Discovery of a novel series of inhibitors of human cytomegalovirus primase

Infection by human cytomegalovirus (hCMV) remains a potent threat to susceptible people throughout the world. We have discovered a series of imidazolyl-pyrimidine compounds, which were found to be irreversible inhibitors of the hCMV UL70 primase based on results from radiolabeling and SAR studies. Two promising analogs are described that rival ganciclovir and cidofovir in antiviral potency and possess improved cytotoxicity profiles.

Graphical abstractWe have identified a new series of non-nucleoside inhibitors that are more potent than ganciclovir and cidofovir with a similar toxicity profile. SAR studies suggest that these inhibitors are specific for hCMV primase.Figure optionsDownload full-size imageDownload as PowerPoint slide