Cyclosulfamide-based derivatives as inhibitors of noroviruses

Abstract

An optimization campaign focused on improving pharmacological activity and physicochemical properties of a recently-identified class of cyclosulfamide-based norovirus inhibitors has been carried out. Dimeric compound 4 was found to be a ~10-fold more potent norovirus inhibitor (ED(50) 0.4 µM) compared to the original hit, however, isonipecotic acid ester derivatives 7e and 10a were shown to have superior therapeutic indices.