Synthesis of Carbocyclic 3-Deazaadenosine Analogs as Potential Agents Against Poxvirus

摘要

Our goal has been the development of new agents against the poxvirus models of variola virus, directing our efforts foward new carbocyclic 3- deazaadenosine (CADO) analogs and adenosine N' -oxide analogs. CADO and some of its analogs (such as the 5'-carboxamide congener) had previously been shown to be active against a number of viruses including vaccinia virus. Based upon the knowledge of CADO and the metabolism of nucleosides in general, we targeted three distinct classes of potentially enhanced agents: (1) CADO analogs with selected alterations at C-5'; (2) similar analogs based on 4'-thio-3- deazaadenosine; and (3) CADO prodrugs resulting from 5'-O-acylation. In the term of this project, we were successful in preparing and delivering more CADO and one of our CADO congeners, the 5'-O-benzoate of CADO.