title: Synthesis and anti-HIV-1 activity of new fluoro-HEPT analogues: an investigation on fluoro versus hydroxy substituents.
abstract: Coupling of 6-benzyl-5-hydroxymethyluracil (1) with formaldehyde acetals followed by fluorination using (diethylamino)sulfur trifluoride (DAST) afforded 1-alkenyloxymethyl and 1-propargyloxymethyl 5-fluoromethyl-6-benzyluracils 3a-c. 6-(3,5-Dimethylbenzyl)-5-ethyl-1-[(2-fluoroethoxy)methyl]pyrimidine-2,4(1H,3H)-dione (6) was synthesized by fluorination of the corresponding hydroxy derivative 5. Sonogoshira reaction was performed on 6-(3,5-dimethylbenzyl)-5-ethyl-1-(4-iodobenzyl)uracil (7) with propargyl alcohol to afford 8 which was fluorinated to give the fluoro propargyl derivative 9. Compound 7 was synthesized by N1-alkylation of the corresponding uracil. Significant activity was found against HIV-1 except for compounds with 5-hydroxymethyl and 5-fluoromethyl substituents.
authors: Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, Odense M, Denmark.
authors: Yasser M
authors: YM
authors: Loksha
authors: Erik B
authors: EB
authors: Pedersen
authors: Roberta
authors: R
authors: Loddo
authors: Paolo
authors: P
authors: La Colla
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005461:Fluorine / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013941:Thymine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; C061818:1-((2-hydroxyethoxy)methyl)-6-(phenylthio)thymine; D005461:Fluorine; D013941:Thymine