title: Synthesis and assessment of 4-aminotetrahydroquinazoline derivatives as tick-borne encephalitis virus reproduction inhibitors.
abstract: 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.
authors: Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia. elaver@org.chem.msu.ru.
authors: Kseniya N
authors: KN
authors: Sedenkova
authors: Evgenia V
authors: EV
authors: Dueva
authors: Elena B
authors: EB
authors: Averina
authors: Yuri K
authors: YK
authors: Grishin
authors: Dmitry I
authors: DI
authors: Osolodkin
authors: Liubov I
authors: LI
authors: Kozlovskaya
authors: Vladimir A
authors: VA
authors: Palyulin
authors: Evgenii N
authors: EN
authors: Savelyev
authors: Boris S
authors: BS
authors: Orlinson
authors: Ivan A
authors: IA
authors: Novakov
authors: Gennady M
authors: GM
authors: Butov
authors: Tamara S
authors: TS
authors: Kuznetsova
authors: Galina G
authors: GG
authors: Karganova
authors: Nikolay S
authors: NS
authors: Zefirov
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004669:Encephalitis Viruses, Tick-Borne / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D000998:Antiviral Agents; D011799:Quinazolines