4.6 Article

Synthesis and assessment of 4-aminotetrahydroquinazoline derivatives as tick-borne encephalitis virus reproduction inhibitors

Journal

ORGANIC & BIOMOLECULAR CHEMISTRY
Volume 13, Issue 11, Pages 3406-3415

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/c4ob02649g

Keywords

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Funding

  1. Russian Foundation for Basic Research [14-03-00469, 14-03-31566, 13-03-00572, 15-04-08365]
  2. Presidium of RAS [8]

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Tick-borne encephalitis virus (TBEV) belonging to Flavivirus genus causes severe infection in humans. The search for therapeutically relevant compounds targeting TBEV requires the exploration of novel chemotypes. A versatile synthesis of previously unknown 4-aminopyrimidines and 4-aminopyrimidine N-oxides based on a fluorosubstituted heterocyclic core is described. A representative series of 4-aminotetrahydroquinazoline derivatives, containing aliphatic and aromatic substituents as well as the adamantane framework, was obtained and their activity against tick-borne encephalitis virus reproduction was studied. Nine compounds were found to inhibit TBEV entry into the host cells. A bulky hydrophobic adamantyl group was identified to be important for the antiviral activity. The developed synthetic route allowed an easy access to a consistent compound library for further structure-activity relationship studies.

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