Imidazolidine-2,4,5- and Pirimidine-2,4,6-triones - New Primary Pharmacophore for Soluble Epoxide Hydrolase Inhibitors with Enhanced Water Solubility

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2019 Dec 25

PMID 31870649

Authors

Vladimir Burmistrov

Christophe Morisseau

Vladimir Dyachenko

Dmitry Karlov

Gennady M Butov

Bruce D Hammock

Affiliations

Soon will be listed here.

Abstract

A series of inhibitors of the soluble epoxide hydrolase (sEH) containing imidazolidine-2,4,5-trione or pirimidine-2,4,6-trione has been synthesized. Inhibition potency of the described compounds ranges from 8.4 μM to 0.4 nM. The tested compounds possess higher water solubility than their preceding ureas. Molecular docking indicates new bond between the triones and the active site of sEH that in part explain the observed potency of the new pharmacophores. While less potent than the corresponding ureas, the modifications of urea group reported herein yield compounds with higher water solubility, thus permitting easier formulation.

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