Chemotherapy of the acquired immune deficiency syndrome (AIDS): non-nucleoside inhibitors of the human immunodeficiency virus type 1 reverse transcriptase.
Several classes of non-nucleotide analogues (i.e. TIBO and HEPT derivatives) have been identified that specifically interact with the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1). These derivatives inhibit the replication of HIV-1 in various cell lines, including peripheral blood lymphocytes and monocytes/macrophages, at concentrations that are 10,000- to 100,000-fold lower than the cytotoxic concentrations. At the HIV-1 RT level, they appear to interact with a specific allosteric "TIBO" site, which may be functionally and also structurally associated with the substrate binding site. The TIBO and TIBO-like compounds are orally bioavailable. In vivo they sustain plasma drug levels that are well above the concentrations required to inhibit virus replication in vitro.
De Clercq
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Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors; D013941:Thymine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D007093:Imidazoles; D018894:Reverse Transcriptase Inhibitors; C061818:1-((2-hydroxyethoxy)methyl)-6-(phenylthio)thymine; D001569:Benzodiazepines; C067413:R-82913; D013941:Thymine