Based on the hybridization of the privileged fragments in DABO and DAPY-typed HIV-1 NNRTIs, a novel series of 4-aminopiperidinyl-linked 3,5-disubstituted-1,2,6-thiadiazine-1,1-dione derivatives were designed, synthesized, and evaluated for their in vitro anti-HIV activities in MT-4 cells. Most of the target compounds showed weak inhibitory activity against WT HIV-1. In order to confirm the mode of action of the target compounds, representative compounds Ba8 and Bb8 were selected to perform the HIV-1 RT inhibitory assay. In this assay, Ba8 and Bb8 displayed good activity with IC50 values of 3.15 and 1.52 μm, respectively. Additionally, preliminary structure-activity relationships (SARs) analysis and molecular docking studies of newly synthesized compounds are also discussed.
Keywords: 1,2,6-thiadiazine-1,1-dione; HIV-1; NNRTIs; RT; bioactivity; drug design; synthesis.
© 2014 John Wiley & Sons A/S.