追溯世界农业的发展史，非洲蝗灾、爱尔兰马铃薯晚疫病等，都是刻骨铭心的悲剧。近年来，我国粮食产量一直稳居历史高位。“中国人要把饭碗端在自己手里，而且要装自己的粮食”，中国的农业人做到了。这种历史伟绩，化学农药功不可没。

化学农药在有力保障农业生产的同时，也给生态环境和人类健康带来诸多负面问题。同时，现有病虫草害对现有农药品种的抗性加剧导致商品药药效大幅降低，这些问题的解决，有赖于农业领域、化学化工等多领域的共同努力。开发新型高效、低毒、针对新靶标具有新作用机制的新型绿色农药，是解决问题的关键举措之一。新型绿色农药的研发，首要工作是发现具有新颖结构的先导分子。

本文以寻找新颖结构的杀菌剂先导分子为目标，开发了高效简便的苯环硫氰基化反应方法，将硫氰基引入苯胺类化合物中，设计合成了26种含硫氰基的苯胺类化合物（其中含有7个新化合物）。以琥珀酸脱氢酶抑制剂为目标，运用活性亚结构拼接、生物电子等排等药物分子设计技术，将（硫）氰基苯胺类化合物与吡唑、噻唑等各种羧酸连接，设计合成了42个含（硫）氰基的吡唑、噻唑等酰胺类化合物，目标化合物均为未见文献报道的新化合物。

采用菌丝生长速率法对所合成的化合物进行杀菌活性测定，供试菌种为：草莓灰霉病菌(Botrytis cinrea)、小麦赤霉病菌(Fusarium graminearum)、番茄早疫病菌(Alternaria solani)、苹果斑点病菌(Alternaria alternata)、黄瓜炭疽病菌(Colletotrichum lagenarium)、水稻纹枯病菌(Rhizoctonia solani)。部分目标化合物对草莓灰霉病菌和水稻纹枯病菌有较高抑制活性，其中化合物B-31和B-35对水稻纹枯病菌的EC50值分别可达到1.83和1.08µg/mL。对中间体硫氰基取代苯胺类化合物也进行了杀菌活性测试，在50µg/mL浓度下，硫氰基苯胺类化合物表现出了很好的广谱抗菌活性，其中A-16对水稻纹枯病菌的的EC50值可达到1.48µg/mL。

在水稻纹枯病活体测试实验中，硫氰基苯胺类化合物A-6和A-16对水稻叶片产生了药害，化合物B-30、B-31和B-38没有出现药害的现象，且具有更好的植物病害防治效果。化合物B-31对水稻纹枯病菌的防治率在200µg/mL浓度时为100%，对照药井冈霉素的防治率为92.1%，化合物B-21对草莓灰霉病菌有一定的防治效果。

在分子对接实验中，化合物B-2、B-21、B-31分别能与TYR-58和TRP-173等重要氨基酸残基形成稳定的氢键，与对照药啶酰菌胺对琥珀酸脱氢酶的作用位点相似，此结果为进一步探索此类活性化合物的作用靶标和分子设计提供了重要参考。

Looking back at the history of the development of world agriculture, the locust plague in Africa and the potato late blight in Ireland were all unforgettable tragedies. In recent years, my country's grain output has remained at a historically high level. "Chinese people have to take their rice bowls in their own hands, and they have to pack their own food." Chinese farmers did it. Chemical pesticides have contributed to this historical feat.

While chemical pesticides effectively guarantee agricultural production, they also bring many negative problems to the ecological environment and human health. At the same time, the intensified resistance of existing pests and weeds to existing pesticide varieties have led to a significant reduction in the efficacy of commercial drugs. The solution to these problems depends on the joint efforts of the agricultural field, chemical industry and other fields. The development of new green pesticides with high efficiency, low toxicity, and new mechanisms of action for new targets is one of the key measures to solve the problem. In the research and development of new green pesticides, the first task is to discover lead molecules with novel structures.

In this paper, with the goal of finding novel biocide lead molecules, an efficient and simple thiocyanation reaction method of benzene ring was developed, thiocyano group was introduced into aniline compounds, 26 thiocyano group-containing anilines were designed and synthesized. (which contains 7 new compounds). Aiming at succinate dehydrogenase inhibitors, using active substructure splicing, bioelectronic isosteric and other drug molecule design technologies, (thio)cyanoaniline compounds were connected with various carboxylic acids such as pyrazoles and thiazoles . 42 pyrazole amides and thiazole amides containing (thio) cyano groups were designed and synthesized. The target compounds are all new compounds that have not been reported in the literature.

The fungicidal activity of the synthesized compounds was determined by the mycelial growth rate method. The tested strains were: Botrytis cinrea、Fusarium graminearum、Alternaria solani、Alternaria alternata、Colletotrichum lagenarium and Rhizoctonia solani. Part of the target compounds had high inhibitory activities against Botrytis cinrea and Rhizoctonia solani. The compounds B-31 and B-35 had EC50 values of 1.83 and 1.08µg/mL against Rhizoctonia solani, respectively. The fungicidal activity test was also carried out on the intermediate thiocyano-substituted aniline compounds. At 50µg/mL, thiocyanoaniline compounds showed good broad-spectrum antifungal activity, and the EC50 value of A-16 against Rhizoctonia solani could reach 1.48µg/mL.

In the in vivo test experiment of Rhizoctonia solani, thiocyanoaniline compounds A-6 and A-16 caused phytotoxicity to rice leaves, while compounds B-30, B-31 and B-38 did not show phytotoxicity and had better plant disease control effect. The control rate of compound B-31 against Rhizoctonia solani was 100% at a concentration of 200 µg/mL, and the control rate of the control drug Validamycin was 92.1%. Compound B-21 had a certain control effect on Botrytis cinerea.

In the molecular docking experiment, compounds B-2, B-21 and B-31 could form stable hydrogen bonds with important amino acid residues such as TYR-58 and TRP-173, respectively, similar to the action site of the reference drug boscalid on succinate dehydrogenase. This result provides an important reference for further exploration of the target and molecular design of such active compounds.