title: Arylazolyl(azinyl)thioacetanilides. Part 20: Discovery of novel purinylthioacetanilides derivatives as potent HIV-1 NNRTIs via a structure-based bioisosterism approach.
abstract: By means of structure-based bioisosterism approach, a series of novel purinylthioacetanilide derivatives were designed, synthesized and evaluated as potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Some of the tested compounds were found to be active against wild-type (WT) HIV-1(IIIB) with EC50 in the range of 0.78-4.46μM. Among them, LAD-8 displayed the most potent anti-HIV activity (EC50=0.78μM, SI=24). In addition, LBD-6 showed moderate activity against L100I mutant (EC50=5.64μM) and double mutant strain RES056 (EC50=22.24μM). Preliminary structure-activity relationships (SARs) were discussed in detail. Molecular modeling study was used to predict the optimal conformation in the NNRTI binding site, which may play a guiding role in further rational optimization.
authors: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.
authors: Xueyi
authors: X
authors: Lu
authors: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.
authors: Xiao
authors: X
authors: Li
authors: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.
authors: Jiapei
authors: J
authors: Yang
authors: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.
authors: Boshi
authors: B
authors: Huang
authors: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.
authors: Dongwei
authors: D
authors: Kang
authors: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.
authors: Fabao
authors: F
authors: Zhao
authors: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.
authors: Zhongxia
authors: Z
authors: Zhou
authors: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors: Erik
authors: E
authors: De Clercq
authors: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors: Dirk
authors: D
authors: Daelemans
authors: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Electronic address: Christophe.Pannecouque@rega.kuleuven.be.
authors: Christophe
authors: C
authors: Pannecouque
authors: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China. Electronic address: zhanpeng1982@sdu.edu.cn.
authors: Peng
authors: P
authors: Zhan
authors: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China. Electronic address: xinyongl@sdu.edu.cn.
authors: Xinyong
authors: X
authors: Liu
mesh_terms: D000083:Acetanilides / Q000737:chemistry / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D015497:HIV-1 / Q000187:drug effects*; D008958:Models, Molecular; D066244:Proton Magnetic Resonance Spectroscopy; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D000083:Acetanilides; D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C039632:thioacetanilide
keywords: AIDS; Anti-HIV activity; Bioisosterism; Drug design; HIV-1; NNRTIs; Purinylthioacetanilide