Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2018-05-23 , DOI: 10.1016/j.bmcl.2018.05.024 Vladimir Burmistrov 1 , Christophe Morisseau 2 , Dmitry Pitushkin 3 , Dmitry Karlov 4 , Robert R Fayzullin 5 , Gennady M Butov 3 , Bruce D Hammock 2
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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 μM to 7.2 nM. 1,7-(Heptamethylene)bis[(adamant-1-yl)thiourea] (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.
中文翻译：
金刚烷基硫脲作为可溶性环氧化物水解酶抑制剂
一系列含有一个或两个硫脲基团的可溶性环氧化物水解酶（sEH）抑制剂已被开发出来。所述化合物的抑制效力范围为 50 μM 至 7.2 nM。 1,7-(庚亚甲基)双[(金刚-1-基)硫脲] ( 6f ) 被发现是所测试的硫脲中最有效的 sEH 抑制剂。硫脲对人sEH的抑制活性更接近对大鼠sEH的活性值，而不是对鼠sEH的活性值。虽然硫脲的活性较低，但其溶解度比尿素高 7 倍，这使得它们的生物利用度更高，因此有望作为 sEH 抑制剂。
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