Adamantyl-ureas with pyrazoles substituted by fluoroalkanes as soluble epoxide hydrolase inhibitors.

A series of soluble epoxide hydrolase (sEH) inhibitors containing halogenated pyrazoles was developed. Inhibition potency of the obtained compounds ranges from 0.8 to 27.5 nM. 1-Adamantyl-3-[(4,5-dichloro-1-methyl-1Н-pyrazol-3-yl)methyl]urea (3f, IC50 = 0.8 nM) and 1-[(Adamantan-1-yl)methyl]-3-[(4,5-dichloro-1-methyl-1Н-pyrazol-3-yl)methyl]urea (4f, IC50 = 1.2 nM) were found to be the most potent sEH inhibitors within the described series.