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

نویسندگان

  • Kseniya N Sedenkova
  • Evgenia V Dueva
  • Elena B Averina
  • Yuri K Grishin
  • Dmitry I Osolodkin
  • Liubov I Kozlovskaya
  • Vladimir A Palyulin
  • Evgenii N Savelyev
  • Boris S Orlinson
  • Ivan A Novakov
  • Gennady M Butov
  • Tamara S Kuznetsova
  • Galina G Karganova
  • Nikolay S Zefirov
چکیده

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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عنوان ژورنال:
  • Organic & biomolecular chemistry

دوره 13 11  شماره 

صفحات  -

تاریخ انتشار 2015