PDF(Pubmed)
Abstract：
The inhibition of soluble epoxide hydrolase (sEH) can reduce the level of dihydroxyeicosatrienoic acids (DHETs) effectively maintaining endogenous epoxyeicosatrienoic acids (EETs) levels, resulting in the amelioration of inflammation and pain. Consequently, the development of sEH inhibitors has been a prominent research area for over two decades. In the present study, we synthesized and evaluated sulfonyl urea derivatives for their potential to inhibit sEH. These compounds underwent extensive in vitro investigation, revealing their potency against human and mouse sEH, with 4f showing the most promising sEH inhibitory potential. When subjected to lipopolysaccharide (LPS)-induced acute lung injury (ALI) in studies in mice, compound 4f manifested promising anti-inflammatory efficacy. We investigated the analgesic efficacy of sEH inhibitor 4f in a murine pain model of tail-flick reflex. These results validate the role of sEH inhibition in inflammatory diseases and pave the way for the rational design and optimization of sEH inhibitors based on a sulfonyl urea template.
摘要：
抑制可溶性环氧化物水解酶（sEH）可以降低二羟基二十碳三烯酸（DHET）的水平，有效维持内源性环氧二十碳三烯酸（EET）的水平，导致炎症和疼痛的改善。因此,20多年来,sEH抑制剂的开发一直是一个突出的研究领域。在本研究中,我们合成并评估了磺酰脲衍生物抑制sEH的潜力。这些化合物进行了广泛的体外研究，揭示了它们对人类和小鼠的功效，4f显示最有希望的sEH抑制潜力。当受到脂多糖（LPS）诱导的急性肺损伤（ALI）在小鼠的研究中，化合物4f表现出有希望的抗炎功效。我们研究了sEH抑制剂4f在甩尾反射的小鼠疼痛模型中的镇痛效果。这些结果验证了sEH抑制在炎性疾病中的作用,并为基于磺酰脲模板的sEH抑制剂的合理设计和优化铺平道路。
