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
Debyser, Z.; Pauwels, R.; Baba, M.; Desmyter, J.; De Clercq, E.
Molecular Pharmacology 41(5): 963-968
1992
ISSN/ISBN: 0026-895X PMID: 1375320 Document Number: 403136
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.