Synthesis and antiviral activity of 6-deoxycyclopropavir, a new prodrug of cyclopropavir

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• 作者：Chengwei Li^a ; Debra C. Quenelle^b ; Mark N. Prichard^b ; John C. Drach^c ; Jiri Zemlicka^a ; ^{ac6051@wayne.edu}
• 关键词：Methylenecyclopropanes ; Cyclopropavir ; 6-Deoxycyclopropavir ; Antiviral agents ; Xanthine oxidase ; Murine cytomegalovirus ; Human cytomegalovirus
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：15 April, 2012
• 卷：20
• 期：8
• 页码：2669-2674
• 文件大小：394 K

摘要

Synthesis of 6-deoxycyclopropavir (10), a prodrug of cyclopropavir (1) and its in vitro and in vivo antiviral activity is described. 2-Amino-6-chloropurine methylenecyclopropane 13 was transformed to its 6-iodo derivative 14 which was reduced to prodrug 10. It is converted to cyclopropavir (1) by the action of xanthine oxidase and this reaction can also occur in vivo. Compound 10 lacked significant in vitro activity against human cytomegalovirus (HCMV), human herpes virus 1 and 2 (HSV-1 and HSV-2), human immunodeficiency virus type 1 (HIV-1), human hepatitis B virus (HBV), Epstein-Barr virus (EBV), vaccinia virus and cowpox virus. In contrast, prodrug 10 given orally was as active as cyclopropavir (1) reported previously [Kern, E. R.; Bidanset, D. J.; Hartline, C. B.; Yan, Z.; Zemlicka, J.; Quenelle, D. C. et al. Antimicrob. Agents Chemother. 2004, 48, 4745] against murine cytomegalovirus (MCMV) infection in mice and against HCMV in severe combined immunodeficient (SCID) mice.