L-valine ester of cyclopropavir: a new antiviral prodrug.
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.
Wu
Zhimeng
Z
Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
Drach
John C
JC
Prichard
Mark N
MN
Yanachkova
Milka
M
Yanachkov
Ivan
I
Bowlin
Terry L
TL
Zemlicka
Jiri
J
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D003521:Cyclopropanes / Q000737:chemistry* / Q000493:pharmacokinetics*; D003587:Cytomegalovirus / Q000187:drug effects; D004952:Esters; D015774:Ganciclovir / Q000031:analogs & derivatives; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D000077562:Valganciclovir; D014633:Valine / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D003521:Cyclopropanes; D004952:Esters; D011355:Prodrugs; D006147:Guanine; C495219:cyclopropavir; D000077562:Valganciclovir; D014633:Valine; D015774:Ganciclovir