title: Synthesis and anti-HIV activity of 4-(naphthalen-1-yl)-1,2,5-thiadiazol-3-hydroxyl derivatives.
abstract: A series of 4-(naphthalen-1-yl)-1,2,5-thiadiazol-3-hydroxyl derivatives (Ia-Im and IIa-IIe) designed as novel HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) was synthesized via an expeditious route and evaluated for their anti-HIV activities in MT-4 cell cultures. All the synthesized compounds were structurally confirmed by spectral analyses. Biological results showed that three analogues displayed moderate inhibitory activity against wild-type (wt) HIV-1 replication with EC(50) values ranging from 16 to 22 μm. Molecular docking of compound Ih with wt HIV-1 RT was performed to understand the binding mode between these inhibitors and the wt HIV-1 RT and to rationalize some SARs.
authors.affiliation: Department of Medicinal Chemistry and Key Laboratory of Chemical Biology (Educational Ministry of China), School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhuaxi Road, Jinan, 250012, China.
authors.forename: Diwakar
authors.initials: D
authors.lastname: Rai
authors.forename: Wenmin
authors.initials: W
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Xin
authors.initials: X
authors.lastname: Liang
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
mesh_terms: D000494:Allosteric Regulation; D001665:Binding Sites; D002460:Cell Line; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology; D006801:Humans; D062105:Molecular Docking Simulation; D009281:Naphthalenes / Q000737:chemistry; D017434:Protein Structure, Tertiary; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D009281:Naphthalenes; D018894:Reverse Transcriptase Inhibitors; D013830:Thiadiazoles; C031721:naphthalene; D054303:HIV Reverse Transcriptase
keywords: 1,2,5-thiadiazole analogues; HIV reverse transcriptase; NNRTIs; anti-HIV activity; structure-activity relationship