Synthesis and biological evaluation of new series of benzamide derivatives containing urea moiety as sEH inhibitors. (15th August 2022)

• Record Type: Journal Article
• Authors: Tian, Ye; Li, Shuo; Yang, Peiyao; Su, Xiaolu; Liu, Jialu; Lv, Xuening; Dong, Kuan; Yang, Ting; Duan, Meibo; Hu, Guangda; Yue, Hao; Sun, Yanping; Sun, Yongjun; Zhang, Huimin; Du, Zhidian; Miao, Zhenyu; Tong, Minghui; Hou, Yunlei; Gao, Zibin; Zhao, Yanfang
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 70(2022)
• Publication Date: 2022-08-15
• Subjects: SEH inhibitor -- Benzamide derivatives -- In vivo anti-inflammation; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2022.128805
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: Benzamide derivatives containing urea moiety were designed and synthesized, and the SAR was explored. Compound B15 exhibited outstanding inhibitory activity against human sEH, with an IC50 value of 0.03 ± 0.01 nM. Compound B15 showed satisfactory metabolic stability in human liver microsomes with a half-time of 197 min. Compound B15 exhibited a better anti-inflammatory and analgesic effect compared to t -AUCB and Celecoxib. Abstract: The pharmacological inhibition of soluble epoxide hydrolase (sEH) was shown to reduce inflammation and pain. Herein, we described a series of newly synthesized sEH inhibitors with the trident-shaped skeleton. Intensive structural modifications led to the identification of compound B15 as a potent sEH inhibitor with an IC50 value of 0.03 ± 0.01 nM. Furthermore, compound B15 showed satisfactory metabolic stability in human liver microsomes with a half-time of 197 min. In carrageenan-induced inflammatory pain rat model, compound B15 exhibited a better therapeutic effect compared to t -AUCB and Celecoxib, which demonstrated the proof of potential as anti-inflammatory agents for pain relief.