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  3. Synthesis and biological evaluation of new series of benzamide derivatives containing urea moiety as sEH inhibitors

Synthesis and biological evaluation of new series of benzamide derivatives containing urea moiety as sEH inhibitors

  • Bioorg Med Chem Lett. 2022 Aug 15;70:128805. doi: 10.1016/j.bmcl.2022.128805.
Ye Tian 1,  Shuo Li 2,  Peiyao Yang 1,  Xiaolu Su 2,  Jialu Liu 1,  Xuening Lv 2,  Kuan Dong 1,  Ting Yang 2,  Meibo Duan 1,  Guangda Hu 2,  Hao Yue 1,  Yanping Sun 2,  Yongjun Sun 2,  Huimin Zhang 2,  Zhidian Du 2,  Zhenyu Miao 3,  Minghui Tong 3,  Yunlei Hou 1,  Zibin Gao 4,  Yanfang Zhao 5
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
  • 2 State Key Laboratory Breeding Base-Hebei Province Key Laboratory of Molecular Chemistry for Drug, Hebei University of Science and Technology, Shijiazhuang, PR China.
  • 3 3D BioOptima Co,. Ltd., Suzhou 215104, PR China.
  • 4 State Key Laboratory Breeding Base-Hebei Province Key Laboratory of Molecular Chemistry for Drug, Hebei University of Science and Technology, Shijiazhuang, PR China. Electronic address: [email protected].
  • 5 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: [email protected].
PMID: 35598794 DOI: 10.1016/j.bmcl.2022.128805
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.

Keywords

Benzamide derivatives; In vivo anti-inflammation; SEH inhibitor.

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