Design, Synthesis, and Pharmacological Characterization of a Potent Soluble Epoxide Hydrolase Inhibitor for the Treatment of Acute Pancreatitis.

Acute pancreatitis (AP) is a potentially life-threatening illness characterized by an exacerbated inflammatory response with limited options for pharmacological treatment. Here, we describe the rational development of a library of soluble epoxide hydrolase (sEH) inhibitors for the treatment of AP. Synthesized compounds were screened for their sEH inhibitory potency and selectivity, and the results were rationalized by means of molecular modeling studies. The most potent compounds were studied for their pharmacokinetic profile, where compound emerged as a promising lead. In fact, compound demonstrated a remarkable efficacy in reducing the inflammatory damage in cerulein-induced AP in mice. Targeted metabololipidomic analysis further substantiated sEH inhibition as a molecular mechanism of the compound underlying anti-AP activity . Finally, pharmacokinetic assessment demonstrated a suitable profile of . Collectively, compound displays strong effectiveness as sEH inhibitor with potential for pharmacological AP treatment.