Discovery of benzamide derivatives containing urea moiety as soluble epoxide hydrolase inhibitors

•Benzamide derivatives containing urea moiety were designed and synthesized, and the structure–activity relationship was fully explored.•Compound A34 exhibited outstanding inhibitory activity against human sEH, with an IC50 value of 0.04 ± 0.01 nM.•Compound A34 showed moderate systemic drug exposure and oral bioavailability in vivo metabolism studies.•In carrageenan-induced inflammatory pain rat model, compound A34 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib.