CN110590656B - 含吡啶酰胺的胍基类衍生物及其制备方法与应用 - Google Patents

含吡啶酰胺的胍基类衍生物及其制备方法与应用 Download PDF

Info

Publication number
CN110590656B
CN110590656B CN201910930892.8A CN201910930892A CN110590656B CN 110590656 B CN110590656 B CN 110590656B CN 201910930892 A CN201910930892 A CN 201910930892A CN 110590656 B CN110590656 B CN 110590656B
Authority
CN
China
Prior art keywords
substituent
formula
phenyl
guanidyl
pyridyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN201910930892.8A
Other languages
English (en)
Other versions
CN110590656A (zh
Inventor
张建军
梁培博
金淑惠
路慧哲
董燕红
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
China Agricultural University
Original Assignee
China Agricultural University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by China Agricultural University filed Critical China Agricultural University
Priority to CN201910930892.8A priority Critical patent/CN110590656B/zh
Publication of CN110590656A publication Critical patent/CN110590656A/zh
Application granted granted Critical
Publication of CN110590656B publication Critical patent/CN110590656B/zh
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/02—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
    • 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
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/12—Powders or granules
    • A01N25/14—Powders or granules wettable
    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
    • A01N47/44—Guanidine; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C07D213/82—Amides; Imides in position 3

Abstract

本发明公开了一种含吡啶酰胺的胍基类衍生物及其制备方法与应用，所述胍基类衍生物结构式如式Ⅰ所示。其中，R为乙基、丙基、异丙基、三氟甲基、呋喃基、吡啶基及带一个取代基的吡啶基、苯基或带有一个取代基的苯基；所述带有一个取代基的吡啶基中的取代基选自卤素、甲基、硝基中的任意一种；所述带有一个取代基的苯基中的取代基选自卤素、甲基、甲氧基、硝基中的任意一种。本发明制备的化合物反应路线简单，产物杀菌谱更广，对油菜菌核病菌、番茄灰霉病菌、苹果腐霉病菌、瓜果腐烂病菌、马铃薯早疫病菌、立枯丝核菌病和水稻纹枯病均具有良好的抑制生长作用。

