The NLRP3 inflammasome is a high molecular weight structure responsible for sensing and reacting to injury and infection during inflammation. Its activation induces caspase-1 activation and interleukin-1beta (IL-1beta) release, a pro-inflammatory cytokine involved in both acute and chronic inflammatory responses. There is increasing evidence that inappropriate activation of the NLRP3 inflammasome and IL-1beta release is associated with a number of sterile, non-communicable diseases including gout, atherosclerosis, type II diabetes and Alzheimer's disease. Thus the NLRP3 inflammasome is regarded as a therapeutic target for the treatment of sterile inflammation. Medicinal chemistry was used to design and synthesise a library of forty novel boron compounds (termed the NBC series) based on the previously identified NLRP3 inflammasome oxazaborine inhibitors BC7 and BC23. The synthesis of 2,2-diphenyl/diaryl-1,3,2-oxaza/dioxaborines involved the borylation of 1,3-dicarbonyls or beta-enaminone intermediates using diphenyborinic anhydride (DPBA) or mono-/diarylborinic acids. 2,2-Diphenyl-1,3,2-diazaborines were synthesised by reacting oxazaborine BC23 with primary amines. The proposed chelation of two NBC molecules was confirmed using X-ray crystallography. NBC compounds were tested for IL-1beta inhibitory activity in an NLRP3-induced human THP-1 cell line. Structure-activity relationship (SAR) analysis revealed that a boron atom chelated in an oxazaborine ring and the presence of a CCl3 group was essential for IL-1beta inhibitory activity. The most potent compound identified in the series, NBC6, is a specific, irreversible inhibitor of IL-1beta release in THP-1 cells with an IC50 of 0.57 microM, and blocks NLRP3 inflammasome activation in vitro and in vivo. The synthesis of a biotinylated NBC probe for target identification purposes was attempted. A bioorthogonal click chemistry approach using the copper(I)-catalysed azide-alkyne cycloaddition reaction of alkyne NBC21 with a fluorescent azide was successful in BMDM cells. Subsequent chemoproteomic studies using biotin are in progress to elucidate the precise cellular target. Mechanism of action studies suggested that the BC/NBC molecules inhibit by covalent modification, however they were not cysteine modifiers. A hypothesis is that they may inhibit a serine protease and further studies are in progress.