Unsymmetrical non-adamantyl N,N-diaryl urea and amide inhibitors of soluble expoxide hydrolase
Unsymmetrical non-adamantyl N,N-diaryl urea and amide inhibitors of soluble expoxide hydrolase
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DOI：
10.1016/j.bmcl.2009.05.102
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发表时间：
2009-08-01
影响因子：
2.7
通讯作者：
Gless, Richard D.
中科院分区：
文献类型：
--
作者：
Anandan, Sampath-Kumar;Webb, Heather K.;Gless, Richard D.
将金刚烷基基团并入原型可溶性二氧化物水解酶（sEH）抑制剂中提供了改善的酶效力。我们探索了用取代的芳基环取代不对称脲和酰胺中的金刚烷基，以鉴定等效且代谢稳定的sEH抑制剂。我们发现，芳基环，特别是在帕拉被强吸电子取代基取代的那些，提供了与醚取代的不对称N，N '-二芳基脲或酰胺支架中的金刚烷基化合物相当的酶IC 50值。(C)2009爱思唯尔有限公司保留所有权利。
Incorporation of an adamantyl group in prototypical soluble expoxide hydrolase (sEH) inhibitors afforded improved enzyme potency. We explored replacement of the adamantyl group in unsymmetrical ureas and amides with substituted aryl rings to identify equipotent and metabolically stable sEH inhibitors. We found that aryl rings, especially those substituted in the para position with a strongly electron withdrawing substituent, afforded enzyme IC50 values comparable to the adamantyl compounds in an ether substituted, unsymmetrical N,N'-diaryl urea or amide scaffold. (C) 2009 Elsevier Ltd. All rights reserved.