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Facile access to potent antiviral quinazoline heterocycles with fluorescence properties via merging metal-free domino reactions

Author

Listed:
  • Felix E. Held

    (Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials, Friedrich-Alexander University of Erlangen-Nürnberg)

  • Anton A. Guryev

    (Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials, Friedrich-Alexander University of Erlangen-Nürnberg)

  • Tony Fröhlich

    (Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials, Friedrich-Alexander University of Erlangen-Nürnberg)

  • Frank Hampel

    (Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials, Friedrich-Alexander University of Erlangen-Nürnberg)

  • Axel Kahnt

    (Physical Chemistry Chair I, Friedrich-Alexander University of Erlangen-Nürnberg)

  • Corina Hutterer

    (Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-Nürnberg)

  • Mirjam Steingruber

    (Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-Nürnberg)

  • Hanife Bahsi

    (Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-Nürnberg)

  • Clemens von Bojničić-Kninski

    (Karlsruhe Institute of Technology, Institute of Microstructure Technology)

  • Daniela S. Mattes

    (Karlsruhe Institute of Technology, Institute of Microstructure Technology)

  • Tobias C. Foertsch

    (Karlsruhe Institute of Technology, Institute of Microstructure Technology)

  • Alexander Nesterov-Mueller

    (Karlsruhe Institute of Technology, Institute of Microstructure Technology)

  • Manfred Marschall

    (Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-Nürnberg)

  • Svetlana B. Tsogoeva

    (Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials, Friedrich-Alexander University of Erlangen-Nürnberg)

Abstract

Most of the known approved drugs comprise functionalized heterocyclic compounds as subunits. Among them, non-fluorescent quinazolines with four different substitution patterns are found in a variety of clinically used pharmaceuticals, while 4,5,7,8-substituted quinazolines and those displaying their own specific fluorescence, favourable for cellular uptake visualization, have not been described so far. Here we report the development of a one-pot synthetic strategy to access these 4,5,7,8-substituted quinazolines, which are fluorescent and feature strong antiviral properties (EC50 down to 0.6±0.1 μM) against human cytomegalovirus (HCMV). Merging multistep domino processes in one-pot under fully metal-free conditions leads to sustainable, maximum efficient and high-yielding organic synthesis. Furthermore, generation of artesunic acid–quinazoline hybrids and their application against HCMV (EC50 down to 0.1±0.0 μM) is demonstrated. Fluorescence of new antiviral hybrids and quinazolines has potential applications in molecular imaging in drug development and mechanistic studies, avoiding requirement of linkage to external fluorescent markers.

Suggested Citation

  • Felix E. Held & Anton A. Guryev & Tony Fröhlich & Frank Hampel & Axel Kahnt & Corina Hutterer & Mirjam Steingruber & Hanife Bahsi & Clemens von Bojničić-Kninski & Daniela S. Mattes & Tobias C. Foertsc, 2017. "Facile access to potent antiviral quinazoline heterocycles with fluorescence properties via merging metal-free domino reactions," Nature Communications, Nature, vol. 8(1), pages 1-9, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15071
    DOI: 10.1038/ncomms15071
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