Synthesis of 5-alkoxymethyl derivatives of 3'-amino-2',3'-dideoxyuridine and evaluation of their activity against HIV and cancer.
5-Alkoxymethyluracils 2a-c have been prepared by acid-catalyzed etherification of 5-hydroxymethyluracil (1). Compounds 1, 2a-c, 5-methoxymethyl- and 5-benzyloxymethyl-uracil were silylated and coupled with 1,5-di-O-acetyl-3-phthalimido-2,3-dideoxy-beta- D-erythro-pentofuranose (3), in the presence of trimethylsilyl triflate as a catalyst, to give the corresponding 3'-phthalimido-2',3'-dideoxynucleosides 5a-f and 6 which on treatment with 33% methylamine-ethanol afforded the corresponding 3'-amino-2',3'-dideoxynucleosides 7a-f and 8 in high yields. Compound 7d showed colony inhibition when tested against human epidermoid cervical cancer cells. Nucleosides 5a-e, 7a-f and 8 did not show any significant activity against HIV-1.
Motawia
M S
MS
Department of Chemistry, Odense University, Denmark.
Abdel-Megied
A E
AE
Pedersen
E B
EB
Nielsen
C M
CM
Ebbesen
P
P
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D015224:Dideoxynucleosides