Design, Synthesis, and Biological Evaluation of Novel 4-Aminopiperidinyl-linked 3,5-Disubstituted-1,2,6-thiadiazine-1,1-dione Derivatives as HIV-1 NNRTIs

作者：Liu, Tao; Huang, Boshi; Tian, Ye; Liang, Xin; Liu, Hong; Liu, Huiqing; Zhan, Peng^*; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong

来源：Chemical Biology & Drug Design, 2015, 86(1): 887-893.

DOI：10.1111/cbdd.12468

• 1,2,6-thiadiazine-1,1-dione
• bioactivity
• drug design
• HIV-1
• NNRTIs
• RT
• synthesis

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 1.52m, respectively. Additionally, preliminary structure-activity relationships (SARs) analysis and molecular docking studies of newly synthesized compounds are also discussed.

• 出版日期2015-7
• 单位山东大学; 河北医科大学