Synthesis of new 2'-deoxy-2'-fluoro-4'-azido nucleoside analogues as potent anti-HIV agents. 2011

Qiang Wang, and Weidong Hu, and Shuyang Wang, and Zhenliang Pan, and Le Tao, and Xiaohe Guo, and Keduo Qian, and Chin-Ho Chen, and Kuo-Hsiung Lee, and Junbiao Chang
Department of Chemistry, Zhengzhou University, Zhengzhou 450001, PR China.

We prepared 1-(4'-azido-2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)cytosine (10) and its hydrochloride salt (11) as potential antiviral agents based on the favorable antiviral profiles of 4'-substituted nucleosides. Compounds 10 and 11 were synthesized from 1,3,5-O-tribenzoyl-2-deoxy-2-fluoro-D-arabinofuranoside in multiple steps, and their structures were unequivocally established by IR, (1)H NMR, (13)C NMR, and (19)F NMR spectroscopy, HRMS, and X-ray crystallography. Compounds 10 and 11 exhibited potent anti-HIV-1 activity (EC(50): 0.3 and 0.13 nM, respectively) without significant cytotoxicity in concentrations up to 100 μM. Compound 11 exhibited extremely potent anti-HIV activity against NL4-3 (wild-type), NL4-3 (K101E), and RTMDR viral strains, with EC(50) values of 0.086, 0.15, and 0.11 nM, respectively. Due to the high potency of 11, it was also screened against an NIH Reagent Program NRTI-resistant virus panel containing eleven mutated viral strains and for cytotoxicity against six different human cell lines. The results of this screening indicated that 11 is a novel NRTI that could be developed as an anti-AIDS clinical trial candidate to overcome drug-resistance issues.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D009705 Nucleosides Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed) Nucleoside,Nucleoside Analog,Nucleoside Analogs,Analog, Nucleoside,Analogs, Nucleoside
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003561 Cytarabine A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472) Ara-C,Arabinofuranosylcytosine,Arabinosylcytosine,Cytosine Arabinoside,Aracytidine,Aracytine,Cytarabine Hydrochloride,Cytonal,Cytosar,Cytosar-U,beta-Ara C,Ara C,Arabinoside, Cytosine,Cytosar U,beta Ara C
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013055 Spectrophotometry, Infrared Spectrophotometry in the infrared region, usually for the purpose of chemical analysis through measurement of absorption spectra associated with rotational and vibrational energy levels of molecules. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) IR Spectra,Infrared Spectrophotometry,IR Spectras,Spectra, IR
D013058 Mass Spectrometry An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers. Mass Spectroscopy,Spectrometry, Mass,Spectroscopy, Mass,Spectrum Analysis, Mass,Analysis, Mass Spectrum,Mass Spectrum Analysis,Analyses, Mass Spectrum,Mass Spectrum Analyses,Spectrum Analyses, Mass
D018360 Crystallography, X-Ray The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) X-Ray Crystallography,Crystallography, X Ray,Crystallography, Xray,X Ray Crystallography,Xray Crystallography,Crystallographies, X Ray,X Ray Crystallographies
D019380 Anti-HIV Agents Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS. AIDS Drug,AIDS Drugs,Anti-AIDS Agents,Anti-AIDS Drug,Anti-HIV Agent,Anti-HIV Drug,Anti-AIDS Drugs,Anti-HIV Drugs,Agent, Anti-HIV,Agents, Anti-AIDS,Agents, Anti-HIV,Anti AIDS Agents,Anti AIDS Drug,Anti AIDS Drugs,Anti HIV Agent,Anti HIV Agents,Anti HIV Drug,Anti HIV Drugs,Drug, AIDS,Drug, Anti-AIDS,Drug, Anti-HIV,Drugs, AIDS,Drugs, Anti-AIDS,Drugs, Anti-HIV

Related Publications

Qiang Wang, and Weidong Hu, and Shuyang Wang, and Zhenliang Pan, and Le Tao, and Xiaohe Guo, and Keduo Qian, and Chin-Ho Chen, and Kuo-Hsiung Lee, and Junbiao Chang
January 2018, European journal of medicinal chemistry,
Qiang Wang, and Weidong Hu, and Shuyang Wang, and Zhenliang Pan, and Le Tao, and Xiaohe Guo, and Keduo Qian, and Chin-Ho Chen, and Kuo-Hsiung Lee, and Junbiao Chang
August 2015, European journal of medicinal chemistry,
Qiang Wang, and Weidong Hu, and Shuyang Wang, and Zhenliang Pan, and Le Tao, and Xiaohe Guo, and Keduo Qian, and Chin-Ho Chen, and Kuo-Hsiung Lee, and Junbiao Chang
March 2010, Nucleosides, nucleotides & nucleic acids,
Qiang Wang, and Weidong Hu, and Shuyang Wang, and Zhenliang Pan, and Le Tao, and Xiaohe Guo, and Keduo Qian, and Chin-Ho Chen, and Kuo-Hsiung Lee, and Junbiao Chang
July 2010, Bioorganic & medicinal chemistry letters,
Qiang Wang, and Weidong Hu, and Shuyang Wang, and Zhenliang Pan, and Le Tao, and Xiaohe Guo, and Keduo Qian, and Chin-Ho Chen, and Kuo-Hsiung Lee, and Junbiao Chang
March 2020, Molecules (Basel, Switzerland),
Qiang Wang, and Weidong Hu, and Shuyang Wang, and Zhenliang Pan, and Le Tao, and Xiaohe Guo, and Keduo Qian, and Chin-Ho Chen, and Kuo-Hsiung Lee, and Junbiao Chang
January 2015, Nucleosides, nucleotides & nucleic acids,
Qiang Wang, and Weidong Hu, and Shuyang Wang, and Zhenliang Pan, and Le Tao, and Xiaohe Guo, and Keduo Qian, and Chin-Ho Chen, and Kuo-Hsiung Lee, and Junbiao Chang
May 2013, European journal of medicinal chemistry,
Qiang Wang, and Weidong Hu, and Shuyang Wang, and Zhenliang Pan, and Le Tao, and Xiaohe Guo, and Keduo Qian, and Chin-Ho Chen, and Kuo-Hsiung Lee, and Junbiao Chang
October 2009, Archiv der Pharmazie,
Qiang Wang, and Weidong Hu, and Shuyang Wang, and Zhenliang Pan, and Le Tao, and Xiaohe Guo, and Keduo Qian, and Chin-Ho Chen, and Kuo-Hsiung Lee, and Junbiao Chang
April 2018, European journal of medicinal chemistry,
Qiang Wang, and Weidong Hu, and Shuyang Wang, and Zhenliang Pan, and Le Tao, and Xiaohe Guo, and Keduo Qian, and Chin-Ho Chen, and Kuo-Hsiung Lee, and Junbiao Chang
June 2019, Bioorganic & medicinal chemistry letters,
Copied contents to your clipboard!