Peptidyl-urea based inhibitors of soluble epoxide hydrolases
Peptidyl-urea based inhibitors of soluble epoxide hydrolases
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DOI：
10.1016/j.bmcl.2006.07.073
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发表时间：
2006-10-15
影响因子：
2.7
通讯作者：
Hammock, Bruce D.
中科院分区：
文献类型：
--
作者：
Morisseau, Christophe;Newman, John W.;Hammock, Bruce D.
我们制备了一系列氨基酸衍生的环己基和金刚烷基脲，并将它们作为人可溶性环氧化物水解酶的抑制剂进行了测试，得到了非常有效的化合物(K-I=15 nM)，它们的可溶性是先前描述的sEH抑制剂的10倍。虽然我们的先导化合物2在狗和大鼠身上的表观生物利用度很低，但这一系列化合物表明sEH抑制剂结构可以接受可能导致更好的口服药物的大基团。(C)2006爱思唯尔有限公司。保留所有权利。
We prepared a series of amino acid derived cyclohexyl and adamantyl ureas and tested them as inhibitors of the human soluble epoxide hydrolase, and obtained very potent compounds (K-I = 15 nM) that are > 10-fold more soluble than previously described sEH inhibitors. While our lead compound 2 showed low apparent bioavailability in dogs and rats, this series of compounds revealed that sEH inhibitor structures could accept large groups that could lead to better orally available drugs. (c) 2006 Elsevier Ltd. All rights reserved.