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 similar to 10-fold more potent norovirus inhibitor (ED50 0.4 mu M) compared to the original hit, however, isonipecotic acid ester derivatives 7e and 10a were shown to have superior therapeutic indices. (C) 2011 Elsevier Masson SAS. All rights reserved.