Merck & Co., Inc., Merck Research Laboratories, Department of Medicinal Chemistry RY800-C114, 126 East Lincoln Avenue, PO Box 2000, Rahway, NJ 07065-0900, USA.
Expert Opin Ther Pat. 2010 Jul;20(7):941-56. doi: 10.1517/13543776.2010.484804.
Soluble epoxide hydrolase (sEH) inhibitors have been shown to effectively increase the levels of epoxyeicosatrienoic acids and reduce the levels of dihydroxyeicosatrienoic acids, which may be translated to therapeutic potentials for multiple disease indications. It has been claimed that sEH inhibitors can be used to treat hypertension, diabetes, stroke, dyslipidemia, pain, immunological disorders, eye diseases, neurological diseases and other indications.
A comprehensive synopsis of patent literature on sEH inhibitors is provided.
A total of more than 100 patent publications describing multiple classes of sEH inhibitors are analyzed. These include amides, ureas, thioamides, thioureas, carbamates, acyl hydrazones, chalcone oxdies, etc. In addition to selected in vitro and in vivo data of representative sEH inhibitors, a wide range of proposed applications of sEH inhibitors are also summarized.
Several sEH inhibitors with potent in vitro and in vivo target inhibition appear promising, including one Phase II clinical candidate. The clinical evaluation will be critical to assess the proclaimed therapeutic utility of sEH inhibition.
已经证明,可溶性环氧化物水解酶 (sEH) 抑制剂能有效地增加环氧二十碳三烯酸的水平并降低二羟二十碳三烯酸的水平,这可能转化为多种疾病适应症的治疗潜力。据称,sEH 抑制剂可用于治疗高血压、糖尿病、中风、血脂异常、疼痛、免疫性疾病、眼部疾病、神经疾病和其他适应症。
提供了 sEH 抑制剂专利文献的全面概述。
分析了总共超过 100 篇描述多种 sEH 抑制剂类别的专利出版物。这些包括酰胺、脲、硫代酰胺、硫代脲、氨基甲酸酯、酰腙、查耳酮氧化物等。除了代表性 sEH 抑制剂的选定体外和体内数据外,还总结了 sEH 抑制剂的广泛应用。
几种具有强大体外和体内靶标抑制作用的 sEH 抑制剂似乎很有前途,其中包括一种处于 II 期临床候选药物。临床评估对于评估 sEH 抑制的宣称治疗效用至关重要。