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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2003-7-10
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pubmed:abstractText |
A biaryl pyridylfuran P(3) substituent on the hydroxyethylene isostere scaffold affords HIV protease inhibitors (PI's) with picomolar (IC(50)) potency against the protease enzymes from PI-resistant HIV-1 strains. Inclusion of a gem-dimethyl substituent afforded compound 3 with 100% oral bioavailability (dogs) and more than double the t(1/2) of indinavir. Inhibition of multiple P450 isoforms is dependent on the regiochemistry of the pyridyl nitrogen in these compounds.
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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 |
Aug
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pubmed:issn |
0960-894X
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pubmed:author |
pubmed-author:ChapmanKevin TKT,
pubmed-author:DuffyJoseph LJL,
pubmed-author:EminiEmilio AEA,
pubmed-author:JinLixiaL,
pubmed-author:KevinNancy JNJ,
pubmed-author:KuoLawrence CLC,
pubmed-author:LinJiunn HJH,
pubmed-author:OlsenDavid BDB,
pubmed-author:RanoThomas ATA,
pubmed-author:RutkowskiCarrie ACA,
pubmed-author:SchleifWilliam AWA,
pubmed-author:StahlhutMarkM,
pubmed-author:TataJames RJR
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pubmed:issnType |
Print
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pubmed:day |
4
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2569-72
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pubmed:meshHeading |
pubmed-meshheading:12852968-Animals,
pubmed-meshheading:12852968-Biological Availability,
pubmed-meshheading:12852968-Cytochrome P-450 Enzyme System,
pubmed-meshheading:12852968-Dogs,
pubmed-meshheading:12852968-Drug Resistance, Viral,
pubmed-meshheading:12852968-HIV Protease Inhibitors,
pubmed-meshheading:12852968-HIV-1,
pubmed-meshheading:12852968-Half-Life,
pubmed-meshheading:12852968-Indinavir,
pubmed-meshheading:12852968-Isoenzymes,
pubmed-meshheading:12852968-Macaca mulatta,
pubmed-meshheading:12852968-Mutation,
pubmed-meshheading:12852968-Structure-Activity Relationship
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pubmed:year |
2003
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pubmed:articleTitle |
HIV protease inhibitors with picomolar potency against PI-Resistant HIV-1 by extension of the P3 substituent.
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pubmed:affiliation |
Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. joseph_duffy@merck.com
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pubmed:publicationType |
Journal Article
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