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KR-20260064878-A - 1-Aryl-1-chloro-2-vinylamides as a mosquito Juvenile Hormone Antagonist

KR20260064878AKR 20260064878 AKR20260064878 AKR 20260064878AKR-20260064878-A

Abstract

The problem that the present invention aims to solve is to provide a new insecticide composition that can act as an antagonist to insect larval hormones. More specifically, the problem that the present invention aims to solve is to provide an insecticidal compound effective for controlling harmful insects as an antagonist that inhibits hormone secretion by binding to and blocking insect larval hormone receptors, and an insecticide composition using the same.

Inventors

  • 이일영
  • 탁준형
  • 제연호
  • 임희승
  • 손데이비드 케사오라오지 난단바
  • 배송미
  • 김태균
  • 김락정
  • 최지혜
  • 최수현
  • 조연재
  • 이은선
  • 이현지
  • 박동환
  • 최재영

Assignees

  • 한국화학연구원
  • 서울대학교산학협력단

Dates

Publication Date
20260508
Application Date
20241030

Claims (7)

  1. A 1-aryl-1-chloro-2-vinylamide compound represented by the following chemical formula 1 or chemical formula 2, or a salt thereof. In the above Chemical Formula 1 or Chemical Formula 2, R is independently hydrogen, halogen, carboxylic acid, C1 - C10 alkyl group, C3 - C8 cycloalkyl group, C2 - C10 alkenyl group, C1 - C10 haloalkyl group, C1 - C10 alkoxy group, C1 - C10 alkyl carboxylate group, mono( C1 - C10 alkyl)amine group, di( C1 - C10 alkyl)amine carboxylate group, mono(halogen-substituted phenyl)amine group, 5 to 7-membered heterocycloalkylamine group containing 1 to 3 heteroatoms selected from O, N, and S, 5 to 7-membered heterocycloalkyl ester containing 1 to 3 heteroatoms selected from O, N, and S, N,N'-C1- C10 dialkylcarboxaamide , or 1 to Substituted with a 5 to 7-membered heterocycloalkyl amide containing 3 groups; A is , , , , or Replaced with; R1 is substituted with hydrogen, a halogen, a hydroxyl group, a C1 - C6 alkyl group, a C1 - C6 haloalkyl group, a C1 - C6 alkoxy group, a C1 - C6 haloalkoxy, or a C1 - C6 alkyl carboxylate group; X is O or NH and; m is an integer from 1 to 3; n is the number of substituents R, an integer from 0 to 5.
  2. A 1-aryl-1-chloro-2-vinylamide compound represented by the following chemical formula 1 or chemical formula 2, or a salt thereof. In the above Chemical Formula 1 or Chemical Formula 2, R is independently substituted with hydrogen, a halogen, a carboxylic acid, a C1 - C10 alkyl group, a C3 - C8 cycloalkyl group, a C2 - C10 alkenyl group, a C1 - C10 haloalkyl group, a C1 - C10 alkoxy group, a C1 - C10 alkyl carboxylate group, a mono( C1 - C10 alkyl)amine group, a di( C1 - C10 alkyl)amine carboxylate group, a mono(halogen-substituted phenyl)amine group, a morpholine group, a 1,1-dioxydothiomorpholine group, 1,3,4-thiadiazole-2-ylamide, or 1,3,4-oxadiazole-2-ylamide; A is , , , , or Replaced with; R1 is substituted with hydrogen, a halogen, a hydroxyl group, a C1 - C6 alkyl group, a C1 - C6 haloalkyl group, a C1 - C6 alkoxy group, a C1 - C6 haloalkoxy, or a C1 - C6 alkyl carboxylate group; X is O or NH and; m is an integer from 1 to 3; n is the number of substituents R, an integer from 0 to 5.
  3. 1-aryl-1-chloro-2-vinylamide compound or salt thereof characterized by being selected from the group below. (E)-1-(2-chloro-2-(4'-chloro-[1,1'-biphenyl]-4-yl)vinyl)pyrrolidin-2-one (Compound No. 1); (E)-1-(2-chloro-2-(4'-chloro-[1,1'-biphenyl]-4-yl)vinyl)piperidin-2-one (compound number 2); (E)-2-(2-chloro-2-(4'-chloro-[1,1'-biphenyl]-4-yl)vinyl)isoindolin-1-one (compound number 3); (E)-2-(2-chloro-2-(4'-chloro-[1,1'-biphenyl]-4-yl)vinyl)-2-azabicyclo[2.2.1]hept-5-en-3-one (Compound No. 4); (E)-1-(2-chloro-2-(4'-chloro-[1,1'-biphenyl]-4-yl)vinyl)azepan-2-one (compound number 5); (E)-3-(2-chloro-2-(4'-chloro-[1,1'-biphenyl]-4-yl)vinyl)oxazolidin-2-one (Compound No. 6); (E)-1-(2-chloro-2-(4'-chloro-[1,1'-biphenyl]-4-yl)vinyl)pyridine-2(1H)-one (Compound No. 7); (E)-4-(2-([1,1'-biphenyl]-4-yl)-2-chlorovinyl)morpholine-3-one (Compound No. 8); (E)-1-(2-([1,1'-biphenyl]-4-yl)-2-chlorovinyl)-5-methylpyrrolidin-2-one (Compound No. 9); (E)-1-(2-chloro-2-(3'-chloro-[1,1'-biphenyl]-4-yl)vinyl)piperidin-2-one (compound number 10); (E)-1-(2-chloro-2-(4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)vinyl)piperidin-2-one (compound number 11); (E)-1-(2-chloro-2-(4'-methoxy-[1,1'-biphenyl]-4-yl)vinyl)piperidin-2-one (compound number 12); (E)-1-(2-chloro-2-(3'-methoxy-[1,1'-biphenyl]-4-yl)vinyl)piperidin-2-one (Compound No. 13); (E)-1-(2-chloro-2-(4'-fluoro-[1,1'-biphenyl]-4-yl)vinyl)piperidin-2-one (compound number 14); (E)-1-(2-(4'-(tert-butyl)-[1,1'-biphenyl]-4-yl)-2-chlorovinyl)piperidin-2-one (Compound No. 15); (E)-1-(2-chloro-2-(3'-fluoro-4'-methoxy-[1,1'-biphenyl]-4-yl)vinyl)piperidin-2-one (Compound No. 16); (E)-1-(2-chloro-2-(3',4'-difluoro-[1,1'-biphenyl]-4-yl)vinyl)piperidin-2-one (Compound No. 17); (E)-1-(2-(4-bromophenyl)-2-chlorovinyl)piperidin-2-one (Compound No. 18); (E)-1-(2-(4-bromophenyl)-2-chlorovinyl)pyrrolidin-2-one (Compound No. 19); (E)-1-(2-chloro-2-(4-morpholinophenyl)vinyl)piperidin-2-one (compound number 20); (E)-1-(2-chloro-2-(4-(1,1-deoxydothiomorpholino)phenyl)vinyl)piperidin-2-one (compound number 21); (E)-1-(2-chloro-2-(4-((4-chlorophenyl)amino)phenyl)vinyl)piperidin-2-one (compound number 22); Methyl (E)-4-(1-chloro-2-(2-oxopiperidin-1-yl)vinyl)benzoate (Compound No. 23); Methyl (E)-4-(1-chloro-2-(2-oxopyrrolidine-1-yl)vinyl)benzoate (Compound No. 24); (E)-4-(1-chloro-2-(2-oxopiperidin-1-yl)vinyl)benzoic acid (compound number 25); (E)-4-(1-chloro-2-(2-oxopiperidin-1-yl)vinyl)-N,N-dimethylbenzamide (Compound No. 26); (E)-1-(2-chloro-2-(4-(1,1-deoxydothiomorpholine-4-carbonyl)phenyl)vinyl)piperidin-2-one (compound number 27); (E)-4-(1-chloro-2-(2-oxopiperidin-1-yl)vinyl)-N-(1,3,4-thiadiazole-2-yl)benzamide (Compound No. 28); (E)-4-(1-chloro-2-(2-oxopiperidin-1-yl)vinyl)-N-(5-methyl-1,3,4-oxadiazole-2-yl)benzamide (Compound No. 29); (E)-4-(2-chloro-2-(4'-chloro-[1,1'-biphenyl]-4-yl)vinyl)morpholine-3-one (compound number 30); (E)-1-(2-chloro-2-(4'-chloro-[1,1'-biphenyl]-4-yl)vinyl)-5-methylpyrrolidin-2-one (Compound No. 31); Ethyl (E)-1-(2-chloro-2-(4'-chloro-[1,1'-biphenyl]-4-yl)vinyl)-2-oxopiperidine-3-carboxylate (Compound No. 32); (E)-1-(2-chloro-2-(4'-chloro-[1,1'-biphenyl]-4-yl)vinyl)piperazine-2-one (Compound No. 33); (R,E)-1-(2-chloro-2-(4'-chloro-[1,1'-biphenyl]-4-yl)vinyl)-4-hydroxypyrrolidin-2-one (Compound No. 34); (E)-2-(2-chloro-2-(4'-chloro-[1,1'-biphenyl]-4-yl)vinyl)-2-azaspiro[4.5]decane-3-one (Compound No. 35); and Methyl (E)-1-(2-chloro-2(4'-chloro-[1,1'-biphenyl]-4-yl)vinyl)-5-oxopyrrolidine-2-carboxylate (Compound No. 36);
  4. An insecticide characterized in that the 1-aryl-1-chloro-2-vinylamide compound of any one of claims 1 to 3 has antagonist activity against insect larval hormone receptors.
  5. In Article 4, The above 1-aryl-1-chloro-2-vinylamide compound is found in Aedes albopictus , Aedes aeypti , Culex pipiens , Anopheles sinensis , Plodia interpunctella , Plutella xylostella , Spodoptera exigua , Spodoptera litura , Hyphantria cunea , Helicoverpa armigera , Riptortus clavatus, Lissorhoptrus oryzophilus , Nilaparvata lugens, Laodelphax striatellus , and Aphis An insecticide characterized by having antagonist activity against insect larval hormone receptors selected from the group consisting of *gossypii *, * Myzus persicae *, and *Bemisia tabaci *.
  6. In Article 4, An insecticide composition characterized in that the above 1-aryl-1-chloro-2-vinylamide compound has antagonist activity against insect larval hormone receptors.
  7. In Article 6, The insecticide composition described above is characterized by further comprising a carrier, a diluent, an excipient, or a surfactant.

