Pharmacophore-based design of HIV-1 integrase strand-transfer inhibitors
Barreca, Maria Letizia × Ferro, Stefania Rao, Angela De Luca, Laura Zappalà, Maria Monforte, Anna-Maria Debyser, Zeger Witvrouw, Myriam Chimirri, Alba #
Journal of Medicinal Chemistry vol:48 issue:22 pages:7084-7088
Using a training set of diketo-like acid HIV-1 integrase (IN) strand-transfer inhibitors, a 3D pharmacophore model was derived having quantitative predictive ability in terms of activity. The best statistical hypothesis consisted of four features (one hydrophobic aromatic region, two hydrogen-bond acceptors, and one hydrogen-bond donor) with r of 0.96. The resulting pharmacophore model guided the rational design of benzylindoles as new potent IN inhibitors, whose microwave-assisted synthesis and biological evaluation are reported.