Synthesis and anti-HIV activity of thymidine analogues bearing a 4'-cyanovinyl group and some derivatives thereof.

Abstract

Treatment of 3'-O-tert-butyldimethylsilyl-2',5'-dideoxy-5'-oxothymidine (4) with potassium or magnesium nitromethanide afforded in good yield the resolvable epimeric mixture of the expected blocked nitronucleosides 5 which upon dehydration led to the corresponding E-nitroenofuranosylthymidine 6. Nucleophilic attack of cyanide onto the nitrovinyl group led to a nucleoside analogue bearing a terminal 1-cyanovinyl group (7), a soft electrophilic group which, upon reaction with benzeneselenol, underwent a conjugate addition to the phenylselenonucleoside derivative 9. All these compounds, eventually de-O-silylated, were subject of in vitro biological testing, some exhibiting interesting cytotoxic or antiviral properties.

• Authors: J M Tronchet, I Kovacs, P Dilda, M Seman, G Andrei, R Snoeck, E De Clercq, J Balzarini
• Journal: Nucleosides, nucleotides & nucleic acids (Nucleosides Nucleotides Nucleic Acids) Vol. 20 Issue 12 Pg. 1927-39 (Dec 2001) ISSN: 1525-7770 [Print] United States
• PMID: 11794798 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3'-O-tert-butyldimethylsilyl-2',5'-dideoxy-5'-oxothymidine
• Anti-HIV Agents
• Silanes
• Thymidine

Topics

• Animals
• Anti-HIV Agents (chemical synthesis, pharmacology)
• Biochemistry (methods)
• Cell Division (drug effects)
• Drug Evaluation, Preclinical
• Humans
• Inhibitory Concentration 50
• Mice
• Microbial Sensitivity Tests
• Silanes (chemical synthesis, pharmacology)
• Structure-Activity Relationship
• Thymidine (analogs & derivatives, chemical synthesis, chemistry, pharmacology)
• Tumor Cells, Cultured