Adamantyl thioureas as soluble epoxide hydrolase inhibitors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:28

Article

Burmistrov, Vladimir^1,2,3  Morisseau, Christophe^1,2  Pitushkin, Dmitry³  Karlov, Dmitry^4,5,6  Fayzullin, Robert R.⁷  Butov, Gennady M.³  Hammock, Bruce D.^1,2 

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

[2] Univ Calif Davis, Ctr Comprehens Canc, 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

[7] Russian Acad Sci, Arbuzov Inst Organ & Phys Chem, FRC Kazan Sci Ctr, Kazan 420088, Russia

关键词: Soluble epoxide hydrolase;    Inhibitor;    Adamantane;    Isothiocyanate;    Thiourea;   

DOI  :  10.1016/j.bmcl.2018.05.024

来源: Elsevier

【 摘 要 】

A series of inhibitors of the soluble epoxide hydrolase (sEH) containing one or two thiourea groups has been developed. Inhibition potency of the described compounds ranges from 50 mu M to 7.2 nM. 1,7-(Heptamethylene) bisRadamant-1-yl)thioureal (6f) was found to be the most potent sEH inhibitor, among the thioureas tested. The inhibitory activity of the thioureas against the human sEH is closer to the value of activity against rat sEH rather than murine sEH. While being less active, thioureas are up to 7-fold more soluble than ureas, which makes them more bioavailable and thus promising as sEH inhibitors.

【 授权许可】

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