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 |
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| Authors: | Tao Liu Boshi Huang Ye Tian Xin Liang Hong Liu Huiqing Liu Peng Zhan Erik De Clercq Christophe Pannecouque Xinyong Liu |
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| Institution: | 1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China;2. Institute of Pharmacology, School of Medicine, Shandong University, Jinan, Shandong, China;3. Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium |
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| Abstract: | 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. |
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| Keywords: | 1 2 6‐thiadiazine‐1 1‐dione bioactivity drug design HIV‐1 NNRTIs RT synthesis |
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