title: Arylazolyl(azinyl)thioacetanilides: Part 19: Discovery of Novel Substituted Imidazo[4,5-b]pyridin-2-ylthioacetanilides as Potent HIV NNRTIs Via a Structure-based Bioisosterism Approach.
abstract: With the continuation of our unremitting efforts toward the discovery of potent HIV-1 NNRTIs, a series of novel imidazo[4,5-b]pyridin-2-ylthioacetanilides were designed, synthesized, and evaluated for their antiviral activities through combining bioisosteric replacement and structure-based drug design. Almost all of the title compounds displayed moderate to good activities against wild-type (wt) HIV-1 strain with EC50 values ranging from 0.059 to 1.41 μm in a cell-based antiviral assay. Thereinto, compounds 12 and 13 were the most active two analogues possessing an EC50 value of 0.059 and 0.073 μm against wt HIV-1, respectively, which was much more effective than the control drug nevirapine (EC50 = 0.26 μm) and comparable to delavirdine (EC50 = 0.038 μm). In addition, one selected compound showed a remarkable reverse transcriptase inhibitory activity compared to nevirapine and etravirine. In the end of this manuscript, preliminary structure-activity relationships (SARs) and molecular modeling studies were detailedly discussed, which may provide valuable insights for further optimization.
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: Xiao
authors.initials: X
authors.lastname: Li
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: Zhongxia
authors.initials: Z
authors.lastname: Zhou
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: Ping
authors.initials: P
authors.lastname: Gao
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000, Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000, Leuven, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Daelemans
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000, Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
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: 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: D000083:Acetanilides / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000737:chemistry*; D055808:Drug Discovery; D007093:Imidazoles / Q000737:chemistry*; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry*
chemical_list: D000083:Acetanilides; D019380:Anti-HIV Agents; D007093:Imidazoles; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; C039632:thioacetanilide
keywords: HIV; NNRTIs; SAR; antiviral activity; drug design; imidazo[4,5-b]pyridin-2-ylthioacetanilides; molecular modeling