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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
23
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pubmed:dateCreated |
2002-10-31
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pubmed:abstractText |
New gamma-lactam TACE inhibitors were designed from known MMP inhibitors. A homology model of TACE was built and examined to identify the S1' site as the key area for TACE selectivity over MMPs. Rational exploration of the P1'-S1' interactions resulted in the discovery of the 3,5-disubstituted benzyl ether as a TACE-selective P1' group. Further optimization led to the discovery of IK682 as a selective and orally bioavailable TACE inhibitor.
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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 |
Nov
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:ChenLihuaL,
pubmed-author:ChristDavid DDD,
pubmed-author:CovingtonMaryanne BMB,
pubmed-author:DeciccoCarl PCP,
pubmed-author:DuanJames J-WJJ,
pubmed-author:HardmanKarl DKD,
pubmed-author:LiuRui-QinRQ,
pubmed-author:LuZhonghuiZ,
pubmed-author:MagoldaRonald LRL,
pubmed-author:NewtonRobert CRC,
pubmed-author:QianMingxinM,
pubmed-author:WassermanZelda RZR,
pubmed-author:WexlerRuth RRR
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pubmed:issnType |
Print
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pubmed:day |
7
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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 |
4954-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12408705-ADAM Proteins,
pubmed-meshheading:12408705-Administration, Oral,
pubmed-meshheading:12408705-Animals,
pubmed-meshheading:12408705-Biological Availability,
pubmed-meshheading:12408705-Dogs,
pubmed-meshheading:12408705-Hydroxamic Acids,
pubmed-meshheading:12408705-Lactams,
pubmed-meshheading:12408705-Matrix Metalloproteinase 3,
pubmed-meshheading:12408705-Metalloendopeptidases,
pubmed-meshheading:12408705-Models, Molecular,
pubmed-meshheading:12408705-Protease Inhibitors,
pubmed-meshheading:12408705-Rats,
pubmed-meshheading:12408705-Rats, Sprague-Dawley,
pubmed-meshheading:12408705-Structure-Activity Relationship,
pubmed-meshheading:12408705-Swine
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pubmed:year |
2002
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pubmed:articleTitle |
Discovery of gamma-lactam hydroxamic acids as selective inhibitors of tumor necrosis factor alpha converting enzyme: design, synthesis, and structure-activity relationships.
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pubmed:affiliation |
Discovery Chemistry, Bristol-Myers Squibb Company, Experimental Station, Wilmington, Delaware 19880-0500, USA. james.duan@bms.com
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pubmed:publicationType |
Journal Article
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