title: Arylazolyl(azinyl)thioacetanilides. Part 10: design, synthesis and biological evaluation of novel substituted imidazopyridinylthioacetanilides as potent HIV-1 inhibitors.
abstract: In continuation of our efforts toward the discovery of potent HIV-1 NNRTIs with novel structures, we have employed a scaffold hopping strategy to explore the chemically diversed space of bioactive compounds. The original arylazolylthioacetanilide platform was replaced with different imidazopyridinylthioacetanilide scaffolds to yield the optimal pharmacophore moieties in order to generate novel NNRTIs with desirable potency. Some of the new compounds proved able to inhibit HIV-1 replication in the low micromolar range. In particular, compound 5b16 displayed the most potent anti-HIV-1 activity (EC(50) = 0.21 ± 0.06 μM), inhibiting HIV-1 IIIB replication in MT-4 cells more effectively than dideoxycytidine (EC(50) = 1.4 ± 0.1 μM) and similarly with nevirapine (EC(50) = 0.20 ± 0.10 μM). Preliminary structure-activity relationship (SAR) of the newly synthesized congeners is discussed, and molecular modeling study is performed to rationalize the SAR conclusions.
authors.affiliation: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012 Jinan, Shandong, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Dongyue
authors.initials: D
authors.lastname: Li
authors.forename: Liu
authors.initials: L
authors.lastname: Wang
authors.forename: Xuwang
authors.initials: X
authors.lastname: Chen
authors.forename: Huiqing
authors.initials: H
authors.lastname: Liu
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
mesh_terms: D000083:Acetanilides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000083:Acetanilides; D019380:Anti-HIV Agents; D007093:Imidazoles; C039632:thioacetanilide