Advertisement

 

 

Design, Synthesis and Evaluation of Novel Oxazaborine Inhibitors of the NLRP3 Inflammasome.

Design, Synthesis and Evaluation of Novel Oxazaborine Inhibitors of the NLRP3 Inflammasome.
Author Information (click to view)

Baldwin AG, Tapia VS, Swanton T, White CS, Beswick JA, Brough D, Freeman S,


Baldwin AG, Tapia VS, Swanton T, White CS, Beswick JA, Brough D, Freeman S, (click to view)

Baldwin AG, Tapia VS, Swanton T, White CS, Beswick JA, Brough D, Freeman S,

Advertisement

ChemMedChem 2018 01 13() doi 10.1002/cmdc.201700731
Abstract

The NLRP3 inflammasome is an important regulator of the sterile inflammatory response and its activation by host-derived sterile molecules leads to the intracellular activation of caspase-1, processing of the pro-inflammatory cytokines interleukin-1β (IL 1β)/IL-18, and pyroptotic cell death. Inappropriate activation of NLRP3 drives a chronic inflammatory response and is implicated in several non-communicable diseases, including gout, atherosclerosis, type II diabetes and Alzheimer’s disease. In this study, we report the design, synthesis and biological evaluation of novel boron compounds (NBCs) as NLRP3 inflammasome inhibitors. Structure-activity relationships (SAR) show that 4-F groups on the phenyl rings retain NLRP3 inhibitory activity, whereas more steric and lipophilic substituents diminish activity. Loss of inhibitory activity is also observed when the CCl3 group on the oxazaborine ring is replaced by a CF3 group. These findings provide additional understanding of the NBC series and will aid in the development of these NLRP3 inhibitors as tool compounds or therapeutic candidates for sterile inflammatory diseases.

Submit a Comment

Your email address will not be published. Required fields are marked *

thirteen − 10 =

[ HIDE/SHOW ]