Amidate Prodrugs of Cyclic 9‑(<i>S</i>)‑[3-Hydroxy-2-(phosphonomethoxy)propyl]adenine with Potent
Anti-Herpesvirus Activity
Min Luo
Elisabetta Groaz
Steven De Jonghe
Robert Snoeck
Graciela Andrei
Piet Herdewijn
10.1021/acsmedchemlett.8b00079.s002
https://acs.figshare.com/articles/journal_contribution/Amidate_Prodrugs_of_Cyclic_9_i_S_i_3-Hydroxy-2-_phosphonomethoxy_propyl_adenine_with_Potent_Anti-Herpesvirus_Activity/6013775
A series
of amidate prodrugs of cyclic 9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine
(cHPMPA) featuring different amino acid motifs were synthesized. All
phosphonamidates derived from (<i>S</i>)-cHPMPA displayed
a broad spectrum activity against herpesviruses with EC<sub>50</sub> values in the low nanomolar range. A phosphonobisamidate prodrug
of (<i>S</i>)-HPMPA also exhibited a remarkably potent antiviral
activity. In addition, the leucine ester prodrug of (<i>S</i>)-cHPMPA and phosphonobisamidate valine ester prodrug of (<i>S</i>)-HPMPA proved stable in human plasma. These data warrant
further development of cHPMPA prodrugs, especially against human cytomegalovirus
(HCMV), for which there is a high need for treatment in transplant
recipients.
2018-03-16 00:00:00
amidate prodrugs
Amidate Prodrugs
leucine ester prodrug
phosphonobisamidate valine ester prodrug
transplant recipients
phosphonobisamidate prodrug
HCMV
Potent Anti-Herpesvirus Activity
EC 50 values
spectrum activity
acid motifs
cHPMPA prodrugs
nanomolar range
data warrant