“In Silico” Design of Potential Anti-HIV Actives Using Fragment Descriptors

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.