Ureas derived from camphor and fenchone reveal enantiomeric preference of human soluble epoxide hydrolase

The soluble epoxide hydrolase (sEH) is a potential target to treat cardiovascular, renal and neuronal diseases. A series of sEH inhibitors containing naturally occurring lipophilic groups (originating from camphor and fenchone) were developed. Inhibitory potency ranging from 0.7 nM to 6.47 mu M was obtained. It was discovered that ureas derived from t-camphor were more active against sEH (2.3-fold average) than the corresponding analogues derived from mcamphor indicating enantiomeric preference of sEH. Ureas derived from fenchone possess lower activity against sEH (ca. 80-fold on average) than their camphor-derived analogs due to the specific structure of the lipophilic fragment and show less enantiomeric preference (1.75-fold on average). Moreover, fenchonederived ureas show no consistency in enantiomeric preference. Endo/exo-form of compound L-3a derived from t-camphor is 4-fold more potent than the corresponding analogue prepared from mcamphor (IC50 = 0.7 nM vs 2.8 nM) making it the most promising sEH inhibitor among the tested series.

Automated summary

The study found that ureas derived from t-camphor exhibited higher activity against sEH, while ureas derived from fenchone showed lower activity. The compound L-3a derived from t-camphor showed greater potency in inhibiting sEH compared to its counterpart derived from m-camphor.