CN112608307B - 一类杂环取代1,3,4-噁二唑酰肼类化合物及其制备方法和应用 - Google Patents
一类杂环取代1,3,4-噁二唑酰肼类化合物及其制备方法和应用 Download PDFInfo
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- CN112608307B CN112608307B CN202110139878.3A CN202110139878A CN112608307B CN 112608307 B CN112608307 B CN 112608307B CN 202110139878 A CN202110139878 A CN 202110139878A CN 112608307 B CN112608307 B CN 112608307B
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- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
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- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Abstract
本发明涉及一类杂环取代1，3，4‑噁二唑酰肼类化合物及其制备方法和应用。该化合物具有如通式(I)所示的结构：
Description
技术领域
本发明涉及药物化学技术领域，尤其是一种含N杂环基或1，3，4-噁二唑酰肼基取代的1，3，4-噁二唑酰肼类化合物及其制备方法与应用。
背景技术
近年来，植物真菌和细菌严重影响着全球农作物的产量和质量，植物真菌病害直接造成农作物产量下降与品质降低，给农民带来了巨大的经济损失。例如，小麦赤霉病菌(Gibberellazeae.Retch)是丝状的子囊菌，是由多种镰刀菌侵染所引起的、发生在小麦上的病害。该病菌能引起小麦苗腐、茎基腐、秆腐和穗腐，它每年给小麦种植的国家带来至少10-20％的减产。此外，水稻白叶枯病菌(Xanthomonas oryzaepv.Oryzae)是杆状的革兰氏阴性菌，该病菌能使水稻的叶片枯萎、变白，它每年给水稻种植的国家带来至少10-50％的减产。柑橘溃疡病菌(Xanthomonas axonopodis pv.Citri)会导致柑橘腐烂，在全球范围内影响着柑橘的产量。在农业生产过程中，由于传统药剂的长期使用，使得植物病原菌对其产生了一定的抗性。因此，创制新型高效、低毒、安全的绿色农药具有十分重要的意义。
据文献报道，1，3，4-噁二唑衍生物展示出了广谱生物活性，比如：抗菌、抗真菌、杀虫、除草及调节植物生长、抗肿瘤、抗炎等。根据本中心前期工作，1，3，4-噁二唑类化合物表现出较好的抗植物病原菌活性。而含氮杂环化合物具有结构多样性和生物活性多样性的特点，引起了医药化学、农药化学和有机化学领域的广泛关注。据文献报道，以吡唑、吡咯、吲哚、噻唑，噁唑等含氮杂环为母体的化合物具有广谱的医药和农药生物活性，如：杀菌、抗病毒、除草、杀虫、抗氧化、抗炎、抗癌、抗疟疾、抗肿瘤、抗结核、抗艾滋病等生物活性。另一方面，含有酰肼(-CO-NH-NH-)骨架的分子表现出杀菌、杀虫、抗病毒等生物活性。
因此，为了寻找高效杀菌的活性化合物，本发明以1，3，4-噁二唑酰肼结构作为连接链，将一系列含氮杂环基引入1，3，4-噁二唑酰肼结构中，合成一系列结构新颖的含氮杂环基团的1，3，4-噁二唑酰肼类化合物，测试其生物活性，为新农药的研发和创制提供重要的科学基础。
基于含氮杂环基的化合物的生物活性研究进展如下：
2017年，Gomha等[Gomha，S.；Dawood，K.Synthetic Utility of PyridiniumBromide：Synthesis and Antimicrobial Activity of Novel 2，4，6-TrisubstitutedPyridines Having Pyrazole Moiety[J].Journal of Heterocyclic Chemistry，2017，54，1943-1948.]设计合成了一系列三取代吡啶类化合物，对金黄色葡萄球菌的生物活性测试结果表明，当测定浓度为2.5μg/ml，化合物4j、4l的抑菌圈大小分别为9mm和10mm，优于对照药剂特比萘芬(抑菌圈大小为6mm)。
