondary pocket with which the SO(2)Me pharmacophore could interact, is hindered. The six-membered pyran-2-one ring system is a suitable central template to design selective COX-2 inhibitors. | lld:pubmed |
| pubmed-article:14584938 | pubmed:language | eng | lld:pubmed |
| pubmed-article:14584938 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14584938 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:14584938 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:14584938 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:14584938 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14584938 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:14584938 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:14584938 | pubmed:issn | 0022-2623 | lld:pubmed |
| pubmed-article:14584938 | pubmed:author | pubmed-author:Praveen... | lld:pubmed |
| pubmed-article:14584938 | pubmed:author | pubmed-author:KnausEdward... | lld:pubmed |
| pubmed-article:14584938 | pubmed:author | pubmed-author:AminiMohsenM | lld:pubmed |
| pubmed-article:14584938 | pubmed:author | pubmed-author:LiHuiyingH | lld:pubmed |
| pubmed-article:14584938 | pubmed:author | pubmed-author:HabeebAmgad... | lld:pubmed |
| pubmed-article:14584938 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:14584938 | pubmed:day | 6 | lld:pubmed |
| pubmed-article:14584938 | pubmed:volume | 46 | lld:pubmed |
| pubmed-article:14584938 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:14584938 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:14584938 | pubmed:pagination | 4872-82 | lld:pubmed |
| pubmed-article:14584938 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
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| pubmed-article:14584938 | pubmed:year | 2003 | lld:pubmed |
| pubmed-article:14584938 | pubmed:articleTitle | Design, synthesis, and biological evaluation of 6-substituted-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-ones: a novel class of diarylheterocyclic selective cyclooxygenase-2 inhibitors. | lld:pubmed |
| pubmed-article:14584938 | pubmed:affiliation | Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2N8, Canada. | lld:pubmed |
| pubmed-article:14584938 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:14584938 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:14584938 | lld:chembl |
