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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
1991-10-31
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pubmed:abstractText |
Certain bis(heteroaryl)piperazines (BHAPs) are potent inhibitors of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) at concentrations lower by 2-4 orders of magnitude than that which inhibits normal cellular DNA polymerase activity. Combination of a BHAP with nucleoside analog HIV-1 RT inhibitors suggested that together these compounds inhibited RT synergistically. In three human lymphocytic cell systems using several laboratory and clinical HIV-1 isolates, the BHAPs blocked HIV-1 replication with potencies nearly identical to those of 3'-azido-2',3'-dideoxythymidine or 2',3'-dideoxyadenosine; in primary cultures of human peripheral blood mononuclear cells, concentrations of these antiviral agents were lower by at least 3-4 orders of magnitude than cytotoxic levels. The BHAPs do not inhibit replication of HIV-2, the simian or feline immunodeficiency virus, or Rauscher murine leukemia virus in culture. Evaluation of a BHAP in HIV-1-infected SCID-hu mice (severe combined immunodeficient mice implanted with human fetal lymph node) showed that the compound could block HIV-1 replication in vivo. The BHAPs are readily obtained synthetically and have been extensively characterized in preclinical evaluations. These compounds hold promise for the treatment of HIV-1 infection.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-1689015,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-1692723,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-1701568,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-1705816,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-2300816,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-2405486,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-2427649,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-2434858,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-2453682,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-2464362,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-2467383,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-2479983,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-2502840,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-2671731,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-3031510,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-3287617,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-3299090,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-3640792,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-3646751,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-3745189,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-6189183,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-6382953,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1717988-949478
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/2',3'-dideoxythymidine triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Antiviral Agents,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/Dideoxynucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/Reverse Transcriptase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Thymine Nucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Zidovudine
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
88
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pubmed:owner |
NLM
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pubmed:authorsComplete |
N
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pubmed:pagination |
8806-10
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:1717988-Animals,
pubmed-meshheading:1717988-Antiviral Agents,
pubmed-meshheading:1717988-Cell Survival,
pubmed-meshheading:1717988-DNA, Viral,
pubmed-meshheading:1717988-Dideoxynucleotides,
pubmed-meshheading:1717988-Drug Synergism,
pubmed-meshheading:1717988-HIV-1,
pubmed-meshheading:1717988-Mice,
pubmed-meshheading:1717988-Mice, Nude,
pubmed-meshheading:1717988-Piperazines,
pubmed-meshheading:1717988-Polymerase Chain Reaction,
pubmed-meshheading:1717988-RNA, Viral,
pubmed-meshheading:1717988-Reverse Transcriptase Inhibitors,
pubmed-meshheading:1717988-Thymine Nucleotides,
pubmed-meshheading:1717988-Virus Replication,
pubmed-meshheading:1717988-Zidovudine
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pubmed:year |
1991
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pubmed:articleTitle |
Nonnucleoside reverse transcriptase inhibitors that potently and specifically block human immunodeficiency virus type 1 replication.
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pubmed:affiliation |
Upjohn Laboratories, Kalamazoo, MI 49001-0199.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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