title: 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.
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.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, Shandong, 250012, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, Shandong, 250012, China.
authors.forename: Boshi
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, Shandong, 250012, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, Shandong, 250012, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, Shandong, 250012, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Pharmacology, School of Medicine, Shandong University, 44 West Culture Road, Jinan, Shandong, 250012, China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, Shandong, 250012, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.affiliation: Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000, Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.affiliation: Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000, Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, Shandong, 250012, China.
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents
keywords: 1,2,6-thiadiazine-1,1-dione; HIV-1; NNRTIs; RT; bioactivity; drug design; synthesis