title: HEPT derivatives as non-nucleoside inhibitors of HIV-1 reverse transcriptase: QSAR studies agree with the crystal structures.
abstract: The interest in the non-nucleoside inhibitors (NNIs) to the reverse transcriptase (RT) as anti-AIDS agents has grown in the last ten years. The compound 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) is the precursor of the most studied class of NNIs, from which hundreds of derivatives have been synthesized and tested. There are at least twelve QSAR studies about the HEPT derivatives as RT inhibitors. Most of the predictions derived by these studies are related to the nature of the active site near the substituents at positions N-1 and C-5, and at the C-6 phenyl ring. The validity of these models has been checked against the 3-D structure of HIV 1 RT-HEPT complexes available. Most of these predictions were confirmed at the molecular level.
authors.affiliation: Departamento de Física, Centro de Ciências Exatas, Universidade Federal do Espírito Santo, Vitória - ES, Brazil. anderson@npd.ufes.br
authors.forename: Anderson Coser
authors.initials: AC
authors.lastname: Gaudio
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Montanari
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013941:Thymine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D018894:Reverse Transcriptase Inhibitors; C061818:1-((2-hydroxyethoxy)methyl)-6-(phenylthio)thymine; D054303:HIV Reverse Transcriptase; D013941:Thymine