Design and Synthesis of Novel sEH Inhibitors for the Treatment of Inflammatory Bowel Disease.

ABSTRACT: The treatment of inflammatory bowel disease (IBD) may rely on the comprehensive regulation of immune inflammatory factors to reach a favorable therapeutic effect. In the current study, we discovered a series of sEH inhibitors containing a squaryl sulfonamide scaffold that potently inhibited the primary proinflammatory signaling pathways of NF-κB. Especially, lead compounds A1 and A9 showed potent inhibitory activities against sEH (A1 and A9; hsEH IC₅₀ = 0.1 nM, msEH IC₅₀ = 0.1 nM). The compound A1 had medium pharmacokinetic characteristics in rats. In vivo, A1 showed a strong anti-inflammatory activity in acute enteritis models and decreased the release of various proinflammatory factors, including IL-6 and TNF-α. More

SUBMITTER: Xu H 

PROVIDER: S-EPMC12288763 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature