Pharmacophore-Based Design of HIV-1 Integrase Strand-Transfer Inhibitors

摘要

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.