1. Imidazolidine-2,4,5- and pirimidine-2,4,6-triones – New primary pharmacophore for soluble epoxide hydrolase inhibitors with enhanced water solubility
- Author
-
Burmistrov, Vladimir, Morisseau, Christophe, D'yachenko, Vladimir, Karlov, Dmitry, Butov, Gennady M, and Hammock, Bruce D
- Subjects
Medicinal and Biomolecular Chemistry ,Chemical Sciences ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Adamantane ,Binding Sites ,Catalytic Domain ,Enzyme Inhibitors ,Epoxide Hydrolases ,Humans ,Imidazolidines ,Inhibitory Concentration 50 ,Molecular Docking Simulation ,Pyrimidines ,Solubility ,Structure-Activity Relationship ,Urea ,Soluble epoxide hydrolase ,Epoxyeicosatrienoic acids ,Inhibitor ,Imidazolidine-2 ,4 ,5-trione ,Pirimidine-2 ,4 ,6-trione ,Organic Chemistry ,Pharmacology and Pharmaceutical Sciences ,Medicinal & Biomolecular Chemistry ,Medicinal and biomolecular chemistry ,Organic chemistry - 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.
- Published
- 2020