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第 36 卷第 3 期 精 细 化 工 Vol.36, No.3
201 9 年 3 月 FINE CHEMICALS Mar. 2019

医药与日化原料
吡啶联异 唑啉类杂环衍生物的合成及生物活性

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杨洪亮 1,2 ，金 博 ，陈俭清 1,2 ，盛尊来 1,2*
（1. 东北农业大学 动物医学学院，黑龙江 哈尔滨 150030；2. 黑龙江省重点实验室 动物疾病防控技术
与制剂创制实验室，黑龙江 哈尔滨 150030）

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摘要：以 2-氯-5-氯甲基吡啶为原料，合成了 12 个吡啶联异唑啉类杂环衍生物（Ⅸa~l），其结构经 HNMR、
13 CNMR、MS 及 IR 确证。体外抗菌活性测试结果表明，所得目标化合物对金黄色葡萄球菌（ATCC25923）、
肺炎链球菌（ATCC49619）和粪肠球菌（ATCC29212）均有抑制作用。其中，化合物Ⅸf 和Ⅸl 对金黄色葡萄球
菌的最小抑菌浓度（MIC）均为 16 mg/L，对肺炎链球菌和粪肠球菌的 MIC 均为 32 mg/L，抗菌效果最佳；体外
驱虫活性测试结果表明：目标化合物均有驱虫效果，在质量浓度 2 g/L 下化合物Ⅸa~b 和Ⅸg~h 对蚯蚓的麻痹时
间和死亡时间均明显少于阿苯达唑，驱虫效果明显强于阿苯达唑。
关键词：吡啶联异唑啉；抗菌活性；驱虫活性；构效关系；医药原料
中图分类号：O626 文献标识码：A 文章编号：1003-5214 (2019) 03-0487-07

Synthesis and Biological Activity of Pyridinyl-4,5-2H-isoxazole

Heterocyclic Derivatives

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1,2
YANG Hong-liang , JIN Bo , CHEN Jian-qing , SHENG Zun-lai 1,2*
（1. College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, Heilongjiang, China; 2. Heilongjiang
Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, Heilongjiang, China）

Abstract: Twelve pyridinyl-4,5-2H-isoxazole heterocyclic derivatives (Ⅸa~l) were synthesized from
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2-chloro-5-chloromethylpyridine and their structures were characterized by HNMR, CNMR, MS and IR.
Antibacterial activities results indicated all of compounds exhibited potent activities against Staphylococcus
aureus (ATCC25923), Streptococcus pneumonia (ATCC49619) and Enterococcus faecalis (ATCC29212).
Especially, compounds Ⅸf and Ⅸl showed the best activities, the minimal inhibitory concentration (MIC)
values of Ⅸf and Ⅸl against Staphylococcus aureus were 16 mg/L, the MIC values of Ⅸf and Ⅸl
against Streptococcus pneumonia and Enterococcus faecalis were 32 mg/L. All the target compounds
displayed excellent anthelmintic activities, paralyzing time and death time of compounds Ⅸa, Ⅸb, Ⅸg
and Ⅸh were significantly less than those of albendazole against Indian earthworm at 2 g/L concentration,
indicating that these four compounds had much stronger anthelmintic effects than albendazole.
Key words: pyridinyl-4,5-2H-isoxazole; antibacterial activity; anthelmintic activities; structure-activity
relationship; drug materials
Foundation items: National Natural Science Foundation of China (31802227); Youth Natural Science
Foundation of Heilongjiang Province (QC2016025); University Nursing Programs for Young Scholars with
Creative Talents in Heilongjiang Province (UNPYSCT-2017003);“Young Talents” Project of Northeast
Agricultural University (17QC13)

细菌耐药性问题已成为全球面临的严峻的公共 已成为威胁人类健康的重大隐患。由于细菌能够不断
卫生安全问题，临床上多种耐药菌引起的感染性疾病 产生新的耐药机制，现有药物的有效抗菌能力正在下

收稿日期：2018-08-30; 定用日期：2018-12-04; DOI: 10.13550/j.jxhg.20180640
基金项目：国家自然科学基金（31802227）；黑龙江省青年科学基金（QC2016025）；黑龙江省普通本科高等学校青年创新人才培养计
划（UNPYSCT-2017003）；东北农业大学“青年才俊”项目（17QC13）
作者简介：杨洪亮（1987—），男，讲师，E-mail：hongl_yang@126.com。联系人：盛尊来（1979—），男，副教授，E-mail：8358410@qq.com。