2015年，Rajurkar等[Rajurkar，V.；Lambe，S.；Deshmukh，V.Synthesis of SomeN-(4-(Ary1)-2-Thioxo-1，3-Thiazol-3(2H)-yl)Pyridine-4-Carboxamide asAntimicrobial and Anti-inflammatory Agents[J].Med chem.，2015，5，285-289.]报道了一些硫代羰基噻唑吡啶类化合物，生物活性测试结果表明，化合物IIj对肺炎杆菌和金黄色葡萄球菌的最小抑制浓度分别为36和28μg/ml，与对照药剂诺氟沙星相当(29和24μg/ml)，此外，在浓度为100μg/ml条件下，该化合物也表现出了较好的抗炎活性，抑制率为75.8％，与对照药剂布洛芬相当(抑制率为80.4％)。
1，3，4-噁二唑衍生物的生物活性研究进展如下：
2017年，Li等[Li，P.；Tian，P.Y.；Chen，Y.Z.；Song，X.P.；Xue，W.；Jin，L.H.；Hu，D.Y.；Yang，S.；Song，B.A.Novel bisthioether derivatives containing a 1，3，4-oxadiazole moiety：design，synthesis，antibacterial and nematocidal activities[J].Pest Manag.Sci.2018，74，844-852.]报道了一系列含1，3，4-噁二唑的双硫醚衍生物，并进行了生物活性测试。其中化合物4f抗水稻白叶枯病菌、水稻细菌条斑病菌、柑橘溃疡病菌的活性最好，其EC50值分别为4.82，11.15，16.57μg/mL，优于对照药剂噻菌铜和噻枯唑。同时，化合物4f在48h内抗秀丽隐杆线虫的活性最好，其LC50值为2.89μg/mL，优于对照药剂灭线磷和噻唑膦。构效关系分析表明，5位为苯环基硫醚的活性较苄基硫醚的好，苯环上为4-Cl取代基的活性优于4-F；5位基团固定时，巯基连接小基团的活性较大基团活性好。
2016年，Zhao等[Zhao，J.J.；Wang，X.F.；Li，B.L.；Zhang，R.L.；Li，B.；Liu，Y.M.；Li，C.W.；Liu，J.B.；Chen，B.Q.Synthesis and in vitro antiproliferative evaluationof novel nonsymmetrical disulfides bearing 1，3，4-oxadiazole moiety[J].Bioorg.Med.Chem.Lett.，2016，26，4414-4416.]报道了一系列不对称含双硫键的新型1，3，4-噁二唑类衍生物，生物活性测试结果表明，这些化合物对不同的癌细胞都有不同程度的抑制效果，其中化合物7j对人肝癌细胞(SMMC-7721)的抑制活性最好，其IC50值为3.40μM，化合物7a对人***细胞(Hela)的抑制活性最好，其IC50值为3.40μM，化合物7g对人肺腺癌细胞株(A549)的抑制活性最好，其IC50值6.26μM。
基于酰肼类化合物的生物活性研究进展如下：
2017年，Wang等[Wang，X.；Dai，Z.C.；Chen，Y.F.；Cao，L.L.；Yan，W.；Li，S.K.；Wang，J.X.；Zhang，Z.G.；Ye，Y.H.，Synthesis of 1，2，3-triazole hydrazidederivatives exhibiting anti-phytopathogenic activity.Eur.J.Med.Chem.2017，126，171-182.]设计合成了三氮唑甲酰肼类衍生物，初步生物活性测试表明，化合物14对水稻纹枯病菌(R.solani)及小麦赤霉菌(F.graminearum)具有很好的抗菌活性，EC50分别为0.18±0.01、0.37±0.020μg/mL，其抗菌活性优于商业杀菌剂多菌灵(EC50分别为1.32±0.18、0.60±0.050μg/mL)。
发明内容
本发明的目的之一提供了一类杂环取代1，3，4-噁二唑酰肼合物或其立体异构体、或其盐或其溶剂化物。
本发明的另一目的在提供了制备上述化合物或其立体异构体、或其盐或其溶剂化物的中间体化合物及其制备方法。
本发明还有一目的是提供了一种含有上述化合物或其立体异构体、或其盐或其溶剂化物的组合物。
本发明还有一目的是提供了上述化合物或其立体异构体、或其盐或其溶剂化物，或所述组合物的用途。
本发明另一目的是提供了利用上述化合物或其立体异构体、或其盐或其溶剂化物，或所述组合物防治农业病虫害的方法。
为实现上述目的，本发明采用了下述技术方案：
一种1，3，4-噁二唑硫醚类化合物或其立体异构体、或其盐或其溶剂化物，该化合物具有如通式(I)所示的结构：
其中，
R1选自氢、氘、硝基、卤素、羟基、氨基、巯基、任意取代或未取代的烷基、任意取代或未取代的烷氧基、任意取代或未取代的烯基、任意取代或未取代的环烷基、任意取代或未取代的芳基、任意取代或未取代的杂芳基中的一个或多个；
R3选自氢、氘、羟基、任意取代或未取代的烷基、任意取代或未取代的烯基、任意取代或未取代的烷氧基、任意取代或未取代的环烷基、任意取代或未取代的芳基、任意取代或未取代的杂芳基中的一个或多个；
其中R2选自氘、氨基、任意取代或未取代的烷基、任意取代或未取代的烷氧基、任意取代或未取代的烯基、任意取代或未取代的环烷基、任意取代或未取代的芳基、任意取代或未取代的杂芳基中的一个或多个。
进一步地，化合物具有如通式(II)所示的结构：
优选地，R1选自氢、氘、硝基、卤素、羟基、氨基、巯基、C1-C6烷基、C1-C6烯基、取代或未取代的C6-C15芳基、取代或未取代的C6-C10杂芳基中的一个或多个；
R3选自氢、氘、羟基、中的一个或多个；
R2选自氘、氨基、C1-C6烷基、C1-C6烯基、取代或未取代的C6-C15芳基、取代或未取代的C6-C10杂芳基中的一个或多个；
优选地，R1和R2各自独立地选自氢、氘、硝基、卤素、羟基、氨基、巯基、甲基、乙基、正丙基、仲丙基、正丁基、仲丁基、异丁基、苯基、苄基、吡啶基、吡唑基、吡咯基、呋喃基、噻吩基、N-甲基吡咯基、噻唑基、苯并吡咯基、
最优选地，所述化合物选自下述具体化合物：
一种制备所述化合物或其立体异构体、或其盐或其溶剂化物的中间体化合物，如下所示：
其中R1如上所述。
所述化合物或其立体异构体、或其盐或其溶剂化物的制备方法，包括：化合物在卤代物存在下生成通式(I)所示化合物的步骤。
所述的制备方法，还包括下述具体步骤：
其中R1、R2和R3如上所述。
此处用到的术语“烷基”是包括具有特定数目碳原子的支链和直链饱和烃基。例如“C1-10烷基”(或亚烷基)目的是C1、C2、C3、C4、C5、C6、C7、C8、C9和C10烷基。另外，例如“C1-6烷基”表示具有1到6个碳原子的烷基。烷基可为非取代或取代的，以使一个或多个其氢原子被其它化学基团取代。烷基的实施例包括但不限于甲基(Me)、乙基(Et)、丙基(如正丙基和异丙基)、丁基(如正丁基、异丁基、叔丁基)、戊基(如正戊基、异戊基、新戊基)及其类似物。
“烯基”是既包括直链或支链结构的烃，且具有一个或多个出现在链中任何稳定点的碳-碳双键。例如“C2-6烯基”(或亚烯基)目的是包括C2、C3、C4、C5和C6烯基。烯基的实例包括但不限于乙烯基、1-丙烯基，2-丙烯基、2-丁烯基、3-丁烯基、2-戊烯基、3-戊烯基、4-戊烯基、2-己烯基、3-己烯基、4-己烯基、5-己烯基、2-甲基-2-丙烯基、4-甲基-3-戊烯基及其类似物。
术语“环烷基”指的是环烷基，包括单-、双-或多环体系。C3-7环烷基目的是包括C3、C4、C5、C6和C7环烷基。环烷基实例包括但不限于环丙基、还丁基、环戊基、环己基、降冰片基及其类似物。此处用到的“碳环”或“碳环残余”指的是任何稳定3、4、5、6或7-元单环或双环或7、8、9、10、11、12或13-元双或三环，其可为饱和、部分不饱和、不饱和或芳香性的。这些碳环实例包括但不限于环丙基、环丁基、环丁烯基、环戊基、戊烯基、环己基、环己烯基、环庚基、环庚烯基、金刚烷基、环辛基、环辛烯基、环辛二烯、[3.3.0]双环辛烷、[4.3.0]双环壬烷、[4.4.0]双环癸烷、[2.2.2]双环辛烷、芴基、苯基、萘基、茚满基、金刚烷基、蒽基和四氢萘基(萘满)。如上所述，桥环也包含于碳环(如[2.2.2]双环辛烷)的定义中。如果没有其它说明，优选的碳环是环丙基、环丁基、环戊基、环己基和苯基。当使用术语“碳环”，目的是包括“芳基”。当一个或多个碳原子连接两个非临近碳原子出现桥环。优选的桥是一个或两个碳原子。指出的是桥总是将单环转化为双环。当环是桥连的，环的取代基也存在于桥上。
术语“芳基”指的是在环部分具有6到12个碳原子的单环或双环芳香烃基，如苯基和萘基，每个可被取代的。
术语“卤素”或“卤素原子”指的是氟、氯、溴和碘。
术语“杂芳基”指的是取代和非取代芳香5或6元单环基团，9-或10-元双环基团，和11到14元三环基团，在至少一个环中具有至少一个杂原子(O，S或N)，所述含杂原子的环优选具有1、2或3个选自O、S和N中的杂原子。含杂原子的杂芳基的每个环可含一个或两个氧或硫原子和/或由1到4个氮原子，前提是每个环中杂原子的总数是4或更少，且每个环具有至少一个碳原子。完成双环和三环基团的稠合环可仅含有碳原子，并可以是饱和、部分饱和或不饱和。氮和硫原子可任选被氧化且氮原子可任选被季铵化。双环或三环的杂芳基必须包括至少一个全芳香环，氮其它稠合环可为芳香性或非芳香性的。杂芳基可在任何环的任何可利用氮或碳原子上连接。当化合价允许，如果所述其它环是环烷基或杂环，其另外任选以＝O(氧)取代。
通过采用上述技术方案，本发明以1，3，4-噁二唑酰肼类化合物为基础，将能够提高目标化合物生物活性的氮杂环基引入到此体系中，合成一系列含氮杂环基的1，3，4-噁二唑酰肼类化合物，且发现该化合物对致病病原真菌和细菌具有良好的抑制作用，针对病原真菌[如黄瓜灰霉病菌(B.cinerea)、辣椒枯萎病原菌(F.oxysporum)、油菜菌核病菌(S.sclerotiorum)、小麦赤霉病菌(G.zeae)、马铃薯晚疫病菌(P.infestans)、蓝莓根腐病菌(P.cinnamomi)等]和病原细菌如水稻白叶枯病菌(Xanthomonas oryzae pv.oryzae，Xoo)、烟草青枯病菌(Ralstonia solanacearum，R.solanacearum)、柑橘溃疡病菌(Xanthomonas axonopodis pv.citri，Xac)等]均具有良好的抑制效果，为新农药的研发和创制提供重要的科学基础。
实施例
下面通过实施例对本发明作进一步说明。应该理解的是，本发明实施例所述方法仅仅是用于说明本发明，而不是对本发明的限制，在本发明的构思前提下对本发明制备方法的简单改进都属于本发明要求保护的范围。实施例中用到的所有原料和溶剂均为市售相应纯度产品。
实施例1：3-(二氟甲基)-1-甲基-1H-吡唑-4-羧酸甲酯的制备
将10.0g(56.8mmol)3-(二氟甲基)-1-甲基-1H-吡唑-4-羧酸溶于100mL甲醇中，再加入浓硫酸(8.0mL，85.2mmol)，75℃反应8h停止反应，脱溶后加入200mL乙酸乙酯，水洗50mL×3次，无水硫酸钠干燥，脱溶得到无色油状物10.5g，收率97.2％。
其它酯中间体化合物，采用相应的原料或取代基，参照实施例1步骤合成。
实施例2：3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰肼的制备
将10.5g(55.2mmol)3-(二氟甲基)-1-甲基-1H-吡唑-4-羧酸甲酯溶于50mL无水甲醇，再加入水合肼(6.0mL，82.8mmol)，0℃反应10h停止反应，脱溶后加入石油醚，再抽滤，将固体烘干得到白色固体8.7g，收率82.9％。
其它酰肼中间体化合物，采用相应的原料或取代基，参照实施例2步骤合成。
实施例3：5-(3-(二氟甲基)-1-甲基-1H-吡唑基)-1，3，4-噁二唑-2-羧酸甲酯的制备
将5.0g(26.3mmol)3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰肼溶于20mL三氯氧磷，再加入甲基草酰氯(3.6mL，39.4mmol)，85℃反应4h停止反应，脱溶后加入200mL乙酸乙酯，水洗50mL×3次，无水硫酸钠干燥，脱溶得到棕色固体，在加入乙醇重结晶得到白色固体3.5g收率51.5％。熔点112.2-113.7℃。
其它酯中间体化合物，采用相应的原料或取代基，参照实施例3步骤合成。
实施例4：5-(3-(二氟甲基)-1-甲基-1H-吡唑基)-N′-苯基-1，3，4-噁二唑-2-碳酰肼的制备
将0.3g(2.3mmol)5-(3-(二氟甲基)-1-甲基-1H-吡唑基)-1，3，4-噁二唑-2-羧酸甲酯加入15mL耐压瓶中，再加入氯化(1-丁基-3-甲基咪唑)(1.0g，5.81mmol)和苯肼(248.9μL，2.32mmol)，85℃反应6h后停止反应，加入80mL乙酸乙酯，水洗20mL×3次，无水硫酸钠干燥，脱溶，柱层析(洗脱剂石油醚∶乙酸乙酯＝6∶1)得黄色固体，产率15.4％，熔点178.8-179.7℃。
酰肼类目标化合物，采用相应的原料或取代基，参照实施例4步骤合成。
合成的部分含氮杂环基1，3，4-噁二唑酰肼类化合物的结构及核磁共振氢谱和碳谱数据如表1所示，物化性质如表2所示。
表1 本申请化合物的核磁共振氢谱和碳谱数据
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表2 本申请化合物的理化性质
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药理实施例1：
采用浊度法测试目标化合物对植物病原菌的抑制率，试验对象为水稻白叶枯病菌(Xoo)、烟草青枯病菌和柑橘溃疡病菌(Xac)。DMSO溶解在培养基中作为空白对照。将水稻白叶枯病菌(水稻白叶枯病原菌在M210固体培养基)放到NB培养基中，在28℃、180rpm恒温摇床中振荡培养到对数生长期备用；将烟草青枯病菌(在M210固体培养基上)放到NB培养基中，在28℃、180rpm恒温摇床中振荡培养到对数生长期备用；将柑橘溃疡病菌(在M210固体培养基上)放到NB培养基中，在28℃、180rpm恒温摇床中振荡培养到对数生长期备用。将药剂(化合物)配置成不同浓度(例：100，50μg/mL)的含毒NB液体培养基5mL加入到试管中，分别加入40μL含有植病细菌的NB液体培养基，在28-30℃、180rpm恒温摇床中振荡，其水稻白叶枯病原菌培养36h，烟草青枯病菌和柑橘溃疡病菌培养48h。将各个浓度的菌液在分光光度计上测定OD595值，并且另外测定对应浓度的含毒无菌NB液体培养基的OD595值。
本发明实施例辅以说明本发明的技术方案，但实施例的内容并不局限于此，部分目标化合物实验结果如表3所示。
表3 本申请化合物对植物病原细菌的抑制活性
从表3中可以看出，在离体试验中，目标化合物对植物致病病原菌(如水稻白叶枯病菌、柑橘溃疡病菌和猕猴桃溃疡病菌)表现出了较好的抑制活性。其中，化合物4、5、9对水稻白叶枯病菌(Xanthomonas oryzae pv.oryzae，Xoo)表现出了极好的抑制活性，其EC50为8.43-13.4μg/mL；化合物4-6、9、19和27对柑橘溃疡病菌(Xanthomonas axonopodispv.citri，Xac)表现出了极好的抑制活性，其EC50为3.98-9.60μg/mL；可用于制备抗植物致病病原细菌农药。
药理实施例1：含氮杂环基的1，3，4-噁二唑酰肼类化合物的抗致病病原真菌应用，用于小麦赤霉病菌(G.zeae)、马铃薯晚疫病菌(P.infestans)、蓝莓根腐病菌(P.cinnamomi)、辣椒枯萎病菌(F.oxysporum)、油菜菌核病菌(S.sclerotiorum)、油菜炭疽病菌(C.higginsianum)、葡萄座腔菌病菌(B.dothidea)、水稻纹枯病菌(R.solani Kühn)抗试验方法。
从表4可以看出，以噁霉灵(HM)、多菌灵(CB)、咪酰胺(PC)、氟吡菌酰胺(FP)、啶酰菌胺(BS)、嘧菌酯(AZX)为对照药剂，选用7种致病病原真菌为供试对象，采用生长速率法对部分化合物进行了生物活性测试，测试结果表明，该系列化合物极好的抗真菌活性，其中化合物2和3对小麦赤霉病菌(G.zeae)表现出了极好的抑制活性，其EC50为0.47-0.56μg/mL；化合物2和3对辣椒枯萎病菌(F.oxysporum)表现出了极好的抑制活性，其EC50为1.05-1.81μg/mL。可见本发明的化合物可用于制备抗植物致病病原真菌农药。
表4 本申请化合物对植物病原真菌的抑制活性
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Claims (1)
1.一种杂环取代1，3，4-噁二唑酰肼类化合物在防治柑橘溃疡病菌方面的用途，所述化合物选自下述具体化合物：
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