Description

含吡啶酰胺的胍基类衍生物及其制备方法与应用
技术领域
本发明涉及含吡啶酰胺的胍基类衍生物及其制备方法与作为杀菌剂和杀线虫剂的应用。
背景技术
含卤素取代的吡啶杂环类化合物一直是新型农药研发的热点。此类化合物往往具有低毒高效，内吸性较好等特点。近年来，国内外已经开发出多种不同类型的商品农药，如杀菌剂啶酰菌胺、氟啶胺以及烟碱类杀虫剂吡虫啉、烯啶虫胺、啶虫脒，内吸性杀虫剂氯虫苯甲酰胺等。胍基片段可以在生理条件下完全质子化，并且在较大pH范围内保持正电性，是许多生物活性化合物中的重要结构成分。被广泛应用于医药农药等领域，如神经氨酸酶抑制剂扎那米韦，杀虫剂戊吡虫胍，广谱性杀菌剂双胍辛乙酸盐、多菌灵等；在农业化学研究中，琥珀酸脱氢酶(SDH)被认为是杀菌剂的重要靶标。在过去的几十年中，以琥珀酸脱氢酶为靶标已经研发了许多酰胺类杀菌剂剂去控制植物病虫害，如Carboxin，fluopyram，fenfuram，flutolanil和bixafen等。这些化合物揭示了酰胺结构可能是抑制真菌琥珀酸脱氢酶的关键片段。
为了研究发现新型高效安全的杀菌杀线虫剂，在国家重点研发计划子课题“基于靶标的新型酰胺类杀线虫剂的设计与活性研究”资助下，发明人组以琥珀酸脱氢酶(SDH)为靶标，将三氟甲基和氯取代的吡啶酰胺片段与不同芳香性或长链基团通过胍基连接，设计新型含吡啶的胍基类衍生物，以期达到广谱性杀菌及杀线虫的效果。通过广泛的杀菌活性，杀线虫活性测试，发现此系列化合物对不同种类真菌，卵菌均具有较好的杀菌活性，同时对南方根结线虫也具有良好的杀虫活性。
发明内容
本发明的目的是提供含吡啶酰胺的胍基类衍生物CAU2019-A及其制备方法与应用。
本发明所提供的化合物CAU2019-A的结构式如式Ⅰ所示：
Figure GDA0002273112550000021
其中，R为乙基、丙基、异丙基、三氟甲基、呋喃基、吡啶基及带一个取代基的吡啶基、苯基或带有一个取代基的苯基；所述吡啶基可以是3位连接或4位连接。
所述带有一个取代基的吡啶基中的取代基选自卤素、甲基、硝基中的任意一种，取代基可为2位取代或3位取代。
所述带有一个取代基的苯基中的取代基选自卤素、甲基、甲氧基、硝基中的任意一种，取代基可为2位取代、3位取代或4位取代。
化合物CAU2019-A的制备方法，包括下述步骤：
1)将式Ⅱ所示的化合物与式Ⅲ所示的硫甲基进行取代反应得到式Ⅳ所示的含胍基化合物；
2)式Ⅳ所示的胍基化合物经TFA-DCM脱除Boc保护，得到式Ⅰ所示化合物；
Figure GDA0002273112550000022
其中，式Ⅲ、式Ⅳ中R的定义同式Ⅰ。
本发明的含吡啶酰胺的胍基类衍生物系列化合物可以作为杀菌剂和杀线虫剂应用。
所述杀菌杀线虫剂具体可用于杀灭下述至少一种病菌：油菜菌核病菌、茄绵疫病菌、番茄灰霉病菌、稻瘟病菌、立枯丝核菌病，棉花枯萎病。并且对南方根结线虫具有良好的杀虫效果。
本发明制备化合物CAU2019-A反应路线简单，产物杀菌谱更广。杀菌活性测定结果表明，CAU2019-A对油菜菌核病菌、番茄灰霉病菌、苹果腐霉病菌、瓜果腐烂病菌、马铃薯早疫病菌、立枯丝核菌病和水稻纹枯病均具有良好的抑制生长作用。
附图说明
图1本发明的化合物CAU2019-A的结构式。
图2为化合物CAU2019-A-01的核磁共振氢谱图。
图3为化合物CAU2019-A-01的核磁共振碳谱图。
具体实施方式
下面通过具体实施例对本发明进行说明。应当注意到，这里给出的描述和实施例仅仅是为了描述本发明的具体实施方式，使技术人员更容易理解本发明，它们并非意欲限定本发明的范围。
下述实施例中所述实验方法，如无特殊说明，均为常规方法；所述试剂和材料，如无特殊说明，均可从商业途径获得。
实施例1、化合物CAU2019-A-01(R＝4-NO2-苯基)的制备及结构鉴定。
Figure GDA0002273112550000031
(1)在50mL圆底烧瓶中加入式Ⅲ-1(1.0克，2.94毫摩尔，1.0当量)；式Ⅱ(0.67g，2.94毫摩尔)，15ml二氯甲烷。室温搅拌6小时，反应结束后浓缩，浓缩物通过柱层析得白色固体1.24g,收率81.6％。
式IV-1结构确证数据如下：
1H NMR(300MHz,CDCl3)δ12.27(s,1H,NH),9.18(s,1H,NH),8.76(s,1H,ArH),8.41–8.33(m,2H,ArH),8.29–8.21(m,2H,ArH),7.89(d,J＝1.6Hz,1H,ArH),4.14(q,J＝6.3Hz,2H,CH2),3.41(t,J＝6.3Hz,2H,CH2),1.52(s,9H,CH3).13C NMR(75MHz,CDCl3)δ174.84,159.86,156.71,152.74,149.4,143.54,143.07,133.45,131.32,129.89,125.94,125.50,124.14,122.68,120.52,83.31,77.10,76.68,76.25,38.34,34.19,27.63。
