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rdf:type |
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|
lifeskim:mentions |
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pubmed:issue |
25
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pubmed:dateCreated |
2004-11-29
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pubmed:abstractText |
A series of 4-alkynyloxy phenyl sulfanyl, sulfinyl and sulfony alkyl and piperidine-4-carboxylic acid hydroxamides were synthesized. Their structure-activity relationships, against tumor necrosis factor-alpha (TACE) and matrix metalloproteinase (MMP) inhibitor activities, are presented by investigating the oxidation state on sulfur and altering the P1' substituent. The sulfonyl derivatives 20-24 carrying a 4-butynyloxy moiety were selective TACE inhibitors over the MMPs tested. The sulfinyl derivatives showed a preference for a specific oxidation on sulfur as in compounds 25-28. The selectivity over MMPs was also demonstrated in the sulfonyl series. The enhanced cellular activity was achieved upon incorporating a butynyloxy substituent in the piperidene series. Compounds 64 and 65 were potent inhibitors of TNF-alpha release in the mouse at 100 mg/kg po.
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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 |
Dec
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BakerJannieJ,
pubmed-author:BaroneDauphineD,
pubmed-author:DavisJamie MJM,
pubmed-author:DijosephJohn FJF,
pubmed-author:EllingboeJohnJ,
pubmed-author:GrosuGeorge TGT,
pubmed-author:JinGuixianG,
pubmed-author:LevinJeremy IJI,
pubmed-author:McCarthyDiane JosephDJ,
pubmed-author:SkotnickiJerauld SJS,
pubmed-author:SungAmyA,
pubmed-author:VenkatesanAranapakam MAM,
pubmed-author:XuWeixinW,
pubmed-author:ZaskArieA
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pubmed:issnType |
Print
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|
pubmed:day |
2
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|
pubmed:volume |
47
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|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
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pubmed:pagination |
6255-69
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15566296-ADAM Proteins,
pubmed-meshheading:15566296-Animals,
pubmed-meshheading:15566296-Crystallography, X-Ray,
pubmed-meshheading:15566296-Humans,
pubmed-meshheading:15566296-Hydroxamic Acids,
pubmed-meshheading:15566296-Matrix Metalloproteinases,
pubmed-meshheading:15566296-Metalloendopeptidases,
pubmed-meshheading:15566296-Mice,
pubmed-meshheading:15566296-Models, Molecular,
pubmed-meshheading:15566296-Molecular Structure,
pubmed-meshheading:15566296-Monocytes,
pubmed-meshheading:15566296-Oxidation-Reduction,
pubmed-meshheading:15566296-Piperidines,
pubmed-meshheading:15566296-Structure-Activity Relationship,
pubmed-meshheading:15566296-Sulfides,
pubmed-meshheading:15566296-Sulfones,
pubmed-meshheading:15566296-Sulfoxides,
pubmed-meshheading:15566296-Tumor Necrosis Factor-alpha
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pubmed:year |
2004
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pubmed:articleTitle |
Synthesis and structure-activity relationships of 4-alkynyloxy phenyl sulfanyl, sulfinyl, and sulfonyl alkyl hydroxamates as tumor necrosis factor-alpha converting enzyme and matrix metalloproteinase inhibitors.
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pubmed:affiliation |
Wyeth Research, Pearl River, New York 10965, USA. venkata@wyeth.com
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pubmed:publicationType |
Journal Article,
In Vitro
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