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

Vladimir V Burmistrov; Christophe Morisseau; Tatyana K Shkineva; Dmitry V Danilov; Boris Gladkikh; Gennady M Butov; Robert R Fayzullin; Tatyana Ya Dutova; Bruce D Hammock; Igor L Dalinger

doi:10.1016/j.jfluchem.2023.110087

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

J Fluor Chem. 2023 Feb:266:110087. doi: 10.1016/j.jfluchem.2023.110087. Epub 2023 Jan 16.

Affiliations

¹ Department of Entomology and Nematology, and Comprehensive Cancer Center, University of California, Davis, CA, 95616, USA.
² Department of Chemistry, Technology and Equipment of Chemical Industry, Volzhsky Polytechnic Institute (branch) Volgograd State Technical University, 42a Engels Street, Volzhsky, 404121, Russia.
³ N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Lenin Avenue, Moscow 119991, Russia.
⁴ Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, 8 Arbuzov Street, Kazan, 420088, Russia.

Abstract

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.

Keywords: adamantane; halogenated pyrazoles; inhibitor; soluble epoxide hydrolase; urea.

Grants and funding

R35 ES030443/ES/NIEHS NIH HHS/United States