Synthesis and anti-HIV-1 activity of 1-substiuted 6-(3-cyanobenzoyl) and [(3-cyanophenyl)fluoromethyl]-5-ethyl-uracils.
1-Substiuted 6-(3-cyanobenzoyl) and [(3-cyanophenyl)fluoromethyl]-5-ethyl-uracils were synthesized and evaluated in cell-based assays against HIV-1 wild-type and its clinically relevant non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutants. Some of the synthesized compounds showed activity against HIV-1 wild-type in the same range as Emivirine (MKC-442). 3-{[3-(Allyloxymethyl)-5-ethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl]fluoromethyl}-benzonitrile 11b showed moderate activity against the Y181C HIV-1 mutant strain.
Loksha
Yasser M
YM
Nucleic Acid Centre, Department of Physics and Chemistry, University of Southern Denmark, Odense M, Denmark.
Pedersen
Erik B
EB
Loddo
Roberta
R
La Colla
Paolo
P
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004048:Diethylamines; D004353:Drug Evaluation, Preclinical; D024882:Drug Resistance, Viral / Q000235:genetics; D005461:Fluorine; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D015394:Molecular Structure; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D014498:Uracil / Q000031:analogs & derivatives* / Q000494:pharmacology
D019380:Anti-HIV Agents; D004048:Diethylamines; D018894:Reverse Transcriptase Inhibitors; D005461:Fluorine; D014498:Uracil; C040394:diethylaminosulfur trifluoride; D054303:HIV Reverse Transcriptase; C083858:emivirine