Structure-Stability Relationship of NLRP3 Inflammasome-Inhibiting Sulfonylureas.

In recent drug development efforts, particular emphasis has been devoted to the chemical interference with the NLRP3 inflammasome. A series of 12 tailored sulfonylureas was designed, prepared through convergent syntheses with a final sodium hydride-promoted reaction of isocyanates and sulfonamides, and subjected to a systematic, high-performance liquid chromatography-based survey of the chemical stability, a critical issue of sulfonylureas in terms of preparation, storage, and application. NLRP3 binding was determined by surface plasmon resonance spectroscopy. Sulfonylurea was identified to be equipotent and similarly stable compared to the prototypical NLRP3 inhibitor MCC950.

© 2022 The Authors. Published by American Chemical Society.

PMID: 35284735