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rdf:type |
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|
lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2008-1-18
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pubmed:abstractText |
The bis-salicylhydrazides class of HIV-1 integrase (IN) inhibitors has been postulated to function by metal chelation. However, members of this series exhibit potent inhibition only when Mn2+ is used as cofactor. The current study found that bis-aroylhydrazides could acquire inhibitory potency in Mg2+ using dihydroxybenzoyl substituents as both the right and left components of the hydrazide moiety. Employing a 2,3-dihydro-6,7-dihydroxy-1 H-isoindol-1-one ring system as a conformationally constrained 2,3-dihydroxybenzoyl equivalent provided good selectivity for IN-catalyzed strand transfer versus the 3'-processing reactions as well as antiviral efficacy in cells using HIV-1 based vectors.
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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 |
Jan
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pubmed:issn |
0022-2623
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pubmed:author |
|
|
pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
51
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
251-9
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pubmed:meshHeading |
pubmed-meshheading:18095643-Benzamides,
pubmed-meshheading:18095643-Catalysis,
pubmed-meshheading:18095643-Cations, Divalent,
pubmed-meshheading:18095643-Cell Line,
pubmed-meshheading:18095643-Cell Line, Tumor,
pubmed-meshheading:18095643-Genetic Vectors,
pubmed-meshheading:18095643-HIV Integrase Inhibitors,
pubmed-meshheading:18095643-HIV-1,
pubmed-meshheading:18095643-Humans,
pubmed-meshheading:18095643-Hydrazines,
pubmed-meshheading:18095643-Isoindoles,
pubmed-meshheading:18095643-Magnesium,
pubmed-meshheading:18095643-Molecular Conformation,
pubmed-meshheading:18095643-Structure-Activity Relationship
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pubmed:year |
2008
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pubmed:articleTitle |
2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one-based HIV-1 integrase inhibitors.
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pubmed:affiliation |
Laboratory of Medicinal Chemistry and HIV Drug Resistance Program, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Intramural
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