新型苯基吡唑类衍生物的设计、合成和杀虫活性研究

doi:10.6023/cjoc202405024

有机化学 ›› 2025, Vol. 45 ›› Issue (1): 227-239.DOI: 10.6023/cjoc202405024 上一篇下一篇

研究论文

新型苯基吡唑类衍生物的设计、合成和杀虫活性研究

田海平^a, 刘东东^a^,^b, 裴鸿艳^a^,^c, 叶家麟^a, 郑子锐^a, 高一星^a, 李昌兴^a, 田欢^a, 张静^a^,^b^,^d^,^*(), 张立新^a^,^b^,^c^,^d^,^*()

a 沈阳化工大学功能分子研究所沈阳 110142
b 辽宁科技大学化学工程学院辽宁鞍山 114051
c 沈阳工业大学材料科学与工程学院沈阳 110870
d 广西思钺生物科技有限责任公司南宁 530000

收稿日期:2024-05-16 修回日期:2024-08-05 发布日期:2024-09-18
作者简介:
†共同第一作者
基金资助:
国家自然科学基金(22277081); 辽宁省自然科学基金计划(2022-KF-15-04); 辽宁省“揭榜挂帅”科技攻关计划(2022JH1/10400018)

Design, Synthesis and Insecticidal Activity of New Phenylpyrazole Derivatives

Haiping Tian^a, Dongdong Liu^a^,^b, Hongyan Pei^a^,^c, Jialin Ye^a, Zirui Zheng^a, Yixing Gao^a, Changxing Li^a, Huan Tian^a, Jing Zhang^a^,^b^,^d(), Lixin Zhang^a^,^b^,^c^,^d()

a Institute of Functional Molecules, Shenyang University of Chemical Technology, Shenyang 110142
b School of Chemical Engineering, University of Science and Technology Liaoning, Anshan, Liaoning 114051
c School of Materials Science and Engineering, Shenyang University of Technology, Shenyang 110870
d Guangxi Siyue Biotechnology Co., Ltd., Nanning 530000

Received:2024-05-16 Revised:2024-08-05 Published:2024-09-18
Contact: *E-mail: zhang-jing@syuct.edu.cn; zhanglixin@syuct.edu.cn
About author:
†These authors contributed equally to this work.
Supported by:
National Natural Science Foundation of China(22277081); Natural Science Foundation Program of Liaoning Province(2022-KF-15-04); “Jiebang Guashuai” Science and Technology Tackling Plan of Liaoning Province(2022JH1/10400018)

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摘要/Abstract

为了发现具有良好生物活性的苯基吡唑类杀虫杀螨剂, 以杀虫杀螨剂(Nicofluprole)为先导化合物, 通过生物电子等排、活性亚结构拼接等设计策略, 设计并合成了25个新型苯基吡唑类似物. 采用¹H NMR、¹³C NMR和HRMS对目标化合物进行了确认. 通过对朱砂叶螨(Tetranychus cinnabarinus)、桃蚜(Myzus persicae)、小菜蛾(Plutella xylostella)杀虫活性的初筛和复筛, 初步探讨了构效关系. 其中1-(2-氯-5-(1-(2,6-二氯-4-(七氟异丙烷-2-基)苯基)-1H-吡唑-4-基)烟酰胺)环丙烷-1-羧酸甲酯(8e)在2.5 mg/L时显示出对朱砂叶螨100%的杀螨率, 5-(1-(2-溴-6-氯-4-(七氟异丙烷-2-基)苯基)-1H-吡唑-4-基)-2-氯-N-环丙基烟酰胺(8i)在5 mg/L时显示出对桃蚜100%的杀虫率, 2-氯-N-环丙基-5-(1-(2,6-二氯- 4-(七氟异丙烷-2-基)苯基)-1H-吡唑-4-基)-N-甲基苯甲酰胺(8a)、2-氯-N-环丙基-5-(1-(2,6-二氯-4-(七氟异丙烷-2-基)苯基)-1H-吡唑-4-基)苯甲酰胺(8b)、8i在2.5 mg/L时显示出对小菜蛾100%的杀虫率. 分子对接结果表明, 化合物8e的杀螨活性的提升原因可能是酯基的引入导致相应的氢键作用增加. 本研究对新型苯基吡唑类杀虫杀螨剂的进一步优化和开发具有指导意义.

关键词: 苯基吡唑, 杀虫活性, 构效关系, 分子对接

To enhance the discovery of phenylpyrazole-based insecticides and acaricides with superior biological activity, leveraging the insecticide and acaricide of Nicoflurole as a lead compound, 25 novel phenylpyrazole analogues were designed and synthesized through the design strategies of bioelectronic rearrangement and active substructures splicing. The target compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. The insecticidal activities against Tetranychus cinnabarinus, Myzus persicae, and Plutella xylostella were preliminarily screened and rescreened to preliminarily explore structure-activity relationship. Among them, methyl 1-(2-chloro-5-(1-(2,6-dichloro-4-(perfluoropropan-2-yl)phenyl)-1H-pyrazol-4-yl)nicotin- amido)cyclopropane-1-carboxylate (8e) showed 100% mite killing efficacy against Tetranychus cinnabarinus at 2.5 mg/L. 5-(1-(2-Bromo-6-chloro-4-(perfluoropropan-2-yl)phenyl)-1H-pyrazol-4-yl)-2-chloro-N-cyclopropylnicotinamide (8i) exhibited an insecticidal efficacy of 100% against Myzus persicae at 5 mg/L. 2-Chloro-N-cyclopropyl-5-(1-(2,6-dichloro-4-(perfluoro-propan-2-yl)phenyl)-1H-pyrazol-4-yl)-N-methylbenzamide (8a), 2-chloro-N-cyclopropyl-5-(1-(2,6-dichloro-4-(perfluoropro- pan-2-yl)phenyl)-1H-pyrazol-4-yl)benzamide (8b), and 8i demonstrated an insecticidal efficacy of 100% against Plutella xylostella at 2.5 mg/L. Molecular docking studies indicated that the enhancement of 8e acaricidal activity may be due to the incorporation of ester groups leading to an increase in corresponding hydrogen bonding interactions. This study provides valuable insights for the continued optimization and development of novel phenylpyrazole insecticides and acaricides.