(2)所得固体(式IV-1)溶于15ml含50vol％三氟乙酸(TFA)的二氯甲烷(DCM)中，室温搅拌2h，TLC监测反应完全。减压旋蒸除去TFA，饱和NaHCO3溶液调节pH至8。粗产品用石油醚/乙酸乙酯(v/v＝5：1)重结晶得白色固体0.8g，收率为80％。CAU2019-A-01(式V-1)重量1.8g。两步收率为83％。
CAU2019-A-01(式V-1)结构确证数据如下：
1H NMR(300MHz,DMSO)δ8.88(d,J＝13.1Hz,1H,ArH),8.33(d,J＝41.9Hz,1H,ArH),8.25–8.18(m,4H,ArH),7.01(s,1H,NH),3.78(d,J＝36.0Hz,2H,CH2),3.26(t,J＝6.3Hz,2H,CH2).13C NMR(75MHz,DMSO)δ172.99,161.46,148.85,144.95,144.01,134.11,131.2,129.71,124.79,122.97,121.17,38.35,35.74。
其他通式为CAU2019-A的系列化合物均按照上述方法制备得到。它们的化合物编号，R对应的取代基团、理化数据见表1，结构鉴定的核磁共振氢谱、质谱数据见表2。
表1 CAU2019-A系列部分化合物的编号、取代基团、理化数据
Figure GDA0002273112550000041
表2 CAU2019-A系列部分化合物核磁共振氢谱、质谱数据
(Pos：质谱测定的正离子模式；Neg：质谱测定的负离子模式)
Figure GDA0002273112550000042
Figure GDA0002273112550000051
Figure GDA0002273112550000061
实施例2、化合物CAU2019-A-01乳油的配制
在100mL容量瓶中加入化合物CAU2019-A-01 1～10g,乳化剂5～15g,渗透剂0.1～1g，然后用溶剂如甲苯，二甲苯等定容得活性成分重量含量为1～10％的乳油。
其他通式为CAU2019-A化合物的乳油均可按照上述方法制备得到。
实施例3、化合物CAU2019-A-01可湿性粉剂的配制
取化合物CAU2019-A-01 15～50g，表面活性剂10～20g，白碳黑30～75g，经混合粉碎后得活性成分重量含量为15～50％的可湿性粉剂。
其他通式为CAU2019-A的化合物的可湿性粉剂均可按照上述方法制备得到。
实施例4、通式为CAU2019-A的化合物的杀菌活性测定
测定方法：采用生长速率测定法，即将不同浓度的药液与融化的培养基混合，制成带毒培养基平面，在平面上接种病原菌，以病菌生长速率的快慢来判定药剂毒力的大小。通式为CAU2019-A的化合物的杀菌活性见表3。
下述供试靶标
1.瓜果腐霉病菌，病原[Pythium aphanidermatum]
2.油菜菌核病菌，病原[Sclerotinia sclerotiorum(Lib.)de Bary]
3.番茄灰霉病菌，病原[(Botrytis cinerea Pers]
4.辣椒疫霉病菌，病原[Phytophthora capsici Leonian.]
5.马铃薯早疫病菌，病原[Alternaria solani]
表3 CAU2019-A系列部分化合物50mg/L浓度下对五种植物病原菌的生长抑制率(％)
Figure GDA0002273112550000071
实施例5、通式为CAU2019-A的化合物的杀线虫活性测定
测定方法：在该实验中使用了南方根结线虫(M.incognita)。在50μg/mL浓度下，使用96-微孔板对南方根结线虫的二龄幼虫测试所有CAU2019-A系列化合物的杀线虫活性。立体显微镜用于观察线虫在48小时的死亡率。线虫被定义为如果它们的身体变直并且没有对机械接触起反应而被杀死。在相同条件下重复实验三次。通式为CAU2019-A的化合物的杀线虫活性见表4。实验方法见参考文献：Bi Y,Gao C,Yu Z.Rhabdopeptides fromXenorhabdus budapestensis SN84 and Their Nematicidal Activities againstMeloidogyne incognita[J].Journal of Agricultural and Food Chemistry,2018:acs.jafc.8b00253。
表4 CAU2019-A系列部分化合物50mg/L浓度下对南方根结线虫的生长抑制率(％)
Figure GDA0002273112550000072
Figure GDA0002273112550000081

