Luo, Min Groaz, Elisabetta Jonghe, Steven De Snoeck, Robert Andrei, Graciela Herdewijn, Piet Amidate Prodrugs of Cyclic 9‑(<i>S</i>)‑[3-Hydroxy-2-(phosphonomethoxy)propyl]adenine with Potent Anti-Herpesvirus Activity 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. 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 2018-03-16
    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
10.1021/acsmedchemlett.8b00079.s002