NOVEL NON-NUCLEOSIDE HUMAN CYTOMEGALOVIRUS INHIBITORS BASED UPON TSAO NUCLEOSIDE DERIVATIVES:STRUCTURE-ACTIVITY RELATIONSHIPS

Abstract

TSAO derivatives are a unique group of potent and highly specific inhibitors of HIV-1 replica-tion. We have recently reported 4′′-ureido TSAO derivatives that are devoid of anti-HIV-1 activity,but inhibit human cytomegalovirus with an activity comparable to that of Ganciclovir. We hereinreport the synthesis and biological evaluation of novel 4′′-ureido TSAO derivatives in order to evalu-ate the structural features required for anti-HCMV activity. Interestingly, these studies revealed thatthe compounds may inhibit HCMV at the DNA polymerase step via a non-nucleoside mechanism.