Claims (5)

1.一种含吡啶酰胺的胍基类衍生物，结构式如式Ⅰ所示：
Figure FDA0002580539130000011
其中，R为乙基、丙基、异丙基、三氟甲基、呋喃基、吡啶基及带有一个取代基的吡啶基、苯基或带有一个取代基的苯基；所述吡啶基是3位连接或4位连接；
所述带有一个取代基的吡啶基中的取代基选自卤素、甲基、硝基中的任意一种，取代基为2位取代或3位取代；
所述带有一个取代基的苯基中的取代基选自卤素、甲基、甲氧基、硝基中的任意一种，取代基为2位取代、3位取代或4位取代。
2.权利要求1所述的含吡啶酰胺的胍基类衍生物的制备方法，包含以下步骤：
1)将式Ⅱ所示的化合物与式Ⅲ所示的化合物进行取代反应得到式Ⅳ所示的含胍基化合物；
2)式Ⅳ所示的含胍基化合物经TFA-DCM脱除Boc保护，得到式Ⅰ所示化合物；
Figure FDA0002580539130000012
其中，式Ⅲ、式Ⅳ中R的定义同式Ⅰ。
3.权利要求1所述的含吡啶酰胺的胍基类衍生物作为杀菌剂和杀线虫剂的应用。
4.一种乳油型农药，由以下重量配比的物质组成：权利要求1所述的含吡啶酰胺的胍基类衍生物1～10％、乳化剂5～15％、渗透剂0.1～1％、余量为有机溶剂。
5.一种可湿性粉剂农药，由以下重量配比的物质组成：权利要求1所述的含吡啶酰胺的胍基类衍生物15～50％、表面活性剂10～20％，白碳黑30～75％。
CN201910930892.8A 2019-09-27 2019-09-27 含吡啶酰胺的胍基类衍生物及其制备方法与应用 Expired - Fee Related CN110590656B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910930892.8A CN110590656B (zh) 2019-09-27 2019-09-27 含吡啶酰胺的胍基类衍生物及其制备方法与应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910930892.8A CN110590656B (zh) 2019-09-27 2019-09-27 含吡啶酰胺的胍基类衍生物及其制备方法与应用

Publications (2)

Publication Number Publication Date
CN110590656A CN110590656A (zh) 2019-12-20
CN110590656B true CN110590656B (zh) 2020-10-09

Family

ID=68864400

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910930892.8A Expired - Fee Related CN110590656B (zh) 2019-09-27 2019-09-27 含吡啶酰胺的胍基类衍生物及其制备方法与应用

Country Status (1)

Country Link
CN (1) CN110590656B (zh)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114292225B (zh) * 2022-01-10 2023-07-11 万华化学集团股份有限公司 一种季铵型强碱性阴离子交换树脂及其催化制备甲基丙烯酸缩水甘油酯的方法

