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

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Held F, Guryev A, Fröhlich T, Hampel F, Kahnt A, Hutterer C, Steingruber M, Bahsi H, Von Bojnicic-Kninski C, Mattes DS, Foertsch TC, Nesterov-Mueller A, Marschall M, Tsogoeva S
Zeitschrift: Nature Communications
Jahr der Veröffentlichung: 2017
Band: 8
ISSN: 2041-1723


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 (EC50down 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 (EC50down 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.


FAU-Autoren / FAU-Herausgeber

Fröhlich, Tony
Lehrstuhl für Organische Chemie I
Guryev, Anton
Professur für Organische Chemie
Hampel, Frank Dr.
Lehrstuhl für Organische Chemie I
Held, Felix
Lehrstuhl für Organische Chemie I
Kahnt, Axel Dr.
Lehrstuhl für Physikalische Chemie I
Steingruber, Mirjam
Virologisches Institut - Klinische und Molekulare Virologie
Tsogoeva, Svetlana Prof. Dr.
Professur für Organische Chemie


Autor(en) der externen Einrichtung(en)
Karlsruhe Institute of Technology (KIT)


Zitierweisen

APA:
Held, F., Guryev, A., Fröhlich, T., Hampel, F., Kahnt, A., Hutterer, C.,... Tsogoeva, S. (2017). Facile access to potent antiviral quinazoline heterocycles with fluorescence properties via merging metal-free domino reactions. Nature Communications, 8. https://dx.doi.org/10.1038/ncomms15071

MLA:
Held, Felix, et al. "Facile access to potent antiviral quinazoline heterocycles with fluorescence properties via merging metal-free domino reactions." Nature Communications 8 (2017).

BibTeX: 

Zuletzt aktualisiert 2018-22-10 um 13:23