新型N-吡唑基吡唑酰胺的合成及生物活性

doi:10.6023/cjoc201505026

摘要/Abstract

为研究新型吡唑类杂环衍生物的生物活性, 从5-烷基-1H-吡唑-3-甲酸乙酯(1)出发, 设计合成了18个具有双杂环结构的N-(取代-1H-吡唑-4-基)-1H-吡唑-3(5)-甲酰胺类化合物, 目标化合物的结构均经过核磁共振氢谱(¹H NMR)和高分辨质谱(HRMS)确证, 并通过X射线衍射法解析了目标物10b的单晶结构. 生物活性测试表明: (i)大部分目标化合物具有较好抗烟草花叶病毒活性, 其中化合物10b和10l的活性高于同浓度的对照药剂宁南霉素(Ningnanmycin)及病毒唑(Virazole); (ii)所有目标物对粘虫(Mythimna separata)和蚊幼虫(Culex pipiens pallens)具有一定的杀灭作用, 但活性普遍不高, 600×10^-6 g/mL浓度下, 10d对粘虫的杀灭活性为40%, 5×10^-6 g/mL浓度下, 10f和10k对蚊的幼虫的杀灭活性达70%; (iii) 50×10^-6 g/mL浓度下, 除10h对芦笋茎枯菌(Phoma asparagi Sacc.)有64%的抑制率, 10q对棉花立枯菌(Rhizoctonia solani)有50%的抑制率外, 其余化合物无明显杀菌活性. 上述结果表明, 此类化合物可作为杀虫剂或抗植物病毒剂先导做进一步深入研究.

关键词: 双杂环骨架, N-(1H-吡唑-4-基)-1H-吡唑-3(5)-甲酰胺, 单晶结构, 抗烟草花叶病毒活性, 杀虫活性, 杀菌活性

In order to investigate the biological activity of novel pyrazole derivatives, a series of N-(substituted-1H-pyra-zol-4-yl)-1H-pyrazole-3(5)-carboxamides with bi-heterocyclic scaffold were designed and synthesized from ethyl 5-alkyl-1H-pyrazole-3-carboxylate via several steps. The structure of all 18 target compounds were confirmed by ¹H NMR and HRMS. The single crystal of 10b was obtained in methanol, and the structural data was collected by X-ray diffraction. As the bioassay data showed, i) most of the target compounds showed good inhibition activity against tobacco mosaic virus (TMV), especially compounds 10b and 10l possessing higher activity compared to ningnanmycin or virazole at the same concentration; (ii) all compounds showed lethal activity against army worm (Mythimna separata) and the larva of mosquito (Culex pipiens pallens), 10d possessing 40% lethal activity against army worm at a concentration of 600×10^-6 g/mL, and 10f, 10k possessing 70% activity against the lava of mosquito at a concentration of 5×10^-6 g/mL; iii) all compounds showed poor fungicidal activity at a concentration of 50×10^-6 g/mL, except for 10h possessing 64% inhibition rate to Phoma asparagi Sacc. and 10q possessing 50% inhibition rate to Rhizoctonia solani. The above results showed that the bi-pyrazole compounds reported here could be used as lead compounds as anti-plant virus or insecticidal agents for further study.

Key words: bi-heterocyclic scaffold, N-(1H-pyrazol-4-yl)-1H-pyrazole-3(5)-carboxamide, single crystal, anti-TMV activity, pesticidal activity, fungicidal activity

引用此文

张大强, 徐高飞, 刘艳红, 王道全, 杨新玲, 袁德凯. 新型N-吡唑基吡唑酰胺的合成及生物活性[J]. 有机化学, 2015, 35(10): 2191-2198.

Zhang Daqiang, Xu Gaofei, Liu Yanhong, Wang Daoquan, Yang Xinling, Yuan Dekai. Synthesis and Biological Study of Novel N-(1H-Pyrazol-4-yl)-1H-pyrazole-3(5)-carboxamides[J]. Chin. J. Org. Chem., 2015, 35(10): 2191-2198.

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