title: "In silico" design of potential anti-HIV actives using fragment descriptors.
abstract: Substructural Molecular Fragments (SMF) method was applied for computer-aided design of new compounds potentially possessing high anti-HIV activities: tetrahydroimidazobenzodiazepinone (TIBO) derivatives and 1-[2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives. Using available experimental data, the SMF method was first applied to build QSAR models based on fragment descriptors (atom/bond sequences and "augmented atoms"). The focused virtual combinatorial libraries containing 891 TIBO derivatives and 2640 HEPT derivatives were then generated systematically attaching selected substituents to corresponding Markush structures. Finally, a screening of those libraries using developed QSAR models led to several hits potentially possessing high anti-HIV activity.
authors.affiliation: Laboratoire d'Infochimie, UMR 7551 CNRS, Université Louis Pasteur, 4, rue B. Pascal, Strasbourg, 67000, France. varnek@chimie.u-strasbg.fr
authors.forename: A
authors.initials: A
authors.lastname: Varnek
authors.forename: V P
authors.initials: VP
authors.lastname: Solov'ev
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D001569:Benzodiazepines / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D015195:Drug Design; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D016571:Neural Networks, Computer; D021281:Quantitative Structure-Activity Relationship; D013941:Thymine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: C476867:4,5,6,7-tetrahydroimidazo-(4,5,1- jk)(1,4)benzodiazepin-2 (1 H)-one; D019380:Anti-HIV Agents; D007093:Imidazoles; C061818:1-((2-hydroxyethoxy)methyl)-6-(phenylthio)thymine; D001569:Benzodiazepines; D013941:Thymine