title: Discovery of dihydro-alkyloxy-benzyl-oxopyrimidines as promising anti-influenza virus agents.
abstract: 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 μm for the A/H1N1 and A/H3N2 subtype, respectively) and influenza B viruses (EC(50) : 33 μm). 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.
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhuaxi Road, Jinan 250012, China.
authors.forename: Mingyan
authors.initials: M
authors.lastname: Yu
authors.forename: Ailin
authors.initials: A
authors.lastname: Liu
authors.forename: Guanhua
authors.initials: G
authors.lastname: Du
authors.forename: Lieve
authors.initials: L
authors.lastname: Naesens
authors.forename: Evelien
authors.initials: E
authors.lastname: Vanderlinden
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D004285:Dogs; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects; D009980:Influenza A virus / Q000187:drug effects*; D009981:Influenza B virus / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy; D009976:Orthomyxoviridae Infections / Q000188:drug therapy*; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D011743:Pyrimidines