title: Common features in the interaction of tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one and -thione and 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives with the human immunodeficiency virus type 1 reverse transcriptase.
abstract: Recently, several classes of compounds have been shown to be potent, selective, and specific inhibitors of human immunodeficiency virus type 1 replication in vitro. These include the tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-one and -thione (TIBO) and the 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives. Both the TIBO and HEPT derivatives specifically inhibit human immunodeficiency virus type 1 reverse transcriptase (RT). From a comparative study of the characteristics of RT inhibition by TIBO and HEPT, and from the competition between TIBO and HEPT for RT inhibition, we infer that both classes of compounds, although structurally unrelated, are targeted at the same site of the enzyme. Detailed functional and kinetic analyses indicate that this target site is functionally and possibly also spatially related to the substrate binding site.
authors.affiliation: Rega Institute for Medical Research, Catholic University of Leuven, Belgium.
authors.forename: Z
authors.initials: Z
authors.lastname: Debyser
authors.forename: R
authors.initials: R
authors.lastname: Pauwels
authors.forename: M
authors.initials: M
authors.lastname: Baba
authors.forename: J
authors.initials: J
authors.lastname: Desmyter
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D054306:Dideoxynucleotides; D015497:HIV-1 / Q000201:enzymology*; D007093:Imidazoles / Q000494:pharmacology*; D007700:Kinetics; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D018894:Reverse Transcriptase Inhibitors; D013329:Structure-Activity Relationship; D013698:Templates, Genetic; D013936:Thymidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013942:Thymine Nucleotides / Q000494:pharmacology; D014498:Uracil / Q000031:analogs & derivatives / Q000494:pharmacology; D015215:Zidovudine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D054306:Dideoxynucleotides; D007093:Imidazoles; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D013942:Thymine Nucleotides; C062687:R 82150; D001569:Benzodiazepines; C071166:5-ethyl-1-ethoxymethyl-6-(phenylthio)uracil; D015215:Zidovudine; D014498:Uracil; C052873:zidovudine triphosphate; D013936:Thymidine