Anandan Sampath-Kumar, Do Zung N, Webb Heather K, Patel Dinesh V, Gless Richard D
Arête Therapeutics, Inc., 3912 Trust Way, Hayward, CA 94545, USA.
Bioorg Med Chem Lett. 2009 Feb 15;19(4):1066-70. doi: 10.1016/j.bmcl.2009.01.013. Epub 2009 Jan 10.
Inhibition of soluble epoxide hydrolase has been proposed as a promising new pharmaceutical target for diseases involving hypertension and vascular inflammation. The most potent sEH inhibitors reported to date contain a urea or amide moiety as the central or 'primary' pharmacophore. We evaluated replacing the urea pharmacophore with other functional groups such as thiourea, sulfonamide, sulfonylurea, aminomethylene amide, hydroxyamide, and ketoamide to identify novel and potent inhibitors. The hydroxyamide moiety was identified as a novel pharmacophore affording potency comparable to urea.
可溶性环氧化物水解酶的抑制作用已被提出作为涉及高血压和血管炎症疾病的一个有前景的新药物靶点。迄今为止报道的最有效的可溶性环氧化物水解酶抑制剂含有脲或酰胺部分作为中心或“主要”药效基团。我们评估了用其他官能团如硫脲、磺酰胺、磺酰脲、氨基亚甲基酰胺、羟基酰胺和酮酰胺取代脲药效基团，以鉴定新型强效抑制剂。羟基酰胺部分被鉴定为一种新型药效基团，其效力与脲相当。