Description

1-Aryl-1-chloro-2-vinylamide compounds as a mosquito juvenile hormone antagonist The present invention relates to an insecticide composition in which 1-aryl-1-chloro-2-vinylamide compounds exhibit insecticidal activity as mosquito larval hormone antagonists. Mosquitoes are a general term for animals belonging to the family Culicidae of the order Diptera, and along with flies and cockroaches, they are representative pests. Female mosquitoes in the egg-laying season have transmitted various diseases through cross-feeding between animals and humans to replenish their protein. Various mosquito species, including Aedes albopictus , have been distributed across many countries worldwide over the past 30 years, including Africa, the Middle East, Europe, and North and South America. They have transmitted various diseases such as malaria, Japanese encephalitis, dengue fever, chikungunya fever, and the Zika virus, and their populations have been increasing due to their remarkable vitality and reproductive capacity. Therefore, the effective control of these mosquitoes associated with human diseases is a major challenge for modern society. To date, mosquito control primarily utilizes repellents such as DEET ( N,N -diethyl- m -toluamide) and mosquito insecticides, such as pyrethroid-based agents and phosphorus-based agents like Temephos, mainly targeting adult mosquitoes. However, mosquitoes have a highly developed sense of smell, so the repellent effect disappears when the scent of the repellent fades. Furthermore, these insecticides are irritating to human skin, cause allergies, and are toxic to the environment, and insect resistance is increasing due to the long-term use of existing agents. Therefore, for mosquito control, there is a need to develop new insecticides that control not only adult mosquitoes but also larvae that appear in breeding grounds such as puddles. Insect growth regulators (IGRs) are agents that regulate hormones interfering with the normal growth, development, and reproduction of insects. They kill mosquito larvae during the larval stage or inhibit the pupal molting stage. In particular, interest in the use of IGRs is increasing as they serve as an attractive alternative to conventional chemical insecticides, as they exhibit selective toxicity to target insects while maintaining very low toxicity to non-target organisms. Insecticides of the IGR class developed and sold to date can be divided according to their mechanism of action into juvenile hormone agonists (JHAs) that interfere with the growth and physiological functions of insect larvae or adults, ecdysone agonists (EAs) that increase the molting speed of insects to induce incomplete molting, and chitin synthesis inhibitors (CSIs) that kill insects by preventing the formation of a new exoskeleton by blocking the formation of chitin, a component of the insect exoskeleton, or kill insect eggs by interfering with normal embryonic development. Juvenile hormone (JH) in insects is a hormone secreted by a pair of endocrine glands called corpora allata (CA) and is known to play a role in various physiological functions such as insect development, molting, metamorphosis, reproduction, and differentiation. Meanwhile, juvenile hormone (JH) can be divided into juvenile hormone agonists (JHA), which bind to receptors and activate them to promote hormone secretion, and juvenile hormone antagonists (JHAN), which bind to receptors and block them to inhibit hormone secretion. As a related study, Methoprene-toleran (Met), a receptor for insect larval hormones, has been identified (Jindra, M., et al., 2013), and novel insect growth regulators that can interact with Met and act as agonists or antagonists of larval hormones are being developed. Among these various types of JH-based insecticides, Methoprene and Pyriproxyfen, which are active ingredients of JHA, have served as effective mosquito insecticides. However, recent studies indicate increasing resistance to Methoprene and Pyriproxyfen in mosquitoes and other pests, making it urgent to develop new IGR-based insecticides. Recently, compounds acting as Juvenile hormone agonists (JHA) and Juvenile hormone antagonists (JHAN) have been developed and reported as Juvenile hormone (JH)-based insecticides. As prior art, Korean Published Patent Application No. 10-2018-0057914 discloses an insecticide composition containing a (1-halovinyl)benzene compound as an active ingredient that has activity as a larval hormone agonist or antagonist, Korean Registered Patent Application No. 2525510 discloses an insecticide composition containing a styryltriazole compound having activity as a larval hormone antagonist, an isomer thereof, or a pesticide-acceptable salt thereof, an insecticide product containing the same, and a method for eradicating pests using the same, and Korean Registered Patent Application No. 2650860 discloses an algaecide composition containing a 1-(1-halovinyl)arene compound. However, the inventors of the p