Synthesis of 5-alkoxymethyl derivatives of 3'-amino-2',3'-dideoxyuridine and evaluation of their activity against HIV and cancer.

Abstract

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.

• Authors: M S Motawia, A E Abdel-Megied, E B Pedersen, C M Nielsen, P Ebbesen
• Journal: Acta chemica Scandinavica (Copenhagen, Denmark : 1989) (Acta Chem Scand (Cph)) Vol. 46 Issue 1 Pg. 77-81 (Jan 1992) ISSN: 0904-213X [Print] Denmark
• PMID: 1599798 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Antiviral Agents
• Dideoxynucleosides

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Antiviral Agents (chemical synthesis, chemistry, pharmacology)
• Dideoxynucleosides (chemical synthesis, chemistry, pharmacology)
• Drug Evaluation, Preclinical
• HIV-1 (drug effects)
• Humans
• Magnetic Resonance Spectroscopy
• Molecular Structure
• Tumor Cells, Cultured (drug effects)