设计、合成及可溶性环氧化物水解酶非尿素抑制剂的评价。
Design, synthesis and evaluation of non-urea inhibitors of soluble epoxide hydrolase.
机构信息
Department of Medicine, Columbia University, 650 W 168th Street, BB 1029, New York, NY 10032, USA.
出版信息
Bioorg Med Chem Lett. 2012 Jan 1;22(1):601-5. doi: 10.1016/j.bmcl.2011.10.074. Epub 2011 Oct 28.
Abstract
Inhibition of soluble epoxide hydrolase (sEH) has been proposed as a new pharmaceutical approach for treating hypertension and vascular inflammation. The most potent sEH inhibitors reported in literature to date are urea derivatives. However, these compounds have limited pharmacokinetic profiles. We investigated non-urea amide derivatives as sEH inhibitors and identified a potent human sEH inhibitor 14-34 having potency comparable to urea-based inhibitors.
摘要
抑制可溶性环氧化物水解酶（sEH）已被提议作为治疗高血压和血管炎症的一种新的药物治疗方法。迄今为止，文献中报道的最有效的 sEH 抑制剂是尿素衍生物。然而，这些化合物的药代动力学特性有限。我们研究了非尿素酰胺衍生物作为 sEH 抑制剂，并鉴定出一种有效的人 sEH 抑制剂 14-34，其效力与基于尿素的抑制剂相当。
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Bioorg Med Chem Lett. 2011 Feb 1;21(3):983-8. doi: 10.1016/j.bmcl.2010.12.042. Epub 2010 Dec 13.
2
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J Med Chem. 2010 Oct 14;53(19):7067-75. doi: 10.1021/jm100691c.
3
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5
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