Synthesis and biological activity of 5-(2,2-difluorovinyl)-2'-deoxyuridine

• Published in: Journal of medicinal chemistry Vol. 30; no. 8; pp. 1494 - 1497
• Main Authors: Bobek, M, Kavai, I, De Clercq, E
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.08.1987
• Subjects: Animals; Carbohydrates. Nucleosides and nucleotides; Cell Line; Chemical Phenomena; Chemistry; Deoxyuridine - analogs & derivatives; Deoxyuridine - chemical synthesis; Deoxyuridine - pharmacology; Deoxyuridine - therapeutic use; Exact sciences and technology; Herpes Simplex - drug therapy; Humans; Mice; Neoplasms, Experimental - drug therapy; Nucleosides, nucleotides and oligonucleotides; Organic chemistry; Preparations and properties; Rabbits; Simplexvirus - drug effects; Structure-Activity Relationship; Vaccinia virus - drug effects; Viruses - drug effects; Virus; α-Herpesvirinae; Herpesvirus hominis 1; Herpesviridae; Antiviral; Ureas; Deoxyribonucleoside; NMR spectrum; Pyrimidine nucleoside; Biological activity
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00391a036

5-(2,2-Difluorovinyl)uracil (IV) was synthesized from 2,4-dimethoxy-5-bromopyrimidine by sequential formylation, difluoromethylenation, and removal of the 2- and 4-methyl groups. Condensation of the trimethylsilyl derivative of IV with protected D-erythro-pentofuranosyl chloride followed by separation of anomers and deblocking gave 5-(2,2-difluorovinyl)-2'-deoxyuridine (V). Compound V was active against herpes simplex virus type 1 (HSV-1) infection as well as tumor cells transformed by the HSV-1 thymidine kinase gene.