Imidazolidine-2,4,5-and pirimidine-2,4,6-triones - New primary pharmacophore for soluble epoxide hydrolase inhibitors with enhanced water solubility

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:30

Article

Burmistrov, Vladimir^1,2,3  Morisseau, Christophe^1,2  D'yachenko, Vladimir³  Karlov, Dmitry^4,5,6  Butov, Gennady M.³  Hammock, Bruce D.^1,2 

[1] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA

[2] Univ Calif Davis, Comprehens Canc Ctr, Davis, CA 95616 USA

[3] Volgograd State Tech Univ, Dept Chem Technol & Equipment Chem Ind, Volzhsky Polytech Inst Branch, Volzhsky 404121, Russia

[4] Skolkovo Innovat Ctr, Skolkovo Inst Sci & Technol, Moscow 143026, Russia

[5] Lomonosov Moscow State Univ, Dept Chem, Moscow 119991, Russia

[6] Russian Acad Sci, Inst Physiol Act Cpds, Chernogolovka 142432, Moscow Region, Russia

关键词: Soluble epoxide hydrolase;    Epoxyeicosatrienoic acids;    Inhibitor;    Adamantane;    Urea;    Imidazolidine-2,4,5-trione;    Pirimidine-2,4,6-trione;   

DOI  :  10.1016/j.bmcl.2019.126908

来源: Elsevier

【 摘 要 】

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 mu M 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.

【 授权许可】

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