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.
Synthesis of 6-deoxycyclopropavir (10), a prodrug of n class="Chemical">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), humanimmunodeficiency 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.
Authors: James R Beadle; Caroll Hartline; Kathy A Aldern; Natalie Rodriguez; Emma Harden; Earl R Kern; Karl Y Hostetler Journal: Antimicrob Agents Chemother Date: 2002-08 Impact factor: 5.191
Authors: Shaoman Zhou; Julie M Breitenbach; Katherine Z Borysko; John C Drach; Earl R Kern; Elizabeth Gullen; Yung-Chi Cheng; Jiri Zemlicka Journal: J Med Chem Date: 2004-01-29 Impact factor: 7.446
Authors: T A Krenitsky; W W Hall; P de Miranda; L M Beauchamp; H J Schaeffer; P D Whiteman Journal: Proc Natl Acad Sci U S A Date: 1984-05 Impact factor: 11.205
Authors: Oliver Manners; James C Murphy; Alex Coleman; David J Hughes; Adrian Whitehouse Journal: Curr Opin Virol Date: 2018-09-28 Impact factor: 7.090