Cyclosulfamide-based derivatives as inhibitors of noroviruses

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 (ED50 0.4 μM) compared to the original hit, however, isonipecotic acid ester derivatives 7e and 10a were shown to have superior therapeutic indices.

An optimization campaign focused on improving pharmacological activity and physicochemical properties of a new class of norovirus inhibitors has been conducted. The dimeric compound 7 was found to be ∼10-fold more potent norovirus inhibitor compared to the original hit.Figure optionsDownload as PowerPoint slideHighlights
► Class of cyclosulfamide-based norovirus inhibitors was further optimized.
► Antiviral effects were exampled in a cell-based system for norovirus replication.
► A dimeric compound was found to be highly potent norovirus inhibitor.
► Isonipecotic acid ester derivatives were shown to have superior therapeutic indices.