Key words: phenylpyrazole, insecticidal activity, structure-activity relationship, molecular docking

引用此文

田海平, 刘东东, 裴鸿艳, 叶家麟, 郑子锐, 高一星, 李昌兴, 田欢, 张静, 张立新. 新型苯基吡唑类衍生物的设计、合成和杀虫活性研究[J]. 有机化学, 2025, 45(1): 227-239.

Haiping Tian, Dongdong Liu, Hongyan Pei, Jialin Ye, Zirui Zheng, Yixing Gao, Changxing Li, Huan Tian, Jing Zhang, Lixin Zhang. Design, Synthesis and Insecticidal Activity of New Phenylpyrazole Derivatives[J]. Chinese Journal of Organic Chemistry, 2025, 45(1): 227-239.

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图/表 10

图1. 相关杀虫杀螨剂结构

Figure 1. Structure of related insecticides and acaricides

图2. 目标化合物8a~8y的设计策略

Figure 2. Design strategy of the target compounds 8a~8y

图式1. 目标化合物8a~8j的合成路线

Scheme 1. Synthetic route of target compounds 8a~8j

图式2. 目标化合物8k~8q的合成路线

Scheme 2. Synthetic route of target compounds 8k~8q

图式3. 目标化合物8r~8y的合成路线

Scheme 3. Synthetic route of target compounds 8r~8y

Compd.	Tetranychus cinnabarinus		Myzus persicae		Plutella xylostella
Compd.	100 mg/L	10 mg/L	100 mg/L	10 mg/L	100 mg/L	10 mg/L
8a	56.3	34.4	0	0	100	100
8b	—	85.4	—	40	100	100
8c	—	0	—	0	—	90
8d	—	0	—	41.7	—	68.9
8e	100	100	0	0	100	69.8
8f	100	31.6	0	0	100	13.3
8g	89.5	81.2	0	0	36.7	0
8h	0	0	0	0	100	0
8i	100	100	100	100	100	100
8j	100	100	100	100	100	100
8k	0	0	0	0	73.3	0
8l	0	0	0	0	0	0
8m	0	0	0	0	0	0
8n	0	0	0	0	0	0
8o	0	0	0	0	0	0
8p	0	0	0	0	0	0
8q	0	0	0	0	0	0
8r	0	0	0	0	0	0
8s	0	0	0	0	0	0
8t	0	0	0	0	0	0
8u	0	0	0	0	0	0
8v	0	0	0	0	0	0
8w	0	0	0	0	0	0
8x	0	0	0	0	20.7	0
8y	0	0	0	0	0	0
Nicofluprole	100	100	100	87.2	100	100
CK1	100	100	100	100	100	100

表1. 化合物8a~8y初筛杀虫活性(死亡率/%)

Table 1. Preliminary screening of insecticidal activity of compounds 8a~8y (mortality rate/%)

Compd.	Mortality rate/%
Compd.	5 mg/L	2.5 mg/L	1.25 mg/L
8b	22.2	0	0
8e	100	100	54.6
8i	100	95.3	71.6
8j	100	84.9	13.2
Nicofluprole	71	44	20.4
CK1	98.6	61.9	34.7

表2. 化合物8b、8e、8j和8k对朱砂叶螨复筛杀虫活性(死亡率/%)

Table 2. Rescreening of insecticidal activity of compounds 8b, 8e, 8j and 8k against Tetranychus cinnabarinus (mortality rate/%)

Compd.	Mortality rate/%
Compd.	5 mg/L	2.5 mg/L	1.25 mg/L
8i	100	31.1	10.2
8j	72.2	45	24.3
Nicofluprole	50.9	26.1	14.7
CK1	80.2	74.0	14.3

表3. 化合物8j和8k对桃蚜复筛杀虫活性(死亡率/%)

Table 3. Rescreening of insecticidal activity of compounds 8j and 8k against Myzus persicae (mortality rate/%)

Compd.	Mortality rate/%
Compd.	5 mg/L	2.5 mg/L	1.25 mg/L
8a	100	100	44.8
8b	100	100	83.3
8c	90	9.1	8.3
8i	100	100	33.3
8j	95	95	26.1
Nicofluprole	100	100	93.3
CK1	100	100	100

表4. 化合物8a~8c、8j和8k对小菜蛾复筛杀虫活性(死亡率/%)

Table 4. Rescreening of insecticidal activity of compounds 8a~8c, 8j and 8k against Plutella xylostella (mortality rate/%)

图3. 目标化合物8e (A, B)和对照组CK1 (C, D)的分子对接研究

Figure 3. Molecular docking studies of target compound 8e (A, B) and control group CK1 (C, D)

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新型苯基吡唑类衍生物的设计、合成和杀虫活性研究

Design, Synthesis and Insecticidal Activity of New Phenylpyrazole Derivatives

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