Synthesis of 6-arylvinyl analogues of the HIV drugs SJ-3366 and Emivirine.
This paper reports the synthesis and the antiviral activities of a series of 6-arylvinyl substituted analogues of SJ-3366, a highly potent agent against HIV. The objective was to investigate whether substitution of the 6-arylketone with a 6-arylvinyl group could lead to an improved antiviral activity against HIV-1. The most active compounds 1-ethoxymethyl, 1-(2-propynyloxymethyl), and 1-(2-methyl-3-phenylallyloxymethyl) substituted 6-[1-(3,5-dimethylphenyl)vinyl]-5-ethyl-1H-pyrimidine-2,4-dione (5b, 16, and 18) showed activities against HIV-1 wild type in the range of Efavirenz, and moderate activities against Y181C and Y181C+K103N mutant strains were also observed.
Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Michael
M
Wamberg
Erik B
EB
Pedersen
Nasser R
NR
El-Brollosy
Claus
C
Nielsen
D019380:Anti-HIV Agents / Q000138:chemical synthesis*; D002461:Cell Line, Transformed; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D020128:Inhibitory Concentration 50; D020125:Mutation, Missense; D011744:Pyrimidinones / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D011744:Pyrimidinones; C425105:SJ3366; D014498:Uracil; C083858:emivirine