HETEROCYCLIC COMPOUNDS AS SELECTIVE INHIBITORS OF HUMAN CYTOMEGALOVIRUS

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This proposal outlines several specific areas for the development of an agent to specifically treat HCMV infections. The target compounds will be elected on the basis of the structure activity relationships which have already been established from current and previous studies in our laboratory. Several areas of research are proposed and the specific aims for the next five years include the following: the synthesis of some polysubstituted benzimidazoles and imidazoles and their corresponding nucleosides and nucleoside analogs based on structure activity relationships derived from structurally related compounds. The synthesize of a few select 5-bromotubercidin and thiosangivamycin analogs is proposed. Synthesis of selected polysubstituted benzimidazole carbamates, unrelated to the above polysubstituted benzimidazoles, using a compound discovered through our very limited screen involving compounds selected at random from our previous synthetic investigations, as our focal point. The in vitro evaluations from Professors Drach, Lopatin and Kern's laboratories will be used to direct the chemical modifications in each new area of potential agents. All of these studies should provide some insights into the modifications which will effect an increase in the selectivity of these compounds against HCMV.