Benzoxazolone-5-Urea Derivatives as Human Soluble Epoxide Hydrolase (sEH) Inhibitors.

ABSTRACT: Inhibition of soluble epoxide hydrolase (sEH) is indicated as a new therapeutic modality against a variety of inflammatory diseases, including metabolic, renal, and cardiovascular disorders. In our ongoing research on sEH inhibitors, we synthesized novel benzoxazolone-5-urea analogues with highly potent sEH inhibitory properties inspired by the crystallographic fragment scaffolds incorporating a single H-bond donor/acceptor pair. The tractable SAR results indicated that the aryl or benzyl fragments flanking the benzoxazolone-urea scaffold conferred potent sEH inhibition, and compounds 31-39 inhibited the sEH activity with IC₅₀ values in the range of 0.39-570 nM. Docking studies and molecular dynamics simulations with the most potent analogue 33 provided valuable in

SUBMITTER: Gur Maz T 

PROVIDER: S-EPMC9850727 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature