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Discovery of Dihydro‐Alkyloxy‐Benzyl‐Oxopyrimidines as Promising Anti‐Influenza Virus Agents
Author(s) -
Yu Mingyan,
Liu Ailin,
Du Guanhua,
Naesens Lieve,
Vanderlinden Evelien,
De Clercq Erik,
Liu Xinyong
Publication year - 2011
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2011.01180.x
Subject(s) - neuraminidase , virus , virology , influenza a virus , influenzavirus b , chemistry , biology , orthomyxoviridae
A series of novel dihydro‐alkyloxy‐benzyl‐oxopyrimidine derivatives were synthesized and evaluated for their activity against influenza virus in Madin–Darby canine kidney cells. Four dihydro‐alkyloxy‐benzyl‐oxopyrimidine derivatives ( 4a1 , 4a2 , 4a3 , and 4d1 ) showed potent activity against influenza virus. Among them, compound 4a3 was the most promising lead with broad activity against influenza A (antiviral EC 50 values of 9 and 18 μ m for the A/H1N1 and A/H3N2 subtype, respectively) and influenza B viruses (EC 50 : 33 μ m ). The antiviral mechanism of action of these dihydro‐alkyloxy‐benzyl‐oxopyrimidine derivatives must be quite different from that of the currently approved anti‐influenza virus drugs that target the viral M2 or neuraminidase proteins. The dihydro‐alkyloxy‐benzyl‐oxopyrimidine derivatives represent a new avenue for further optimization and development of novel anti‐influenza virus agents.