Synthesis and anti-viral activity of azolo-adamantanes against influenza A virus.
Chemotherapy and chemoprophylaxis of influenza is one of the most important directions of health protection activity. Due to the high rate of drug-resistant strains of influenza virus, there is a need for the search and further development of new potent antivirals against influenza with a broad spectrum of activity. In the present study, a set of di-, tri- and tetrazole derivatives of adamantane was efficiently prepared and their anti-influenza activities evaluated against rimantadine-resistant strain A/Puerto Rico/8/34. In general, derivatives of tetrazole possessed the highest virus-inhibiting activity. We demonstrated that several compounds of this set exhibited much higher activity than the currently used antiviral rimantadine, a compound of related structure. Moreover, we showed that these azolo-adamantanes were significantly less toxic. This study demonstrates that influenza viruses can be inhibited by adamantyl-azoles and thus have potential for developing antiviral agents with an alternate mechanism of action.
Zarubaev
Vladimir V
VV
Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376 St. Petersburg, Russia. zarubaev@influenza.spb.ru
Golod
Efim L
EL
Anfimov
Pavel M
PM
Shtro
Anna A
AA
Saraev
Victor V
VV
Gavrilov
Alexey S
AS
Logvinov
Alexander V
AV
Kiselev
Oleg I
OI
D000218:Adamantane / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001393:Azoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004285:Dogs; D009980:Influenza A virus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D001393:Azoles; D000218:Adamantane