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL96436A0 (en) * 1989-11-28 1991-08-16 Ishihara Sangyo Kaisha Pyridylcarbamates,their preparation and biocidal compositions containing them
US6110925A (en) * 1997-08-07 2000-08-29 Research Corporation Technologies, Inc. Antibiotic for methicillin resistant bacteria
JP5611535B2 (ja) * 2008-04-17 2014-10-22 石原産業株式会社 有害生物防除剤組成物及び有害生物の防除方法
CN102216288A (zh) * 2008-11-17 2011-10-12 石原产业株式会社 吡啶衍生物或其盐、包含其的农药及其制备方法
CN102070607A (zh) * 2011-01-25 2011-05-25 南京农业大学 具有杀虫活性的吡啶氮氧化物类新烟碱化合物及其用途
BR112018076800A2 (pt) * 2016-07-29 2019-04-02 Toray Industries, Inc. derivado de guanidina, medicamento, inibidor da proteína 1 da translocação de linfoma de tecido linfóide associado com mucosa, e, agente terapêutico ou profilático.
CN106905193B (zh) * 2017-02-15 2018-11-27 中国药科大学 芳酰基胍基奥司他韦羧酸衍生物及其制备方法和应用

Also Published As

Publication number Publication date
CN110590656A (zh) 2019-12-20

Similar Documents

Publication Publication Date Title
CA2100011C (en) Amide compounds and their salts, processes for their production and pesticidal compositions containing them
Zhao et al. Design, synthesis and insecticidal activity of novel phenylpyrazoles containing a 2, 2, 2-trichloro-1-alkoxyethyl moiety
US7442672B2 (en) Picolinamine derivatives and their use as fungicides
JP2020128397A (ja) ジアリールアゾール化合物および有害生物防除剤
EP0256503A2 (en) Pyridinecarboxamide derivatives and their use as fungicide
KR100314350B1 (ko) 치환된 트리아졸리논
KR20020058089A (ko) 살진균제로서의 피라졸카복스아미드 및 피라졸티오아미드
KR20020063277A (ko) 살균제로서의 트리플루오로메틸피롤카복사미드 및트리플루오로메틸피롤티오아미드
WO2007093599A1 (en) Pyridin-4 -ylmethylamides for combating pests
JP7315563B2 (ja) ヘテロアリールアゾール化合物および有害生物防除剤
CN109320471A (zh) 3-(2,6-二氟苯基)-1,2,4-噁二唑类化合物及其应用
CN110590656B (zh) 含吡啶酰胺的胍基类衍生物及其制备方法与应用
Zhao et al. Synthesis of novel pesticidal n, n′-disubstituted sulfamide derivatives using sulfur (vi) fluorine exchange click reaction
JPH0249281B2 (zh)
CN106008390A (zh) 一种含1,3,4-噁二唑硫基乙酰胺衍生物、制备方法及其应用
CN106831647B (zh) 一种噻二唑酰胺类化合物及其用途
CN109232550B (zh) 一种含3-氯-5-三氟甲基吡啶基-1,3,4-噁二唑-2-酮类化合物及其应用
TW202110803A (zh) 化合物、有害生物防治劑、殺蟲或殺蟎劑、外部寄生蟲防治劑以及內部寄生蟲防治或驅除劑
Wu et al. Design, Synthesis, and Fungicidal Activity against Rice Sheath Blight of Novel N-Acyl-1, 2, 3, 4-tetrahydroquinoline Derivatives
CN107074770B (zh) 新颖的杀真菌的吡啶脒
JP7071962B2 (ja) ピリドン化合物と有害生物防除剤を含有する有害生物防除組成物および有害生物の防除方法
EP4219491A1 (en) Imidazo[1,2-a]pyridine compound and pest control agent
CN106045982A (zh) N’‑5‑（取代苯基)‑2‑呋喃甲酰基‑5‑丙基‑1h‑吡唑‑3‑甲酸乙酯类化合物及其制备方法和应用
CN109232534B (zh) 含杂环二芳胺基吡唑甲酰胺类化合物及其制备方法与应用
JP7118961B2 (ja) ピリドン化合物およびそれを有効成分とする農園芸用殺菌剤

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20201009

Termination date: 20210927