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/m L浓度下,10d对粘虫的杀灭活性为40%,5×10-6 g/m L浓度下,10f和10k对蚊的幼虫的杀灭活性达70%;(iii)50×10-6 g/m L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.
In order to investigate the biological activity of novel pyrazole derivatives, a series of N-(substituted-1H-pyrazol-4-yl)-1H-pyrazole-3(5)-carboxamides with bi-heterocyclic scaffold were designed and synthesized from ethyl 5-alkyl-1Hpyrazole-3-carboxylate via several steps. The structure of all 18 target compounds were confirmed by 1H NMR and HRMS. The single crystal of 10 b 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 10 b and 10 l 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), 10 d possessing 40% lethal activity against army worm at a concentration of 600×10-6 g/m L, and 10 f, 10 k possessing 70% activity against the lava of mosquito at a concentration of 5×10-6 g/m L; iii) all compounds showed poor fungicidal activity at a concentration of 50×10-6 g/m L, except for 10 h possessing 64% inhibition rate to Phoma asparagi Sacc. and 10 q 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.