BACKGROUND: Following the example of L-valine prodrugs of antiviral nucleoside analogues, L-valine ester of cyclopropavir (valcyclopropavir) was synthesized. METHODS: The known tetrahydropyranylcyclopropavir was transformed to N-(tert-butoxycarbonyl)-L-valine ester, which was deprotected to valcyclopropavir. RESULTS: Stability of valcyclopropavir towards hydrolysis at pH 7.0 roughly corresponded to that of valganciclovir. Valcyclopropavir inhibited replication of human cytomegalovirus (HCMV, Towne and AD169 strains) to approximately the same extent as the parent drug cyclopropavir. Pharmacokinetic studies in mice established that the oral bioavailability of valcyclopropavir was 95%. CONCLUSIONS: The prodrug valcyclopropavir offers some improved therapeutic parameters over the parent compound cyclopropavir.
BACKGROUND: Following the example of L-valine prodrugs of antiviralnucleoside analogues, L-valine ester of cyclopropavir (valcyclopropavir) was synthesized. METHODS: The known tetrahydropyranylcyclopropavir was transformed to N-(tert-butoxycarbonyl)-L-valine ester, which was deprotected to valcyclopropavir. RESULTS: Stability of valcyclopropavir towards hydrolysis at pH 7.0 roughly corresponded to that of valganciclovir. Valcyclopropavir inhibited replication of human cytomegalovirus (HCMV, Towne and AD169 strains) to approximately the same extent as the parent drug cyclopropavir. Pharmacokinetic studies in mice established that the oral bioavailability of valcyclopropavir was 95%. CONCLUSIONS: The prodrug valcyclopropavir offers some improved therapeutic parameters over the parent compound cyclopropavir.
Authors: Claire Pierra; Agnès Amador; Samira Benzaria; Erika Cretton-Scott; Marc D'Amours; John Mao; Steven Mathieu; Adel Moussa; Edward G Bridges; David N Standring; Jean-Pierre Sommadossi; Richard Storer; Gilles Gosselin Journal: J Med Chem Date: 2006-11-02 Impact factor: 7.446
Authors: M L Bryant; E G Bridges; L Placidi; A Faraj; A G Loi; C Pierra; D Dukhan; G Gosselin; J L Imbach; B Hernandez; A Juodawlkis; B Tennant; B Korba; P Cote; P Marion; E Cretton-Scott; R F Schinazi; J P Sommadossi Journal: Antimicrob Agents Chemother Date: 2001-01 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: Mark N Prichard; John D Williams; Gloria Komazin-Meredith; Atiyya R Khan; Nathan B Price; Geraldine M Jefferson; Emma A Harden; Caroll B Hartline; Norton P Peet; Terry L Bowlin Journal: Antimicrob Agents Chemother Date: 2013-05-13 Impact factor: 5.191