Synthesis and antiviral activity of C-5 substituted analogues of d4T bearing methylamino- or methyldiamino-linker arms.
A general strategy is reported for the preparation of C-5-methylamino- or methyldiamino-d4T analogues of "different sizes". Reactions of the 2',3'-didehydro-2',3'-dideoxy-C-5 hydroxymethyl precursor (7) with either polymethylene diamines (n = 6, 8, 10 and 12) or propargylamine proceed regioselectively via substitution reactions at the C-5 position of uracil. The compounds were evaluated for antiviral activity and cytotoxicity. No significant activity was observed for compounds 9, 11, and 13, but 10 and 12 exhibited a weak activity against HIV-1.
Gavriliu
D
D
Centre d'Etudes et de Recherche sur le Médicament de Normandie U.F.R. des Sciences Pharmaceutiques, Caen, France.
Fossey
C
C
Fontaine
G
G
Benzaria
S
S
Ciurea
A
A
Delbederi
Z
Z
Lelong
B
B
Ladurée
D
D
Aubertin
A M
AM
Kirn
A
A
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line / Q000187:drug effects; D002478:Cells, Cultured; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D018119:Stavudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D019380:Anti-HIV Agents; D018119:Stavudine; D012194:RNA-Directed DNA Polymerase