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[1]刘思思,周 媛,付瑞新,等.五氟硫基脲衍生物的合成及其对人可溶性环氧化物水解酶的抑制活性[J].武汉工程大学学报,2025,47(05):473-479.[doi:10.19843/j.cnki.CN42-1779/TQ.202309014]
　LIU Sisi,ZHOU Yuan,FU Ruixin,et al.Synthesis of pentafluorosulfanyl urea derivatives and their inhibitory activity on human soluble epoxide hydrolase[J].Journal of Wuhan Institute of Technology,2025,47(05):473-479.[doi:10.19843/j.cnki.CN42-1779/TQ.202309014]
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五氟硫基脲衍生物的合成及其对人可溶性环氧化物水解酶的抑制活性
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《武汉工程大学学报》[ISSN:1674-2869/CN:42-1779/TQ]

卷:
47
期数:
2025年05期
页码:
473-479
栏目:
现代大化工
出版日期:
2025-10-31

文章信息/Info

Title:
Synthesis of pentafluorosulfanyl urea derivatives and their inhibitory activity on human soluble epoxide hydrolase
文章编号:
1674 - 2869（2025）05 - 0473- 07
作者:
1. 武汉工程大学化学与环境工程学院,湖北 武汉 430205；
2. 武汉熙瑞医药科技有限公司, 湖北 武汉 437000；
3. 武汉伯瑞恒医药科技有限公司， 湖北 武汉 437000

Author(s):
1. School of Chemistry and Environmental Engineering，Wuhan Institute of Technology，Wuhan 430205，China；
2. Wuhan Xirui Pharmaceutical Technology Co. Ltd., Wuhan 437000，China；
3. Wuhan Bo Ruiheng Pharmaceutical Technology Co. Ltd., Wuhan 437000，China

关键词:
Keywords:
分类号:
TQ463
DOI:
10.19843/j.cnki.CN42-1779/TQ.202309014
文献标志码:
A
摘要:
以4-五氟硫基苯胺和三光气为原料，经异氰酸酯合成、亲核加成、N-酰胺缩合和烷基化等反应，合成了7个新的含五氟硫基苯基的双取代脲衍生物。对人可溶性环氧化物水解酶（hsEH）抑制活性测试结果表明：1-(4-五氟硫基苯基)-3-(1-(3,3,3-三氟丙基)哌啶-4-基)脲的抑制活性弱于对照物(S)-1-(1-(2-甲基丁酰基)哌啶-4-基)-3-(4-(三氟甲氧基)苯基)脲，其他6个脲衍生物的抑制能力均强于对照物，其中，(S)-1-(1-(2-甲基丁酰基)哌啶-4-基)-3-(4-(五氟硫基)苯基)脲的抑制活性最强，在2 μg/mL质量浓度下的hsEH IC50为2.4 nmol/L。构效关系表明，目标分子中五氟硫基的引入和哌啶环上N-取代基团的水溶性对hsEH的抑制活性有较大影响。
Abstract:
Seven new bis-substituted urea derivatives containing pentafluorothiophenyl groups were synthesized from 4-(pentafluorosulfanyl)aniline and triphosgene through isocyanate synthesis, nucleophilic addition, N-amide condensation, and alkylation reactions. The results of the inhibition activity test on human soluble epoxide hydrolase (hsEH) showed that except for 1-(4-pentafluorothiophenyl)-3-(1-(3,3,3-trifluoropropyl) piperidin-4-yl) urea, which had weaker inhibitory activity than the control substance (S) -1- (1-(2-methylbutyryl) piperidin-4-yl)-3-(4-(trifluoromethoxy) phenyl) urea, the inhibitory ability of the other six urea derivatives was stronger than the control substance. Among them, (S)-1-(1- (2-methylbutyryl) piperidin-4-yl)-3-(4-(pentafluorothio) phenyl) urea had the strongest inhibitory activity, with an IC50 of 2.4 nmol/L at a mass concentration of 2 mg/mL. The structure-activity relationship indicates that the introduction of pentafluorosulfanyl groups in the target molecule and the water solubility of N-substituted groups on the pyridine ring have a significant impact on the inhibitory activity of hsEH.

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备注/Memo

备注/Memo:
收稿日期：2023-09-27
基金项目：湖北省教育厅科学研究计划指导性项目(B2019055)
作者简介：刘思思，硕士研究生。Email：1954687582@qq.com
*通信作者：尹传奇，博士，教授。Email：zhyfyin@126.com
引文格式：刘思思，周媛，付瑞新，等. 五氟硫基脲衍生物的合成及其对人可溶性环氧化物水解酶的抑制活性［J］. 武汉工程大学学报，2025，47（5）：473-479.

更新日期/Last Update: 2025-11-03