Chinese Journal of Organic Chemistry ›› 2023, Vol. 43 ›› Issue (8): 2826-2836.DOI: 10.6023/cjoc202212015 Previous Articles     Next Articles


王锋a,b, 陈钰b, 裴鸿艳b, 张静a,b,*(), 张立新a,b,*()   

  1. a 辽宁科技大学化学工程学院 辽宁鞍山 114051
    b 沈阳化工大学功能分子研究所 辽宁省绿色功能分子设计与开发重点实验室 沈阳市靶向农药重点实验室 沈阳 110142
  • 收稿日期:2022-12-12 修回日期:2023-02-15 发布日期:2023-04-21
  • 基金资助:
    南宁市科学研究与技术开发计划项目重大科技专项(20201043); 南宁市创新创业领军人才“邕江计划”创业(2020002-1)

Design, Synthesis and Antifungal Activities of Novel 1,2,4-Oxadiazole Derivatives Containing Piperidine

Feng Wanga,b, Yu Chenb, Hongyan Peib, Jing Zhanga,b(), Lixin Zhanga,b()   

  1. a College of Chemical Engineering, University of Science and Technology Liaoning, Anshan, Liaoning 114051
    b Shenyang Key Laboratory of Targeted Pesticides, Liaoning Key Laboratory of Green Functional Molecular Design and Development, Institute of Functional Molecules, Shenyang University of Chemical Technology, Shenyang 110142
  • Received:2022-12-12 Revised:2023-02-15 Published:2023-04-21
  • Contact: *E-mail:;
  • Supported by:
    The Nanning Scientific Research and Technology Development Program(20201043); The Nanning Innovation and Entrepreneurship Leading Talents “YongJiang Plan” Entrepreneurship Project(2020002-1)

To search the novel and efficient antifungal lead compounds, seventeen 1,2,4-oxadiazole derivatives 4a~4b and 6a~6o containing piperidine with novel chemical structures were designed and synthesized, which were based on the method of the splicing of bioactive substructures. The structures of target compounds were characterized by 1H NMR, 13C NMR and high-resolution mass spectra (HRMS), and the structure of N-(1-benzoylpiperidin-4-yl)-4-(5-(trifluoromethyl)-1,2,4-oxadia- zol-3-yl)benzamide (6e) was further confirmed by X-ray single crystal diffraction. The bioassay results showed that, at the concentration of 3.13 mg/L, the inhibition rates of N-(1-acetylpiperidin-4-yl)-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)- benzamide (6a)、N-(1-(cyclopropanecarbonyl)piperidin-4-yl)-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzamide (6c)、6etert-butyl 4-((4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzamido)methyl)piperidine-1-carboxylate (4b) and N-((1-benzoyl- piperidin-4-yl)methyl)-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzamide (6o) against Soybean rust (Phakopsora pachyrhiz) were 70%, 82%, 95%, 78% and 98%, respectively. The above activities were all better than flufenoxadiazam (30%) and control agent difenoconazole (50%). Among them, compounds 6e and 6o could still reach 80% and 75% inhibition rates, respectively at the concentration of 1.56 mg/L. Compounds 6e and 6o also showed prominent antifungal activity against corn rust (Puccinia sorghi), which inhibition rates were 92% and 90%, respectively at the concentration of 0.10 mg/L. The molecular docking simulation revealed that compound 6e has various interactions with histone deacetylase 4 (HDACs 4), and the hydrogen bonding formed with PHE 227 and PHE 226 may be an important reason for the prominent antifungal activity of compound 6e.

Key words: piperidine, 1,2,4-oxadiazole, synthesis, antifungal activity, molecular docking