Facile access to potent antiviral quinazoline heterocycles with fluorescence properties via merging metal-free domino reactions.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28462939.
- Also identified by DOI 10.1038/ncomms15071 and PMC identifier 5418574.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (EC<sub>50</sub> 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 (EC<sub>50</sub> 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.