Identification of a novel orally bioavailable NLRP3 inflammasome inhibitor.

NLRP3 inflammasome mediated release of interleukin-1β (IL-1β) has been implicated in various diseases, including COVID-19. In this study, rationally designed alkenyl sulfonylurea derivatives were identified as novel, potent and orally bioavailable NLRP3 inhibitors. Compound 7 was found to be potent (IL-1β IC = 35 nM; IL-18 IC = 33 nM) and selective NLRP3 inflammasome inhibitor with excellent pharmacokinetic profile having oral bioavailability of 99% in mice.

Discovery of -Cyano-sulfoximineurea Derivatives as Potent and Orally Bioavailable NLRP3 Inflammasome Inhibitors.

NLRP3 inflammasome mediated release of interleukin-1β (IL-1β) has been implicated in various diseases. In this study, rationally designed mimics of sulfonylurea moiety were investigated as NLRP3 inhibitors. Our results culminated into discovery of series of unprecedented -cyano sulfoximineurea derivatives as potent NLRP3 inflammasome inhibitors.