title: Synthesis and Preliminary Antiviral Activities of Piperidine-substituted Purines against HIV and Influenza A/H1N1 Infections.
abstract: We have developed a series of N(2) -(1-(substituted-aryl)piperidin-4-yl)-N(6) -mesityl-9H-purine-2,6-diamine derivatives as potent antiviral agents. Preliminary biological evaluation indicated that nearly half of them possessed remarkable HIV inhibitory potencies in cellular assays. In particular, FZJ13 appeared to be the most notable one, which displayed anti-HIV-1 activity compared to 3TC. Moreover, an unexpected finding was that FZJ05 displayed significant potency against influenza A/H1N1 (strain A/PR/8/34) in Madin-Darby canine kidney cells with EC50 values much lower than those of ribavirin, amantadine, and rimantadine. The results suggest that these novel purine derivatives have the potential to be further developed as new therapeutic agents against HIV-1 or influenza virus.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Ji'nan, 250012, Shandong, China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Kang
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Ji'nan, 250012, Shandong, China.
authors.forename: Zengjun
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Ji'nan, 250012, Shandong, 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, Ji'nan, 250012, Shandong, China.
authors.forename: Lingzi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Pharmacology, School of Medicine, Shandong University, 44 West Culture Road, Ji'nan, 250012, Shandong, China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Liu
authors.affiliation: K.U.Leuven, Rega Institute for Medical Research, Minderbroedersstraat 10, Leuven, B-3000, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.affiliation: K.U.Leuven, Rega Institute for Medical Research, Minderbroedersstraat 10, Leuven, B-3000, Belgium.
authors.forename: Lieve
authors.initials: L
authors.lastname: Naesens
authors.affiliation: K.U.Leuven, Rega Institute for Medical Research, Minderbroedersstraat 10, Leuven, B-3000, 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, Ji'nan, 250012, Shandong, 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, Ji'nan, 250012, Shandong, China.
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004285:Dogs; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000188:drug therapy*; D061985:Madin Darby Canine Kidney Cells; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011687:Purines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D010880:Piperidines; D011687:Purines
keywords: HIV; NNRTIs; bioactivity; heterocycle; influenza virus; structure-activity relationship; synthesis